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Hay, K David; Gear, Kim J
The aims of management of patients with xerostomia include the provision of a definitive aetiology and diagnosis, and a prognosis for the salivary dysfunction. Salivary flow assessment and function testing, other relevant laboratory tests, and even referrals should be performed as necessary. Management of the condition depends on diagnosis and severity, and includes enhancement of salivary flow, oral lubrication, control of soft-tissue infections and discomfort, and prevention of dental caries. PMID:12125329
Xerostomia in hereditary gelsolin amyloidosis.
Juusela, Pirjo; Tanskanen, Maarit; Nieminen, Anja; Kari, Kirsti; Suominen, Liisa; Uitto, Veli-Jukka; Kiuru-Enari, Sari
Hereditary gelsolin amyloidosis (AGel amyloidosis) is a rare, dominantly inherited systemic disease with worldwide distribution, caused by c.654G > A or c.654G > T gelsolin gene mutation. The disease mainly manifests with late-onset dystrophy of the cornea, laxity of the skin and dysfunction of the cranial nerves whereas the oral manifestations have remained less-studied. To examine if AGel amyloidosis also affects salivary gland function, we studied 27 patients. In a questionnaire, 89% of them reported oral dryness, and 74% oral and ocular dryness. Unstimulated (UWS) and stimulated whole salivary flow (SWS) rates were measured, and salivary proteins were analyzed in the patients and controls. Hyposalivation according to UWS was detected in 67% of the patients, while decreased SWS occurred in 63% of the patients and 19% of the controls (p = 0.001). The secretion rates of salivary total protein and IgA were significantly lower in patients than controls. Histopathological analyses of labial salivary gland biopsies showed deposition of gelsolin amyloid, atrophy and inflammation. This study showed that AGel amyloidosis belongs to the differential diagnostic choices to be kept in mind in the patients presenting with xerostomia, low secretion rates of salivary total protein and IgA and/or deposition of amyloid in the minor salivary glands. AGel amyloidosis patients should be advised for efficient dental care. PMID:23356404
Different Saliva Substitutes for Treatment of Xerostomia Following Radiotherapy
Felix Momm; Natalja Jurievna Volegova-Neher; Jürgen Schulte-Mönting; Roland Guttenberger
Background and Purpose: Xerostomia is an important chronic side effect of radiotherapy in the head and neck area. The authors investigated the efficacy of different artificial saliva compounds in patients with postirradiation xerostomia. Patients and Methods: In 120 patients with xerostomia after radiotherapy for head and neck cancer, four different saliva substitute compounds (gel, carmellose spray, oil, mucin spray) were
Metabolic Imaging Biomarkers of Postradiotherapy Xerostomia
Cannon, Blake [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Schwartz, David L., E-mail: firstname.lastname@example.com [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Medicine, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, New York (United States); Feinstein Institute for Medical Research, Manhasset, New York (United States); Dong Lei [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)] [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)
Purpose: Xerostomia is a major complication of head and neck radiotherapy (RT). Available xerostomia measures remain flawed. [{sup 18}F]fluorodeoxyglucose-labeled positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-RT xerostomia. Methods and Materials: Ninety-eight locally advanced head and neck cancer patients receiving definitive RT underwent baseline and post-RT FDG-PET-CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled in a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre- and post-RT standard uptake values (SUVs) for all voxels contained within parotid gland ROI were deformably registered. Results: Average whole-gland or voxel-by-voxel models incorporating parotid D{sub Met} (defined as the pretreatment parotid SUV weighted by dose) accurately predicted posttreatment changes in parotid FDG uptake (e.g., fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by posttreatment salivary output (p < 0.01) and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia scores (p < 0.01). Conclusions: In this pilot series, loss of parotid FDG uptake was strongly associated with acute clinical post-RT parotid toxicity. D{sub Met} may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET-CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing.
Treatment of xerostomia following radiotherapy: does age matter?
Felix Momm; Roland Guttenberger
The goals of this work were to investigate the effect of a mucin-containing spray on chronic xerostomia after radiotherapy in the head and neck region and to learn about the influence of age on the results of this treatment. A total of 73 patients with xerostomia following radiotherapy for various malignant disease in the head and neck region tested a
Type 1 diabetes mellitus, xerostomia, and salivary flow rates
Paul A. Moore; James Guggenheimer; Kenneth R. Etzel; Robert J. Weyant; Trevor Orchard
Objective: The Oral Health Science Institute at the University of Pittsburgh has completed a cross-sectional epidemiologic study of 406 subjects with type 1 diabetes and 268 control subjects without diabetes that assessed the associations between oral health and diabetes. This report describes the prevalence of dry-mouth symptoms (xerostomia), the prevalence of hyposalivation in this population, and the possible interrelationships between
Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment
H.-J. Guchelaar; A. Vermes; J. H. Meerwaldt
Xerostomia, or oral dryness, is one of the most common complaints experienced by patients who have had radiotherapy of the\\u000a oral cavity and neck region. The hallmarks of radiation-induced damage are acinar atrophy and chronic inflammation of the\\u000a salivary glands. The early response, resulting in atrophy of the secretory cells without inflammation might be due to radiation-induced\\u000a apoptosis. In contrast,
Radiotherapy induced xerostomia: mechanisms, diagnostics, prevention and treatment--evidence based up to 2013.
Ka?u?ny, Jaros?aw; Wierzbicka, Ma?gorzata; Nogala, Hanna; Milecki, Piotr; Kope?, Tomasz
Definition and prevalence of xerostomia were shortly presented. Radiosensitivity of the salivary glands, mechanism, diagnostics, and possible prediction methods of the intensity of xerostomia in the pre-radiotherapy period are widely discussed. Prevention of xerostomia: salivary gland sparing radiotherapy, cytoprotective agents, preservation by stimulation with cholinergic muscarinic agonists, surgical transfer of submandibular glands according to ASCO Management Guidelines and Quality of Life Recommendations were cited. Oral Care Study Group (2010) therapeutic approaches for relieving xerostomia are referred. Current therapies, restricted to symptom relief such as oral hygiene with fluoride agents, antimicrobials to prevent dental caries, saliva substitutes to relieve symptoms, and sialogenic agents to stimulate saliva were also discussed. PMID:24484943
Postradiotherapy quality of life for head-and-neck cancer patients is independent of xerostomia
Ringash, Jolie [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada)]. E-mail: email@example.com; Warde, Padraig [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Lockwood, Gina [Department of Biostatistics, Princess Margaret Hospital and the University of Toronto, Toronto, ON (Canada); O'Sullivan, Brian [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Waldron, John [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada); Cummings, Bernard [Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Toronto, ON (Canada)
Purpose: To determine the relationship between quality of life (QOL) and xerostomia over time for patients undergoing radiotherapy (RT) for head-and-neck cancer in a prospective clinical trial. Methods and materials: Patients with head-and-neck cancer were randomized to pilocarpine (n = 65) vs. placebo (n = 65) during RT. QOL was measured using the McMaster Head and Neck Radiotherapy Questionnaire (HNRQ). Xerostomia was measured on a linear analog scale. No statistically significant differences were observed between arms; all 130 patients were analyzed together. Results: Baseline QOL data were obtained for 98.5% of participants. The baseline HNRQ score of 5.7 declined significantly to 4.0 (p <0.0001) by RT Week 6 and returned to baseline (5.8) by 6 months after treatment. This represents a large, clinically important change of 1.7 of 7 (24%; effect size 1.34). The decline in HNRQ score during RT paralleled the onset of xerostomia on the linear analog scale (r = 0.36 at 1 month). After treatment, the QOL scores recovered without improvement in xerostomia. The trajectory of the linear analog scale score resembled that of the HNRQ's single xerostomia question (r = 0.75 at 1 month). Conclusion: Quality of life recovers to baseline after RT, despite persistent xerostomia. Either a response shift occurs or xerostomia in the absence of acute mucositis has a relatively small influence on overall QOL.
Xerostomia Due to Systemic Disease: A Review of 20 Conditions and Mechanisms
Mortazavi, H; Baharvand, M; Movahhedian, A; Mohammadi, M; Khodadoustan, A
Xerostomia is a common complaint of nearly half of the elderly population and about one-fifth of younger adults. It causes several signs and symptoms, and compromise oral functions and health-related quality-of-life. Multiple reasons are proposed to describe the etiology of xerostomia such as local factors, psychogenic factors, and systemic diseases. In order to manage xerostomia effectively, identification of the main causality is mandatory. The aim of this review was to present systemic diseases leading to xerostomia with their mechanisms of action. We used various general search engines and specialized databases such as Google, Google Scholar, Yahoo, PubMed, PubMed Central, MedLine Plus, Medknow, EBSCO, ScienceDirect, Scopus, WebMD, EMBASE, and authorized textbooks to find relevant topics by means of Medical Subject Headings keywords such as "xerostomia," "hyposalivations," "mouth dryness," "disease," and "systemic." We appraised 97 English-language articles published over the last 40 years in both medical and dental journals including reviews, meta-analysis, original papers, and case reports. Upon compilation of relevant data, it was concluded that autoimmune diseases most frequently involve salivary glands and cause xerostomia followed by diabetes mellitus, renal failure, and graft-versus-host disease. Moreover, the underlying mechanisms of systemic disease-related xerostomia are: autoimmunity, infiltration of immunocompetent cells, granuloma formation, fibrosis and dehydration, deposition of proteinaceous substances, bacterial infection, and side-effects of medications. PMID:25221694
Impact of Radiation-Induced Xerostomia on Quality of Life After Primary Radiotherapy Among Patients With Head and Neck Cancer
Jellema, Anke Petra [Department of Radiation Oncology, University Medical Center, Utrecht (Netherlands); Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)], E-mail: firstname.lastname@example.com; Slotman, Ben J.; Doornaert, Patricia [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Leemans, C. Rene M.D. [Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands)
Purpose: To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy. Methods and Materials: A total of 288 patients with Stage I-IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy. Results: A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001). A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18-65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia. Conclusions: The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade {>=}2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia.
Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life
CM van Rij; W. D. Oughlane-Heemsbergen; A. H. Ackerstaff; E. A. Lamers; A. J. M. Balm; C. R. N. Rasch
BACKGROUND AND PURPOSE: To assess the impact of intensity modulated radiotherapy (IMRT) versus conventional radiation on late xerostomia and Quality of Life aspects in head and neck cancer patients. PATIENTS AND NETHODS: Questionnaires on xerostomia in rest and during meals were sent to all patients treated between January 1999 and December 2003 with a T1-4, N0-2 M0 head and neck
Xerostomia, Hyposalivation, and Oral Microbiota in Type 2 Diabetic Patients: A Preliminary Study
Tongchat Suwantuntula DDS; Soisiri Thaweboon DDS; Somsak Mitrirattanakul DDS; Weerapan Khovidhunkit
Background and Objective: Mouth dryness is one of the major problems that can lead to several oral diseases such as dental caries, periodontitis and oral infection. Mouth dryness has also been associated with type 2 diabetes mellitus (DM). The objective of the present study was to investigate the prevalence of xerostomia (feeling of mouth dryness), hyposalivation (the reduction of saliva),
Effectiveness of malic acid 1% in patients with xerostomia induced by antihypertensive drugs
Guardia, Javier; Aguilar-Salvatierra, Antonio; Cabrera-Ayala, Maribel; Maté-Sánchez de-Val, José E.; Calvo-Guirado, José L.
Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student's T-test was used to analyse salivary flows. Critical p-value was established at p<0.05. Results: DMQ scores increased significantly (clinical recovery) from 1.21 to 3.36 points (p<0.05) after malic acid (1%) application whereas DMQ scores increased from 1.18 to 1.34 points (p>0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p<0.05). After placebo application unstimulated flow ranged from 0.152 to 0.146 mL/min and stimulated flow increased from 0.67 to 0.70 mL/min (p>0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva. Key words:Xerostomia, hyposialia, malic acid, antihypertensive drugs. PMID:22926481
Clinical management of salivary gland hypofunction and xerostomia in head and neck cancer patients: successes and barriers*
Vissink, Arjan; Mitchell, James B; Baum, Bruce J; Limesand, Kirsten H; Jensen, Siri Beier; Fox, Philip C; Elting, Linda S; Langendijk, Johannes A; Coppes, Robert P; Reyland, Mary E
The most significant long-term complication of radiotherapy in the head and neck region is hyposalivation and its related complaints, particularily xerostomia. This paper addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to: (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy. PMID:20970030
Clinical Management of Salivary Gland Hypofunction and Xerostomia in Head-and-Neck Cancer Patients: Successes and Barriers
Vissink, Arjan [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Grongingen (Netherlands); Mitchell, James B. [Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD (United States); Baum, Bruce J. [Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Limesand, Kirsten H. [Department of Nutritional Sciences, University of Arizona, Tucson, AZ (United States); Jensen, Siri Beier [Department of Oral Medicine, Institute of Odontology, Faculty of Health Sciences, University of Copenhagen, Copenhagen (Denmark); Fox, Philip C. [PC Fox Consulting, Spello (Italy); Elting, Linda S. [Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Department of Cell Biology, Section of Radiation and Stress Biology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Reyland, Mary E., E-mail: email@example.com [Department of Craniofacial Biology, University of Colorado Denver, Aurora, CO (United States)
The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.
Xerostomia After Treatment for Oral and Oropharyngeal Cancer Using the University of Washington Saliva Domain and a Xerostomia-Related Quality-of-Life Scale
Rogers, Simon N., E-mail: email@example.com [Evidence-Based Practice Research Centre, Faculty of Health, Edge Hill University, Ormskirk (United Kingdom); Regional Maxillofacial Unit, University Hospital Aintree, Liverpool (United Kingdom); Johnson, Ian A. [Faculty of Medicine, University of Liverpool, Liverpool (United Kingdom); Lowe, Derek [Evidence-Based Practice Research Centre, Faculty of Health, Edge Hill University, Ormskirk (United Kingdom)
Purpose: The first aim of this study was to identify which clinical factors are associated with xerostomia in patients after treatment for oral and oropharyngeal squamous cell carcinoma, using the Xerostomia-Related Quality-of-Life Scale (XeQoLS) and the University of Washington Quality-of-Life Questionnaire Version 4 dry mouth item (UW-QOL v4). The second aim was to compare these two questionnaires and postulate a cutoff in the UW-QOL below which patients are doing sufficient badly to warrant further evaluation and support. Methods and Materials: In all, 371 patients alive and disease free treated between 1992 and 2005 were sent the survey, of whom 250 (67%) responded. Various clinical factors correlated with xerostomia, particularly adjuvant radiotherapy and Pstage. Results: In logistic regression analyses to predict three or more problems on the XeQoLS, only adjuvant radiotherapy (p < 0.001) was significant at the 5% level. There were significant (p < 0.001) correlations between the XeQoLS scores (total average and domain) with all the UW-QOL domain scores, the strongest with swallowing (-0.69), taste (-0.64), chewing (-0.64), mood (-0.60), and saliva (-0.59) domains. Patients scoring <70 (i.e., 0 or 30) on the UW-QOL could be used as a screening cutoff because it formed 1 in 5 of all patients (49/242) but accounted for half (299/566) of the significant problems generated by the XeQoLS. This also identified 13/21 patients with 10 or more problems. Conclusion: The UW-QOL saliva domain seems to be a suitable means of screening for dry mouth in head-and-neck clinics and could be used to trigger interventions.
Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer
Avraham Eisbruch; Hyungjin M Kim; Jeffrey E Terrell; Lon H Marsh; Laura A Dawson; Jonathan A Ship
Purpose: To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy (RT) for head-and-neck cancer, and to find the patient and therapy-related factors that affect its severity.Patients and Methods: From March 1994 through January 2000, 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT (IMRT) aiming to spare the major salivary glands. Before RT and periodically
Evaluation of Radiation-induced Xerostomia in Patients with Nasopharyngeal Carcinomas
Mohammadi, Narmin; Seyyednejhad, Farshad; Alizadeh Oskoee, Parnian; Savadi Oskoee, Siavash; Mofidi, Niloofar
Background and aims Salivary glands are extremely susceptible to radiation injuries. The aim of this study was to evaluate radiation-induced xerostomia in patients with nasopharyngeal carcinomas, referring to Tabriz Imam Khomeini Hospital in 2005-2006. Materials and methods Thirty patients with nasopharyngeal carcinomas, who received conventional radiotherapy, were included in the present study. The patients' unstimulated saliva samples were collected at three intervals, i.e. before treatment, 3 weeks after the initiation of treatment and at the end of treatment by spitting, and measured with a graduated pipette. Results The differences in the mean values of the patients' salivary flow rates at three afore-mentioned intervals were statistically significant (p<0.001). Two-by-two comparison of the mean values of salivary flow rates of all the patients and of males and females, carried out separately, demonstrated statistically significant differences (p<0.0025). However, there were no statistically significant differences between males and females before treatment (p = 0.723), 3 weeks after the initiation of treatment (p = 0.724) and at the end of treatment (p = 0.595). There were no statistically significant relationships between age and a decrease in salivary flow rate in the total sample (p = 0.76, r = -0.057), in males (p = 0.96, r = 0.011) and in females (p = 0.539, r = -0.208). Conclusion Conventional radiotherapy results in severe xerostomia in 3 weeks in patients with nasopharyngeal carcinomas. Age and sex do not influence radiotherapy-induced xerostomia. PMID:23277836
Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy
Sasportas, Laura S.; Hosford, Andrew T.; Sodini, Maria A.; Waters, Dale J.; Zambricki, Elizabeth A.; Barral, Joëlle K.; Graves, Edward E.; Brinton, Todd J.; Yock, Paul G.; Le, Quynh-Thu; Sirjani, Davud
Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%–85% of the patients. Not only does xerostomia significantly impair patients' quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape. PMID:23643579
Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer
Meirovitz, Amichay [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Murdoch-Kinch, Carol Anne [School of Dentistry, University of Michigan, Ann Arbor, MI (United States); Schipper, Mathew [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Department of Biostatistics, University of Michigan, Ann Arbor, MI (United States); Pan, Charlie [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States)]. E-mail: firstname.lastname@example.com
Purpose: To assess observer-based vs. patient self-reported scoring of xerostomia after intensity-modulated radiotherapy (IMRT) of head-and-neck (HN) cancer. Methods: A total of 38 patients who had received IMRT for HN cancer underwent xerostomia evaluations 6 to 24 months after completion of therapy using three methods each time: (1) Grading by 3 observers according to the Radiotherapy Oncology Group/European Organization for Research and Therapy of Cancer (RTOG/EORTC) system; (2) patient self-reported validated xerostomia questionnaire (XQ); and (3) major salivary gland flow measurements. Results: The interobserver agreement regarding the RTOG/EORTC grades was moderate: {kappa}-coefficient 0.54 (95% CI = 0.31-0.76). The correlations between the average RTOG/EORTC grades and the salivary flow rates were not statistically significant. A trend for significant correlation was observed between these grades and the percent (relative to the pretherapy) nonstimulated salivary flow rates (p = 0.07), but not with the percent stimulated flow rates. Better correlations were found between grading made more than the median time (15 min) after the last liquid sipping and the nonstimulated (but not the stimulated) flows compared with grading made shortly after sipping. In contrast, significant correlations were found between the XQ scores and the nonstimulated (p < 0.005) and the stimulated (p < 0.005) salivary flow rates, as well as with the percentages of the corresponding pretherapy values (p = 0.002 and 0.038, respectively). No significant correlation was found between the RTOG/EORTC grades and the XQ scores. The observer-based grades underestimated the severity of xerostomia compared with the patient self-reported scores. Conclusions: Patient self-reported, rather than physician-assessed scores, should be the main end points in evaluating xerostomia.
LASSO NTCP predictors for the incidence of xerostomia in patients with head and neck squamous cell carcinoma and nasopharyngeal carcinoma.
Lee, Tsair-Fwu; Liou, Ming-Hsiang; Huang, Yu-Jie; Chao, Pei-Ju; Ting, Hui-Min; Lee, Hsiao-Yi; Fang, Fu-Min
To predict the incidence of moderate-to-severe patient-reported xerostomia among head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Multivariable normal tissue complication probability (NTCP) models were developed by using quality of life questionnaire datasets from 152 patients with HNSCC and 84 patients with NPC. The primary endpoint was defined as moderate-to-severe xerostomia after IMRT. The numbers of predictive factors for a multivariable logistic regression model were determined using the least absolute shrinkage and selection operator (LASSO) with bootstrapping technique. Four predictive models were achieved by LASSO with the smallest number of factors while preserving predictive value with higher AUC performance. For all models, the dosimetric factors for the mean dose given to the contralateral and ipsilateral parotid gland were selected as the most significant predictors. Followed by the different clinical and socio-economic factors being selected, namely age, financial status, T stage, and education for different models were chosen. The predicted incidence of xerostomia for HNSCC and NPC patients can be improved by using multivariable logistic regression models with LASSO technique. The predictive model developed in HNSCC cannot be generalized to NPC cohort treated with IMRT without validation and vice versa. PMID:25163814
Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice
Yeh, Chih-Ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-Hee Patricia; Jorgensen, James; MacDougall, Mary; Abboud-Werner, Sherry
Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita ?/? mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita ?/? and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita ?/? mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita ?/? teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia and hyposalivation may provide a useful strategy for preventing the dental complications of diabetes and promoting oral health in this population. PMID:22449801
Treatment Planning Constraints to Avoid Xerostomia in Head-and-Neck Radiotherapy: An Independent Test of QUANTEC Criteria Using a Prospectively Collected Dataset
Moiseenko, Vitali, E-mail: firstname.lastname@example.com [Department of Medical Physics, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC (Canada); Wu, Jonn [Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC (Canada); Hovan, Allan [Department of Oral Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC (Canada); Saleh, Ziad; Apte, Aditya; Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Harrow, Stephen [Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC (Canada); Rabuka, Carman; Muggli, Adam [Department of Oral Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC (Canada); Thompson, Anna [Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, Vancouver, BC (Canada)
Purpose: The severe reduction of salivary function (xerostomia) is a common complication after radiation therapy for head-and-neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group and by Ortholan et al. We perform a validation test of these guidelines against a prospectively collected dataset and compared with a previously published dataset. Methods and Materials: Whole-mouth stimulated salivary flow data from 66 head-and-neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50 patients at 3 months, and 60 patients at 12-month follow-up. Previously published data from a second institution, Washington University in St. Louis (WUSTL), were used for comparison. A logistic model was used to describe the incidence of Grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value [NPV]) was computed for both the QUANTEC constraints and Ortholan et al. recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%. Results: Both datasets showed a rate of xerostomia of less than 20% when the mean dose to the least-irradiated parotid gland is kept to less than 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D{sub 50} = 32.4 Gy and and {gamma} = 0.97. NPVs for QUANTEC guideline were 94% (BCCA data), and 90% (WUSTL data). For Ortholan et al. guideline NPVs were 85% (BCCA) and 86% (WUSTL). Conclusion: These data confirm that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy.
... High School and College Students Recent College Graduates Dental and Medical Students See All Careers & Training Opportunities Job Openings ... and speaking can increase your chance of developing dental decay and other ... by certain medications or medical treatments Dry mouth is not a normal part ...
... of baking soda in one cup of warm water. When radiation therapy starts, use fluoride rinses and gels. These are ... for the health of your mouth during cancer treatment. Drink sips of water throughout the day, and use artificial saliva to ...
SU-E-T-399: Determination of the Radiobiological Parameters That Describe the Dose-Response Relations of Xerostomia and Disgeusia From Head and Neck Radiotherapy
Mavroidis, P; Stathakis, S; Papanikolaou, N [University of Texas Health Science Center, UTHSCSA, San Antonio, TX (United States); Peixoto Xavier, C [University of Coimbra, Coimbra, Coimbra (Portugal); Costa Ferreira, B [University of Aveiro, Coimbra, Coimbra (Portugal); Khouri, L; Carmo Lopes, M do [IPOCFG, EPE, Coimbra, Coimbra (Portugal)
Purpose: To estimate the radiobiological parameters that describe the doseresponse relations of xerostomia and disgeusia from head and neck cancer radiotherapy. To identify the organs that are best correlated with the manifestation of those clinical endpoints. Finally, to evaluate the goodnessof- fit by comparing the model predictions against the actual clinical results. Methods: In this study, 349 head and neck cancer patients were included. For each patient the dose volume histograms (DVH) of parotids (separate and combined), mandible, submandibular glands (separate and combined) and salivary glands were calculated. The follow-up of those patients was recorded at different times after the completion of the treatment (7 weeks, 3, 7, 12, 18 and 24 months). Acute and late xerostomia and acute disgeusia were the clinical endpoints examined. A maximum likelihood fitting was performed to calculate the best estimates of the parameters used by the relative seriality model. The statistical methods of the error distribution, the receiver operating characteristic (ROC) curve, the Pearson's test and the Akaike's information criterion were utilized to assess the goodness-of-fit and the agreement between the pattern of the radiobiological predictions with that of the clinical records. Results: The estimated values of the radiobiological parameters of salivary glands are D50 = 25.2 Gy, ? = 0.52, s = 0.001. The statistical analysis confirmed the clinical validity of those parameters (area under the ROC curve = 0.65 and AIC = 38.3). Conclusion: The analysis proved that the treatment outcome pattern of the patient material can be reproduced by the relative seriality model and the estimated radiobiological parameters. Salivary glands were found to have strong volume dependence (low relative seriality). Diminishing the biologically effective uniform dose to salivary glands below 30 Gy may significantly reduce the risk of complications to the patients irradiated for prostate cancer.
Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial
Pow, Edmond [Oral Rehabilitation, Faculty of Dentistry, University of Hong Kong, Hong Kong (China); Kwong, Dora [Department of Clinical Oncology, Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong (China); McMillan, Anne S. [Oral Rehabilitation, Faculty of Dentistry, University of Hong Kong, Hong Kong (China)]. E-mail: email@example.com; Wong, May [Periodontology and Dental Public Health, Faculty of Dentistry, University of Hong Kong, Hong Kong (China); Sham, Jonathan [Department of Clinical Oncology, Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong (China); Leung, Lucullus [Department of Clinical Oncology, Faculty of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong (China); Leung, W. Keung [Periodontology and Dental Public Health, Faculty of Dentistry, University of Hong Kong, Hong Kong (China)
Purpose: To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC). Methods and Materials: Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H and N35) were completed at baseline and 2, 6, and 12 months after radiotherapy. Results: Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy. Conclusions: IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.
Impact of Salivary Gland Dosimetry on Post-IMRT Recovery of Saliva Output and Xerostomia Grade for Head-and-Neck Cancer Patients Treated With or Without Contralateral Submandibular Gland Sparing: A Longitudinal Study
Wang Zhonghe; Yan Chao [Division of Radiation Oncology, the Shanghai Ninth Peoples Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Zhang Zhiyuan; Zhang Chenping [Department of Oral and Maxillofacial Surgery, the Shanghai Ninth Peoples Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Hu Haisheng; Tu Wenyong [Division of Radiation Oncology, the Shanghai Ninth Peoples Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (China); Kirwan, Jessica [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida (United States); Mendenhall, William M., E-mail: email@example.com [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida (United States)
Purpose: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. Methods and Materials: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n = 5 patients) and postoperative (n = 47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGs spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). Results: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. Conclusions: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.
Community-Based, Phase III Trial of acupuncture to treat chronic Xerostomia | Division of Cancer Prevention
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[An electro-stimulating oral splint for dry mouth treatment].
