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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologist, pediatric oncologist/hematologist, rehabilitation specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. (Refer to the PDQ summary on Pediatric Supportive Care for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.
Dramatic improvements in survival have been achieved for children and adolescents with cancer.[1] Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%. For rhabdomyosarcoma, the 5-year survival rate has increased over the same time from 53% to 65% for children younger than 15 years and from 30% to 47% for adolescents aged 15 to 19 years.[1] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Incidence and Epidemiology
Childhood rhabdomyosarcoma, a soft tissue malignant tumor of mesenchymal origin, accounts for approximately 3.5% of the cases of cancer among children aged 0 to 14 years and 2% of the cases among adolescents and young adults aged 15 to 19 years.[3,4] The incidence is 4.5 per 1 million children and 50% of cases are seen in the first decade of life.[5]
Incidence may depend on the histologic subtype of rhabdomyosarcoma:
The most common primary sites for rhabdomyosarcoma are the head, the genitourinary tract, and the extremities.[7,8] Within extremity tumors, tumors of the hand and foot occur more often in older patients and have an alveolar histology; these tumors also have a higher rate of metastatic spread.[9] Other less common primary sites include the trunk, chest wall, perineal/anal region, and abdomen including the retroperitoneum and biliary tract.
Most cases of rhabdomyosarcoma occur sporadically, with no recognized predisposing factor or risk factor.[10] For patients with embryonal tumors, high birth weight and large size for gestational age are associated with an increased incidence of rhabdomyosarcoma.[11] Genetic conditions associated with rhabdomyosarcoma include Li-Fraumeni cancer susceptibility syndrome (with germline p53 mutations),[12,13,14] neurofibromatosis type I,[15] Costello syndrome (with germline HRAS mutations),[16,17,18] Beckwith-Wiedemann syndrome (with which Wilms tumor and hepatoblastoma are more commonly associated),[19,20] and Noonan syndrome.[21]
Prognostic Factors
The prognosis for a child or adolescent with rhabdomyosarcoma is related to the age of the patient, site of origin, tumor size (widest diameter), resectability, presence of metastases, number of metastatic sites or tissues involved, presence or absence of regional lymph node involvement, histopathologic subtype (alveolar vs. embryonal), and delivery of radiation therapy in selected cases,[7,8,22,23,24,25,26,27,28]; [29][Level of evidence: 3iiiA] as well as unique biological characteristics of rhabdomyosarcoma tumor cells.[30] It is unclear whether response to induction chemotherapy, as judged by anatomic imaging, correlates with the likelihood of survival in patients with rhabdomyosarcoma, as one study found an association and another study did not.[31,32][Level of evidence: 3iiA]
Rhabdomyosarcoma is usually curable in most children with localized disease who receive combined-modality therapy, with more than 70% surviving 5 years after diagnosis.[7,8,33] Relapses are uncommon after 5 years of disease-free survival, with a 9% late-event rate at 10 years. Relapses, however, are more common for patients who have gross residual disease in unfavorable sites following initial surgery and those who have metastatic disease at diagnosis.[34]
Examples of both clinical and biological factors with proven or possible prognostic significance include the following:
A retrospective review of soft tissue sarcomas in children and adolescents suggests that the 5 cm cutoff used for adults with soft tissue sarcoma may not be ideal for smaller children, especially infants. The review identified an interaction between tumor diameter and body surface area (BSA).[41] This was not confirmed by a Children's Oncology Group study of patients with intermediate-risk rhabdomyosarcoma.[42] This relationship requires prospective study to determine the therapeutic implications of the observation.
Patients with otherwise localized disease but with proven regional lymph node involvement have a worse prognosis than do patients without regional nodal involvement.[27,28]
Patients with alveolar rhabdomyosarcoma who have regional lymph node involvement have significantly worse outcomes (5-year FFS, 43%) than patients who do not have regional lymph node involvement (5-year FFS, 73%).[48]
Anaplasia has been observed in 13% of cases of rhabdomyosarcoma and its presence may adversely influence clinical outcome in patients with intermediate-risk embryonal rhabdomyosarcoma. However, anaplasia was not shown to be an independent prognostic variable in a multivariate analysis (P = .081).[49]
Adult patients with rhabdomyosarcoma have a high incidence of pleomorphic histology (19%). Pleomorphic histology is extremely rare in children and young adults with rhabdomyosarcoma. Adults also have a higher incidence of tumors in unfavorable sites compared with children.[35]
Because treatment and prognosis depend, in part, on the histology and molecular genetics of the tumor, it is necessary that the tumor tissue be reviewed by pathologists and cytogeneticists/molecular geneticists with experience in the evaluation and diagnosis of tumors in children. Additionally, the diversity of primary sites, the distinctive surgical and radiation therapy treatments for each primary site, and the subsequent site-specific rehabilitation underscore the importance of treating children with rhabdomyosarcoma in medical centers with appropriate experience in all therapeutic modalities.
Rhabdomyosarcoma can be divided into several histologic subsets: embryonal rhabdomyosarcoma, which has embryonal, botryoid, and spindle cell subtypes; alveolar rhabdomyosarcoma; and pleomorphic rhabdomyosarcoma.[1,2]
Embryonal Rhabdomyosarcoma
The embryonal subtype is the most frequently observed subtype in children, accounting for approximately 60% to 70% of rhabdomyosarcomas of childhood.[1] Tumors with embryonal histology typically arise in the head and neck region or in the genitourinary tract, although they may occur at any primary site.
Botryoid and spindle cell subtypes
Botryoid tumors represent about 10% of all rhabdomyosarcoma cases and are embryonal tumors that arise under the mucosal surface of body orifices such as the vagina, bladder, nasopharynx, and biliary tract. The spindle cell variant of embryonal rhabdomyosarcoma is most frequently observed at the paratesticular site.[3] Both the botryoid and the spindle cell subtypes are associated with very favorable outcomes.[2]
Alveolar Rhabdomyosarcoma
Approximately 20% of children with rhabdomyosarcoma have the alveolar subtype. An increased frequency of this subtype is noted in adolescents and in patients with primary sites involving the extremities, trunk, and perineum/perianal region.[1]
For current trials developed by the Soft Tissue Sarcoma Committee of the Children's Oncology Group, to be designated as alveolar, the tumor must have greater than 50% alveolar elements; if the alveolar component is 50% or less, the tumor is considered embryonal. In some earlier studies (the D series, 1997–2005), any alveolar focus was sufficient, but that criterion was later abandoned.
Pleomorphic (Anaplastic) Rhabdomyosarcoma
Pleomorphic rhabdomyosarcoma occurs predominantly in adults aged 30 to 50 years and is rarely seen in children.[4] In adults, pleomorphic rhabdomyosarcoma is associated with a worse prognosis. In children, the term anaplasia is preferred.[5] In a retrospective review of 546 pediatric patients, the presence of anaplasia was only associated in univariate analysis with inferior clinical outcome in patients with intermediate-risk rhabdomyosarcoma.[6]
Molecular Classification
The embryonal and alveolar histologies have distinctive molecular characteristics that have been used for diagnostic confirmation, and may be useful for assigning therapy and monitoring residual disease during treatment.[7,8,9,10,11]
Alveolar cases associated with the PAX7 gene, with or without metastases, appear to occur in patients at a younger age, and may be associated with longer event-free survival (EFS) rates than those associated with PAX3 gene rearrangements.[14,15,16,17] Alveolar cases associated with the PAX3 gene are older and have a higher incidence of invasive tumor (T2). Around 22% of cases showing alveolar histology have no detectable PAX gene translocation.[11,13]
These findings highlight the important differences between embryonal and alveolar tumors. There are data that alveolar tumors carrying either a t(1;13) or a t(2;13) translocation (translocation-positive) are biologically and clinically different from alveolar tumors that do not have a translocation (translocation-negative) and from embryonal tumors.[11,21,22,23] In a study of Intergroup Rhabdomyosarcoma Study Group (IRSG) cases, the outcome for patients with translocation-negative alveolar rhabdomyosarcoma was better than that observed for translocation-positive cases and was similar to that seen in patients with embryonal rhabdomyosarcoma, suggesting that fusion status is a critical factor for risk stratification in pediatric rhabdomyosarcoma.[22] However, a German study of 121 patients with alveolar rhabdomyosarcoma found no significant difference in EFS at 5 years among patients who were PAX-FOXO1–positive compared with those who were translocation-negative.[24]
A study suggests that metagene expression analyses can classify patients with rhabdomyosarcoma into the three distinct risk groups and may be particularly helpful in identifying intermediate-risk patients with poor-risk features. Further studies are needed to confirm these findings.[21]
Before a biopsy of a suspected tumor mass is performed, imaging studies of the mass and baseline laboratory studies should be obtained. After the diagnosis of rhabdomyosarcoma has been made, an extensive evaluation to determine the extent of the disease should be done prior to instituting therapy. This evaluation should include a chest x-ray, computed tomography (CT) scan of the chest, bilateral bone marrow aspirates and biopsies, bone scan, magnetic resonance imaging (MRI) of the base of the skull and brain (for parameningeal primary tumors only), and CT scan of the abdomen and pelvis (for lower extremity or genitourinary primary tumors).
A CT or MRI scan of regional lymph nodes should be considered. Abnormal-appearing lymph nodes should be biopsied when possible. One study has demonstrated that sentinel lymph node biopsies can be safely performed in children with rhabdomyosarcoma, and tumor-positive biopsies may alter the treatment plan.[1] Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) scans can identify areas of possible metastatic disease not seen by other imaging modalities.[2,3,4] However, the efficacy of these two procedures for identifying involved lymph nodes or other sites is currently under investigation, and these procedures are not required by current treatment protocols.
Terms used in this summary section are defined below in Table 1.