Fedele, S; Wolff, A; Strietzel, F P; Granizo López, R M; Porter, S; Konttinen, Y T
Dentists encounter regularly patients with xerostomia, which is the accepted term for dry mouth complaint. Left untreated, xerostomia can lead to psychosocial distress and to impaired quality of life. Oral complications of the most frequent cause of xerostomia, salivary gland hypofunction, include dental caries and candidiasis. In addition, quality of life is significantly hampered. The etiology of xerostomia is multiple, but the most common conditions are Sjögren's syndrome, radiotherapy to the head and neck and use of medications. Current therapies offered by dentists rely on saliva substitutes and stimulants such as chewing gum, and are somewhat limited by their short-term efficacy. Oral mucosal electro-stimulation increases salivary secretion and relieves symptoms of dry mouth in patients with xerostomia. Therefore, intra-oral electronic devices have been developed aimed at stimulating salivary gland function. They offer promise as an optional safe and non-chemical treatment of xerostomia. PMID:19263865
Xerostomia-Sjögren syndrome; Keratoconjunctivitis sicca - Sjögren; Sicca syndrome ... in children. Primary Sjögren syndrome is defined as dry eyes and dry mouth without another autoimmune disorder. Secondary ...
Adenoviral delivery of Tousled kinase for the protection of salivary glands against ionizing radiation damage
S Palaniyandi; Y Odaka; W Green; F Abreo; G Caldito; A De Benedetti; G Sunavala-Dossabhoy
Oral complications of salivary hypofunction often afflict cancer patients undergoing radiotherapy for head and neck cancers. Dry mouth or xerostomia is an undesirable consequence of radiotherapy that compromises normal oral functions in addition to causing odynophagia and increasing the patient's risk of oral infections and dental caries. Radiation-induced xerostomia is irreversible, and palliative measures to provide symptomatic relief remain the
Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels
Swati Pradhan
Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal
... irritations in the mouth Nerve damage from tooth extractions Trauma (injury) Dry mouth (xerostomia) Vitamin or mineral ... reserved. All information is intended for your general knowledge only and is not a substitute for medical ...
The effect of X-ray irradiation on the function and saliva composition of rat parotid and submandibular\\/ sublingual glands
Tatsuo Hashida; Hiromasa Kamemoto; Hajime Fuchihata; Takashi Ooshima
Radiation therapy to the head and neck area frequently causes severe salivary gland dysfunction and xerostomia. Morphological\\u000a studies of irradiated salivary glands have suggested that the submandibular\\/sublingual gland may be less radiosensitive than\\u000a the parotid gland. The purpose of this study was to evaluate the effect of radiation on major salivary gland functions in\\u000a rats with radiation-induced xerostomia.\\u000a \\u000a The effect
Intensity-Modulated Radiotherapy Reduces Radiation-Induced Morbidity and Improves Health-Related Quality of Life: Results of a Nonrandomized Prospective Study Using a Standardized Follow-Up Program
Vergeer, Marije R. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)], E-mail: email@example.com; Doornaert, Patricia A.H.; Rietveld, Derek H.F. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Leemans, C. Rene [Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam (Netherlands); Slotman, Ben J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands)
Purpose: The purpose of this study was to compare intensity-modulated radiation therapy (IMRT) and three-dimensional conventional radiotherapy (3D-CRT) with regard to patient-rated xerostomia, Radiation Therapy Oncology Group (RTOG) acute and late xerostomia and health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma (HNSCC). Methods and Materials: Included were 241 patients with HNSCC treated with bilateral irradiation {+-} chemotherapy. Since 2000, all patients treated with HNSCC were included in a program, which prospectively assessed acute and late morbidity according to the RTOG and HRQoL on a routine basis at regular intervals. Before October 2004, all patients were treated with 3D-CRT (N = 150). After clinical implementation in October 2004, 91 patients received IMRT. In this study, the differences regarding RTOG toxicity, xerostomia, and other items of HRQoL were analyzed. Results: The use of IMRT resulted in a significant reduction of the mean dose of the parotid glands (27 Gy vs. 43 Gy (p < 0.001). During radiation, Grade 2 RTOG xerostomia was significantly less with IMRT than with 3D-CRT. At 6 months, the prevalence of patient-rated moderate to severe xerostomia and Grade 2 or higher RTOG xerostomia was significantly lower after IMRT versus 3D-CRT. Treatment with IMRT also had a positive effect on several general and head and neck cancer-specific HRQoL dimensions. Conclusions: IMRT results in a significant reduction of patient- and observer-rated xerostomia, as well as other head and neck symptoms, compared with standard 3D-CRT. These differences translate into a significant improvement of the more general dimensions of HRQoL.
Submandibular gland-sparing intensity-modulated radiotherapy.
Mendenhall, William M; Mendenhall, Charles M; Mendenhall, Nancy P
Xerostomia is one of the most debilitating late effects of head and neck radiotherapy (RT) and significantly impacts quality of life. The submandibular gland (SMG) provides approximately 70% of the unstimulated saliva that accounts for about 95% of the salivary flow during a 24-hour period. Intensity-modulated RT (IMRT) has been used in recent years to lower the RT dose to the parotid gland(s) to reduce long-term xerostomia. There is little experience with SMG-sparing IMRT. Mean RT doses to the SMG exceeding 39 Gy cause permanent ablation of both stimulated and unstimulated salivary flow. Limited data suggest that SMG-sparing IMRT in selected patients results in reduced long-term xerostomia without increasing the risk of a local-regional recurrence. PMID:22892434
Radiotherapy Dose-Volume Effects on Salivary Gland Function
Deasy, Joseph O., E-mail: firstname.lastname@example.com [Department of Radiation Oncology, Washington University School of Medicine and Alvin J. Siteman Cancer Center, St. Louis, MO (United States); Moiseenko, Vitali [Department of Medical Physics, British Columbia Cancer Agency-Vancouver Cancer Center, Vancouver, BC (Canada); Marks, Lawrence [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Chao, K.S. Clifford [Department of Radiation Oncology, Columbia School of Medicine, New York, NY (United States); Nam, Jiho [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI (United States)
Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than {approx}20 Gy or if both glands are spared to less than {approx}25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. A lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.
Sustained improvement of quality of life for nasopharyngeal carcinoma treated by intensity modulated radiation therapy in long-term survivors
Song, Tao; Fang, Ming; Zhang, Xue-Bang; Zhang, Ping; Xie, Rui-Fei; Wu, Shi-Xiu
IMRT has achieved an excellent survival and less radiation-induced sequelae with improvement of QoL within 2 years compared to conventional radiotherapy for NPC. Whether IMRT could sustained decrease incidence of late sequelae and improve QoL further for long-term survivors remained unknown. 176 patients from Aug. 2002 to Jun. 2009 were retrospectively analyzed. Radiation-related toxicities were graded according to both the Acute and the Late Radiation Morbidity Scoring Criteria of the EORTC/RTOG; QoL was assessed by the EORTC QLQ-C30 and H&N35 questionnaires at 5 and 8 years. The 5-year overall survival rate was 68.2% with a median follow-up time of 86 months. The most common radiation-related acute and late toxicity was xerostomia, the incidence of Grade ? 1 xerostomia was 90.3%, 84.1%, 75.9% and 59.2%, respectively at acute, 6 months, 2 years and 5 years. Statistical analysis indicated a close relationship between 5 years with 6 months and 2 years for patients who had ? 3 xerostomia at acute phase (r = 0.538 for late xerostomia at 6 months with 5 years, r = 0.732 for 2 years with 5 years); Sustained amelioration of other sequelae was also observed; QoL questionnaires at 5 years showed a significant improvement of most items and got stable between 5 to 8 years. In conclusion: IMRT could sustain reduce late radiation sequelae and improve QoL for long-term survivors over time; Patients with severe acute xerostomia (? grade 3) would have a significant correlation of mitigatory xerostomia during the late follow-up time.
Intensity Modulated Radiotherapy Improves Target Coverage and Parotid Gland Sparing When Delivering Total Mucosal Irradiation in Patients With Squamous Cell Carcinoma of Head and Neck of Unknown Primary Site
Shreerang Bhide; Catherine Clark; Kevin Harrington; Christopher M. Nutting
Head and neck squamous cell carcinoma with occult primary site represents a controversial clinical problem. Conventional total mucosal irradiation (TMI) maximizes local control, but at the expense of xerostomia. IMRT has been shown to spare salivary tissue in head and cancer patients. This study has been performed to investigate the potential of IMRT to perform nodal and TMI and also
Solitary extramedullary plasmacytoma and granulomatous sialadenitis of the parotid gland preceding a B-cell non-Hodgkin's lymphoma
H. Gouveris; T. Hansen; K. Franke
A patient with swelling of the left parotid gland of four-months duration, sicca syndrome (xerophthalmia and xerostomia) and a history of progressive systemic sclerosis with an incomplete form of the CREST syndrome was referred to our department. On ultrasound a parotid mass of reduced echogenicity without any enlarged cervical lymph nodes was found. Ultrasonographically guided fine-needle biopsy could not provide
A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: Implications for future trials
Judith M.. Roesink; Maria Schipper; Wim Busschers; Cornelis P. J. Raaijmakers; Chris H. J. Terhaard
Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related
Genetic aspects of Sjögren's syndrome
Anne Isine Bolstad; Roland Jonsson
Sjögren's syndrome is a multisystem inflammatory rheumatic disease that is classified into primary and secondary forms, with cardinal features in the eye (keratoconjunctivitis sicca) and mouth (xerostomia). The aetiology behind this autoimmune exocrinopathy is probably multifactorial and influenced by genetic as well as by environmental factors that are as yet unknown. A genetic predisposition to Sjögren's syndrome has been suggested
Secondary Sjogren's syndrome presenting with hypokalemic periodic paralysis
Dormohammadi Toosi, Taraneh; Naderi, Neda; Movassaghi, Shafieh; Seradj, Mehran Heydari; Khalvat, Ali; Shahbazi, Fatemeh
Renal tubular acidosis (RTA) may develop in a large population of patients with Sjogren's syndrome (SS), but most of the subjects are asymptomatic. Here, we report a patient with known rheumatoid arthritis and symptoms of xerostomia, xerophthalmia and periodic paralysis. SS should be considered as a cause of RTA. The treatment of the underlying disorder may ameliorate the symptoms. PMID:25988057
Desipramine induced changes in salivary proteins, cultivable oral microbiota and gingival health in aging female NIA Fischer 344 rats
Markus M. Koller; Karnam R. Purushotham; Nobuko Maeda; Philip J. Scarpace; Michael G. Humphreys-Beher
Cyclic antidepressants are still a dominating group of psychotherapeutic drugs used in the treatment of depression. One of their major side effect is salivary gland dysfunction (oral dryness, xerostomia), leading in humans to increased oral disease and dysfunction of speech, chewing, swallowing and taste. The purpose of this study was to assess the effects of the long-term administration of the
The potential for sparing of parotids and escalation of biologically effective dose with intensity-modulated radiation treatments of head and neck cancers: a treatment design study
Qiuwen Wu; Matthew Manning; Rupert Schmidt-Ullrich; Radhe Mohan
Purpose: Conventional radiotherapy for cancers of the head and neck (HN) can yield acceptable locoregional tumor control rates, but toxicity of many normal tissues limits our ability to escalate dose. Xerostomia represents one of the most common complications. The purpose of this study is to investigate the potential of intensity-modulated radiotherapy (IMRT) to achieve adequate sparing of parotids and to
Graft-versus-host disease, an eight case report and literature review
Ronell Bologna Molina; María Teresa de Jesús; Vega González
Graft versus host disease (GVHD) is a common complication in bone marrow transplant (BMT) patients. It is cha- racterized by systemic and oral cavity alterations. Depending on the timing of lesions, GVHD is classified as acute or chronic. Alterations in the oral cavity are lichenoid reticular lesions, erythema, ulcerations, and xerostomia. Sporadically, mucocele and pyogenic granulomas can be present. Aim:
Efectos adversos del tratamiento del cáncer oral
F. J. Silvestre-Donat; A. Puente Sandoval
SUMMARY In this article a revision of most frequent adverse effects of head and neck surgery, radiotherapy and chemotherapy is maid, because frequently general dentists deal with complications at their practises like mucositis, xerostomia, osteonecrosis, taste alterations and other pathologies which will cause disturbances to the patients, affecting their quality of live. The role of the dentist in the multidisciplinary
The effect of hyperbaric oxygen therapy on quality of life in oral and oropharyngeal cancer patients treated with radiotherapy
N. L. Gerlach; R. Barkhuysen; J. H. A. M. Kaanders; G. O. R. J. Janssens; W. Sterk; M. A. W. Merkx
Radiotherapy is used in the setting of curative treatment for head and neck cancer. Xerostomia and related problems occur when major salivary glands are included in the irradiation fields. This reduces quality of life (QOL). Hyperbaric oxygen therapy (HBOT) is a well accepted treatment or prevention modality for osteoradionecrosis of the jawbones and soft-tissue necrosis. It is unknown if and
Tissue Levels of WR-1065, the Active Metabolite of Amifostine (Ethyol®), Are Equivalent following Intravenous or Subcutaneous Administration in Cynomolgus Monkeys
Christine M. Bachy; Christine A. Fazenbaker; Gizachew Kifle; Michael P. McCarthy; David R. Cassatt
Amifostine (Ethyol®) is a cytoprotective drug approved for the reduction of xerostomia in head and neck cancer when administered to patients receiving postoperative radiation therapy. Although amifostine is approved for intravenous infusion, the off-label subcutaneous route of administration has become more prevalent. Although human patient data indicate higher plasma bioavailability of the active metabolite (WR-1065) following intravenous compared to subcutaneous
Functional magnetic resonance imaging (fMRI) changes and saliva production associated with acupuncture at LI2 acupuncture point: a randomized controlled study
Gary Deng; Bob L Hou; Andrei I Holodny; Barrie R Cassileth
BACKGROUND: Clinical studies suggest that acupuncture can stimulate saliva production and reduce xerostomia (dry mouth). We were interested in exploring the neuronal substrates involved in such responses. METHODS: In a randomized, sham acupuncture controlled, subject blinded trial, twenty healthy volunteers received true and sham acupuncture in random order. Cortical regions that were activated or deactivated during the interventions were evaluated
Cai, Long
generosity NEWS 543 The sun puts his hat on for oral health campaign Students debate dietary advice BDJ improves xerostomia BRITISH DENTAL JOURNAL incorporating DENTAL BUSINESS The sun puts his hat on for oral VOLUME 214 NO. 11 JUN 8 2013 OPINION 547 Improving oral healthcare for children - a great opportunity S
Amylase and cyclic amp receptor protein expression in human diabetic parotid glands
Terasaki, Mark
with xerostomia and the resulting oral complications, which may include increases in mucosal abnormalities of Oral Health and Diagnostic Sciences, University of Connecticut Health Center, Farmington, CT, USA BACKGROUND: Salivary dysfunction and oral disorders have been described in both type 1 and type 2 diabetes
Les manifestations buccofaciales de la sclérodermie systémique : étude de 30 patients consécutifs
C. Vincent; C. Agard; S. Barbarot; J.-M. N'Guyen; B. Planchon; C. Durant; M.-A. Pistorius; B. Dreno; T. Ponge; J.-F. Stalder; J.-M. Mercier; M. Hamidou
IntroductionThe face is frequently involved in systemic sclerosis. The main stomatologic manifestations include limited mouth opening, xerostomia, skin atrophy, trigeminal neuralgia. The objective of this study was to describe oral and facial manifestations observed in scleroderma patients from our cohort.
Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer
Avraham Eisbruch; Jonathan A. Ship; Laura A. Dawson; Hyungjin M. Kim; Carol R. Bradford; Jeffrey E. Terrell; Douglas B. Chepeha; Theodore N. Teknos; Norman D. Hogikyan; Yoshimi Anzai; Lon H. Marsh; Randall K. Ten Haken; Gregory T. Wolf
The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with
Quality of life after parotid-sparing IMRT for head-and-neck cancer: A prospective longitudinal study
Alexander Lin; Hyungjin M Kim; Jeffrey E Terrell; Laura A Dawson; Jonathan A Ship; Avraham Eisbruch
PurposeParotid-sparing intensity-modulated radiotherapy (IMRT) for head-and-neck cancer reduces xerostomia compared with standard RT. To assess potential improvements in broader aspects of quality of life (QOL), we initiated a study of patient-reported QOL and its predictors after IMRT.
Complete occlusal rehabilitation of patient with radiation caries - a case report.
Dangra, Zishan Rashid; Gandhewar, Mahesh Arvind
One of the most distressing and dramatic causes of xerostomia is radiotherapy for the cure of maxillofacial and neck carcinomas. Patient with radiotherapy induced xerostomia presents with challenges in prosthodontic management and in unique radiation caries control. This clinical report illustrates step by step execution of complex treatment planning that lead to successful outcome in 34-year-old man, who had been treated with Radical Neck Dissection (RND) and therapeutic radiotherapy for squamous cell carcinoma of tongue and due to radiation caries, was presented with chief complaint of difficulty in mastication. Rehabilitation was carried out with metal-ceramic fixed restorations and cast removable prostheses after extensive endodontic intervention. This article also discusses the maintenance strategies for radiation caries patient requiring complete occlusal reconstruction, who certainly presents with special needs in post-treatment management. PMID:25386544
Complete Occlusal Rehabilitation of Patient with Radiation Caries – A Case Report
Gandhewar, Mahesh Arvind
One of the most distressing and dramatic causes of xerostomia is radiotherapy for the cure of maxillofacial and neck carcinomas. Patient with radiotherapy induced xerostomia presents with challenges in prosthodontic management and in unique radiation caries control. This clinical report illustrates step by step execution of complex treatment planning that lead to successful outcome in 34-year-old man, who had been treated with Radical Neck Dissection (RND) and therapeutic radiotherapy for squamous cell carcinoma of tongue and due to radiation caries, was presented with chief complaint of difficulty in mastication. Rehabilitation was carried out with metal-ceramic fixed restorations and cast removable prostheses after extensive endodontic intervention. This article also discusses the maintenance strategies for radiation caries patient requiring complete occlusal reconstruction, who certainly presents with special needs in post-treatment management. PMID:25386544
Recent Advances in Oncology Acupuncture and Safety Considerations in Practice
Weidong Lu; David S. Rosenthal
Opinion statement Oncology acupuncture is a new and emerging field of research. Recent advances from published clinical trials have added evidence\\u000a to support the use of acupuncture for symptom management in cancer patients. Recent new developments include (1) pain and\\u000a dysfunction after neck dissection; (2) radiation-induced xerostomia in head and neck cancer; (3) aromatase inhibitor-associated\\u000a arthralgia in breast cancer; (4) hot
Effects of EGF and bFGF on Irradiated Parotid Glands
Taili T. Thula; Gregory Schultz; Roger Tran-Son-Tay; Christopher Batich
Radiotherapy is common treatment for head-and-neck cancer, during which the salivary glands are often included within the radiation field. The most common side effect of this treatment is the development of oral dryness (xerostomia). This study considers the administration of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF or FGF2) at physiological concentrations before and after irradiation in
Jaborandi (Pilocarpus sp., rutaceae): A wild species
CLAUDIO URBANO B. PINHEIRO; Claudio Urbano; B. Pinheiro
Jaborandi (Pilocarpus sp.;) is a shrub or small tree 3-7.5 m tall that can be found in native stands or as isolated individuals throughout Brazil.\\u000a The leaves of jaborandi contain the alkaloid pilocarpine, widely used in ophthalmology for treatment of certain types of glaucoma\\u000a and more recently for xerostomia. This paper discusses the current systems of production of jaborandi leaves
Clinical consequences of oral mucositis 1 1 The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense
Carlton G. Brown; John Wingard
OBJECTIVE: To identify the clinical manifestations, risk factors, secondary complications, and assessment and management of oral mucositis.DATA SOURCES: Professional journals, websites, and books.CONCLUSION: Secondary consequences of oral mucositis include infection, xerostomia, hemorrhage, and nutritional deficits.IMPLICATIONS FOR NURSING PRACTICE: Nurses should have an extensive knowledge base about the appropriate interventions that can be used to alleviate or lessen the consequences often
Oral manifestations associated with HIV infection
Mostafa Nokta
Oral lesions are among the early signs of HIV infection and can predict progression to AIDS. The lesions commonly associated\\u000a with the infection include oral candidiasis, herpes simplex infection, oral Kaposi's sarcoma, oral hairy leukoplakia, parotid\\u000a gland enlargement, gingival diseases, xerostomia, and recurrent oral ulcerations. The introduction of highly active antiretroviral\\u000a therapy has changed the epidemiology of some of the
Multicentric reticulohistiocytosis and Sjögren's syndrome.
Carey, R N; Blotzer, J W; Wolfe, I D; Glusman, S M; Arnett, F C
A 66-year-old man with an 18-year history of cutaneous multicentric reticulohistiocytosis (MRH) developed a chronic destructive symmetrical arthritis and xerostomia. Biopsies of synovium and minor salivary glands established a diagnosis of MRH polyarthritis and lymphocytic infiltrative Sjögren's syndrome, respectively. Anti-Ro(SSA) antibody was present. Hypothyroidism was also identified. This report of Sjögren's syndrome in MRH may enlarge the spectrum of autoimmune diseases associated with MRH. PMID:4093930
Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study
Burlage, Fred R. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands)], E-mail: email@example.com; Roesink, Judith M. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Kampinga, Harm H. [Department of Cell Biology, Section for Radiation and Stress Cell Biology, University Medical Center Groningen, Groningen (Netherlands); Coppes, Rob P. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Terhaard, Chris [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Langendijk, Johannes A.; Luijk, Peter van [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Stokman, Monique A.; Vissink, Arjan [Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, Groningen (Netherlands)
Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.
Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: Dosimetric and clinical evaluation
Portaluri, Maurizio [Department of Radiotherapy, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy) and National Research Council, IFC, Lecce (Italy)]. E-mail: email@example.com; Fucilli, Fulvio I.M. [Department of Medical Physics, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy); Castagna, Roberta [Department of Radiotherapy, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy); Bambace, Santa [Department of Radiotherapy, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy); Pili, Giorgio [Department of Medical Physics, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy); Tramacere, Francesco [Department of Radiotherapy, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy); Russo, Donatella [Department of Radiotherapy, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy); Francavilla, Maria Carmen [Department of Radiotherapy, AUSL Br-1, 'Di Summa-Perrino' Hospital, Brindisi (Italy)
Purpose: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. Methods and Materials: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). Results: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 {+-} 4.82 Gy (51.53 {+-} 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. Conclusion: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.
Beam intensity modulation using tissue compensators or dynamic multileaf collimation in three-dimensional conformal radiotherapy of primary cancers of the oropharynx and larynx, including the elective neck
Erik B van Dieren; Peter J. C. M Nowak; Oda B Wijers; John R van Sörnsen de Koste; Henri van der Est; Dirk P Binnekamp; Ben J. M Heijmen; Peter C Levendag
Introduction: The treatment of midline tumors in the head and neck by conventional radiotherapy almost invariably results in xerostomia. This study analyzes whether a simple three-dimensional conformal radiotherapy (3D-CRT) technique with beam intensity modulation (BIM) (using a 10-MV beam of the MM50 Racetrack Microtron) can spare parotid and submandibular glands without compromising the dose distribution in the planning target volume
Is dentistry going to get into the salivary diagnostics game or watch from the sidelines?
Jacobson, Jed J
What is salivary diagnostics and why should you care? Most of us dentists try to avoid or control saliva as it interferes with access, or chemical interactions in dental materials, or impression materials, or when it is simply a nuisance. Periodically, we may note reduced flow or encounter a patient with xerostomia. Correspondingly, we then manage the reduced flow in an attempt to maintain homeostasis. However, with the discovery of salivary biomarkers, saliva is taking on a new role. PMID:23505758
Diagnostic Accuracy of Ultrasonic Histogram Features to Evaluate Radiation Toxicity of the Parotid Glands
Yang, Xiaofeng; Tridandapani, Srini; Beitler, Jonathan J.; Yu, David S.; Chen, Zhengjia; Kim, Sungjin; Bruner, Deborah W.; Curran, Walter J.; Liu, Tian
Rationale and Objectives To investigate the diagnostic accuracy of ultrasound histogram features in the quantitative assessment of radiation-induced parotid gland injury and to identify potential imaging biomarkers for radiation-induced xerostomia (dry mouth)—the most common and debilitating side effect after head-and-neck radiotherapy (RT). Materials and Methods Thirty-four patients, who have developed xerostomia after RT for head-and-neck cancer, were enrolled. Radiation-induced xerostomia was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity scale. Ultrasound scans were performed on each patient's parotids bilaterally. The 34 patients were stratified into the acute-toxicity groups (16 patients, ?3 months after treatment) and the late-toxicity group (18 patients, >3 months after treatment). A separate control group of 13 healthy volunteers underwent similar ultrasound scans of their parotid glands. Six sonographic features were derived from the echo-intensity histograms to assess acute and late toxicity of the parotid glands. The quantitative assessments were compared to a radiologist's clinical evaluations. The diagnostic accuracy of these ultrasonic histogram features was evaluated with the receiver operating characteristic (ROC) curve. Results With an area under the ROC curve greater than 0.90, several histogram features demonstrated excellent diagnostic accuracy for evaluation of acute and late toxicity of parotid glands. Significant differences (P < .05) in all six sonographic features were demonstrated between the control, acute-toxicity, and late-toxicity groups. However, subjective radiologic evaluation cannot distinguish between acute and late toxicity of parotid glands. Conclusions We demonstrated that ultrasound histogram features could be used to measure acute and late toxicity of the parotid glands after head-and-neck cancer RT, which may be developed into a low-cost imaging method for xerostomia monitoring and assessment. PMID:25088832
Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: A randomized placebo-controlled phase III study
Buentzel, Jens [Department of Otolaryngology, Head and Neck Surgery, Suedharzkrankenhaus Nodhausen, Nordhausen (Germany)]. E-mail: email@example.com; Micke, Oliver [Department of Radiotherapy, Muenster University Hospital, Muenster (Germany); Adamietz, Irenaus A. [Department of Radiooncology, Ruheuniversitat Bochum, Herne (Germany); Monnier, Alain [Centre Hospitalier Andre-Boulloche, Monbeliard (France); Glatzel, Michael [Department of Radio-Therapy, Zentralklinikum Suhl, Suhl (Germany); Vries, Alexander de [Department of Radiooncology, Leopold Franz University of Innsbruck, Innsbruck (Austria)
Purpose: Clinical trials demonstrated the efficacy and safety of intravenous (i.v.) or subcutaneous (s.c.) amifostine for reducing xerostomia and mucositis after radiotherapy or radiochemotherapy for head-and-neck cancer. This randomized, double-blinded, placebo-controlled, phase III study evaluated the efficacy and safety of i.v. amifostine during radiochemotherapy for head-and-neck cancer. Methods and Materials: Patients from European and American study centers received i.v. amifostine 300 mg/m{sup 2} (n = 67) or placebo (n = 65) before carboplatin 70 mg/m{sup 2} and radiotherapy on Days 1 to 5 and 21 to 25, and i.v. amifostine 200 mg/m{sup 2} or placebo before radiotherapy on other days. Results: Toxicity incidences were (amifostine, placebo, p value): Grade 2 or higher acute xerostomia (39%, 34%, 0.715), Grade 3 or higher acute mucositis (39%, 22%, 0.055), Grade 2 or higher late xerostomia (37%, 24%, 0.235), and Grade 3 or higher treatment-related adverse events (42%, 20%, 0.008). One-year rates of locoregional failure, progression-free survival, and overall survival were not significantly different between treatments. Conclusions: The used amifostine doses were not able to reduce the toxicity of simultaneous radiochemotherapy for head-and-neck cancer. The safety of amifostine and the lack of tumor protection were consistent with previous studies.
Sialometry of Upper Labial Minor Glands: A Clinical Approach by the Use of Weighing Method Schirmer's Test Strips Paper
Falcăo, Denise Pinheiro; Leal, Soraya Coelho; Vieira, Celi Novaes; Filgueira Galdino Almeida, Tayana; Nunes, Fernanda de Paula e Silva
Objectives. To establish referential values ranges of hyposalivation and normosalivation for the salivary flow rate (SFR) of upper labial (LS) and palatal (PS) mucosa using Schirmer's test strips paper and as a second goal to determine the values ranges of the SFR of palatal (PS) and upper labial (LS) mucosa in subjects with and without xerostomia. Methods. A cross-sectional study was conducted among subjects distributed in three groups according to their unstimulated and stimulated whole saliva. Results. 144 subjects were enrolled in groups as follows: severe hyposalivation (n = 24), mild hyposalivation (n = 78), and normosalivation (n = 42). The mean and the 95% confidence interval for the LS flow rate (?L/cm2/min) were 3.2 (2.46 to 3.94), 5.86 (4.96 to 6.75), and 9.08 (7.63 to 10.53) (P < 0.001) for each group, respectively. The PS results were 1.01 (0.68 to 1.34), 1.72 (1.31 to 2.13), and 2.44 (1.66 to 3.22) (P = 0.014). Xerostomia complainers presented lower rates of LS (5.17 (4.06 to 6.23)) than non-complainers (7.33 (6.4 to 8.27)) (P = 0.003). Conclusions. The test was reliable to provide referential values ranges for LS flow rate measurement and was shown to be valid to distinguish normosalivation from severe and mild hyposalivation and also to predict xerostomia. PMID:24737963
Investigations on Parotid Gland Recovery after IMRT in Head and Neck Tumor Patients
Markus Stock; Wolfgang Dörr; Carmen Stromberger; Ulrike Mock; Susanne Koizar; Richard Pötter; Dietmar Georg
\\u000a \\u000a Purpose:\\u000a In recent years, the role of intensity-modulated radiotherapy (IMRT) for head and neck irradiation has increased. The\\u000a main motivation is sparing the parotid gland and reduction of xerostomia. Generally, relative parotid volumes have been evaluated\\u000a for treatment outcome and planning constraints, neglecting that absolute parotid volumes can vary significantly. The aim of\\u000a the present study was to investigate changes
Longitudinal Assessment of Parotid Function in Patients Receiving Tomotherapy for Head-and-Neck Cancer
Mia Voordeckers; Hendrik Everaert; Koen Tournel; Dirk Verellen; Ilan Baron; Gretel Van Esch; Chris Vanhove; Guy Storme
\\u000a \\u000a Background and Purpose:\\u000a Conventional radiotherapy is associated with high doses to the salivary glands which causes xerostomia and adverse effects\\u000a on quality of life. The study aims to investigate the potential of helical tomotherapy (Hi-Art Tomotherapy®) to preserve parotid function in head-and-neck cancer patients.\\u000a \\u000a \\u000a \\u000a \\u000a Patients and Methods:\\u000a Seven consecutive patients treated with helical tomotherapy at the UZ Brussel, Belgium, were
3D-conformal-intensity modulated radiotherapy with compensators for head and neck cancer: clinical results of normal tissue sparing
Wendt, Thomas G; Abbasi-Senger, Nasrin; Salz, Henning; Pinquart, Ines; Koscielny, Sven; Przetak, Susi-Marie; Wiezorek, Tilo
Background To investigate the potential of parotic gland sparing of intensity modulated radiotherapy (3D-c-IMRT) performed with metallic compensators for head and neck cancer in a clinical series by analysis of dose distributions and clinical measures. Materials and methods 39 patients with squamous cell cancer of the head and neck irradiated using 3D-c-IMRT were evaluable for dose distribution within PTVs and at one parotid gland and 38 patients for toxicity analysis. 10 patients were treated primarily, 29 postoperatively, 19 received concomittant cis-platin based chemotherapy, 20 3D-c-IMRT alone. Initially the dose distribution was calculated with Helax ® and photon fluence was modulated using metallic compensators made of tin-granulate (n = 22). Later the dose distribution was calculated with KonRad ® and fluence was modified by MCP 96 alloy compensators (n = 17). Gross tumor/tumor bed (PTV 1) was irradiated up to 60–70 Gy, [5 fractions/week, single fraction dose: 2.0–2.2 (simultaneously integrated boost)], adjuvantly irradiated bilateral cervical lymph nodes (PTV 2) with 48–54 Gy [single dose: 1.5–1.8]). Toxicity was scored according the RTOG scale and patient-reported xerostomia questionnaire (XQ). Results Mean of the median doses at the parotid glands to be spared was 25.9 (16.3–46.8) Gy, for tin graulate 26 Gy, for MCP alloy 24.2 Gy. Tin-granulate compensators resulted in a median parotid dose above 26 Gy in 10/22, MCP 96 alloy in 0/17 patients. Following acute toxicities were seen (°0–2/3): xerostomia: 87%/13%, dysphagia: 84%/16%, mucositis: 89%/11%, dermatitis: 100%/0%. No grade 4 reaction was encountered. During therapy the XQ forms showed °0–2/3): 88%/12%. 6 months postRT chronic xerostomia °0–2/3 was observed in 85%/15% of patients, none with °4 xerostomia. Conclusion 3D-c-IMRT using metallic compensators along with inverse calculation algorithm achieves sufficient parotid gland sparing in virtually all advanced head and neck cancers. Since the concept of lower single (and total) doses in the adjuvantly treated volumes reduces acute morbidity 3D-c-IMRT nicely meets demands of concurrent chemotherapy protocols. PMID:16790059
Temporary diplopia upon hyoscine-N-butyl bromide administration: case report
Migliorini, R; Malagola, R; Mafrici, M; Spena, R; Arrico, L
Hyoscine-N-butyl bromide is a widely used antispasmodic belonging to the belladonna alkaloid class of semisynthetic quaternary ammonium compounds. These compounds exert a spasmolytic action on the smooth muscles of the bile-gastrointestinal tract, genitourinary tract, salivary glands (xerostomia), and also on the visual apparatus - in particular, the irido-ciliary complex. As a consequence, they provoke collateral effects such as mydriasis and accommodation disturbances. We report the case of a 23-year-old woman who complained of not only "dry mouth" but also "cloudy vision" and a "diplopia", both of temporary type, 2 hours after oral administration of hyoscine-N-butyl bromide. PMID:23723687
Management of Sjogren's Syndrome Patient: A Case Report of Prosthetic Rehabilitation with 6-Year Follow-Up
de Mendonça Invernici, Marcos; Vale Nicolau, Gastăo; Naval Machado, Maria Ângela; Soares de Lima, Antônio Adilson
Completely and partially edentulous patients with Sjogren's syndrome (SS) experience severe hyposalivation, xerostomia, and considerable difficulty in using tissue-supported prosthesis. This clinical paper describes the management, treatment, and 6-year follow-up of a patient diagnosed with SS type II, who uses corticosteroids and antihyperglycemic drugs. The patient received restorative, periodontal, and surgical treatments followed by implant-supported fixed prosthesis. Radiographic evaluation and probing depth showed gingival health and no bone loss after 6 years. Treatment with implant-retained dental prosthesis greatly increased comfort and function, offering an alternative to patients with SS. PMID:25478245
[The x-ray changes in the parotid salivary glands of patients with Sjögren's disease].
Varshavski?, A I; Guberskaia, T A; Panchenko, K I
The data obtained upon sialography of the parotid glands (PG) in 28 patients with Sjogren's disease (SD) were compared to clinical SD manifestations, PG regional circulation and histological picture of the labial salivary glands. 24 patients exhibited classical sialography characterized by sialoectasias, enlarged ducts, obscure outlines of the latter. 4 sialograms displayed the duct narrowing, noncontrast parenchyma outlines, unclear images of sialoectasias. Severe xerostomia, marked dryness of the vermilion border, rare enlargement of the salivary glands and parotitis recurrences occurred more frequently in patients with narrow efferent PG ducts. These changes are attributed to vascular sclerosis, devascularization, stromal sclerosis and parenchymal PG atrophy. PMID:7940341
A Multicenter Review of Contralateral Submandibular Gland Sparing in Locally Advanced Oropharyngeal Cancers: Is is Safe?
Robin, Tyler P; Gan, Gregory; Tam, Moses; Westerly, David; Riaz, Nadeem; Karam, Sana; Lee, Nancy; Raben, David
Purpose/objective: Previous groups have shown contralateral submandibular gland (cSMG) sparing to improve xerostomia with safe outcomes, but primarily in early stage disease. Here we present a large cohort of patients with locally advanced HNC that underwent cSMG-sparing radiotherapy, to demonstrate feasibility and safety specifically in locally advanced patients. Methods: We retrospectively analyzed patients who were treated prospectively with cSMG sparing. Only patients that underwent bilateral neck radiotherapy with cSMG doses < 39 Gy were included. Results: We identified 71 patients. Approximately 80% of patients had ? N2b disease. The cSMG mean dose was 33 Gy and at a median follow-up of 27.3 months, no patients failed in the contralateral level IB lymph nodes. Conclusions: Xerostomia remains a significant morbidity despite parotid sparing and can be minimized further by cSMG sparing. These data provide important preliminary evidence that cSMG sparing is feasible and may be safe even in locally advanced cancers. This article is protected by copyright. All rights reserved. PMID:25482748
Amifostine reduces side effects and improves complete response rate during radiotherapy: Results of a meta-analysis
Sasse, Andre Deeke [Nucleo Brasileiro de Oncologia Baseada em Evidencias, Campinas, Sao Paulo (Brazil); Gontijo de Oliveira Clark, Luciana [Nucleo Brasileiro de Oncologia Baseada em Evidencias, Campinas, Sao Paulo (Brazil); Sasse, Emma Chen [Nucleo Brasileiro de Oncologia Baseada em Evidencias, Campinas, Sao Paulo (Brazil)]. E-mail: email@example.com; Clark, Otavio Augusto Camara [Nucleo Brasileiro de Oncologia Baseada em Evidencias, Campinas, Sao Paulo (Brazil)
Purpose: To evaluate the efficacy of amifostine in diminishing radiotherapy side effects and whether or not it protects the tumor. Methods and Materials: We performed a systematic review and meta-analysis of 14 included randomized controlled trials, comprising 1451 patients, comparing the use of radiotherapy vs. radiotherapy plus amifostine for cancer treatment. Results: The use of amifostine significantly reduced the risk of developing mucositis (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.29-0.48; p < 0.00001), esophagitis (OR, 0.38; CI, 0.26-0.54; p < 0.00001), acute xerostomia (OR, 0.24; CI, 0.15-0.36; p < 0.00001), late xerostomia (OR, 0.33; CI, 0.21-0.51; p < 0.00001), dysphagia (OR, 0.26; CI, 0.07-0.92; p 0.04), acute pneumonitis (OR, 0.15; CI, 0.07-0.31; p < 0.00001) and cystitis (OR, 0.17; CI, 0.09-0.32; p < 0.00001). There was no difference in overall response rate between the groups. However, complete response rate was superior for patients using amifostine (OR, 1.81; CI, 1.10-2.96; p = 0.02). Conclusions: This systematic review shows that amifostine significantly reduces the side effects of radiation therapy. The efficacy of radiotherapy was not itself affected by the use of this drug and patients receiving amifostine were able to achieve higher rates of complete response.
Gastrointestinal and hepatic manifestations of Sjogren syndrome.
Ebert, Ellen Catherine
Sjogren syndrome (SS) is an autoimmune disease that affects exocrine glands and therefore may affect the gastrointestinal system, from the mouth, esophagus, and bowel to the liver and pancreas. Oral involvement in SS is mainly characterized by dryness, with a wide spectrum of symptoms, from mild-to-severe xerostomia with dysgeusia and tooth decay. The dysphagia, although common, does not correlate with the reduced salivary flow rate or the dysmotility that may be present. Dyspepsia, found in up to 23% of patients, may be associated with gastritis, reduced acid production, and antiparietal cell antibodies, but rarely pernicious anemia. Pancreatic involvement, although rare, includes pancreatitis and pancreatic insufficiency. The most common causes of liver disease are primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatitis C virus (HCV). Although abnormal liver tests are found in up to 49% of patients, they are usually mild. Although sicca syndrome, abnormal histology of the salivary glands, and abnormal sialograms are common in primary biliary cirrhosis, the antibodies to Ro/SSA or La/SSB antigens are infrequent. Xerostomia, sialadenitis, abnormal salivary flow rates, and abnormal Schirmer test in HCV vary widely among the studies, although the antibodies to Ro/SSA or La/SSB are only 1%. Several studies show that HCV is in saliva, although how this may impact sicca syndrome or SS in HCV is unclear. SS as a disease of exocrine glands affects many parts of the gastrointestinal system. PMID:22157220
Acupuncture Research at Memorial Sloan Kettering Cancer Center.
Javdan, Bahar; Cassileth, Barrie
Acupuncture may help treat specific cancer-related symptoms. Here, we summarize our clinical trials that sought to determine acupuncture's role in managing cancer-related symptoms. Trials have been conducted to determine acupuncture's ability to mitigate cancer-related symptoms including dyspnea, fatigue, xerostomia, lymphedema, hot flashes, postoperative ileus, pain and dysfunction after neck dissection, and postthoracotomy pain. Published studies indicate that acupuncture versus placebo acupuncture failed to reduce cancer-related dyspnea. Both true and sham acupuncture alleviated fatigue slightly, but no significant differences between groups emerged. Compared with sham acupuncture, our research showed that acupuncture significantly improved saliva production in patients with xerostomia and significantly reduced lymphedema patients' arm circumference in a pilot study. However, acupuncture failed to significantly reduce hot flashes and was no more successful than sham acupuncture in reducing postoperative ileus. Significant reductions in pain and dysfunction occurred in cancer patients after neck dissection. In a feasibility study, acupuncture was found to be acceptable to lung cancer patients and did not interfere with standard postoperative care. In summary, acupuncture is a potential candidate for the treatment of some important cancer-related symptoms. Large clinical trials and research to investigate mechanistic pathways are warranted. PMID:26100064
Oral mucosal status and major salivary gland function
Wolff, A.; Fox, P.C.; Ship, J.A.; Atkinson, J.C.; Macynski, A.A.; Baum, B.J. (National Institute of Dental Research, Bethesda, MD (USA))
Normal salivary function is considered to be critical for the maintenance of healthy oral mucosa. However, few studies have examined mucosal changes in patients with objectively documented salivary gland performance. In the present report, the mucosal status of 298 subjects being evaluated in a dry mouth clinic was assessed. A complete oral examination was performed and unstimulated and stimulated salivary samples were collected separately from the parotid and submandibular/sublingual glands. Data were analyzed according to diagnosis and salivary output after the assignment of an oral mucosal rating to each subject. In general, the mucosal surfaces were well preserved and infections were not seen. Patients evaluated for Sjoegren's syndrome and radiation-induced xerostomia had the lowest salivary gland performance but displayed a mucosal status similar to denture-wearing healthy subjects or patients with normal salivary flow who had idiopathic xerostomia. However, those patients with a total lack of salivary flow rarely had normal-appearing oral mucosa. These results confirm a role for saliva in oral mucosal preservation and also suggest that other factors may act to maintain oral mucosal integrity.
Current cell models for bioengineering a salivary gland: a mini-review of emerging technologies
Nelson, J; Manzella, K; Baker, OJ
Saliva plays a major role in maintaining oral health. Patients afflicted with a decrease in saliva secretion (symptomatically, xerostomia) exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. Despite recent improvements in treating xerostomia (e.g., saliva stimulants, saliva substitutes, and gene therapy), there is a need of more scientific advancements that can be clinically applied toward restoration of compromised salivary gland function. Here we provide a summary of the current salivary cell models that have been used to advance restorative treatments via development of an artificial salivary gland. These models represent initial steps toward clinical and translational research, to facilitate creation of clinically safe salivary glands. Further studies in salivary cell lines and primary cells are necessary to improve survival rates, cell differentiation, and secretory function. Additionally, the characterization of salivary progenitor and stem cell markers are necessary. Although these models are not fully characterized, their improvement may lead to the construction of an artificial salivary gland that is in high demand for improving the quality of life of many patients suffering from salivary secretory dysfunction. PMID:22805753
Polaprezinc prevents oral mucositis associated with radiochemotherapy in patients with head and neck cancer.
Watanabe, Tomoko; Ishihara, Masashi; Matsuura, Katsuhiko; Mizuta, Keisuke; Itoh, Yoshinori
Oral mucositis is frequent but serious adverse event associated with radiotherapy or radiochemotherapy in head and neck cancer severely impairs health-related quality of life, leading to poor prognosis due to discontinuation of the therapy. Although a number of compounds have been tested for prophylaxis of oral mucositis, few of them are satisfactory. We investigated the effect of polaprezinc (zinc L-carnosine), a gastric mucosal protective drug, on radiochemotherapy-induced oral mucositis, pain, xerostomia and taste disturbance in patients with head and neck cancer. Patients were randomly assigned to receive polaprezinc (n = 16) or azulene oral rinse as the control (n = 15). The incidence rates of mucositis, pain, xerostomia and taste disturbance were all markedly lower in polaprezinc group than in control. Moreover, the use of analgesics was significantly (p = 0.003) less frequent and the amount of food intake was significantly (p = 0.002) higher in polaprezinc group than in control. On the other hand, tumor response rate in patients with neoadjuvant radiochemotherapy was not significantly affected by polaprezinc, in which the response rate (complete plus partial response) was 88% for polaprezinc and 92% for control (p = 1.000). Therefore, it is highly assumable that polaprezinc is potentially useful for prevention of oral mucositis and improvement of quality of life without reducing the tumor response. PMID:20104529
Meta-analysis of Selective Serotonin Reuptake Inhibitors (SSRIs) Compared to Tricyclic Antidepressants (TCAs) in the Efficacy and Safety of Anti-depression Therapy in Parkinson's Disease(PD) Patients.
Qiu, Bao-Yue; Qiao, Jun-Xiao; Yong, Jiang
To assess the efficacy and safety of selective serotonin reuptake inhibitors(SSRIs) and tricyclic antidepressants(TCAs) in treatment of Parkinsonian depression. A computer-based search was conducted in the databases of PUBMED, MEDLINE, EMBASE and CochraneControlled Trails Register up to December 2011. The random controlled clinic trials about SSRIs and TCAs in treatment of Parkinsonian depression were collected. Statistical analysis was completed using Review Manager, version 5.0. Five clinic controlled trials were identified for this meta-analysis. There was no significant statistical difference in the response rate of treatment [RR 0.95, 95%CI (0.78, 1.16)] and Hamilton depression score [RR -2.54, 95%CI (-5.35, 0.26)] between two groups. In term of complications, no statistical difference was observed in the insomnia rate between two groups [RR 0.82, 95%CI (0.24, 2.84)]. Moreover, the incidence rate of xerostomia [RR 0.21, 95%CI (0.07, 0.65)] and constipation [RR 0.12, 95%CI(0.02, 0.63)] was lower in SSRIs group rather than those in TCAs group. In general, SSRIs and TCAs have comparable efficacy and equal acceptability in treatment of Parkinson's disease-induced depression. However, SSRIs are superior to TCAs in the terms of xerostomia and constipation. PMID:25587309
Value of Intensity-Modulated Radiotherapy in Stage IV Head-and-Neck Squamous Cell Carcinoma
Dirix, Piet, E-mail: firstname.lastname@example.com [Department of Radiation Oncology, Leuvens Kankerinstituut, University Hospitals Leuven, campus Gasthuisberg, Leuven (Belgium); Nuyts, Sandra [Department of Radiation Oncology, Leuvens Kankerinstituut, University Hospitals Leuven, campus Gasthuisberg, Leuven (Belgium)
Purpose: To review outcome and toxicity of Stage IVa and IVb head-and-neck squamous cell carcinoma patients treated with concomitant chemotherapy and intensity-modulated radiotherapy (IMRT) according to a hybrid fractionation schedule. Methods and Materials: Between 2006 and 2008, 42 patients with Stage IV head-and-neck squamous cell carcinoma were irradiated according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily), followed by 20 fractions of 1.6 Gy (twice daily), to a total dose of 72 Gy. Chemotherapy (cisplatinum, 100mg/m{sup 2}) was administered at the start of Weeks 1 and 4. Treatment outcome and toxicity were retrospectively compared with a previous patient group (n = 55), treated according to the same schedule, but without intensity modulation. Results: Locoregional control (LRC) and overall survival were 81% and 56% after 2 years, respectively. In comparison with the previous cohort, no significant differences were observed regarding either LRC (66%, p = 0.38) or overall survival (73%, p = 0.29). No Grade 4 or 5 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of late Grade 2 or 3 xerostomia (52.9% vs. 90.2%, p < 0.001). No difference was observed regarding late Grade 2 or 3 dysphagia (p = 0.66). Conclusions: Intensity-modulated chemoradiotherapy does not compromise LRC and significantly reduces late toxicity, especially regarding xerostomia.
Is dentistry going to get into the salivary diagnostics game or watch from the sidelines?
Jacobson, Jed J
What is salivary diagnostics and why should you care? Most of us dentists try to avoid or control saliva as it interferes with access, or chemical interactions in dental materials or impression materials, or when it is simply a nuisance. Periodically, we may note reduced flow or encounter a patient with xerostomia. Correspondingly, we then manage the many of today's existing commercialized oral-based tests were yesterday's proposed ideas or concepts, captured in the 1993 New York Academy of Sciences Conference on oral based diagnostics. When coupled with the emerging point-of-care technology, the potential of salivary diagnostics is even more compelling. In this section, I hope to elucidate for the reader the potential of salivary diagnostics for the dental profession and So what is the value proposition? How could this disruptive technology serve the dentist and the patients they treat? What must occur to facilitate the ongoing development and introduction of salivary diagnostics into the marketplace? PMID:23858673
Impact of inhalation therapy on oral health
Godara, Navneet; Godara, Ramya; Khullar, Megha
Inhalation therapy has been employed as the mainstay of the treatment in chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Beta-2 agonists, anticholinergic bronchodilators, inhaled corticosteroids, and sodium cromoglycate are often used alone or in combination in an inhaled form. Studies have shown that inhaled drugs used in the treatment have some adverse effects on the oral health based on their dosage, frequency, and duration of use. Several oral conditions such as xerostomia, dental caries, candidiasis, ulceration, gingivitis, periodontitis, and taste changes have been associated with inhalation therapy. Since the prevalence of chronic respiratory diseases is rising, it is important to provide optimal oral care to the individuals receiving inhalation therapy. This article will review the influence of inhaled drugs on the oral health of individuals and adequate management and prevention of the same. PMID:22084541
Effect of reserpine on salivary gland radioiodine uptake in thyroid cancer
Levy, H.A.; Park, C.H.
Nine patients with thyroid cancer were treated with reserpine in an attempt to reduce radiation exposure to the salivary glands from 100-150 mCi doses of I-131 therapy to thyroid remnants or metastases. Three control patients were not treated with reserpine but did receive 100-150 mCi of I-131. Parotid/background ratios of activity after radioablative doses of I-131 in patients not treated with reserpine were significantly higher than the patients treated with reserpine, and this was also true seven days after the radioablative dose. Combined therapy with reserpine, chewing gum, lemon candies, and hydration is suggested for the prevention of sialadenitis and xerostomia due to large doses of radioiodine.
A review of dental treatment of head and neck cancer patients, before, during and after radiotherapy: part 1.
Jawad, H; Hodson, N A; Nixon, P J
The incidence of head and neck cancer is on the rise. Most head and neck cancers are treated with surgery, radiotherapy, chemotherapy or a combination of these modalities. Patients undergoing radiotherapy can experience several unwanted oral side effects, which have both short and long term implications. Dental general practitioners should be aware of these implications and should liaise closely with the restorative consultants and the oncology team to establish the best oral care pathway. This two-part series is a review of the oral changes that occur during and after radiotherapy and the oral management of head and neck oncology before, during and after radiotherapy. This article deals with both immediate sequelae such as cellulitis, mucositis, dysphagia, dysguesia and weight loss as well as long term sequelae such as rampant caries, trismus, xerostomia and osteoradionecrosis. It also encompasses the importance and need for pre-radiotherapy assessment. PMID:25613260
Steroid dysregulation and stomatodynia (burning mouth syndrome).
Woda, Alain; Dao, Thuan; Gremeau-Richard, Christelle
Stomatodynia ( burning mouth syndrome) is characterized by a spontaneous, continuous burning pain felt in the oral mucosa typically of anxiodepressive menopausal women. Because there is no obvious organic cause, it is considered a nonspecific pain. This Focus Article proposes a hypothesis based on the following pathophysiological cascade: chronic anxiety or post traumatic stress leads to a dysregulation of the adrenal production of steroids. One consequence is a decreased or modified production of some major precursors for the neuroactive steroid synthesis occurring in the skin, mucosa, and nervous system. At menopause, the drastic fall of the other main precursor supply , the gonadal steroids, leads to a brisk alteration of the production of neuroactive steroids. This results in neurodegenerative alterations of small nerves fibers of the oral mucosa and /or some brain areas involved in oral somatic sensations. These neuropathic changes become irreversible and precipitate the burning pain, dysgeusia, and xerostomia associated with stomatodynia, which all involve thin nerve fibers. PMID:19639097
Objective and subjective nutritional assessment of patients with cancer in palliative care.
Kwang, Ang Yee; Kandiah, Mirnalini
This study aimed to evaluate the nutritional status of patients with cancer in palliative care and to examine the interrelationship between objective and subjective nutritional assessment measures. Patients' nutritional status in a palliative care unit of a Malaysian government hospital and a hospice facility were assessed using anthropometric measurements, weight loss at 1/6 months, and the scored patient-generated subjective global assessment (PG-SGA). Moderate-to-severe malnutrition was observed in a range from 31% to 69% using both measurements. Common nutritional impact symptoms were pain, xerostomia, and anorexia. Patient-generated subjective global assessment scores were significantly correlated with anthropometric measurements (P < .050). The PG-SGA is equally informative as objective indicators and is recommended as a quickly applied tool for nutritional status assessment of patients with cancer in palliative care. PMID:19959839
Caries prevention for patients with dry mouth.
Su, Nan; Marek, Cindy L; Ching, Victor; Grushka, Miriam
Patients with xerostomia, or dry mouth, resulting from various causes, are at higher risk for developing caries because of a loss of saliva and its benefits. A loss of saliva increases the acidity of the mouth, which affects many factors that contribute to the development of caries, such as proliferation of acid-producing bacteria, inability to buffer the acid produced by bacteria or from ingested foods, loss of minerals from tooth surfaces and inability to replenish the lost minerals, and loss of lubrication. Currently, a number of new products that can substitute for these functions of saliva or induce production of saliva are available in Canada. Some of these products are reviewed and a protocol for caries prevention in this high-risk population is proposed. PMID:21774875
Lacrimal-auricular-dental-digital (LADD) syndrome with diffuse ophthalmoplegia--a new finding.
Lim, Lik Thai; Blum, Robert; Chia, Seen Nee; Ting, Darren S J; Lavy, Timothy E; Dutton, Gordon N
Lacrimal-auricular-dental-digital (LADD) syndrome comprises multiple anomalies. It can be inherited as autosomal dominant with variable expressivity or can be sporadic in nature. The clinical features of LADD syndrome include variably, lacrimal system hypoplasia, ear anomalies (with or without hearing impairment), salivary system hypoplasia, epiblepharon, dry eyes, corneal limbal stem cells deficiency, hypodontia, microdontia, xerostomia, and clinodactyly. We would like to report a unique case series of LADD syndrome patients presenting with diffuse ophthalmoplegia and facial muscle dysfunction, which may be a distinct subset of LADD syndrome or a new syndrome itself. We believe this to be the first such report. We suggest careful examination of ocular movements in all newly diagnosed LADD syndrome patients. PMID:22784266
Harlequin ichthyosis: a case report.
Vergotine, Rodney Joseph; de Lobos, Maribel Reyes; Montero-Fayad, Marilia
Harlequin Ichthyosis (HI) is a very rare subtype of a group of hereditary disorders that have in common the accumulation and shedding of significant amounts of hyperkeratotic epidermis. HI has a very specific clinical presentation that includes eclabium, fish mouth appearance, mouth breathing and xerostomia. The addition of a very high caloric demand to the clinical features place these affected individuals at extremely high risk for developing rampant dental decay. This case report discusses a two-year-old boy with HI that presents with severe early childhood caries. The specific accommodations that were made to accomplish required dental work under general anesthesia are presented. A case is made for the inclusion of dentists in the management of these cases once a diagnosis is made. PMID:24553270
Dysphagia in head and neck cancer patients treated with chemoradiotherapy.
Platteaux, Nele; Dirix, Piet; Dejaeger, Eddy; Nuyts, Sandra
Dysphagia is a very common complaint of head and neck cancer patients and can exist before, during, and after chemoradiotherapy. It leads to nutritional deficiency, weight loss, and prolonged unnatural feeding and also has a major potential risk for aspiration. This has a significant negative impact on the patient's entire quality of life. Because treatment of dysphagia in this setting is rarely effective, prevention is paramount. Several strategies have been developed to reduce dysphagia. These include swallowing exercises, treatment modification techniques such as intensity-modulated radiotherapy, selective delineation of elective nodes, reducing xerostomia by parotid-sparing radiotherapy, and adding of radioprotectors. However, more research is needed to further decrease the incidence of dysphagia and improve quality of life. PMID:19711127
[Dental state in patients with head and neck cancers].
Rouers, M; Truntzer, P; Dubourg, S; Guihard, S; Antoni, D; Noël, G
In France, in 2005, there were approximately 16,000 new cases of head and neck cancer. These cancers have an unfavourable prognosis: the survival rates at 3 and 10 years are 50% and 10% respectively. The consumption of alcohol and tobacco is the most important risk factor; in some countries HPV infection was identified as a risk factor of head and neck tumours. Furthermore, a poor oral hygiene seems to raise this risk. We found many decay and periodontium problems in patients with an upper aerodigestive tract cancer. An evaluation of dental state is necessary before any cancer treatment. Treatments by radiotherapy engender noxious effects: hypocellular, hypovascularization, hypoxie of the irradiated tissues, which lead to immediate and chronically oral complications such as mucositis, fibrosis, xerostomia, decay, or osteoradionecrosis. An oral follow-up of these patients can prevent these complications, or reduce the severity of oral complications, and promote a good oral state. PMID:25937188
Image-Guided Radiotherapy for Locally Advanced Head and Neck Cancer
Nguyen, Nam P.; Kratz, Sarah; Lemanski, Claire; Vock, Jacqueline; Vinh-Hung, Vincent; Olena Gorobets; Chi, Alexander; Almeida, Fabio; Betz, Michael; Khan, Rihan; Godinez, Juan; Karlsson, Ulf; Ampil, Fred
Treatment of locally advanced head and neck cancer remains a challenge because of the head and neck complex anatomy and the tumor invasion to the adjacent organs and/or metastases to the cervical nodes. Postoperative irradiation or concurrent chemoradiation may lead to damage of radiosensitive structures such as the salivary glands, mandible, cochlea, larynx, and pharyngeal muscles. Xerostomia, osteoradionecrosis, deafness, hoarseness of the voice, dysphagia, and aspiration remain serious complications of head and neck irradiation and impair patient quality of life. Intensity-modulated and image-guided radiotherapy by virtue of steep dose gradient and daily imaging may allow for decreased radiation of the organs at risk for complication while preserving loco-regional control. PMID:23847763
Medulloblastoma: Long-term follow-up of patients treated with electron irradiation of the spinal field
Gaspar, L.E.; Dawson, D.J.; Tilley-Gulliford, S.A.; Banerjee, P. (London Regional Cancer Centre, Ontario (Canada))
Thirty-two patients with posterior fossa medulloblastoma underwent treatment with electron irradiation to the spinal field. The 5- and 10-year actuarial survival rates were 57% and 50%, respectively. Late complications observed in the 15 patients followed up for more than 5 years were short stature (six patients), decreased sitting-standing height ratio (four patients), scoliosis (two patients), poor school performance (seven patients), xerostomia (one patient), esophageal stricture (one patient), pituitary dysfunction (four patients), primary hypothyroidism (one patient), bilateral eighth-nerve deafness (one patient), and carcinoma of the thyroid (one patient). Complications following treatment with electrons to a spinal field are compared with reported complications following treatment with photons to the spinal field. Although short-term reactions were minimal, the authors found no difference in late complications. More sophisticated treatment planning may show such a long-term benefit in the future.
Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models
Xu Chengjian, E-mail: email@example.com [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van't [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)
Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.
Statistical Validation of Normal Tissue Complication Probability Models
Xu Chengjian, E-mail: email@example.com [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Veld, Aart A. van't; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)] [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands) [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)
Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.
Prevalence of Candida Species in the Oral Cavity of Patients Undergoing Head and Neck Radiotherapy
Azizi, Arash; Rezaei, Masood
Background and aims Candidiasis is a common opportunistic infection in immunocompromised patients. Radiation to the head and neck affects the oral mucous membrane and produces xerostomia. Xerostomia alters the oral mucosa and predisposes them to colonization by Candida species. The aim of this study was evaluation of Candida species before and after radiotherapy. Materials and methods Twenty patients undergoing radiation therapy were selected. None of the patients had taken any antibiotics and antifungals during the 3-month period prior to the study and did not take any during the study; in addition, they did not have any systemic conditions predisposing them to Candida infections. Swabs were collected from all the patients for Candida species culturing procedures 3±1 days before treatment and 2 and 4 weeks after radiotherapy. Swabs were inoculated on 2% Sabouraud's dextrose agar. Different types of Candida species are specified by colony color. Analysis of variance was used to assess the difference between the periods before and after treatment. Results Mean age of the patients were 59.4 years. Ten patients were Candida-positive before the initiation of radiotherapy. Eighteen and 20 patients were Candida-positive after two and four weeks of radiotherapy, respectively. The most frequent type of Candida in this study was Candida albicans both before and after radiotherapy. Conclusion The present study suggests that patients undergoing head and neck radiotherapy should take antifungal agents, especially sugar-free agents, topical fluoride and salivary substitutes. The most commonly found Candida in this study was Candida albicans, which might be attributed to its high pathogenecity. PMID:23230489
Development of poly(ethylene glycol) hydrogels for salivary gland tissue engineering applications.
Shubin, Andrew D; Felong, Timothy J; Graunke, Dean; Ovitt, Catherine E; Benoit, Danielle S W
More than 40,000 patients are diagnosed with head and neck cancers annually in the United States with the vast majority receiving radiation therapy. Salivary glands are irreparably damaged by radiation therapy resulting in xerostomia, which severely affects patient quality of life. Cell-based therapies have shown some promise in mouse models of radiation-induced xerostomia, but they suffer from insufficient and inconsistent gland regeneration and accompanying secretory function. To aid in the development of regenerative therapies, poly(ethylene glycol) hydrogels were investigated for the encapsulation of primary submandibular gland (SMG) cells for tissue engineering applications. Different methods of hydrogel formation and cell preparation were examined to identify cytocompatible encapsulation conditions for SMG cells. Cell viability was much higher after thiol-ene polymerizations compared with conventional methacrylate polymerizations due to reduced membrane peroxidation and intracellular reactive oxygen species formation. In addition, the formation of multicellular microspheres before encapsulation maximized cell-cell contacts and increased viability of SMG cells over 14-day culture periods. Thiol-ene hydrogel-encapsulated microspheres also promoted SMG proliferation. Lineage tracing was employed to determine the cellular composition of hydrogel-encapsulated microspheres using markers for acinar (Mist1) and duct (Keratin5) cells. Our findings indicate that both acinar and duct cell phenotypes are present throughout the 14 day culture period. However, the acinar:duct cell ratios are reduced over time, likely due to duct cell proliferation. Altogether, permissive encapsulation methods for primary SMG cells have been identified that promote cell viability, proliferation, and maintenance of differentiated salivary gland cell phenotypes, which allows for translation of this approach for salivary gland tissue engineering applications. PMID:25762214
Concurrent Chemotherapy and Intensity-Modulated Radiotherapy for Locoregionally Advanced Laryngeal and Hypopharyngeal Cancers
Lee, Nancy Y. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)], E-mail: email@example.com; O'Meara, William; Chan, Kelvin [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Della-Bianca, Cesar; Mechalakos, James G. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zhung, Joanne; Wolden, Suzanne L.; Narayana, Ashwatha [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Kraus, Dennis; Shah, Jatin P. [Department of Surgery, Division of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Pfister, David G. [Department of Medicine, Division of Head and Neck Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Purpose: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. Results: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. Conclusion: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser extent, those with laryngeal cancer. Strategies using IMRT to limit the dose delivered to the esophagus/inferior constrictor musculature without compromising target coverage might be useful to further minimize this late complication.
High-Dose and Extended-Field Intensity Modulated Radiation Therapy for Early-Stage NK/T-Cell Lymphoma of Waldeyer's Ring: Dosimetric Analysis and Clinical Outcome
Bi, Xi-Wen; Li, Ye-Xiong, E-mail: firstname.lastname@example.com; Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Ren, Hua; Dai, Jian-Rong
Purpose: To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Methods and Materials: Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV{sub 50}]) and 40 Gy to the negative cervical nodes (PTV{sub 40}). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Results: The median mean doses to the PTV{sub 50} and PTV{sub 40} were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV{sub 50} and 0.9% of the PTV{sub 40} received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ?3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ?grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. Conclusions: IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.
Efficacy and Toxicity of Chemoradiotherapy Using Intensity-Modulated Radiotherapy for Unknown Primary of Head and Neck
Sher, David J., E-mail: firstname.lastname@example.com [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA (United States); Balboni, Tracy A. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA (United States); Haddad, Robert I. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (United States); Department of Medicine, Brigham and Women's Hospital, Boston, MA (United States); Norris, Charles M. [Department of Surgery, Division of Otolaryngology, Brigham and Women's Hospital, Boston, MA (United States); Posner, Marshall R. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (United States); Department of Medicine, Brigham and Women's Hospital, Boston, MA (United States); Wirth, Lori J. [Department of Medical Oncology, Massachusetts General Hospital, Boston, MA (United States); Goguen, Laura A.; Annino, Donald [Department of Surgery, Division of Otolaryngology, Brigham and Women's Hospital, Boston, MA (United States); Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA (United States)
Purpose: No single standard treatment paradigm is available for head-and-neck squamous cell carcinoma of an unknown primary (HNCUP). Bilateral neck radiotherapy with mucosal axis irradiation is widely used, with or without chemotherapy and/or surgical resection. Intensity-modulated radiotherapy (IMRT) is a highly conformal method for delivering radiation that is becoming the standard of care and might reduce the long-term treatment-related sequelae. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for HNCUP. Patients and Materials: A retrospective study of all patients treated at the Dana-Farber Cancer Institute for HNCUP with IMRT between August 2004 and January 2009. The primary endpoint was overall survival; the secondary endpoints were locoregional and distant control, and acute and chronic toxicity. Results: A total of 24 patients with HNCUP were included. Of these patients, 22 had Stage N2 disease or greater. All patients underwent neck computed tomography, positron emission tomography-computed tomography, and examination under anesthesia with directed biopsies. Of the 24 patients, 22 received concurrent chemotherapy, and 7 (29%) also underwent induction chemotherapy. The median involved nodal dose was 70 Gy, and the median mucosal dose was 60 Gy. With a median follow-up of 2.1 years, the 2-year actuarial overall survival and locoregional control rate was 92% and 100%, respectively. Only 25% of the patients had Grade 2 xerostomia, although 11 patients (46%) required esophageal dilation for stricture. Conclusion: In a single-institution series, IMRT-based chemoradiotherapy for HNCUP was associated with superb overall survival and locoregional control. The xerostomia rates were promising, but the aggressive therapy was associated with significant rates of esophageal stenosis.
Total lymphoid irradiation for multiple sclerosis
Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.
Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.
Oral disease profiles in chronic graft versus host disease.
Bassim, C W; Fassil, H; Mays, J W; Edwards, D; Baird, K; Steinberg, S M; Cowen, E W; Naik, H; Datiles, M; Stratton, P; Gress, R E; Pavletic, S Z
At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ? 1 mL/5 min, mouth-opening ? 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials. PMID:25740857
Implantable Three-Dimensional Salivary Spheroid Assemblies Demonstrate Fluid and Protein Secretory Responses to Neurotransmitters
Pradhan-Bhatt, Swati; Harrington, Daniel A.; Duncan, Randall L.; Jia, Xinqiao; Witt, Robert L.
Radiation treatment in patients with head and neck tumors commonly results in hyposalivation and xerostomia due to the loss of fluid-secreting salivary acinar cells. Patients develop susceptibility to oral infections, dental caries, impaired speech and swallowing, reducing the quality of life. Clinical management is largely unsatisfactory. The development of a tissue-engineered, implantable salivary gland will greatly benefit patients suffering from xerostomia. This report compares the ability of a 2.5-dimensional (2.5D) and a three-dimensional (3D) hyaluronic acid (HA)-based culture system to support functional salivary units capable of producing fluid and phenotypic proteins. Parotid cells seeded on 2.5D, as well as those encapsulated in 3D HA hydrogels, self-assembled into acini-like structures and expressed functional neurotransmitter receptors. Structures in 3D hydrogels merged to form organized 50??m spheroids that could be maintained in culture for over 100 days and merged to form structures over 500??m in size. Treatment of acini-like structures with the ?-adrenergic agonists norepinephrine or isoproterenol increased granule production and ?-amylase staining in treated structures, demonstrating regain of protein secretion. Upon treatment with the M3 muscarinic agonist acetylcholine, acini-like structures activated the fluid production pathway by increasing intracellular calcium levels. The increase in intracellular calcium seen in structures in the 3D hydrogel culture system was more robust and prolonged than that in 2.5D. To compare the long-term survival and retention of acini-like structures in vivo, cell-seeded 2.5D and 3D hydrogels were implanted into an athymic rat model. Cells in 2.5D failed to maintain organized acini-like structures and dispersed in the surrounding tissue. Encapsulated cells in 3D retained their spheroid structure and structural integrity, along with the salivary biomarkers and maintained viability for over 3 weeks in vivo. This report identifies a novel hydrogel culture system capable of creating and maintaining functional 3D salivary spheroid structures for long periods in vitro that regain both fluid and protein secreting functions and are suitable for tissue restoration. PMID:23442148
Growth Factors Polymerized Within Fibrin Hydrogel Promote Amylase Production in Parotid Cells
McCall, Andrew D.; Nelson, Joel W.; Leigh, Noel J.; Duffey, Michael E.; Lei, Pedro; Andreadis, Stelios T.
Salivary gland cell differentiation has been a recurring challenge for researchers as primary salivary cells show a loss of phenotype in culture. Particularly, parotid cells show a marked decrease in amylase expression, the loss of tight junction organization and proper cell function. Previously, Matrigel has been used successfully as an extracellular matrix; however, it is not practical for in vivo applications as it is tumorigenic. An alternative method could rely on the use of fibrin hydrogel (FH), which has been used extensively in biomedical engineering applications ranging from cardiovascular tissue engineering to wound-healing experiments. Although several groups have examined the effects of a three-dimensional (3D) environment on salivary cell cultures, little is known about the effects of FH on salivary cell cultures. The current study developed a 3D cell culture model to support parotid gland cell differentiation using a combination of FH and growth factor-reduced Matrigel (GFR-MG). Furthermore, FH polymerized with a combination of EGF and IGF-1 induced formation of 3D spheroids capable of amylase expression and an agonist-induced increase in the intracellular Ca2+ concentration ([Ca2+]i) in salivary cells. These studies represent an initial step toward the construction of an artificial salivary gland to restore salivary gland dysfunction. This is necessary to reduce xerostomia in patients with compromised salivary function. PMID:23594102
Advances in Soft Denture Liners: An Update.
Hashem, Mohammed Ibrahim
Soft denture liners are used in complete and partial removable dentures to distribute functional loads homogeneously on the denture-bearing tissues. These materials are recommended in cases of irregular bone resorption, bony undercuts, thin atrophic mucosa, immediate prosthesis, healing after implant placement, and for patients with bruxism and xerostomia. The resilient lining materials can be categorized as plasticized acrylic resins or silicone elastomers. The plasticized acrylic resin comprises of acrylic polymers and copolymers, a liquid containing an acrylic monomer and plasticisers, such as ethyl alcohol and/or ethyl acetate responsible for preserving the material softness. The silicone elastomers, consisting of dimethylsiloxane polymers, with a chemical composition similar to that of the silicone impression materials devoid of leachable plasticisers, retain their elastic properties for prolonged periods. Most of the currently available materials have several disadvantages, including color stability, long-term resiliency, abrasion resistance, bond strength and porosity. Several modifications have been done recently to overcome of these disadvantages of the soft liners. The current review summarizes the recent developments in soft liners. PMID:26067736
Salivary Acetylcholinesterase Activity Is Increased in Parkinson's Disease: A Potential Marker of Parasympathetic Dysfunction
Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per
Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737
Palliative care for patients with head and neck cancer: "I would like a quick return to a normal lifestyle".
Goldstein, Nathan E; Genden, Eric; Morrison, R Sean
Head and neck cancers constitute a diverse group of diseases including malignancies of the oral cavity, oropharynx, larynx, sinuses, and skull base. Treatment of these cancers includes a combination of surgical resection, chemotherapy, and radiation. Due to both the patterns of disease recurrence and the adverse effects of treatments, patients with head and neck cancer often have a complex and prolonged course of illness that is marked by periods of freedom from disease and symptoms interspersed with bouts of serious illness, debility, and numerous physical and psychological symptoms including pain, dysphagia, weight loss, disfigurement, depression, and xerostomia. Thus, management of this disease is best provided by an interdisciplinary team that includes individuals from the disciplines of otolaryngology, palliative care, radiation oncology, oncology, nutrition, speech, and physical and occupational therapy. Using the case of Mr K, we describe the symptoms encountered by patients with head and neck cancer and suggest options for management. We discuss the psychological aspects that affect these patients, including issues such as changes in body image, quality of life, anxiety, and guilt. Finally, we discuss the importance of the interdisciplinary team in the care of these patients and outline the roles of each team member. By providing comprehensive care to patients with malignancies of the head and neck, clinicians can increase the likelihood that patients and their families will be able to obtain the best possible outcomes and quality of life. PMID:18413876
Oral Health of Drug Abusers: A Review of Health Effects and Care
SHEKARCHIZADEH, Hajar; KHAMI, Mohammad R.; MOHEBBI, Simin Z.; EKHTIARI, Hamed; VIRTANEN, Jorma I.
Abstract Oral health problems, among the most prevalent comorbidities related to addiction, require more attention by both clinicians and policy-makers. Our aims were to review oral complications associated with drugs, oral health care in addiction rehabilitation, health services available, and barriers against oral health promotion among addicts. Drug abuse is associated with serious oral health problems including generalized dental caries, periodontal diseases, mucosal dysplasia, xerostomia, bruxism, tooth wear, and tooth loss. Oral health care has positive effects in recovery from drug abuse: patients' need for pain control, destigmatization, and HIV transmission. Health care systems worldwide deliver services for addicts, but most lack oral health care programs. Barriers against oral health promotion among addicts include difficulty in accessing addicts as a target population, lack of appropriate settings and of valid assessment protocols for conducting oral health studies, and poor collaboration between dental and general health care sectors serving addicts. These interfere with an accurate picture of the situation. Moreover, lack of appropriate policies to improve access to dental services, lack of comprehensive knowledge of and interest among dental professionals in treating addicts, and low demand for non-emergency dental care affect provision of effective interventions. Management of drug addiction as a multi-organ disease requires a multidisciplinary approach. Health care programs usually lack oral health care elements. Published evidence on oral complications related to addiction emphasizes that regardless of these barriers, oral health care at various levels including education, prevention, and treatment should be integrated into general care services for addicts.
Gurvits, Grigoriy E; Tan, Amy
Burning mouth syndrome is a debilitating medical condition affecting nearly 1.3 million of Americans. Its common features include a burning painful sensation in the mouth, often associated with dysgeusia and xerostomia, despite normal salivation. Classically, symptoms are better in the morning, worsen during the day and typically subside at night. Its etiology is largely multifactorial, and associated medical conditions may include gastrointestinal, urogenital, psychiatric, neurologic and metabolic disorders, as well as drug reactions. BMS has clear predisposition to peri-/post menopausal females. Its pathophysiology has not been fully elucidated and involves peripheral and central neuropathic pathways. Clinical diagnosis relies on careful history taking, physical examination and laboratory analysis. Treatment is often tedious and is aimed at correction of underlying medical conditions, supportive therapy, and behavioral feedback. Drug therapy with alpha lipoic acid, clonazepam, capsaicin, and antidepressants may provide symptom relief. Psychotherapy may be helpful. Short term follow up data is promising, however, long term prognosis with treatment is lacking. BMS remains an important medical condition which often places a recognizable burden on the patient and health care system and requires appropriate recognition and treatment. PMID:23429751
Long term chemoradiotherapy-related dental and skeletal complications in a young female with nasopharyngeal carcinoma
Ioannidou-Marathiotou, Ioulia; Pistevou-Gompaki, Kyriaki; Eleftheriadis, Nikolaos; Papaloukas, Christos
We describe the long-term complications six years after chemoradiotherapy in a 20-year old woman with nasopharyngeal carcinoma. We wanted to know whether the radiation dose was constant throughout the oral cavity, and thus uniformly affecting the corresponding dental and skeletal structures. Clinical and radiologic findings are described six years after chemoradiotherapy based on a two-dimensional computerized treatment planning system. This revealed radiation caries limited only to posterior teeth, proximal caries in the anterior teeth, limited but continuous salivary flow, mild periodontal infection, mild xerostomia, and a regenerative capacity of bones and the developmental process. The quantitative assessment of radiation delivered to the mandible revealed a high radiation dose in the posterior area and a minimal dose in the anterior area. This explains the differences in caries manifestation between the anterior and posterior teeth. According to the present study, individualized radiation fields, using a two-dimensional treatment planning system, result in restriction of severe damage of the dental and skeletal structures, which usually follows chemoradiotherapy. Orthodontic treatment could be initiated according to individual patient needs. PMID:20689692
Complementary strategies for the management of radiation therapy side effects.
Stubbe, Christine E; Valero, Meighan
Patients with cancer utilize complementary and alternative medicine (CAM) for a variety of purposes, one of which is the reduction of side effects of conventional treatment. With a large number of their patients using CAM, it is important for advanced practitioners in oncology to have an understanding of these therapies to better guide their patients. Side effects of radiation therapy that may have dose-limiting poten-tial include diarrhea, mucositis, skin toxicity, and xerostomia. A com-mon side effect that is not necessarily dose-limiting but considerably troublesome to patients is cancer- and treatment-related fatigue. The CAM therapies that may alleviate some of the side effects of radiation therapy include probiotics, psyllium, exercise, melatonin, honey, acu-puncture, and calendula. Therapies that require more research or have been shown to be ineffective include aloe vera, glutamine, and deglyc-yrrhizinated licorice. This article provides an overview of these thera-pies as well as related research and analysis. PMID:25032003
Submandibular gland excision: long-term clinical outcome in 139 patients operated in a single institution.
Springborg, Line Kanstrup; Mřller, Martin Nue
In transcervical resection of the submandibular gland for benign lesions, only a limited risk of damage to neural structures can be accepted and a cosmetically satisfactory result is mandatory. In this retrospective case series, we evaluated 139 patients operated over a 10-year period and completed long-term clinical follow-up of 113 of these patients after a median of 81 months. In all patients, the operation was effective. We found a 4.3 % risk of reoperation for wound infection or postoperative hematomas and an 18.7 % risk of early paresis of the marginal branch of the facial nerve, which decreased to 2.7 % on long-term follow-up. We found a 4.4 % risk of permanent lingual nerve paresis, and no patients had damage to the hypoglossal nerve. Xerostomia was found in 22.1 % of the patients and could be quantified by the easily performed biscuit test. Only 2.5 % reported an unsatisfactory cosmetic result and all scars were ? 6 on the Vancouver Scar Scale. Problems with scarring were more common if there had been postoperative infection. We continue to use the lateral transcervical approach as standard in our institution for patients who cannot be managed by gland-sparing procedures. PMID:22941392
The efficacy of chlorhexidine gel in reduction of Streptococcus mutans and Lactobacillus species in patients treated with radiation therapy
Epstein, J.B.; McBride, B.C.; Stevenson-Moore, P.; Merilees, H.; Spinelli, J. (Cancer Control Agency of British Columbia, Vancouver (Canada))
Xerostomia may develop in patients with cancer who receive radiotherapy that includes the salivary glands in the field. These patients are at high risk of rampant dental caries. Streptococcus mutans and Lactobacillus species have been associated with dental caries. Quantitative counts of these organisms demonstrated high caries risk due to streptococci in 66% and due to lactobacilli in 100% of patients studied. Use of chlorhexidine rinse was shown to reduce S. mutans counts 1.1 logs and lactobacilli 1.1 logs. The use of chlorhexidine gel resulted in a reduction of S. mutans 1.2 logs and lactobacilli 2.2 logs. In the subjects using the rinse, caries risk due to streptococci was reduced to low levels in 44% and due to lactobacilli in only one subject, with reduction to moderate risk in one third and no change in risk in the remaining patients. The use of chlorhexidine gel was found to reduce the caries risk associated with streptococci to low levels in all patients, and the risk associated with lactobacilli to low and moderate risk in two thirds of patients.
Burning mouth syndrome: a review and update.
Silvestre, Francisco J; Silvestre-Rangil, Javier; López-Jornet, Pía
Burning mouth syndrome (BMS) is mainly found in middle aged or elderly women and is characterized by intense burning or itching sensation of the tongue or other regions of the oral mucosa. It can be accompanied by xerostomia and dysgeusia. The syndrome generally manifests spontaneously, and the discomfort is typically of a continuous nature but increases in intensity during the evening and at night. Although BMS classically has been attributed to a range of factors, in recent years evidence has been obtained relating it peripheral (sensory C and/or trigeminal nerve fibers) or central neuropathic disturbances (involving the nigrostriatal dopaminergic system). The differential diagnosis requires the exclusion of oral mucosal lesions or blood test alterations that can produce burning mouth sensation. Patient management is based on the avoidance of causes of oral irritation and the provision of psychological support. Drug treatment for burning sensation in primary BMS of peripheral origin can consist of topical clonazepam, while central type BMS appears to improve with the use of antidepressants such as duloxetine, antiseizure drugs such as gabapentin, or amisulpride. PMID:25952601
Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities
Guo, Rui; Tang, Ling-Long; Mao, Yan-Ping; Zhou, Guan-Qun; Qi, Zhen-Yu; Liu, Li-Zhi; Lin, Ai-Hua; Liu, Meng-Zhong
Background To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC). Material and Methods 205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68–70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria. Results The median follow-up period was 37.3 months (range, 6.3–45.1 months). The 3-year estimated local failure–free survival, regional failure–free survival, locoregional failure–free survival, distant metastasis–free survival, disease–free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2–3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively. Conclusions VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy. PMID:26146828
Oral health status in a population of Nigerian diabetics.
Ogunbodede, Eyitope O; Fatusi, Olawunmi A; Akintomide, Anthony; Kolawole, Kikelomo; Ajayi, Adesuyi
Oral manifestations of diabetes mellitus have been documented, but the effect of glycemic control on the oral tissues has been scantily reported. The oral health status of 65 metabolically controlled adult diabetic patients attending the Diabetes Clinic of Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria, was prospectively assessed over six months and compared with that of 54 non-diabetic acting as controls. The mean duration of diabetes was 100.5+/-85.1 months. The difference in periodontal status of the patients and control, assessed using the Community Periodontal Index of Treatment Needs (CPITN), was not statistically significant (p=0.07). The degree of hyposalivation between the two groups was, however, statiscally significant (p<0.05). No significant difference was observed in the altered taste, burning mouth sensation, angular cheilitis, glossitis, and stomatitis status of the two groups. We conclude, with adequate metabolic control, the oral health status of a diabetic may not be significantly different from that of a non-diabetic except for xerostomia. A good understanding of the interactions between systemic diseases and oral health is imperative for physicians and dental practitioners. The need for early detection and closer linkages between the dental and medical professions in managing diabetic patients is emphasized. PMID:16299609
Salivary acetylcholinesterase activity is increased in Parkinson's disease: a potential marker of parasympathetic dysfunction.
Fedorova, Tatyana; Knudsen, Cindy Soendersoe; Mouridsen, Kim; Nexo, Ebba; Borghammer, Per
Introduction. Decreased salivary flow and xerostomia are frequent findings in Parkinson's disease (PD), possibly caused by alterations in the parasympathetic tonus. Here we explore salivary acetylcholinesterase (AChE) activity as a potential biomarker in PD. Methods. We measured salivary flow, AChE activity, and total protein concentration in 30 PD patients and 49 healthy controls. We also performed exploratory correlation analyses with disease duration, motor symptom severity, autonomic complaints, and other nonmotor symptoms. Results. PD patients displayed significantly decreased salivary flow rate, significantly increased salivary AChE activity, and total protein concentration. Importantly, the AChE activity/total protein ratio was significantly increased in PD patients, suggesting that increased AChE activity cannot be explained solely by upconcentration of saliva. The Unified PD Rating Scale (UPDRS) score displayed significant correlation with total salivary protein (P = 0.002) and near-significant correlation with salivary flow (P = 0.07). Color vision test scores were also significantly correlated with AChE activity (P = 0.04) and total protein levels (P = 0.002). Conclusion. Salivary AChE activity is increased in PD patients compared to healthy controls. Future studies are needed to elucidate whether this parameter reflects the extent of neuronal damage and parasympathetic denervation in the salivary glands of PD patients. PMID:25767737
Urban legends series: Sjögren's syndrome.
Aframian, D J; Konttinen, Y T; Carrozzo, M; Tzioufas, A G
Sjögren's syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti-SSA/Ro and anti-SSB/La relevant for the diagnosis of SjS? (iv) Are the American-European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti-Ro/La autoantibodies, anti ?-fodrin IgA and anti-MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS. PMID:22490059
[Solifenacin in the treatment of patients with hyperactive urinary bladder].
Al-Shukri, S Kh; Kuz'min, I V
Efficacy and tolerance of a novel antimuscarinic drug solifenacin succinate (vesicar) were studied in 55 patients with hyperactive urinary bladder (HUB). All the patients were divided into two groups: 27 patients of group 1 received solifenacin in a dose 5 mg/day, 28 patients of group 2--in a dose 10 mg/day. The 3-month treatment has improved symptoms of the HUB compared to the initial level: a daily number of vesical tenesmus reduced in patients of groups 1 and 2 by 47 and 51%, respectively; a number of episodes of urgent urine incontinence by 53 and 65%, voiding--by 24 and 26%, respectively. Most symptom incidence reduction (by 2/3) occurred within the first month of therapy. Tolerance to 5 and 10 mg/day solifenacine was satisfactory. The most frequent side effect was xerostomia (18.5 and 28.5%, respectively). The results of the study show that solifenacine in doses 5 and 10 mg/day is effective and safe drug for therapy of patients with hyperactive urinary bladder. PMID:17722615
Outcomes of Postoperative Simultaneous Modulated Accelerated Radiotherapy for Head-and-Neck Squamous Cell Carcinoma
Moon, Sung Ho [Proton Therapy Center, National Cancer Center, Goyang (Korea, Republic of); Center for Specific Organs Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Jung, Yuh-Seog; Ryu, Jun Sun; Choi, Sung Weon; Park, Joo Yong; Yun, Tak; Lee, Sang Hyun [Center for Specific Organs Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Cho, Kwan Ho, E-mail: firstname.lastname@example.com [Proton Therapy Center, National Cancer Center, Goyang (Korea, Republic of); Center for Specific Organs Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)
Purpose: To evaluate the treatment efficacy and toxicity of postoperative simultaneous modulated accelerated radiotherapy (SMART) for patients with head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Between February 2003 and September 2008, 51 patients with histologically confirmed HNSCC received postoperative intensity-modulated radiotherapy (N = 33) or helical tomotherapy (N = 18) using SMART after curative surgical resection. The sites included were the oral cavity (OC), oropharynx (OP), larynx, and hypopharynx in 23, 20, 5, and 3 patients, respectively. Results: The median follow-up duration of all patients and surviving patients were 32 (range, 5-78 months) and 39 months (range, 9-77 months), respectively. The 3-year overall survival, cause-specific survival, disease-free survival, locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) in all patients were 71%, 77%, 75%, 85%, and 82%, respectively. Although no significant difference in 3-year LRRFS were found between OC (82%) and OP (82%) carcinomas, the 3-year DMFS was worse in cases of OC (66%) carcinoma compared with OP carcinoma (95%; p = 0.0414). Acute Grade 3 dermatitis, mucositis, and esophagitis occurred in 10%, 10%, and 2% of patients, respectively. At the last follow-up, Grade 3 xerostomia was documented in 10% of the patients. Young age ({<=}40 years) (p < 0.001) and OC carcinoma primary (p = 0.0142) were poor risk factors on univariate analysis for DMFS. Conclusion: Postoperative SMART was observed to be effective and safe in patients with HNSCC.
Oral Health of Drug Abusers: A Review of Health Effects and Care.
Shekarchizadeh, Hajar; Khami, Mohammad R; Mohebbi, Simin Z; Ekhtiari, Hamed; Virtanen, Jorma I
Oral health problems, among the most prevalent comorbidities related to addiction, require more attention by both clinicians and policy-makers. Our aims were to review oral complications associated with drugs, oral health care in addiction rehabilitation, health services available, and barriers against oral health promotion among addicts. Drug abuse is associated with serious oral health problems including generalized dental caries, periodontal diseases, mucosal dysplasia, xerostomia, bruxism, tooth wear, and tooth loss. Oral health care has positive effects in recovery from drug abuse: patients' need for pain control, destigmatization, and HIV transmission. Health care systems worldwide deliver services for addicts, but most lack oral health care programs. Barriers against oral health promotion among addicts include difficulty in accessing addicts as a target population, lack of appropriate settings and of valid assessment protocols for conducting oral health studies, and poor collaboration between dental and general health care sectors serving addicts. These interfere with an accurate picture of the situation. Moreover, lack of appropriate policies to improve access to dental services, lack of comprehensive knowledge of and interest among dental professionals in treating addicts, and low demand for non-emergency dental care affect provision of effective interventions. Management of drug addiction as a multi-organ disease requires a multidisciplinary approach. Health care programs usually lack oral health care elements. Published evidence on oral complications related to addiction emphasizes that regardless of these barriers, oral health care at various levels including education, prevention, and treatment should be integrated into general care services for addicts. PMID:26060654
Sicca symptoms and their impact on quality of life among very long-term survivors after hematopoietic SCT.
Daikeler, T; Mauramo, M; Rovó, A; Stern, M; Halter, J; Buser, A; Tyndall, A; Häusermann, P; Gratwohl, A; Tichelli, A; Brennan, M T; Waltimo, T
The objective of this prospective cross-sectional case-control study was to examine the prevalence of dryness symptoms and its impact on quality of life (QoL) among very long-term survivors after hematopoietic SCT (HSCT) in comparison with their respective sibling donors. Forty-four allogeneic HSCT recipients with a long-term survival (median: 17.5; range: 11-26 years) were included. Their respective, HLA-identical sibling donors served as controls. Clinical examinations included saliva flow rates (SFR) and the Schirmer's test. The presence of sicca symptoms of mouth, eyes and skin were inquired. The social functioning (SF)-36 questionnaire was applied. Recipients had lower (P<0.01) unstimulated and stimulated mean SFR than donors. Schirmer's test results <5 mm was found in 45% of the recipients in comparison with 27% of the donors (P = 0.07). Xerostomia (34 vs 4 subjects), xerophtalmia (23 vs 3) and dry skin (32 vs 12) were reported more often by the recipients than donors (P<0.001). Sicca symptoms and their objective findings correlated with QoL. The mean SF-36 scores of the donors were significantly higher than those of the recipients for physical component summary. In conclusion, sicca symptoms are common amongst long-term survivors of HSCT and affect remarkably the QoL. PMID:23292241
Combined treatment in carcinoma of the nasopharynx
Souhami, L.; Rabinowits, M.
From October 1982 to August 1984, 30 previously untreated patients with biopsy-proven carcinoma of the nasopharynx, stage III (26.5%) and stage IV (73.5%), received combined radiotherapy (6,000 to 7,000 cGy over a period of 7 to 7.5 weeks) and chemotherapy (mitomycin-C 10 mg/M2, IV; 5-fluorouracil 750 mg/M2, IV; and methotrexate 30 mg/M2, IV) concomitantly. There were 20 males and 10 females, with a median age of 40 years. Minimal follow-up duration was 24 months. Actuarial overall survival rate at 48 months was 49%. Complete local response was achieved in 75% of the patients, with 31% of the cases failing distantly. The complication rate was high and included severe mucositis, xerostomia, and septicemia (fatal in two cases). Despite high local disease control, survival rate did not increase. A randomized trial is urgently needed to establish whether or not combined treatment is of value in advanced carcinoma of the nasopharynx.
Symptoms and attitudes of 100 consecutive patients admitted to an acute hospice/palliative care unit.
Ng, K; von Gunten, C F
One hundred patients admitted to an acute hospice/palliative care unit in a U.S. teaching hospital were evaluated using a standardized data acquisition tool that assessed the presence of physical symptoms and attitudes concerning admission to such a specialty unit. Patients entering the unit between June 1995 and October 1995 completed the tool within 24 hours of admission. Symptoms reported were fatigue in 81 patients, anorexia in 70, dyspnea in 61, xerostomia in 58, cough in 52, pain in 49, confusion in 37, depression in 37, constipation in 35, nausea in 30, insomnia in 23, and vomiting in 22. Of the 59 patients and family/friends that responded to the question "How do you feel about hospice care?", 53 gave a positive response. When asked about the best aspects of the unit, the most common response related to the care the patient and family received (23 responses, 39%). We conclude that patients admitted to an acute inpatient hospice/palliative care unit have multiple symptoms and a high degree of satisfaction with the environment. PMID:9846025
Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck. Experience at a single institution with a review of the literature
Fromm, M.; Littman, P.; Raney, R.B.; Nelson, L.; Handler, S.; Diamond, G.; Stanley, C.
Twenty children with soft tissue sarcomas of the head and neck, treated at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania from 1972 to 1981, were evaluated for the late deleterious effects of treatment. All patients received radiation therapy and combination chemotherapy with vincristine, dactinomycin, and cyclophosphamide; certain patients also received Adriamycin (doxorubicin). All had ophthalmologic, otologic, growth, and cosmetic evaluations; 15 also had dental and maxillofacial examinations. The median age at diagnosis was 6 years (range, 7 months-13 years). Median follow-up from time of diagnosis was 5.5 years with a minimum of 3 years in all but four patients. The major problems encountered were related to the eyes (xerophthalmia and cataracts), ears (hearing loss), teeth (maleruption and caries), glandular structures (xerostomia, hypopituitarism), and development (craniofacial deformity). It is concluded that children treated for soft tissue sarcomas of the head and neck with combined modality therapy, including radiation enhancers, may show a variety of late treatment-related adversities. These children require close multidisciplinary follow-up for detection of late effects in order that appropriate prophylactic or symptomatic treatment can be instituted to minimize their consequences.
Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction.
Baum, Bruce J; Alevizos, Ilias; Zheng, Changyu; Cotrim, Ana P; Liu, Shuying; McCullagh, Linda; Goldsmith, Corinne M; Burbelo, Peter D; Citrin, Deborah E; Mitchell, James B; Nottingham, Liesl K; Rudy, Susan F; Van Waes, Carter; Whatley, Millie A; Brahim, Jaime S; Chiorini, John A; Danielides, Stamatina; Turner, R James; Patronas, Nicholas J; Chen, Clara C; Nikolov, Nikolay P; Illei, Gabor G
No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2-3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 10(7) to 5.8 × 10(9) vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 10(9) vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects. PMID:23129637
Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.
Hill, Grace; Headon, Denis; Harris, Zoey I; Huttner, Kenneth; Limesand, Kirsten H
Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage. PMID:25409170
Anatomy, biogenesis, and regeneration of salivary glands
Holmberg, Kyle V.; Hoffman, Matthew P.
An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients per year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients' quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland (SMG), which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of three general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy, and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph. PMID:24862590
Gurvits, Grigoriy E; Tan, Amy
Black hairy tongue (BHT) is a benign medical condition characterized by elongated filiform lingual papillae with typical carpet-like appearance of the dorsum of the tongue. Its prevalence varies geographically, typically ranging from 0.6% to 11.3%. Known predisposing factors include smoking, excessive coffee/black tea consumption, poor oral hygiene, trigeminal neuralgia, general debilitation, xerostomia, and medication use. Clinical presentation varies but is typically asymptomatic, although aesthetic concerns are common. Differential diagnosis includes pseudo-BHT, acanthosis nigricans, oral hairy leukoplakia, pigmented fungiform papillae of the tongue, and congenital melanocytic/melanotic nevi/macules. Clinical diagnosis relies on visual observation, detailed history taking, and occasionally microscopic evaluation. Treatment involves identification and discontinuation of the offending agent, modifications of chronic predisposing factors, patient's re-assurance to the benign nature of the condition, and maintenance of adequate oral hygiene with gentle debridement to promote desquamation. Complications of BHT (burning mouth syndrome, halitosis, nausea, gagging, dysgeusia) typically respond to therapy. Prognosis is excellent with treatment of underlying medical conditions. BHT remains an important medical condition which may result in additional burden on the patient and health care system and requires appropriate prevention, recognition and treatment. PMID:25152586
Implants in the medically compromised patient.
Beikler, Thomas; Flemmig, Thomas F
Dental clinicians are confronted with an increasing number of medically compromised patients who require implant surgery for their oral rehabilitation. However, there are few guidelines on dental implant therapy in this patient category, so that numerous issues regarding pre- and post-operative management remain unclear to the dental clinician. Therefore, the aim of the present review is to offer a critical evaluation of the literature and to provide the clinician with scientifically based data for implant therapy in the medically compromised patient. This review presents the current knowledge regarding the influence of the most common systemic and local diseases on the outcome of dental implant therapy, e.g., abnormalities in bone metabolism, diabetes mellitus, xerostomia, and ectodermal dysplasias. Specific pathophysiologic aspects of the above-mentioned diseases as well as their potential implications for implant success are critically appraised. In line with these implications, guidelines for pre- and post-operative management that may assist in the successful implant-supported rehabilitation of this patient category are proposed. PMID:12907698
Polaprezinc prevents oral mucositis in patients treated with high-dose chemotherapy followed by hematopoietic stem cell transplantation.
Hayashi, Hiroko; Kobayashi, Ryo; Suzuki, Akio; Ishihara, Masashi; Nakamura, Nobuhiko; Kitagawa, Junichi; Kanemura, Nobuhiro; Kasahara, Senji; Kitaichi, Kiyoyuki; Hara, Takeshi; Tsurumi, Hisashi; Moriwaki, Hisataka; Itoh, Yoshinori
We have previously reported that polaprezinc in sodium alginate suspension (P-AG) inhibited the incidence of oral mucositis induced by radiochemotherapy in patients with head and neck cancer. The present study was designed to investigate whether P-AG prevents oral mucositis in all patients (36 patients) with hematological malignancy receiving high-dose chemotherapy and radiotherapy followed by hematopoietic stem cell transplantation (HSCT). P-AG dramatically reduced the incidence of moderate-to-severe oral mucositis as compared to the control group treated with azulene gargle (20% versus 82% for grade ? 2, p<0.01; 0% versus 45% for grade ? 3, p<0.01). Pain associated with oral mucositis was also significantly (p=0.004) relieved by P-AG, resulting in a reduction in the use of analgesic agents (28% versus 73%, p=0.025). The incidence of xerostomia and taste disturbance tended to be lowered but not significantly by P-AG. On the other hand, P-AG had no influence on the incidence of other adverse events, tumor remission rate or the survival rate. Therefore, P-AG was found to be highly effective in preventing oral mucositis induced not only by radiochemotherapy for head and neck cancer but also by high-dose chemotherapy and radiotherapy followed by HSCT. PMID:25503160
Multidisciplinary Management of Laryngeal Carcinoma
Mendenhall, William M. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States)], E-mail: email@example.com; Mancuso, Anthony A. [Department of Diagnostic Radiology, University of Florida College of Medicine, Gainesville, FL (United States); Hinerman, Russell W.; Malyapa, Robert S. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Werning, John W. [Department of Otolaryngology, University of Florida College of Medicine, Gainesville, FL (United States); Amdur, Robert J. [Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL (United States); Villaret, Douglas B. [Department of Otolaryngology, University of Florida College of Medicine, Gainesville, FL (United States)
The management of head and neck cancer has evolved into a multidisciplinary approach in which patients are evaluated before treatment and decisions depend on prospective multi-institutional trials, as well as retrospective outcome studies. The choice of one or more modalities to use in a given case varies with the tumor site and extent, as exemplified in the treatment of laryngeal squamous cell carcinomas. The goals of treatment include cure, laryngeal voice preservation, voice quality, optimal swallowing, and minimal xerostomia. Treatment options include transoral laser excision, radiotherapy (both definitive and postoperative), open partial laryngectomy, total laryngectomy, and neck dissection. The likelihood of local control and preservation of laryngeal function is related to tumor volume. Patients who have a relatively high risk of local recurrence undergo follow-up computed tomography scans every 3-4 months for the first 2 years after radiotherapy. Patients with suspicious findings on computed tomography might benefit from fluorodeoxyglucose positron emission tomography to differentiate post-radiotherapy changes from tumor.
Gurvits, Grigoriy E; Tan, Amy
Black hairy tongue (BHT) is a benign medical condition characterized by elongated filiform lingual papillae with typical carpet-like appearance of the dorsum of the tongue. Its prevalence varies geographically, typically ranging from 0.6% to 11.3%. Known predisposing factors include smoking, excessive coffee/black tea consumption, poor oral hygiene, trigeminal neuralgia, general debilitation, xerostomia, and medication use. Clinical presentation varies but is typically asymptomatic, although aesthetic concerns are common. Differential diagnosis includes pseudo-BHT, acanthosis nigricans, oral hairy leukoplakia, pigmented fungiform papillae of the tongue, and congenital melanocytic/melanotic nevi/macules. Clinical diagnosis relies on visual observation, detailed history taking, and occasionally microscopic evaluation. Treatment involves identification and discontinuation of the offending agent, modifications of chronic predisposing factors, patient's re-assurance to the benign nature of the condition, and maintenance of adequate oral hygiene with gentle debridement to promote desquamation. Complications of BHT (burning mouth syndrome, halitosis, nausea, gagging, dysgeusia) typically respond to therapy. Prognosis is excellent with treatment of underlying medical conditions. BHT remains an important medical condition which may result in additional burden on the patient and health care system and requires appropriate prevention, recognition and treatment. PMID:25152586
Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction
Baum, Bruce J.; Alevizos, Ilias; Zheng, Changyu; Cotrim, Ana P.; Liu, Shuying; McCullagh, Linda; Goldsmith, Corinne M.; Burbelo, Peter D.; Citrin, Deborah E.; Mitchell, James B.; Nottingham, Liesl K.; Rudy, Susan F.; Van Waes, Carter; Whatley, Millie A.; Brahim, Jaime S.; Chiorini, John A.; Danielides, Stamatina; Turner, R. James; Patronas, Nicholas J.; Chen, Clara C.; Nikolov, Nikolay P.; Illei, Gabor G.
No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2–3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 107 to 5.8 × 109 vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 109 vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects. PMID:23129637
Intensity-Modulated Radiotherapy for Sinonasal Cancer: Improved Outcome Compared to Conventional Radiotherapy
Dirix, Piet, E-mail: firstname.lastname@example.com [Department of Radiation Oncology, Leuvens Kankerinstituut (LKI), University Hospitals Leuven, campus Gasthuisberg, Leuven (Belgium); Vanstraelen, Bianca [Department of Radiation Oncology, Leuvens Kankerinstituut (LKI), University Hospitals Leuven, campus Gasthuisberg, Leuven (Belgium); Jorissen, Mark; Vander Poorten, Vincent [Department of Otorhinolaryngology-Head and Neck Surgery, Leuvens Kankerinstituut (LKI), University Hospitals Leuven, campus Gasthuisberg, Leuven (Belgium); Nuyts, Sandra [Department of Radiation Oncology, Leuvens Kankerinstituut (LKI), University Hospitals Leuven, campus Gasthuisberg, Leuven (Belgium)
Purpose: To evaluate clinical outcome and toxicity of postoperative intensity-modulated radiotherapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between 2003 and 2008, 40 patients with cancer of the paranasal sinuses (n = 34) or nasal cavity (n = 6) received postoperative IMRT to a dose of 60 Gy (n = 21) or 66 Gy (n = 19). Treatment outcome and toxicity were retrospectively compared with that of a previous patient group (n = 41) who were also postoperatively treated to the same doses but with three-dimensional conformal radiotherapy without intensity modulation, from 1992 to 2002. Results: Median follow-up was 30 months (range, 4-74 months). Two-year local control, overall survival, and disease-free survival were 76%, 89%, and 72%, respectively. Compared to the three-dimensional conformal radiotherapy treatment, IMRT resulted in significantly improved disease-free survival (60% vs. 72%; p = 0.02). No grade 3 or 4 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of acute as well as late side effects, especially regarding skin toxicity, mucositis, xerostomia, and dry-eye syndrome. Conclusions: Postoperative IMRT for sinonasal cancer significantly improves disease-free survival and reduces acute as well as late toxicity. Consequently, IMRT should be considered the standard treatment modality for malignancies of the nasal cavity and paranasal sinuses.
Perlecan domain IV peptide stimulates salivary gland cell assembly in vitro.
Pradhan, Swati; Zhang, Chu; Jia, Xinqiao; Carson, Daniel D; Witt, Robert; Farach-Carson, Mary C
Treatment of xerostomia would benefit from development of a functional implantable artificial salivary gland. Salivary gland tissue from surgical patients was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Ductal and acinar cells were identified in tissue and cultured cells from dispersed tissue. High levels of laminin and perlecan/HSPG2 (heparan sulfate proteoglycan 2) were noted in basement membranes, and perlecan also was secreted and organized by cultured acinar populations, which formed lobular structures that mimicked intact glands when cultured on Matrigel or a bioactive peptide derived from domain IV of perlecan. On either matrix, large acini-like lobular structures grew and formed connections between the lobes. alpha-Amylase secretion was confirmed by staining and activity assay. Biomarkers, including tight junction protein E-cadherin and water channel protein aquaporin 5 found in tissue, were expressed in cultured acinar cells. Cells cultured on Matrigel or domain IV of perlecan peptide organized stress fibers and activated focal adhesion kinase. We report a novel technique to isolate acinar cells from human salivary gland and identify a human peptide sequence in perlecan that triggers differentiation of salivary gland cells into self-assembling acini-like structures that express essential biomarkers and which secrete alpha-amylase. PMID:19382872
Radioprotective Effect of Lidocaine on Function and Ultrastructure of Salivary Glands Receiving Fractionated Radiation
Hakim, Samer George, E-mail: email@example.com [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Benedek, Geza Attila [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Su Yuxiong [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Department of Oral and Maxillofacial Surgery, Sun Yat-Sen University, Guanghua School of Stomatology, Guanghua (China); Jacobsen, Hans Christian [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Klinger, Matthias [Institute of Anatomy, University of Luebeck, Luebeck (Germany); Dendorfer, Andreas [Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Luebeck (Germany); Hemmelmann, Claudia [Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck (Germany); Meller, Birgit [Department of Radiology and Nuclear Medicine, University of Luebeck, Luebeck (Germany); Nadrowitz, Roger; Rades, Dirk [Department of Radiation Oncology, University of Luebeck, Luebeck (Germany); Sieg, Peter [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany)
Purpose: Radiation-induced xerostomia still represents a common side effect after radiotherapy for head-and-neck malignancies. The aim of the present study was to examine the radioprotective effect of lidocaine hydrochloride during fractionated radiation in an experimental animal model. Methods and Materials: To evaluate the influence of different radiation doses on salivary gland function and the radioprotective effect of lidocaine, rabbits were irradiated with 15, 25, 30, and 35 Gy (equivalent doses in 2-Gy fractions equivalent to 24, 40, 48, and 56 Gy, respectively). Lidocaine hydrochloride (10 and 12 mg/kg) was administered before every radiation fraction in the treatment groups. Salivary gland function was assessed by flow sialometry and sialoscintigraphy, and the morphologic changes were evaluated using transmission electron microscopy. Results: Functional impairment was first observed after 35 Gy and pretreatment with lidocaine improved radiation tolerance of both parotid and submandibular glands. The use of 12 mg/kg lidocaine was superior and displayed significant radioprotection with regard to flow sialometry and sialoscintigraphy. The ultrastructure was largely preserved after pretreatment with both lidocaine doses. Conclusions: Lidocaine represents an effective radioprotective agent and a promising approach for clinical application to avoid radiation-induced functional impairment of salivary glands.
Nutritional Interventions in Head and Neck Cancer Patients Undergoing Chemoradiotherapy: A Narrative Review
Bossola, Maurizio
The present review aimed to define the role of nutritional interventions in the prevention and treatment of malnutrition in HNC patients undergoing CRT as well as their impact on CRT-related toxicity and survival. Head and neck cancer patients are frequently malnourished at the time of diagnosis and prior to the beginning of treatment. In addition, chemo-radiotherapy (CRT) causes or exacerbates symptoms, such as alteration or loss of taste, mucositis, xerostomia, fatigue, nausea and vomiting, with consequent worsening of malnutrition. Nutritional counseling (NC) and oral nutritional supplements (ONS) should be used to increase dietary intake and to prevent therapy-associated weight loss and interruption of radiation therapy. If obstructing cancer and/or mucositis interfere with swallowing, enteral nutrition should be delivered by tube. However, it seems that there is not sufficient evidence to determine the optimal method of enteral feeding. Prophylactic feeding through nasogastric tube or percutaneous gastrostomy to prevent weight loss, reduce dehydration and hospitalizations, and avoid treatment breaks has become relatively common. Compared to reactive feeding (patients are supported with oral nutritional supplements and when it is impossible to maintain nutritional requirements enteral feeding via a NGT or PEG is started), prophylactic feeding does not offer advantages in terms of nutritional outcomes, interruptions of radiotherapy and survival. Overall, it seems that further adequate prospective, randomized studies are needed to define the better nutritional intervention in head and neck cancer patients undergoing chemoradiotherapy. PMID:25569622
Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels
NASA Astrophysics Data System (ADS)
Pradhan, Swati
Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar cells were identified in cultured cells from dispersed tissue. Biomarker studies with the salivary enzyme, alpha-amylase, and tight junction proteins, such as zonula occludens-1 and E-cadherin, confirmed the phenotype of these cells. Strong staining for laminin and perlecan/HSPG2 were noted in basement membranes and perlecan also was secreted and organized by cultured acinar populations, which formed lobular structures that mimicked intact glands when cultured on Matrigel(TM) or a bioactive peptide derived from domain IV of perlecan (PlnDIV). On either matrix, large acini-like lobular structures grew and formed connections between the lobes. alpha-Amylase secretion was confirmed by staining and activity assay. Biomarkers including tight junction protein E-cadherin and water channel protein, aquaporin 5 (AQP5) found in tissue, were expressed in cultured acinar cells. Cells cultured on Matrigel(TM) or PlnDIV peptide organized stress fibers and activated focal adhesion kinase (FAK). HA, a natural polysaccharide and a major component of the ECM, can be used to generate soft and pliable hydrogels. A culture system consisting of HA hydrogel and PlnDIV peptide was used to generate a 2.5D culture system. Acinar cells cultured on these hydrogels self-assembled into lobular structures and expressed tight junction components such as ZO-1. Acini-like structures were stained for the presence of alpha-amylase. Live/dead staining revealed the presence of apoptotic cells in the center of the acini-like structures, indicative of lumen formation. The functionality of these acini-like structures was studied by stimulating them with neurotransmitters to enhance their fluid and protein production. Acini-like structures treated with norepinephrine and isoproterenol showed increased granule formation as observed by phase contrast microscopy and alpha-amylase staining in the structures. Lobular structures on hydrogels were treated with acetylcholine to increase fluid production. The increase in intracellular calcium due to the activation of the M3 muscarinic receptor via binding to ac
Mechanism involved in Danshen-induced fluid secretion in salivary glands
Wei, Fei; Wei, Mu-Xin; Murakami, Masataka
AIM: Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia. METHODS: Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium. The artery was cannulated and vascularly perfused at a constant rate. The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance. The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated. In addition, the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption. In order to assess the mechanism involved in Danshen-induced fluid secretion, either ouabain (an inhibitor of Na+/K+ ATPase) or bumetanide (an inhibitor of NKCC1) was additionally applied during the Danshen stimulation. In order to examine the involvement of the main membrane receptors, atropine was added to block the M3 muscarinic receptors, or phentolamine was added to block the ?1 adrenergic receptors. In order to examine the requirement for extracellular Ca2+, Danshen was applied during the perfusion with nominal Ca2+ free solution. RESULTS: Although Danshen induced salivary fluid secretion, 88.7 ± 12.8 ?L/g-min, n = 9, (the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 ?L/g-min by carbamylcholine, P = 0.00093 by t-test) in the submandibular glands, the time course of that secretion differed from that induced by carbamylcholine. There was a latency associated with the fluid secretion induced by Danshen, followed by a gradual increase in the secretion to its highest value, which was in turn followed by a slow decline to a near zero level. The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%, and suppressed the oxygen consumption by 49% or 66%, respectively. These results indicated that Danshen activates Na+/K+ ATPase and NKCC1 to maintain Cl- release and K+ release for fluid secretion. Neither atropine or phentolamine inhibited the fluid secretion induced by Danshen (263% ± 63% vs 309% ± 45%, 227% ± 63% vs 309% ± 45%, P = 0.899, 0.626 > 0.05 respectively, by ANOVA). Accordingly, Danshen does not bind with M3 or ?1 receptors. These characteristics suggested that the mechanism involved in DS-induced salivary fluid secretion could be different from that induced by carbamylcholine. Carbamylcholine activates the M3 receptor to release inositol trisphosphate (IP3) and quickly releases Ca2+ from the calcium stores. The elevation of [Ca2+]i induces chloride release and quick osmosis, resulting in an onset of fluid secretion. An increase in [Ca2+]i is essential for the activation of the luminal Cl- and basolateral K+ channels. The nominal removal of extracellular Ca2+ totally abolished the fluid secretion induced by Danshen (1.8 ± 0.8 ?L/g-min vs 101.9 ± 17.2 ?L/g-min, P = 0.00023 < 0.01, by t-test), suggesting the involvement of Ca2+ in the activation of these channels. Therefore, IP3-store Ca2+ release signalling may not be involved in the secretion induced by Danshen, but rather, there may be a distinct signalling process. CONCLUSION: The present findings suggest that Danshen can be used in the treatment of xerostomia, to avoid the systemic side effects associated with muscarinic drugs. PMID:25663764
A comparison of mean parotid gland dose with measures of parotid gland function after radiotherapy for head-and-neck cancer: Implications for future trials
Roesink, Judith M. [Department of Radiotherapy, University Hospital Utrecht, University Medical Center Utrecht, Utrecht (Netherlands)]. E-mail: firstname.lastname@example.com; Schipper, Maria [Center for Biostatistics, Utrecht University, Utrecht (Netherlands); Busschers, Wim [Center for Biostatistics, Utrecht University, Utrecht (Netherlands); Raaijmakers, Cornelis P.J.; Terhaard, Chris H.J. [Department of Radiotherapy, University Hospital Utrecht, University Medical Center Utrecht, Utrecht (Netherlands)
Purpose: To determine the most adequate parameter to measure the consequences of reducing the parotid gland dose. Methods and Materials: One hundred eight patients treated with radiotherapy for various malignancies of the head and neck were prospectively evaluated using three methods. Parotid gland function was objectively determined by measuring stimulated parotid flow using Lashley cups and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck cancer module European Organization for Research and Treatment of Cancer QLQ (Quality of Life Questionnaire) H and N35 was used. Measurements took place before radiotherapy and 6 weeks and 12 months after the completion of radiotherapy. Complication was defined for each method using cutoff values. The correlation between these complications and the mean parotid gland dose was investigated to find the best measure for parotid gland function. Results: For both flow and scintigraphy data, the best definition for objective parotid gland toxicity seemed to be reduction of stimulated parotid flow to {<=}25% of the preradiotherapy flow. Of all the subjective variables, only the single item dry mouth 6 weeks after radiotherapy was found to be significant. The best correlation with the mean parotid gland dose was found for the stimulated flow measurements. The predictive ability was the highest for the time point 1 year after radiotherapy. Subjective findings did not correlate with the mean parotid dose. Conclusions: Stimulated flow measurements using Lashley cups, with a complication defined as flow {<=}25% of the preradiotherapy output, correlated best with the mean parotid gland dose. When reduction of the mean dose to the parotid gland is intended, the stimulated flow measurement is the best method for evaluating parotid gland function.
Clinical observation and quality of life in terms of nasal sinusitis after radiotherapy for nasopharyngeal carcinoma: long-term results from different nasal irrigation techniques
Luo, H-H; Fu, Z-C; Liao, S-G; Li, D-S
Objective: The aim of our study was to investigate the relationship between nasal irrigation techniques (NIT) and the survival rate and the quality of life (QOL) in patients with nasal sinusitis (NS). Methods: We studied data from 1134 patients with nasopharyngeal carcinoma (NPC) who received radical radiotherapy, which were randomly divided into three groups (A, B and C). Group A used nasal irrigator; Group B used homemade nasal irrigation (NI) connector combined with enemator; and Group C used nasal sprayer. The clinical effects, 5-year overall survival (OS) and progression-free survival (PFS) were observed. Furthermore, the QOL in patients with NS was evaluated using the Sino-Nasal Outcome Test 20. Results: The median follow-up time was 69 months. The 5-year OS and PFS were 80.5% and 73.2%, respectively, for all patients. There was no significant difference in OS, PFS, xerostomia and neck skin toxicity grade 3 and greater among groups. There was no difference among groups. The incidence of NS was the highest in group C. Conclusion: The symptoms of NS seriously affected the QOL period of 1 year. Group C showed no improvement during the follow-up period, which for A and B, by contrast, had after 1 year. Although the exact mechanism remains to be explored in NIT, our findings suggest that patients with NPC should nasal irrigate for 2 years after radiotherapy. Advances in knowledge: Our study shows that a nasal irrigator is necessary for patients with NPC for a high QOL in terms of NS. PMID:24814695
Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head and Neck Cancer
Kankaanranta, Leena [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Seppaelae, Tiina; Koivunoro, Hanna [Department of Physical Sciences, University of Helsinki, Helsinki (Finland); Boneca Corporation Ltd (Finland); Saarilahti, Kauko [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Atula, Timo [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Collan, Juhani [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Salli, Eero; Kortesniemi, Mika [HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Uusi-Simola, Jouni [Department of Physical Sciences, University of Helsinki, Helsinki (Finland); HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Maekitie, Antti [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Seppaenen, Marko [Turku PET Centre, Turku University Hospital, Turku (Finland); Minn, Heikki [Department of Oncology, Turku University Hospital, Turku (Finland); Kotiluoto, Petri; Auterinen, Iiro [VTT Technical Research Centre of Finland, Espoo (Finland); Savolainen, Sauli [Department of Physical Sciences, University of Helsinki, Helsinki (Finland); HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Kouri, Mauri [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Joensuu, Heikki [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland)], E-mail: email@example.com
Purpose: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. Methods and Materials: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria and adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). Conclusions: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites.
Intensity-Modulated Radiotherapy for Cervical Lymph Node Metastases From Unknown Primary Cancer
Madani, Indira [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)], E-mail: email@example.com; Vakaet, Luc [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien [Division of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; Neve, Wilfried de [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)
Purpose: To compare the effectiveness of intensity-modulated radiotherapy (IMRT) and conventional (two-dimensional) radiotherapy in the treatment of cervical lymph node metastases from unknown primary cancer (UPC). Methods and Materials: Between February 2003 and September 2006, 23 patients with UPC of squamous cell carcinoma were treated with IMRT. Extended putative mucosal and bilateral nodal sites were irradiated to a median dose of 66 Gy. In 19 patients, IMRT was performed after lymph node dissection, and in 4 patients primary radiotherapy was given. The conventional radiotherapy group (historical control group) comprised 18 patients treated to a median dose of 66 Gy between August 1994 and October 2003. Results: Twenty patients completed treatment. As compared with conventional radiotherapy, the incidence of Grade 3 acute dysphagia was significantly lower in the IMRT group (4.5% vs. 50%, p = 0.003). By 6 months, Grade 3 xerostomia was detected in 11.8% patients in the IMRT group vs. 53.4% in the historical control group (p = 0.03). No Grade 3 dysphagia or skin fibrosis was observed after IMRT but these were noted after conventional radiotherapy (26.7%, p = 0.01) and 26.7%, p = 0.03) respectively). With median follow-up of living patients of 17 months, there was no emergence of primary cancer. One patient had persistent nodal disease and another had nodal relapse at 5 months. Distant metastases were detected in 4 patients. The 2-year overall survival and distant disease-free probability after IMRT did not differ significantly from those for conventional radiotherapy (74.8% vs. 61.1% and 76.3% vs. 68.4%, respectively). Conclusions: Use of IMRT for UPC resulted in lower toxicity than conventional radiotherapy, and was similar in efficacy.
A Novel Aldehyde Dehydrogenase-3 Activator (Alda-89) Protects Submandibular Gland Function from Irradiation without Accelerating Tumor Growth
Xiao, Nan; Cao, Hongbin; Chen, Che-Hong; Kong, Christina S.; Ali, Rehan; Chan, Cato; Sirjani, Davud; Graves, Edward; Koong, Albert; Giaccia, Amato; Mochly-Rosen, Daria; Le, Quynh-Thu
Purpose To determine the effect of Alda-89 (an ALDH3 activitor) on (1) the function of irradiated (RT) submandibular gland (SMG) in mice, (2) its toxicity profile and (3) its effect on the growth of head and neck cancer (HNC) in vitro and in vivo. Experimental Design Adult mice were infused with Alda-89 or vehicle before, during and after RT. Saliva secretion was monitored weekly. Hematology, metabolic profile and post-mortem evaluation for toxicity were examined at the time of sacrifice. Alda-89 or vehicle was applied to HNC cell lines in vitro, and SCID mice transplanted with HNC in vivo with or without radiation; HNC growth was monitored. The ALDH3A1 and ALDH3A2 protein expression was evaluated in 89 HNC patients and correlated to freedom from relapse (FFR) and overall survival (OS). Results Alda-89 infusion significantly resulted in more whole saliva production and a higher percentage of preserved acini after RT compared to vehicle control. There was no difference in the complete blood count, metabolic profile, and major organ morphology between the Alda-89 and vehicle groups. Compared to vehicle control, Alda-89 treatment did not accelerate HNC cell proliferation in vitro, nor did it affect tumor growth in vivo with or without RT. Higher expression of ALDH3A1 or ALDH3A2 was not significantly associated with worse FFR or OS in either HPV-positive or HPV-negative group. Conclusion Alda-89 preserves salivary function after RT without affecting HNC growth or causing measurable toxicity in mice. It is a promising candidate to mitigate RT-related xerostomia. PMID:23812668
Efficacy of intensity-modulated radiotherapy with concurrent carboplatin in nasopharyngeal carcinoma
Songthong, Anussara; Chakkabat, Chakkapong; Kannarunimit, Danita; Lertbutsayanukul, Chawalit
Background. The aim of the prospective phase II study was to evaluate the efficacy and toxicities of concurrent carboplatin with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC). Patients and methods. Between October 2005 and November 2011, 73 stage II–IVB NPC patients received IMRT 70 Gy concurrently with three cycles of carboplatin (AUC 5) every three weeks, followed by three cycles of adjuvant carboplatin (AUC 5) and 5-FU (1,000 mg/m2/day for four days) every four weeks. All patients were evaluated for tumour response using response evaluation criteria in solid tumour (RECIST) criteria, survival analysis using Kaplan-Meier methods, and toxicities according to common terminology criteria for adverse events (CTCAE) version 4.0. Results. At three months after chemoradiation, 82.2% and 17.8% of patients achieved complete and partial response, respectively. With a median follow-up of 48.1 months (1.3–97.8 months), 9.6% and 17.8% had local recurrence and distant metastasis, respectively. The median survival was not reached. A three-year overall survival was 83.6% and a progression-free survival was 65.3%. Regarding treatment compliance, 97.2%, 68.5% and 69.8% completed radiation treatment, concurrent carboplatin and adjuvant chemotherapy, respectively. Grade 3–4 acute toxicities were oral mucositis (16.4%), dysphagia (16.4%), xerostomia (15.1%) and haematotoxicity (6.8%). Conclusions. Carboplatin concurrently with IMRT provided excellent tumour response, manageable toxicities and good compliance. This should be considered as an alternative treatment for NPC patients. PMID:26029027
[Survey of treatment-seeking complete denture wearers concerning tooth loss, retention behavior and treatment expectations].
Zitzmann, Nicola U; Marinello, Carlo P
The aim of the current study was to gather information about time and etiology of tooth loss, and to analyze the reasons for treatment needs with a questionnaire used among edentulous patients. 60 patients (age 44-98 years) who requested dental treatment were included. More than half of the patients were edentulous before the age of 60, in almost all cases the maxilla was affected first. This difference was more pronounced in women, who experienced tooth loss in the maxilla 17 years prior to the mandible. At the time of edentulism women were about ten years younger than men. According to patients'report, periodontal disease was the most common reason for tooth loss. In the mandible, prosthesis retention was influenced by alveolar ridge resorption, while in the maxilla there was no relation between the amount of resorption and perceived retention. This indicates that maxillary prostheses retention is influenced by other factors besides the alveolar ridge morphology. So, permanent intake of drugs potentially causing xerostomia was related to poorer assessment of prostheses retention in the upper jaw. The results of the questionnaire "Patient satisfaction related to prosthetic restoration" before treatment indicated that the general satisfaction with the existing complete denture in the mandible was influenced by functional problems and the impairment of patients'self-confidence (R-squared = 0.754). The main reason for requesting treatment was the poor retention of the lower denture. More than half of the participants stated that they refrained from eating certain foods due to a reduced chewing ability. PMID:16610458
Early Hyperbaric Oxygen Therapy for Reducing Radiotherapy Side Effects: Early Results of a Randomized Trial in Oropharyngeal and Nasopharyngeal Cancer
Teguh, David N. [Department of Radiation Oncology, Rotterdam (Netherlands); Levendag, Peter C., E-mail: email@example.com [Department of Radiation Oncology, Rotterdam (Netherlands); Noever, Inge; Voet, Peter; Est, Henrie van der; Rooij, Peter van [Department of Radiation Oncology, Rotterdam (Netherlands); Dumans, Antoine G. [Department of Maxillofacial Surgery, Rotterdam (Netherlands); Boer, Maarten F. de [Department of Otorhinolaryngology and Head and Neck Surgery, Rotterdam (Netherlands); Huls, Michiel van der; Sterk, Wouter [Institute for Hyperbaric Medicine, Rotterdam (Netherlands); Schmitz, Paul [Department of Biostatistics of Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)
Purpose: Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT). Methods and Materials: From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H and N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up. Results: On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H and N35 Swallowing (p = 0.011), EORTC H and N35 Dry Mouth (p = 0.009), EORTC H and N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001). Conclusions: Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth.
Klubo-Guriezdzinska, Joanna; Burman, Kenneth D.; Van Nostrand, Douglas; Mete, Mihriye; Jonklaas, Jacqueline; Wartofsky, Leonard
Objective In order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC. Methods We have searched the PubMed database for articles including the keywords "rhTSH", "thyroid cancer", and "distant metastases" published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines. Results Exogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-deterrnined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW. Conclusion The rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC. PMID:23186979
Long-term survival (>13 years) in a child with recurrent diffuse pontine gliosarcoma: a case report.
Burzynski, Stanislaw R; Janicki, Tomasz J; Burzynski, Gregory S; Marszalek, Ania
Pediatric gliosarcoma (GS) is a rare variant of glioblastoma multiforme. The authors describe the case of an unusual pontine location of GS in a 9-year-old boy who was initially diagnosed with low-grade astrocytoma (LGA) that was successfully controlled for 4 years. Subsequently, his brain tumor transformed into a GS. Prior treatment of his LGA included subtotal tumor resection 3 times, standard radiation therapy, and Gamma Knife procedure twice. His LGA was also treated with a standard chemotherapy regimen of carboplatin and vincristine, and his GS with subtotal resection, high-dose cyclophosphamide, and thiotepa with stem cell rescue and temozolomide. Unfortunately, he developed disseminated disease with multiple lesions and leptomeningeal involvement including a tumor occupying 80% of the pons. Upon presentation at our clinic, he had rapidly progressing disease. He received treatment with antineoplastons (ANP) A10 and AS2-1 for 6 years and 10 months under special exception to our phase II protocol BT-22. During his treatment with ANP his tumor stabilized, then decreased, and, ultimately, did not show any metabolic activity. The patient's response was evaluated by magnetic resonance imaging and positron emission tomography scans. His pathology diagnosis was confirmed by external neuropathologists, and his response to the treatment was determined by central radiology review. He experienced the following treatment-related, reversible toxicities with ANP: fatigue, xerostomia and urinary frequency (grade 1), diarrhea, incontinence and urine color change (grade 2), and grade 4 hypernatremia. His condition continued to improve after treatment with ANP and, currently, he complains only of residual neurological deficit from his previous surgery. He achieved a complete response, and his overall and progression-free survival is in excess of 13 years. This report indicates that it is possible to obtain long-term survival of a child with a highly aggressive recurrent GS with diffuse pontine involvement with a currently available investigational treatment. PMID:24136026
Prospective study on prevalence of dermatological changes in patients under hemodialysis in hemodialysis units in Tanta University hospitals, Egypt
Mourad, Basma; Hegab, Doaa; Okasha, Kamal; Rizk, Sarah
Introduction Chronic hemodialysis patients experience frequent and varied mucocutaneous manifestations in addition to hair and nail disorders. The aim of this study was to evaluate the prevalence of dermatological changes among patients with end-stage renal disease under hemodialysis in a hemodialysis unit in Tanta University hospitals over a period of 6 months, and to evaluate the relations of these dermatological disorders with the duration of hemodialysis as well as with different laboratory parameters in these patients. Patients and methods Ninety-three patients with end-stage renal disease on regular hemodialysis (56 males and 37 females) were selected and included in this cross-sectional, descriptive, analytic study. Their ages ranged from 18–80 years. All patients underwent thorough general and dermatological examinations. Laboratory investigations (complete blood counts, renal and liver function tests, serum parathormone levels, serum electrolytes, alkaline phosphatase, random blood sugar, and Hepatitis C virus (HCV) antibodies) were evaluated. Results This study revealed that most patients had nonspecific skin changes, including xerosis, pruritus, pallor, ecchymosis, hyperpigmentation, and follicular hyperkeratosis. Nail and hair changes were commonly found, especially half and half nail, koilonychia, subungal hyperkeratosis, melanonychia, onychomycosis, and brittle and lusterless hair. Mucous membrane changes detected were pallor, xerostomia, macroglossia, bleeding gums, aphthous stomatitis, and yellow sclera. There was a significant positive correlation between the presence of pruritus and serum parathormone level. There was a significant negative correlation between the presence of mucous membrane changes and hemoglobin level. Conclusion Nonspecific mucocutaneous manifestations are common in patients on hemodialysis, particularly xerosis, dyspigmentation, and pruritus. Early and prompt recognition and treatment of dermatological conditions in patients on dialysis may improve their quality of life. PMID:25419152
The epidemiology of Sjögren's syndrome
Patel, Ruchika; Shahane, Anupama
Sjögren's syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. It can present as an entity by itself, primary Sjögren's syndrome (pSS), or in addition to another autoimmune disease, secondary Sjögren's syndrome (sSS). pSS has a strong female propensity and is more prevalent in Caucasian women, with the mean age of onset usually in the 4th to 5th decade. Clinical presentation varies from mild symptoms, such as classic sicca symptoms of dry eyes and dry mouth, keratoconjunctivitis sicca, and xerostomia, to severe systemic symptoms, involving multiple organ systems. Furthermore, a range of autoantibodies can be present in Sjögren's syndrome (anti-SSA/Ro and anti-SSB/La antibodies, rheumatoid factor, cryoglobulins, antinuclear antibodies), complicating the presentation. The heterogeneity of signs and symptoms has led to the development of multiple classification criteria. However, there is no accepted universal classification criterion for the diagnosis of Sjögren's syndrome. There are a limited number of studies that have been published on the epidemiology of Sjögren's syndrome, and the incidence and prevalence of the disease varies according to the classification criteria used. The data is further confounded by selection bias and misclassification bias, making it difficult for interpretation. The aim of this review is to understand the reported incidence and prevalence on pSS and sSS, the frequency of autoantibodies, and the risk of malignancy, which has been associated with pSS, taking into account the different classification criteria used. PMID:25114590
Biomacromolecule conjugated nanofiber scaffold for salivary gland tissue engineering
NASA Astrophysics Data System (ADS)
Jayarathanam, Kavitha
Xerostomia or dry mouth, resulting from loss of salivary gland secretion can be alleviated by tissue engineering approaches to restore glandular cell function. Engineering an artificial salivary gland structure requires closely mimicking the natural environment, both physically and functionally, to promote epithelial cell proliferation, monolayer formation and apico-basal polarization. While the physical structure of the salivary gland extracellular matrix (ECM) can be reconstructed using biocompatible nanofiber scaffolds, the chemical signals from ECM macromolecules are equally involved in the gland morphogenesis. In these glands, Hyaluronic acid (HA), a biomacromolecule that is a major component of the ECM, plays a crucial role in recruiting growth factors to improve cell viability and growth in these glands. Another molecule of interest that improved salivary epithelial cell viability and apico-basal differentiation is laminin, a major protein found in the basement membrane. We hypothesize that these biomacromolecules, when conjugated nanofiber scaffolds, will provide the essential chemical signals that promote cell viability, proliferation, polarity in the salivary cell line of interest. These morphological changes will in turn promote the secretory function (salivary production). The nanofiber scaffold consisting of poly(lactic-co-glycolic)acid is conjugated with HA using a polyethylene glycol (PEG) diamine crosslinker. This conjugation was confirmed using fluorescence spectrometry, water contact angle test and immunocytochemistry analysis using confocal microscopy. The effect of HA in promoting cell survival in-vitro was established with MTT assay using SIMS (mouse submandibular immortalized ductal SIMS cells) cells. The effect of HA in improving the apico - basal polarity of SIMS cells will be assessed. Chemical modification of synthetic nanopolymeric scaffolds with ECM molecules e.g., HA, laminin are the next step towards developing "smart scaffolds", that can be used to specifically induce proper salivary gland function. These scaffolds can potentially be used to provide a viable approach for creating future artificial tissue engineered glands.
Long-term Survival (>13 Years) in a Child With Recurrent Diffuse Pontine Gliosarcoma: A Case Report
Burzynski, Stanislaw R.; Janicki, Tomasz J.; Marszalek, Ania
Pediatric gliosarcoma (GS) is a rare variant of glioblastoma multiforme. The authors describe the case of an unusual pontine location of GS in a 9-year-old boy who was initially diagnosed with low-grade astrocytoma (LGA) that was successfully controlled for 4 years. Subsequently, his brain tumor transformed into a GS. Prior treatment of his LGA included subtotal tumor resection 3 times, standard radiation therapy, and Gamma Knife procedure twice. His LGA was also treated with a standard chemotherapy regimen of carboplatin and vincristine, and his GS with subtotal resection, high-dose cyclophosphamide, and thiotepa with stem cell rescue and temozolomide. Unfortunately, he developed disseminated disease with multiple lesions and leptomeningeal involvement including a tumor occupying 80% of the pons. Upon presentation at our clinic, he had rapidly progressing disease. He received treatment with antineoplastons (ANP) A10 and AS2-1 for 6 years and 10 months under special exception to our phase II protocol BT-22. During his treatment with ANP his tumor stabilized, then decreased, and, ultimately, did not show any metabolic activity. The patient's response was evaluated by magnetic resonance imaging and positron emission tomography scans. His pathology diagnosis was confirmed by external neuropathologists, and his response to the treatment was determined by central radiology review. He experienced the following treatment-related, reversible toxicities with ANP: fatigue, xerostomia and urinary frequency (grade 1), diarrhea, incontinence and urine color change (grade 2), and grade 4 hypernatremia. His condition continued to improve after treatment with ANP and, currently, he complains only of residual neurological deficit from his previous surgery. He achieved a complete response, and his overall and progression-free survival is in excess of 13 years. This report indicates that it is possible to obtain long-term survival of a child with a highly aggressive recurrent GS with diffuse pontine involvement with a currently available investigational treatment. PMID:24136026
IMRT and carbon ion boost for malignant salivary gland tumors: interim analysis of the COSMIC trial
Background The COSMIC trial is designed to evaluate toxicity in dose-escalated treatment with intensity-modulated radiotherapy (IMRT) and carbon ion boost for malignant salivary gland tumors (MSGT) of the head and neck including patients with inoperable/ incompletely resected MSGTs (R2-group) and completely resected tumors plus involved margins or perineural spread (R1-group). Methods COSMIC is a prospective phase II trial of IMRT (25 × 2 Gy) and carbon ion boost (8 × 3 GyE). Primary endpoint is mucositis CTC°III, secondary endpoints are local control, progression-free survival, and toxicity. Evaluation of disease response is carried out according to the Response Evaluation Criteria in Solid Tumors (RECIST); toxicity is assessed using NCI CTC v 3.0. Results Twenty-nine patients were recruited from 07/2010 to 04/2011, all patients have at least completed first follow-up. Sixteen patients were treated in the R2-group, 13 in the R1-group. All treatments were completed as planned and well tolerated, mucositis CTC grade III was 25% (R2) and 15.4% (R1), no dysphagia CTC grade III was observed, no feeding tubes were necessary. Side-effects rapidly resolved, only 4 patients (13.8%) reported xerostomia grade II at first follow-up. Overall response rate (complete and partial response) according to RECIST in the R2-group is 68.8% at 6–8 weeks post treatment, all patients within this group showed radiological signs of treatment response. Conclusion No unexpected toxicity was observed, mucositis rates and other side effects do not differ between patients with visible residual tumor and macroscopically completely resected tumors. Initial treatment response is promising though longer follow-up is needed to assess local control. Trial registration Clinical trial identifier NCT 01154270 PMID:22551422
The Rapalogue, CCI-779, Improves Salivary Gland Function following Radiation
Morgan-Bathke, Maria; Harris, Zoey I.; Arnett, Deborah G.; Klein, Rob R.; Burd, Randy; Ann, David K.; Limesand, Kirsten H.
The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy. PMID:25437438
Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma
Background To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC). Methods Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction. Results After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively. Conclusion HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings. PMID:21838917
Intensity-Modulated Radiation Therapy with Concurrent Carboplatin and Paclitaxel for Locally Advanced Head and Neck Cancer: Toxicities and Efficacy
Vlacich, Gregory; Diaz, Roberto; Thorpe, Steven W.; Murphy, Barbara A.; Kirby, Wyndee; Sinard, Robert J.; Shakhtour, Bashar; Shyr, Yu; Murphy, Patrick; Netterville, James L.; Yarbrough, Wendell G.
Background. Intensity-modulated radiation therapy (IMRT) and alternative chemotherapy regimens strive to maintain efficacy while minimizing toxicity in locally advanced head and neck cancer (LAHNC) treatment. Our experience with concurrent IMRT and taxane-based chemotherapy is presented. Methods. A retrospective review of 150 consecutive patients with LAHNC treated with IMRT and concurrent taxane-based chemotherapy with curative intent was performed. The IMRT fractionation regimen consisted of 69.3 Gy to gross disease (2.1 Gy/fraction) and 56.1 Gy to prophylactic nodal sites (1.7 Gy/fraction). Weekly paclitaxel (30 mg/m2) and carboplatin (area under the concentration–time curve [AUC], 1) were given concurrently to all patients, and 69% received weekly induction with paclitaxel (60 mg/m2) and carboplatin (AUC, 2). Results. Over 90% of patients received the prescribed radiation dose. Ninety-six percent completed five or more cycles of concurrent chemotherapy, with similar tolerability for induction chemotherapy. A percutaneous endoscopic gastrostomy (PEG) tube was required in 80 patients, with 10 maintaining PEG use >18 months. Acute grade 4 mucositis and dermatitis developed in 2.0% and 4.0% of patients, respectively. No patient experienced nadir sepsis, grade ?3 late xerostomia, or significant nephropathy or gastrointestinal toxicity. Median follow-up was 30 months. The 3-year locoregional control rate was 83.2% with disease-free survival and overall survival rates of 78.8% and 76.5%, respectively. Conclusion. Rates of acute and late toxicities were low, with excellent radiation dose delivery and impressive tumor control at 3 years, suggesting that concurrent carboplatin and paclitaxel with IMRT is a reasonable therapeutic option for the curative treatment of LAHNC. PMID:22550060
Antifungal effect of mouth rinses on oral Candida counts and salivary flow in treatment-naďve HIV-infected patients.
Patel, Mrudula; Shackleton, Jo-Anne; Coogan, Maeve M; Galpin, Jacky
Oral candidiasis is a major problem in developing countries where antiretroviral therapy is available to a small percentage of the infected population. HIV patients are prone to xerostomia and predisposed to Candida infection. Preventing oral candidiasis is better than the frequent use of antifungals that may lead to the development of drug resistance. This study investigated the ability of commercial mouth rinses and sodium bicarbonate to reduce salivary Candida and to improve the saliva flow of HIV-positive patients. One hundred fifty HIV patients without oral candidiasis were examined for oral lesions initially and after 2, 4, and 12 weeks. Unstimulated saliva was collected; the volume was measured and cultured for yeasts. Subjects were provided with mouth rinses containing either benzydamine hydrochloride, benzydamine hydrochloride with chlorhexidine gluconate, triclosan with sodium fluoride, 5% sodium bicarbonate, or placebo and asked to rinse twice daily for 12 weeks. The effect of the mouth rinses and placebo on Candida counts and saliva flow was analyzed using analysis of variance (ANOVA). A total of 108 patients completed the trial, 35 missed appointments, 4 died, 2 developed oral candidiasis, and 1 herpetic lesion. Triclosan/fluoride decreased the Candida count more than the placebo (p = 0.005) while chlorhexidine/benzydamine hydrochloride (p = 0.001) and triclosan/fluoride mouthrinses (p = 0.002) increased the salivary flow during the initial 4 weeks. The most effective mouth rinse triclosan/fluoride decreased oral Candida counts and increased saliva flow. Studies are needed to determine the efficacy of these mouth rinses for the long-term prevention of clinical oral candidiasis in adult HIV-positive patients. PMID:18627277
Predicting radiotherapy outcomes using statistical learning techniques*
El Naqa, Issam; Bradley, Jeffrey D; Lindsay, Patricia E; Hope, Andrew J; Deasy, Joseph O
Radiotherapy outcomes are determined by complex interactions between treatment, anatomical and patient-related variables. A common obstacle to building maximally predictive outcome models for clinical practice is the failure to capture potential complexity of heterogeneous variable interactions and applicability beyond institutional data. We describe a statistical learning methodology that can automatically screen for nonlinear relations among prognostic variables and generalize to unseen data before. In this work, several types of linear and nonlinear kernels to generate interaction terms and approximate the treatment-response function are evaluated. Examples of institutional datasets of esophagitis, pneumonitis and xerostomia endpoints were used. Furthermore, an independent RTOG dataset was used for 'generalizabilty' validation. We formulated the discrimination between risk groups as a supervised learning problem. The distribution of patient groups was initially analyzed using principle components analysis (PCA) to uncover potential nonlinear behavior. The performance of the different methods was evaluated using bivariate correlations and actuarial analysis. Over-fitting was controlled via cross-validation resampling. Our results suggest that a modified support vector machine (SVM) kernel method provided superior performance on leave-one-out testing compared to logistic regression and neural networks in cases where the data exhibited nonlinear behavior on PCA. For instance, in prediction of esophagitis and pneumonitis endpoints, which exhibited nonlinear behavior on PCA, the method provided 21% and 60% improvements, respectively. Furthermore, evaluation on the independent pneumonitis RTOG dataset demonstrated good generalizabilty beyond institutional data in contrast with other models. This indicates that the prediction of treatment response can be improved by utilizing nonlinear kernel methods for discovering important nonlinear interactions among model variables. These models have the capacity to predict on unseen data. PMID:19687564
Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma
Lee, Sang-wook [Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of)]. E-mail: firstname.lastname@example.com; Back, Geum Mun [Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Yi, Byong Yong [Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Choi, Eun Kyung [Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Ahn, Seung Do [Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Shin, Seong Soo; Kim, Jung-hun [Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Kim, Sang Yoon [Department of Otolaryngology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Lee, Bong-Jae [Department of Otolaryngology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Nam, Soon Yuhl [Department of Otolaryngology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Choi, Seung-Ho [Department of Otolaryngology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Kim, Seung-Bae [Dept. of Medical Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Park, Jin-hong [Department of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of); Lee, Kang Kyoo [Department of Radiation Oncology, School of Medicine, Wonkwang University, Icksan (Korea, Republic of); Park, Sung Ho; Kim, Jong Hoon [Dept. of Radiation Oncology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of)
Purpose: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. Results: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. Conclusion: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.
Improved Dosimetric and Clinical Outcomes With Intensity-Modulated Radiotherapy for Head-and-Neck Cancer of Unknown Primary Origin
Chen, Allen M., E-mail: firstname.lastname@example.com [Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA (United States); Li Baoqing [Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA (United States); Farwell, D. Gregory [Department of Otolaryngology-Head and Neck Surgery, University of California Davis School of Medicine, Sacramento, CA (United States); Marsano, Joseph; Vijayakumar, Srinivasan; Purdy, James A. [Department of Radiation Oncology, University of California Davis School of Medicine, Sacramento, CA (United States)
Purpose: To compare differences in dosimetric, clinical, and quality-of-life endpoints among a cohort of patients treated by intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (CRT) for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 51 patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Twenty-four patients (47%) were treated using CRT, and 27 (53%) were treated using IMRT. The proportions of patients receiving concurrent chemotherapy were 54% and 63%, respectively. Results: The 2-year estimates of overall survival, local-regional control, and disease-specific survival for the entire patient population were 86%, 89%, and84%, respectively. There were no significant differences in any of these endpoints with respect to radiation therapy technique (p > 0.05 for all). Dosimetric analysis revealed that the use of IMRT resulted in significant improvements with respect to mean dose and V30 to the contralateral (spared) parotid gland. In addition, mean doses to the ipsilateral inner and middle ear structures were significantly reduced with IMRT (p < 0.05 for all). The incidence of severe xerostomia in the late setting was 58% and 11% among patients treated by CRT and IMRT, respectively (p < 0.001). The percentages of patients who were G-tube dependent at 6 months after treatment were 42% and 11%, respectively (p < 0.001). Conclusions: IMRT results in significant improvements in the therapeutic ratio among patients treated by radiation therapy for head-and-neck cancer of unknown primary origin.
Ipsilateral Irradiation for Oral and Oropharyngeal Carcinoma Treated With Primary Surgery and Postoperative Radiotherapy
Vergeer, Marije R., E-mail: email@example.com [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Doornaert, Patricia [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Jonkman, Anja [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands); Kaanders, Johannes H.A.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands); Ende, Piet L.A. van den [MAASTRO Clinic, Maastricht (Netherlands); Jong, Martin A. de [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands); Leemans, C. Rene [Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam (Netherlands); Slotman, Ben J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, Groningen (Netherlands)
Purpose: The purpose was to evaluate the contralateral nodal control (CLNC) in postoperative patients with oral and oropharyngeal cancer treated with ipsilateral irradiation of the neck and primary site. Late radiation-induced morbidity was also evaluated. Methods and Materials: The study included 123 patients with well-lateralized squamous cell carcinomas treated with surgery and unilateral postoperative irradiation. Most patients had tumors of the gingiva (41%) or buccal mucosa (21%). The majority of patients underwent surgery of the ipsilateral neck (n = 102 [83%]). The N classification was N0 in 73 cases (59%), N1 or N2a in 23 (19%), and N2b in 27 cases (22%). Results: Contralateral metastases developed in 7 patients (6%). The 5-year actuarial CLNC was 92%. The number of lymph node metastases was the only significant prognostic factor with regard to CLNC. The 5-year CLNC was 99% in N0 cases, 88% in N1 or N2a cases, and 73% in N2b cases (p = 0.008). Borderline significance (p = 0.06) was found for extranodal spread. Successful salvage could be performed in 71% of patients with contralateral metastases. The prevalence of Grade 2 or higher xerostomia was 2.6% at 5 years. Conclusions: Selected patients with oral or oropharyngeal carcinoma treated with primary surgery and postoperative ipsilateral radiotherapy have a very high CLNC with a high probability of successful salvage in case of contralateral metastases. However, bilateral irradiation should be applied in case of multiple lymph node metastases in the ipsilateral neck, particularly in the presence of extranodal spread. The incidence of radiation-induced morbidity is considerably lower as observed after bilateral irradiation.
Oral Health-Related Complications of Breast Cancer Treatment: Assessing Dental Hygienists' Knowledge and Professional Practice
Taichman, L. Susan; Gomez, Grace; Inglehart, Marita Rohr
Objective Approximately 200,000 women are diagnosed with breast cancer in the U.S. every year. These patients commonly suffer from oral complications of their cancer therapy. The purpose of this study was to assess dental hygienists' knowledge and professional practice related to providing care for breast cancer patients. Methods A pre-tested 43-item survey was mailed to a random sample of 10% of all licensed dental hygienists in the State of Michigan (N=962). The survey assessed the respondents' knowledge of potential oral complications of breast cancer treatments as well as their professional practices when treating patients with breast cancer. After two mailings, the response rate was 37% (N=331). Descriptive and inferential analyses were conducted using SAS. Results Many dental hygienists were unaware of the recommended clinical guidelines for treating breast cancer patients and lacked specific knowledge pertaining to the commonly prescribed anti-estrogen medications for pre-and postmenopausal breast cancer patients. Over 70% of the respondents indicated they were unfamiliar with the AI class of medications. Only 13% of dental hygienists correctly identified the mechanism of action of anti-estrogen therapy. Dental hygienists reported increased gingival inflammation, gingival bleeding, periodontal pocketing, xerostomia and burning tissues in patients receiving anti-estrogen therapies. Less than 10% believed that their knowledge of breast cancer treatments and the oral side effects is up to date. Conclusions Results indicate a need for more education about the potential oral effects of breast cancer therapies and about providing the best possible care for patients undergoing breast cancer treatment. PMID:24771774
Acquired immune deficiency syndrome: review.
Scully, C; Cawson, R A; Porter, S R
Acquired immunodeficiency syndrome (AIDS) is reviewed for dental practitioners, with an emphasis on oral findings; the clinical course, diagnosis, reporting, treatment, prognosis, transmission, and epidemiology are also covered. HIV infection has an incubation period that may be associated with glandular fever, a prodrome called AIDS-Related Complex (ARC) characterized by lymphadenopathy, low fever, weight loss, night sweats, diarrhea, oral candidosis, nonproductive cough and recurrent infections. AIDS is characterized by opportunistic infections. Over 50% present with pneumocystis carinii pneumonia, 21% with Kaposi's sarcoma, and 6% have both. The AIDS virus causes direct neurological symptoms in some cases. Oral candidosis (thrush) in a young male without a local cause such as xerostomia or immune suppression is strongly suggestive of AIDS. Other oral manifestations are severe herpes simplex, varicella-zoster, Epstein-Barr virus, cytomegalovirus, venereal warts, aphthous ulceration, mycobacterial oral ulcers, oral histoplasmosis, sinusitis and osteomyelitis of the jaw. Hairy leukoplakia, usually seen on the lateral border of the tongue, is probably caused by Epstein-Barr virus. Kaposi's sarcoma, an endothelial cell tumor, is characteristic of AIDS, and in 50% of patients is oral or perioral. Cervical lymph node enlargement will be seen in those with ARC as well as AIDS. No guidelines have been issued by the Department of Health and Social Security for dental surgeons in the UK for reporting AIDS cases. Although HIV virions have been isolated from saliva, there are no known incidents of transmission via saliva. HIV is less likely to be transmitted by needle stick injuries than, for example hepatitis B (25% risk), especially if the blood is from a carrier rather than a full blown AIDS case. PMID:3524629
The Potential of Helical Tomotherapy in the Treatment of Head and Neck Cancer
Verellen, Dirk; Van De Voorde, Lien; de Ost, Bie; De Kerf, Geert; Vanderveken, Olivier; Van Laer, Carl; Van den Weyngaert, Danielle; Vermorken, Jan B.; Gregoire, Vincent
A decade after its first introduction into the clinic, little is known about the clinical impact of helical tomotherapy (HT) on head and neck cancer (HNC) treatment. Therefore, we analyzed the basics of this technique and reviewed the literature regarding HT's potential benefit in HNC. The past two decades have been characterized by a huge technological evolution in photon beam radiotherapy (RT). In HNC, static beam intensity-modulated radiotherapy (IMRT) has shown superiority over three-dimensional conformal RT in terms of xerostomia and is considered the standard of care. However, the next-generation IMRT, the rotational IMRT, has been introduced into the clinic without any evidence of superiority over static beam IMRT other than being substantially faster. Of these rotational techniques, HT is the first system especially developed for IMRT in combination with image-guided RT. HT is particularly promising for the treatment of HNC because its sharp dose gradients maximally spare the many radiosensitive organs at risk nearby. In addition, HT's integrated computed tomography scan assures a very precise dose administration and allows for some adaptive RT. Because HT is specifically developed for IMRT in combination with (integrated) image-guidance, it allows for precise dose distribution ("dose painting"), patient setup, and dose delivery. As such, it is an excellent tool for difficult HNC irradiation. The literature on the clinical results of HT in HNC all show excellent short-term (?2 years) results with acceptable toxicity profiles. However, properly designed trials are still warranted to further substantiate these results. PMID:23723331
Mature Results of a Randomized Trial of Accelerated Hyperfractionated Versus Conventional Radiotherapy in Head-and-Neck Cancer
Saunders, Michele I. [Marie Curie Research Wing, Mount Vernon Hospital, Northwood (United Kingdom); Academic Department of Oncology, University College Hospital, London (United Kingdom); Rojas, Ana M., E-mail: firstname.lastname@example.com [Marie Curie Research Wing, Mount Vernon Hospital, Northwood (United Kingdom); Parmar, Mahesh K.B. [Medical Research Council Clinical Trials Office, London (United Kingdom); Dische, Stanley [Marie Curie Research Wing, Mount Vernon Hospital, Northwood (United Kingdom)
Purpose: To evaluate long-term late adverse events and treatment outcome of a randomized, multicenter Phase III trial of continuous, hyperfractionated, accelerated radiotherapy (CHART) compared with conventional radiotherapy (CRT) in 918 patients with advanced squamous cell carcinomas of the head and neck. Methods and Materials: Survival estimates were obtained for locoregional relapse-free survival, local relapse-free survival, overall survival, disease-specific survival, disease-free survival and for late adverse events. Results: The 10-year estimates (+-1 standard error) for locoregional relapse-free survival, overall survival, disease-free survival, and disease-specific survival were 43% +- 2% for CHART and 50% +- 3% with CRT (log-rank p = 0.2); 26% +- 2% and 29% +- 3% (p = 0.4), respectively; 41% +- 2% and 46% +- 3% (p = 0.3), respectively; and 56% +- 3% and 58% +- 3% (p = 0.5), respectively. There was a small but significant reduction in the incidence of slight or worse and moderate or worse epidermal adverse events with CHART (p = 0.002 to 0.05). Severe xerostomia, laryngeal edema, and mucosal necrosis were also significantly lower with CHART (p = 0.02 to 0.05). Conclusions: Despite the reduction in total dose from 66 Gy to 54 Gy, control of locoregional disease and survival with CHART were similar to those with CRT. These findings, together with the low incidence of long-term severe adverse events, suggest that CHART is a treatment option for patients with low-risk disease and for those unable to withstand the toxicity of concurrent chemoradiotherapy.
Long-Term Outcomes and Toxicity of Concurrent Paclitaxel and Radiotherapy for Locally Advanced Head-and-Neck Cancer
Citrin, Deborah [Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)], E-mail: firstname.lastname@example.com; Mansueti, John; Likhacheva, Anna; Sciuto, Linda [Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Albert, Paul S. [Biometric Research Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Rudy, Susan F. [Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD (United States); Cooley-Zgela, Theresa [Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Cotrim, Ana [National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Solomon, Beth [Speech Language Pathology Section, Rehabilitation Medicine Department, National Institutes of Health, Bethesda, MD (United States); Colevas, A. Dimitrios [Head and Neck Oncology Program, Stanford Cancer Center, Stanford University, Stanford, CA (United States); Russo, Angelo [Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Morris, John C. [Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Herscher, Laurie [Department of Radiation Oncology, Suburban Hospital, Bethesda, MD (United States); Smith, Sharon [Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)] (and others)
Purpose: To report the long-term outcomes and toxicity of a regimen of infusion paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck. Patients and Methods: Between 1995 and 1999, 35 patients with nonmetastatic, Stage III or IV squamous cell carcinoma of the head and neck were treated with three cycles of paclitaxel as a 120-h continuous infusion beginning on Days 1, 21, and 42, concurrent with radiotherapy. The initial 16 patients received 105 mg/m{sup 2}/cycle, and the subsequent 19 patients received 120 mg/m{sup 2}/cycle. External beam radiotherapy was delivered to a dose of 70.2-72 Gy at five fractions weekly. Patients were followed to evaluate the disease outcomes and late toxicity of this regimen. Results: The median follow-up for all patients was 56.5 months. The median survival was 56.5 months, and the median time to local recurrence was not reached. Of the 35 patients, 15 (43%) developed hypothyroidism. Of the 33 patients who underwent percutaneous endoscopic gastrostomy tube placement, 11 were percutaneous endoscopic gastrostomy tube dependent until death or their last follow-up visit. Also, 5 patients (14%) required a tracheostomy until death, and 3 (9%) developed a severe esophageal stricture. All evaluated long-term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%). Conclusion: The results of our study have shown that concurrent chemoradiotherapy with a 120-h infusion of paclitaxel provides long-term local control and survival in patients with squamous cell carcinoma of the head and neck. Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2.
Systematic Review of Acupuncture in Cancer Care: A Synthesis of the Evidence
Garcia, M. Kay; McQuade, Jennifer; Haddad, Robin; Patel, Sonya; Lee, Richard; Yang, Peiying; Palmer, J. Lynn; Cohen, Lorenzo
Purpose Many cancer centers offer acupuncture services. To date, a comprehensive systematic review of acupuncture in cancer care has not been conducted. The purpose of this review was to evaluate the efficacy of acupuncture for symptom management in patients with cancer. Methods Medline, Embase, CINAHL, Cochrane (all databases), Scopus, and PubMed were searched from inception through December 2011 for prospective randomized clinical trials (RCT) evaluating acupuncture for symptom management in cancer care. Only studies involving needle insertion into acupuncture points were included. No language limitations were applied. Studies were assessed for risk of bias (ROB) according to Cochrane criteria. Outcomes by symptom were designated as positive, negative, or unclear. Results A total of 2,151 publications were screened. Of those, 41 RCTs involving eight symptoms (pain, nausea, hot flashes, fatigue, radiation-induced xerostomia, prolonged postoperative ileus, anxiety/mood disorders, and sleep disturbance) met all inclusion criteria. One positive trial of acupuncture for chemotherapy-induced nausea and vomiting had low ROB. Of the remaining studies, eight had unclear ROB (four positive, three negative, and one with unclear outcomes). Thirty-three studies had high ROB (19 positive, 11 negative, and three with both positive and negative outcomes depending on the symptom). Conclusion Acupuncture is an appropriate adjunctive treatment for chemotherapy-induced nausea/vomiting, but additional studies are needed. For other symptoms, efficacy remains undetermined owing to high ROB among studies. Future research should focus on standardizing comparison groups and treatment methods, be at least single-blinded, assess biologic mechanisms, have adequate statistical power, and involve multiple acupuncturists. PMID:23341529
Impact of Node Negative Target Volume Delineation on Contralateral Parotid Gland Dose Sparing Using IMRT in Head and Neck Cancer.
Magnuson, William J; Urban, Erich; Bayliss, R Adam; Harari, Paul M
There is considerable practice variation in treatment of the node negative (N0) contralateral neck in patients with head and neck cancer. In this study, we examined the impact of N0 neck target delineation volume on radiation dose to the contralateral parotid gland. Following institutional review board approval, 12 patients with head and neck cancer were studied. All had indications for treatment of the N0 neck, such as midline base of tongue or soft palate extension or advanced ipsilateral nodal disease. The N0 neck volumes were created using the Radiation Therapy Oncology Group head and neck contouring atlas. The physician-drawn N0 neck clinical target volume (CTV) was expanded by 25% to 200% to generate volume variation, followed by a 3-mm planning target volume (PTV) expansion. Surrounding organs at risk were contoured and complete intensity-modulated radiation therapy plans were generated for each N0 volume expansion. The median N0 target volume drawn by the radiation oncologist measured 93 cm(3) (range 71-145). Volumetric expansion of the N0 CTV by 25% to 200% increased the resultant mean dose to the contralateral parotid gland by 1.4 to 8.5 Gray (Gy). For example, a 4.1-mm increase in the N0 neck CTV translated to a 2.0-Gy dose increase to the parotid, 7.4 mm to a 4.5 Gy dose increase, and 12.5 mm to an 8.5 Gy dose increase, respectively. The treatment volume designated for the N0 neck has profound impact on resultant dose to the contralateral parotid gland. Variations of up to 15 mm are routine across physicians in target contouring, reflecting individual preference and training expertise. Depending on the availability of immobilization and image guidance techniques, experts commonly recommend 3 to 10 mm margin expansions to generate the PTV. Careful attention to the original volume of the N0 neck CTV, as well as expansion margins, is important in achieving effective contralateral gland sparing to reduce the resultant xerostomia and dysguesia that may ensue after radiotherapy. PMID:25782188
Sjögren Syndrome-Associated Small Fiber Neuropathy: Characterization From a Prospective Series of 40 Cases.
Sčne, Damien; Cacoub, Patrice; Authier, François-Jérôme; Haroche, Julien; Créange, Alain; Saadoun, David; Amoura, Zahir; Guillausseau, Pierre-Jean; Lefaucheur, Jean-Pascal
We conducted the current study to analyze the clinical, immunologic, and neurophysiologic features of primary Sjögren syndrome (pSS)-associated sensory small fiber neuropathies (SFNs). Forty consecutive pSS patients with SFN were included. SFN was defined by the presence of suggestive sensory painful symptoms with normal nerve conduction studies and abnormal neurophysiologic tests for small nerve fibers or a low intraepidermal nerve fiber density at skin biopsy. Included patients were compared to 100 pSS patients without peripheral neuropathy.SFN patients were mainly female (92.5%). Age at pSS diagnosis was 55.3 ± 13.1 years, and at SFN diagnosis, 58.9 ± 11.8 years, with a median time to SFN diagnosis after symptom onset of 3.4 years. Clinical symptoms included burning pains (90%), numbness (87.5%), tingling (82.5%), pins and needles (72.5%), electric discharges (70%), and allodynia (55%). Dysautonomia included vasomotor symptoms (66%) and hyperhidrosis (47%). Abnormal neurophysiologic tests included laser evoked potentials (97.5%), thermal quantitative sensory testing (67.5%), and sympathetic skin reflex (40%). A skin biopsy revealed low intraepidermal nerve fiber density in 76% of the 17 tested patients.Compared to the 100 pSS patients without peripheral neuropathy, the 40 pSS-SFN patients were older at pSS diagnosis (55.3 ± 13.1 vs. 49.5 ± 14.9 yr; p = 0.03), and more often had xerostomia (97.5% vs. 81%; p = 0.01) and arthralgia (82.5% vs. 65.0%; p = 0.04). Immunologically, they were characterized by a lower prevalence of serum B-cell activation markers, that is, antinuclear antibodies (65% vs. 85%; p = 0.01), anti-SSA (42.5% vs. 71%; p = 0.002), and anti-SSB (17.5% vs. 39%; p = 0.017); rheumatoid factor (32.5% vs. 66%; p = 0.0005); and hypergammaglobulinemia (35% vs. 62%; p = 0.005).In conclusion, we report the main features of SFN in patients with pSS, the first such study to our knowledge. Our results show that patients with pSS-associated SFN are characterized by an older age at pSS diagnosis and a distinctive immunologic profile hallmarked by a lower frequency of serum B-cell activation markers. PMID:23982054
Sjogren's syndrome-onset lupus patients have distinctive clinical manifestations and benign prognosis: a case-control study.
Xu, D; Tian, X; Zhang, W; Zhang, X; Liu, B; Zhang, F
The objective of this study was to investigate the clinical characteristics and prognosis of Sjögren's syndrome-onset systemic lupus erythematosus (SS/SLE) patients. Medical charts of 41 consecutive SS/SLE inpatients admitted to Peking Union Medical College Hospital (PUMCH) from February 1998 to February 2008 were systematically reviewed, including demographic data, clinical features, laboratory findings, treatment as well as outcomes. Two hundred and fourteen cases were randomly selected as controls from 2331 SLE-only inpatients treated in PUMCH at the same time period. There were significant differences between SS/SLE and SLE-only patients in the following manifestations (p < 0.05): (1) sex ratio (F/M) (41/0 versus 184/30), age (42.8 +/- 41.0 years versus 31.8 +/- 31.0 years), disease duration (113.8 +/- 84.0 months versus 44.9 +/- 18.0 months); (2) clinical features, xerostomia (85.4% versus 6.1%), xerophthalmia (75.6% versus 2.3%), renal tubular acidosis (21.9% versus 0%), interstitial lung disease (12.2% versus 2.8%), facial rash (9.8% versus 46.3%), nephrotic syndrome (7.3% versus 31.3%), central nervous system involvement (4.9% versus 19.6%); (3) laboratory findings, ESR (64.6+/-75.0mm/h versus 46.5+/-34.0mm/h), C4 (14.8 +/- 12.2 g/dl versus 12.0 +/- 10.9 g/dl), IgG elevation (56.4% versus 29.9%) and IgA elevation (38.5% versus 20.4%), RF, anti-SSA and anti-SSB positive rates (70.8% versus 20.3%, 82.9% versus 43.4% and 39.0% versus 7.9%); (4) SLEDAI score (8.0 +/- 8.0 versus 10.2 +/- 10.0), glucocorticoid treatment (methylprednisolone bolus/1-2 mg kg(-1) day(-1) prednisone/<1 mg kg(-1) day(-1) prednisone) (8/26/7 versus 91/102/21), and importantly, rate of death and/or severe irreversible organ failure (2.4% versus 14.9%). SS/SLE patients were followed up for 33.0 +/- 34.0 months, 40 cases remained stable at a low dose of corticosteroid. In conclusion, different from SLE-only patients, SS/SLE patients have distinctive clinical manifestations and benign prognosis that require less vigorous treatment with glucocorticoids and/or immunosuppressants. PMID:19900977
Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs)
Head and neck cancer is treated mainly by surgery and radiotherapy. Normal tissue toxicity due to x-ray exposure is a limiting factor for treatment success. Many efforts have been employed to develop predictive tests applied to clinical practice. Determination of lymphocyte radio-sensitivity by radio-induced apoptosis arises as a possible method to predict tissue toxicity due to radiotherapy. The aim of the present study was to analyze radio-induced apoptosis of peripheral blood lymphocytes in head and neck cancer patients and to explore their role in predicting radiation induced toxicity. Seventy nine consecutive patients suffering from head and neck cancer, diagnosed and treated in our institution, were included in the study. Toxicity was evaluated using the Radiation Therapy Oncology Group scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Radiation-induced apoptosis increased in order to radiation dose and fitted to a semi logarithmic model defined by two constants: ? and ?. ?, as the origin of the curve in the Y axis determining the percentage of spontaneous cell death, and ?, as the slope of the curve determining the percentage of cell death induced at a determined radiation dose, were obtained. ? value was statistically associated to normal tissue toxicity in terms of severe xerostomia, as higher levels of apoptosis were observed in patients with low toxicity (p = 0.035; Exp(B) 0.224, I.C.95% (0.060-0.904)). These data agree with our previous results and suggest that it is possible to estimate the radiosensitivity of peripheral blood lymphocytes from patients determining the radiation induced apoptosis with annexin V/propidium iodide staining. ? values observed define an individual radiosensitivity profile that could predict late toxicity due to radiotherapy in locally advanced head and neck cancer patients. Anyhow, prospective studies with different cancer types and higher number of patients are needed to validate these results. PMID:20109191
Monitoring Dosimetric Impact of Weight Loss With Kilovoltage (KV) Cone Beam CT (CBCT) During Parotid-Sparing IMRT and Concurrent Chemotherapy
Ho, Kean Fatt, E-mail: firstname.lastname@example.com [Academic Radiation Oncology, The Christie NHS Foundation Trust, Manchester (United Kingdom); Marchant, Tom; Moore, Chris; Webster, Gareth; Rowbottom, Carl [North Western Medical Physics, The Christie NHS Foundation Trust, Manchester (United Kingdom); Penington, Hazel [Wade Radiotherapy Research Centre, The Christie NHS Foundation Trust, Manchester (United Kingdom); Lee, Lip; Yap, Beng; Sykes, Andrew; Slevin, Nick [Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester (United Kingdom)
Purpose: Parotid-sparing head-and-neck intensity-modulated radiotherapy (IMRT) can reduce long-term xerostomia. However, patients frequently experience weight loss and tumor shrinkage during treatment. We evaluate the use of kilovoltage (kV) cone beam computed tomography (CBCT) for dose monitoring and examine if the dosimetric impact of such changes on the parotid and critical neural structures warrants replanning during treatment. Methods and materials: Ten patients with locally advanced oropharyngeal cancer were treated with contralateral parotid-sparing IMRT concurrently with platinum-based chemotherapy. Mean doses of 65 Gy and 54 Gy were delivered to clinical target volume (CTV)1 and CTV2, respectively, in 30 daily fractions. CBCT was prospectively acquired weekly. Each CBCT was coregistered with the planned isocenter. The spinal cord, brainstem, parotids, larynx, and oral cavity were outlined on each CBCT. Dose distributions were recalculated on the CBCT after correcting the gray scale to provide accurate Hounsfield calibration, using the original IMRT plan configuration. Results: Planned contralateral parotid mean doses were not significantly different to those delivered during treatment (p > 0.1). Ipsilateral and contralateral parotids showed a mean reduction in volume of 29.7% and 28.4%, respectively. There was no significant difference between planned and delivered maximum dose to the brainstem (p = 0.6) or spinal cord (p = 0.2), mean dose to larynx (p = 0.5) and oral cavity (p = 0.8). End-of-treatment mean weight loss was 7.5 kg (8.8% of baseline weight). Despite a {>=}10% weight loss in 5 patients, there was no significant dosimetric change affecting the contralateral parotid and neural structures. Conclusions: Although patient weight loss and parotid volume shrinkage was observed, overall, there was no significant excess dose to the organs at risk. No replanning was felt necessary for this patient cohort, but a larger patient sample will be investigated to further confirm these results. Nevertheless, kilovoltage CBCT is a valuable tool for patient setup verification and monitoring of dosimetric variation during radiotherapy.
Automated Segmentation of the Parotid Gland Based on Atlas Registration and Machine Learning: A Longitudinal MRI Study in Head-and-Neck Radiation Therapy
Yang, Xiaofeng; Wu, Ning; Cheng, Guanghui; Zhou, Zhengyang; Yu, David S.; Beitler, Jonathan J.; Curran, Walter J.; Liu, Tian
Purpose To develop an automated magnetic resonance imaging (MRI) parotid segmentation method to monitor radiation-induced parotid gland changes in patients after head and neck radiation therapy (RT). Methods and Materials The proposed method combines the atlas registration method, which captures the global variation of anatomy, with a machine learning technology, which captures the local statistical features, to automatically segment the parotid glands from the MRIs. The segmentation method consists of 3 major steps. First, an atlas (pre-RT MRI and manually contoured parotid gland mask) is built for each patient. A hybrid deformable image registration is used to map the pre-RT MRI to the post-RT MRI, and the transformation is applied to the pre-RT parotid volume. Second, the kernel support vector machine (SVM) is trained with the subject-specific atlas pair consisting of multiple features (intensity, gradient, and others) from the aligned pre-RT MRI and the transformed parotid volume. Third, the well-trained kernel SVM is used to differentiate the parotid from surrounding tissues in the post-RT MRIs by statistically matching multiple texture features. A longitudinal study of 15 patients undergoing head and neck RT was conducted: baseline MRI was acquired prior to RT, and the post-RT MRIs were acquired at 3-, 6-, and 12-month follow-up examinations. The resulting segmentations were compared with the physicians' manual contours. Results Successful parotid segmentation was achieved for all 15 patients (42 post-RT MRIs). The average percentage of volume differences between the automated segmentations and those of the physicians' manual contours were 7.98% for the left parotid and 8.12% for the right parotid. The average volume overlap was 91.1% ± 1.6% for the left parotid and 90.5% ± 2.4% for the right parotid. The parotid gland volume reduction at follow-up was 25% at 3 months, 27% at 6 months, and 16% at 12 months. Conclusions We have validated our automated parotid segmentation algorithm in a longitudinal study. This segmentation method may be useful in future studies to address radiation-induced xerostomia in head and neck radiation therapy. PMID:25442347
Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer – a retrospective single center analysis
Background We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT). Methods The medical records of 49 patients with histologically proven primary nasopharygeal carcinoma treated with IMRT and concurrent platin-based CHT (predominantly cisplatin weekly) were retrospectively reviewed. The majority of patients showed advanced clinical stages (stage III/IV:72%) with undifferentiated histology (82%). IMRT was performed in step-and-shoot technique using an integrated boost concept in 84%. In this concept, the boost volume covered the primary tumor and involved nodes with doses of 66–70.4 Gy (single dose 2.2 Gy). Uninvolved regional nodal areas were covered with doses of 54–59.4 Gy (median single dose 1.8 Gy). At least one parotid gland was spared. None of the patients received adjuvant CHT. Results The median follow-up for the entire cohort was 48 months. Radiation therapy was completed without interruption in all patients and 76% of the patients received at least 80% of the scheduled CHT. Four local recurrences have been observed, transferring into 1-, 3-, and 5-year Local Control (LC) rates of 98%, 90% and 90%. One patient developed an isolated regional nodal recurrence, resulting in 1-, 3-, and 5-year Regional Control (RC) rates of 98%. All locoregional failures were located inside the radiation fields. Distant metastases were found in six patients, transferring into 1-, 3, and 5-year Distant Control (DC) rates of 92%, 86% and 86%. Progression free survival (PFS) rates after 1, 3 and 5 years were 86%, 70% and 69% and 1-, 3- and 5-year Overall Survival (OS) rates were 96%, 82% and 79%. Acute toxicity???grade III mainly consisted of dysphagia (32%), leukopenia (24%), stomatitis (16%), infection (8%) and nausea (8%). Severe late toxicity (grade III) was documented in 18% of the patients, mainly as xerostomia (10%). Conclusion Concurrent chemoradiation without the addition of adjuvant chemotherapy cycles using IMRT with an integrated boost concept yielded good disease control and overall survival in patients suffering from primary nasopharyngeal cancer with acceptable acute side effects and limited rates of late toxicity. PMID:23347410
Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy
Schoenfeld, Jonathan D., E-mail: email@example.com [Department of Radiation Oncology, Harvard Radiation Oncology Program, Boston, MA (United States); Sher, David J. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA (United States); Norris, Charles M. [Department of Surgery, Division of Otolaryngology, Brigham and Women's Hospital, Boston, MA (United States); Haddad, Robert I.; Posner, Marshall R. [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (United States); Department of Medicine, Brigham and Women's Hospital, Boston, MA (United States); Balboni, Tracy A.; Tishler, Roy B. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA (United States)
Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions: Treatment of salivary gland malignancies with postoperative IMRT was well tolerated with a high rate of local control. Chemoradiotherapy resulted in excellent local control in a subgroup of patients with adverse prognostic factors and might be warranted in select patients.
IMRT With Simultaneous Integrated Boost and Concurrent Chemotherapy for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck
Montejo, Michael E.; Shrieve, Dennis C. [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Bentz, Brandon G.; Hunt, Jason P.; Buchman, Luke O. [Division of Otolaryngology-Head Neck Surgery, Department of Surgery, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Agarwal, Neeraj [Department of Internal Medicine, Oncology Division, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States); Hitchcock, Ying J., E-mail: firstname.lastname@example.com [Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah (United States)
Purpose: To evaluate the efficacy and toxicity of accelerated radiotherapy with concurrent chemotherapy in advanced head-and-neck squamous cell carcinoma. Methods and Materials: Between April 2003 and May 2008, 43 consecutive patients with advanced head-and-neck squamous cell carcinoma received accelerated chemoradiation with concurrent cisplatin or cetuximab. The doses for intensity-modulated radiotherapy with simultaneous integrated boost were 67.5, 60.0, and 54 Gy in 30 daily fractions of 2.25, 2.0, and 1.8 Gy to the planning target volumes for gross disease, high-risk nodes, and low-risk nodes, respectively. Results: Of the patients, 90.7% completed chemoradiotherapy as prescribed. The median treatment duration was 43 days (range, 38-55 days). The complete response rate was 74.4%. With median follow-up of 36.7 months (range, 16.8-78.1 months) in living patients, the estimated 1-, 2-, and 5-year locoregional control, overall survival, and disease-free survival rates were 82%, 82%, and 82%; 73%, 65%, and 61%; and 73%, 73%, and 70%, respectively. One treatment-related death occurred from renal failure. Grade 3 mucositis and dermatitis occurred in 13 patients (30.2%) and 3 patients (6.9%), respectively. Grade 2 xerostomia occurred in 12 patients (27.9%). In patients with adequate follow-up, 82% were feeding tube free by 6 months after therapy; 13% remained feeding tube dependent at 1 year. Grade 3 soft-tissue fibrosis, esophageal stricture, osteoradionecrosis, and trismus occurred in 3 patients (6.9%), 5 patients (11.6%), 1 patient (2.3%), and 3 patients (6.9%), respectively. Conclusions: Our results show that intensity-modulated radiotherapy with simultaneous integrated boost with concurrent chemotherapy improved local and regional control. Acute and late toxicities were tolerable and acceptable. A prospective trial of this fractionation regimen is necessary for further assessment of its efficacy and toxicity compared with other approaches.
The outcome of local radiation injuries: 14 years of follow-up after the Chernobyl accident.
Gottlöber, P; Steinert, M; Weiss, M; Bebeshko, V; Belyi, D; Nadejina, N; Stefani, F H; Wagemaker, G; Fliedner, T M; Peter, R U
The Chernobyl nuclear power plant accident on April 26, 1986 was the largest in the history of the peaceful use of nuclear energy. Of the 237 individuals initially suspected to have been significantly exposed to radiation during or in the immediate aftermath of the accident, the diagnosis of acute radiation sickness (ARS) could be confirmed in 134 cases on the basis of clinical symptoms. Of these, 54 patients suffered from cutaneous radiation syndrome (CRS) to varying degrees. Among the 28 patients who died from the immediate consequences of accidental radiation exposure, acute hemopoietic syndrome due to bone marrow failure was the primary cause of death only in a minority. In 16 of these 28 deaths, the primary cause was attributed to CRS. This report describes the characteristic cutaneous sequelae as well as associated clinical symptoms and diseases of 15 survivors of the Chernobyl accident with severe localized exposure who were systematically followed up by our groups between 1991 and 2000. All patients presented with CRS of varying severity, showing xerosis, cutaneous telangiectasias and subungual splinter hemorrhages, hemangiomas and lymphangiomas, epidermal atrophy, disseminated keratoses, extensive dermal and subcutaneous fibrosis with partial ulcerations, and pigmentary changes including radiation lentigo. Surprisingly, no cutaneous malignancies have been detected so far in those areas that received large radiation exposures and that developed keratoses; however, two patients first presented in 1999 with basal cell carcinomas on the nape of the neck and the right lower eyelid, areas that received lower exposures. During the follow-up period, two patients were lost due to death from myelodysplastic syndrome in 1995 and acute myelogenous leukemia in 1998, respectively. Other radiation-induced diseases such as dry eye syndrome (3/15), radiation cataract (5/15), xerostomia (4/15) and increased FSH levels (7/15) indicating impaired fertility were also documented. This study, which analyzes 14 years in the clinical course of a cohort of patients with a unique exposure pattern, corroborates the requirement for long-term, if not life-long, follow-up not only in atomic bomb survivors, but also after predominantly local radiation exposure. PMID:11182791
Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial
Kankaanranta, Leena [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Seppaelae, Tiina; Koivunoro, Hanna [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Saarilahti, Kauko [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Atula, Timo [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Collan, Juhani [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Salli, Eero; Kortesniemi, Mika [Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Uusi-Simola, Jouni [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Vaelimaeki, Petteri [Department of Physics, University of Helsinki, Helsinki (Finland); Boneca Corporation, Helsinki (Finland); Maekitie, Antti [Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki (Finland); Seppaenen, Marko [Turku PET Centre, Turku University Hospital, Turku (Finland); Minn, Heikki [Department of Oncology, Turku University Central Hospital, Turku (Finland); Revitzer, Hannu [Aalto University School of Science and Technology, Esopo (Finland); Kouri, Mauri [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland); Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro [VTT Technical Research Centre of Finland, Espoo (Finland); Savolainen, Sauli [Department of Physics, University of Helsinki, Helsinki (Finland); Helsinki and Uusimaa Hospital District Medical Imaging Center, Helsinki University Central Hospital, Helsinki (Finland); Joensuu, Heikki, E-mail: email@example.com [Department of Oncology, Helsinki University Central Hospital, Helsinki (Finland)
Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by use of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was acceptable. Further research on novel modifications of the method is warranted.
Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy Alone
Su Shengfa [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Department of Oncology, GuiYang Medical College Hospital, Guiyang, Guizhou (China); Han Fei; Zhao Chong; Chen Chunyan; Xiao Weiwei; Li Jiaxin [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Lu Taixiang, E-mail: firstname.lastname@example.com [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou (China)
Purpose: Reports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone. Methods and Materials: Between February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity. Results: At a median follow-up of 50.9 months (range, 12-104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions (p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively (p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed. Conclusions: IMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively greater risk of local recurrence and those with T2bN1 disease mighth have a greater risk of distant metastasis.
Modulation of Sodium/Iodide Symporter Expression in the Salivary Gland
La Perle, Krista M.D.; Kim, Dong Chul; Hall, Nathan C.; Bobbey, Adam; Shen, Daniel H.; Nagy, Rebecca S.; Wakely, Paul E.; Lehman, Amy; Jarjoura, David
Background Physiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine–induced damage following 131I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland. Methods NIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative 123I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after 123I administration in 50 thyroid cancer patients. Results NIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of 123I accumulation between parotid and submandibular glands is 2.38±0.19. However, the corresponding ratio of 123I accumulation normalized by volume of interest is 1.19±0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthin's tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake. Conclusions NIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment. PMID:23441638
Assessment of oral mucositis in adult and pediatric oncology patients: an evidence-based approach.
Farrington, Michele; Cullen, Laura; Dawson, Cindy
Oral mucositis is a frequent side effect of cancer treatment and can lead to delayed treatment, reduced treatment dosage, altered nutrition, dehydration, infections, xerostomia, pain, and higher healthcare costs. Mucositis is defined as "inflammatory lesions of the oral and/or gastrointestinal tract caused by high-dose cancer therapies. Alimentary tract mucositis refers to the expression of mucosal injury across the continuum of oral and gastrointestinal mucosa, from the mouth to the anus" (Peterson, Bensadoun, & Roila, 2008, p. ii122). Evidence demonstrates that oral mucositis is quite distressing for patients. In addition, the majority of oncology nurses are unaware of available guidelines related to the care of oral mucositis. A multidisciplinary Oral Mucositis Committee was formed by the University of Iowa Hospitals and Clinics to develop evidence-based prevention and treatment strategies for adult and pediatric oncology patients experiencing oral mucositis. The first step was implementing an evidence-based nursing oral assessment. The Iowa Model was used to guide this evidence-based practice initiative. The Oral Assessment Guide (OAG) is reliable and valid, feasible, and sensitive to changing conditions. The OAG was piloted on an Adult Leukemia and Bone Marrow Transplant Unit leading to modification and adaptation. The pilot evaluation found 87% of patients had an abnormal oral assessment involving all categories in the tool. Nursing questionnaires showed that staff (8/23; 35% response) felt they were able to identify at risk patients using the OAG (3.3; 1-4 scale), and the tool accurately identifies mucosal changes (2.9; 1-4 scale). A knowledge assessment found nurses correctly identified OAG components 63% of the time. Unlike results from a national survey, most University of Iowa Hospitals and Clinics nurses (63%) were aware of national guidelines for prevention and treatment of oral mucositis. Developing an evidence-based nursing policy and updating documentation systems was done before implementation occurred. Computer-based and printed educational materials were developed for nursing staff caring for oncology patients. Team members were responsible for facilitating adoption in clinical areas. After organizational roll out, the nursing assessment was documented in all patients 87% of the time, and 99% for inpatients. The highest risk population, head and neck cancer patients receiving radiation, had documentation in 88% of audited visits. Other clinics required further work. Changing the system to the electronic medical record created an additional need for integration of the evidence-based practice with housewide documentation of oral assessment being completed 60.9% of the time. Use of an evidence-based assessment is the first step in a comprehensive program to reduce a common and highly distressing side effect of cancer treatment. Nursing documentation of oral assessment is well integrated on inpatient units. Opportunities for improvement remain in ambulatory care. Multidisciplinary team collaborations to expand evidence-based assessment and research questions generated from this work will be shared. PMID:20863028
The evaluation of amifostine for mucosal protection in patients with advanced loco-regional squamous cell carcinomas of the head and neck (SCCHN) treated with concurrent weekly carboplatin, paclitaxel, and daily radiotherapy (RT).
Suntharalingam, Mohan; Jaboin, Jerry; Taylor, Rodney; Wolf, Jeffrey; Banglore, Madan; Van Echo, David; Ord, Robert
Concurrent chemotherapy and radiation has improved the outcome for patients presenting with locally advanced squamous cell carcinomas of the head and neck (SCCHN). These improvements have come at a cost of increased treatment-related toxicities. We previously reported the results of a phase II trial examining the role of concurrent carboplatin, paclitaxel, and daily radiotherapy (RT) in SCCHN. In an attempt to decrease these side effects, we conducted a prospective phase II trial evaluating the role of amifostine (Ethyol, MedImmune Oncology, Inc, Gaithersburg, MD) in patients treated with this concurrent chemoRT scheme. From April 2002 to September 2004, 19 patients with stage III-IV SCCHN were enrolled on a prospective phase II trial. Treatment consisted of daily RT delivered to 70.2 Gy (1.8 Gy/fx) with amifostine 500 mg IV (<1 hour before RT), and concurrent weekly carboplatin (100 mg/m2) and paclitaxel (40 mg/m2). Median age was 58.5 years (range, 48 to 70 years); male to female ratio was, 83%:17%; Caucasian versus other was, 61%/39%. Tumor characteristics based on histology were: primary cancers of the oropharynx (55.6%); supraglottic larynx (16.7%); hypopharynx (16.7%); oral cavity (5.6%); and unknown primaries (5.6%). All patients presented with locally advanced, unresectable disease T4 (50%), T3 (27.8%), and advanced nodal disease (N2b-N3) (78%). Toxicities were measured weekly during treatment and at each follow-up visit. Disease response to therapy was determined 2 months after completion of therapy. Seventeen patients are evaluable for response and survival at 2 months following completion of RT. Eighty-four percent completed the prescribed radiation treatment, and 84% of patients received more than six cycles of chemotherapy. The median number of missed chemotherapy cycles was 1.5 (range, 0 to 5 cycles). Fifty-six percent of patients received more than 90% of prescribed amifostine doses, with chemoRT-related toxicity being the most common reason for withholding the dose (77%). Median doses of missed amifostine were three (range, 0 to 30 doses). Grade 3 toxicities associated with therapy were: mucositis and dysphagia (40% of patients each), dehydration (27%), xerostomia (20%), and dermatitis (20%); 53% of patients experienced grade 3 leukopenia, while grade 3/4 neutropenia developed in 20%/13%. No grade 4/5 nonhematologic toxicities were encountered. Forty percent of patients completed RT without unscheduled treatment breaks secondary to treatment-related toxicity. Median treatment-break time was 5 days (range, 0 to 20 days). Clinical complete response at both the primary site of disease and neck was achieved in 75% of patients 2 months following completion of RT. Weekly carboplatin and paclitaxel administered concurrently with definitive RT and daily amifostine is well tolerated, with over 85% of patients completing therapy with acceptable toxicity. The addition of amifostine appears to decrease treatment-related toxicity without impacting efficacy. PMID:15726515
Intensity-modulated radiation therapy for the treatment of oropharyngeal carcinoma: The Memorial Sloan-Kettering Cancer Center experience
Arruda, Fernando F. de [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Puri, Dev R. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zhung, Joanne [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Narayana, Ashwatha [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Wolden, Suzanne [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Hunt, Margie [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Stambuk, Hilda [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Pfister, David [Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Kraus, Dennis [Department of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Shaha, Ashok [Department of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Shah, Jatin [Department of Head and Neck Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Lee, Nancy Y. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)]. E-mail: email@example.com
Purpose: To review the Memorial Sloan-Kettering Cancer Center's experience in using intensity-modulated radiation therapy (IMRT) for the treatment of oropharyngeal cancer. Methods and Materials: Between September 1998 and June 2004, 50 patients with histologically confirmed cancer of the oropharynx underwent IMRT at our institution. There were 40 men and 10 women with a median age of 56 years (range, 28-78 years). The disease was Stage I in 1 patient (2%), Stage II in 3 patients (6%), Stage III in 7 (14%), and Stage IV in 39 (78%). Forty-eight patients (96%) received definitive treatment, and 2 (4%) were treated in the postoperative adjuvant setting. Concurrent chemotherapy was used in 43 patients (86%). Patients were treated using three different IMRT approaches: 76% dose painting, 18% concomitant boost with IMRT in both am and pm deliveries, and 6% concomitant boost with IMRT only in pm delivery. Regardless of the approach, the average prescription dose to the gross tumor planning target volume was 70 Gy, while the average dose delivered to the subclinical volume was 59.4 Gy in the dose painting group and 54 Gy in the concomitant boost group. Percutaneous endoscopic gastrostomy feeding tubes (PEGs) were placed before the beginning of treatment in 84% of the patients. Acute and late toxicity were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Toxicity was also evaluated using subjective criteria such as the presence of esophageal stricture, and the need for PEG usage. The local progression-free, regional progression-free, and distant metastases-free rates, and overall survival were calculated using the Kaplan-Meier method. Results: Three patients had persistent locoregional disease after treatment. The 2-year estimates of local progression-free, regional progression-free, distant metastases-free, and overall survival were 98%, 88%, 84%, and 98%, respectively. The worst acute mucositis experienced was Grade 1 in 4 patients (8%), Grade 2 in 27 (54%), and Grade 3 in 19 (38%). Xerostomia decreased with increasing time interval from the end of radiotherapy, and among the patients with at least 9 months of follow-up there was 67% Grade 0-1 and 33% Grade 2 toxicity. Of the 42 patients who required upfront PEG placement, 6 were still using PEG for nutrition at the time of this analysis. Three patients had cervical esophageal strictures, and of these, 1 was still PEG dependent 1 year after treatment. Two of these patients were treated with the IMRT concomitant boost am and pm approach, whereas the other was treated with the dose painting technique. Conclusions: Intensity-modulated radiotherapy achieved encouraging local control rates in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings.
Tissue engineering in otorhinolaryngology.
Bücheler, M; Haisch, A
Tissue engineering is a field of research with interdisciplinary cooperation between clinicians, cell biologists, and materials research scientists. Many medical specialties apply tissue engineering techniques for the development of artificial replacement tissue. Stages of development extend from basic research and preclinical studies to clinical application. Despite numerous established tissue replacement methods in otorhinolaryngology, head and neck surgery, tissue engineering techniques opens up new ways for cell and tissue repair in this medical field. Autologous cartilage still remains the gold standard in plastic reconstructive surgery of the nose and external ear. The limited amount of patient cartilage obtainable for reconstructive head and neck surgery have rendered cartilage one of the most important targets for tissue engineering in head and neck surgery. Although successful in vitro generation of bioartificial cartilage is possible today, these transplants are affected by resorption after implantation into the patient. Replacement of bone in the facial or cranial region may be necessary after tumor resections, traumas, inflammations or in cases of malformations. Tissue engineering of bone could combine the advantages of autologous bone grafts with a minimal requirement for second interventions. Three different approaches are currently available for treating bone defects with the aid of tissue engineering: (1) matrix-based therapy, (2) factor-based therapy, and (3) cell-based therapy. All three treatment strategies can be used either alone or in combination for reconstruction or regeneration of bone. The use of respiratory epithelium generated in vitro is mainly indicated in reconstructive surgery of the trachea and larynx. Bioartificial respiratory epithelium could be used for functionalizing tracheal prostheses as well as direct epithelial coverage for scar prophylaxis after laser surgery of shorter stenoses. Before clinical application animal experiments have to prove feasability and safety of the different experimental protocols. All diseases accompanied by permanently reduced salivation are possible treatment targets for tissue engineering. Radiogenic xerostomia after radiotherapy of malignant head and neck tumors is of particular importance here due to the high number of affected patients. The number of new diseases is estimated to be over 500,000 cases worldwide. Causal treatment options for radiation-induced salivary gland damage are not yet available; thus, various study groups are currently investigating whether cell therapy concepts can be developed with tissue engineering methods. Tissue engineering opens up new ways to generate vital and functional transplants. Various basic problems have still to be solved before clinically applying in vitro fabricated tissue. Only a fraction of all somatic organ-specific cell types can be grown in sufficient amounts in vitro. The inadequate in vitro oxygen and nutrition supply is another limiting factor for the fabrication of complex tissues or organ systems. Tissue survival is doubtful after implantation, if its supply is not ensured by a capillary network. PMID:14577908