Staging of rhabdomyosarcoma is relatively complex. The process includes the following steps:
As noted previously, prognosis for children with rhabdomyosarcoma depends predominantly on the primary site, tumor size, Group, and histologic subtype. Favorable prognostic groups were identified in previous Intergroup Rhabdomyosarcoma Study Group (IRSG) studies, and treatment plans were designed on the basis of assignment of patients to different treatment groups according to prognosis. Several years ago, the IRSG merged with the National Wilms Tumor Study Group and two large cooperative pediatric cancer treatment groups to form the Children's Oncology Group (COG). New protocols for children with soft tissue sarcoma are developed by the Soft Tissue Sarcoma Committee of the COG (COG-STS).
Current COG-STS protocols for rhabdomyosarcoma use the TNM-based pretreatment staging system that incorporates the primary tumor site, presence or absence of tumor invasion of surrounding tissues, tumor size, regional lymph node status, and the presence or absence of metastases. This staging system is described in Table 2 below.[5,6]
The IRS-I, IRS-II, and IRS-III studies prescribed treatment plans based on the Surgical-pathologic Group system. In this system, Groups are defined by the extent of disease and by the completeness or extent of initial surgical resection after pathologic review of the tumor specimen(s). The definitions for these Groups are shown in Table 3 below.[7,8]
After patients are categorized by Stage and Surgical-pathologic Group, a Risk Group is assigned. This takes into account Stage, Group, and histology. Patients are classified for protocol purposes as having a low risk, intermediate risk, or high risk of disease recurrence.[9,10] Treatment assignment is based on Risk Group, as shown in Table 4. To be designated as alveolar, the tumor must have greater than 50% alveolar elements; if the alveolar component is 50% or less, the tumor is considered embryonal.
Since 2006, patients with undifferentiated sarcomas are treated on the COG-STS protocol for nonrhabdomyosarcomatous soft tissue sarcoma. Refer to the PDQ summary on Childhood Soft Tissue Sarcoma for more information.
All children with rhabdomyosarcoma require multimodality therapy with systemic chemotherapy, in conjunction with either surgery, radiation therapy (RT), or both modalities to maximize local tumor control.[1,2,3] Surgical resection may be performed prior to chemotherapy if it will not result in disfigurement, substantial functional compromise, or organ dysfunction. In most cases, this is not possible, and therefore, only an initial biopsy is performed. The majority of patients have Group III (gross residual) disease. After initial chemotherapy, Group III patients receive definitive RT for control of the primary tumor. Some patients with initially unresected tumors may undergo second-look surgery (delayed primary excision) to remove residual tumor. This is most appropriate if the delayed excision is deemed feasible with acceptable functional/cosmetic outcome, and if a modest reduction in radiation dose is expected to significantly reduce the risk of long-term adverse effects. RT is given to clinically suspicious lymph nodes (detected by palpation or imaging) unless the suspicious lymph nodes are biopsied and shown to be free of rhabdomyosarcoma.
The discussion of treatment options for children with rhabdomyosarcoma is therefore divided into separate sections describing the following local control options:
The treatment of rhabdomyosarcoma by the Children's Oncology Group (COG) and in Europe (as exemplified by trials from the Intergroup Rhabdomyosarcoma Study Group [IRSG], the Soft Tissue Sarcoma Committee of the COG [COG-STS], and the International Society of Pediatric Oncology Malignant Mesenchymal Tumor [MMT] Group) differs in management and overall treatment philosophy.[2] In the MMT trials, the main objective is to reduce the use of local therapies using initial front-line chemotherapy followed by second-line therapy in the presence of poor response. Subsequent surgical resection is preferred over RT, which is used only after incomplete resection, documented regional lymph node involvement, or a poor clinical response to initial chemotherapy. This approach is designed to avoid major surgical procedures and long-term damaging effects from RT. Conversely, the primary COG-STS objective has been to employ local therapy soon after the initial operation or biopsy (except in patients with metastatic disease), using RT for patients with residual disease. Event-free survival (EFS) is the target endpoint, attempting to avoid relapse and subsequent salvage therapy.[3] The MMT Group approach led to an overall survival (OS) rate of 71% in the European MMT89 study compared with an OS rate of 84% in the IRS-IV study. Similarly, EFS rates at 5 years were 57% in the MMT89 study versus 78% in the IRS-IV study. Differences in outcome were most striking for patients with extremity and head and neck nonparameningeal tumors, whereas results were similar for patients with genitourinary tumors. The overall impression is that survival for most patient subsets is superior with the use of early local therapy, including RT. However, in the MMT trials, some patients are spared aggressive local therapy, which may reduce the potential for morbidities associated with such therapy.[1,2,3]
Patients with undifferentiated sarcomas were treated in trials coordinated by the IRSG from 1972 until 2006,[4] and more recently were eligible for the nonrhabdomyosarcoma soft tissue sarcoma protocol using agents active in adult soft tissue sarcoma, ifosfamide and doxorubicin (COG-ARST0332). However, this trial has now been closed.
Local Control Management: Surgery
In recent years, the predominant site of treatment failure in patients with initially localized rhabdomyosarcoma has been local recurrence. Both surgery and radiation therapy are primarily measures taken to produce local control, but each has risks, as well as benefits. Surgical removal of the entire tumor should be considered initially, but only if major functional/cosmetic impairment will not result.[1] With that proviso, complete resection of the primary tumor with a surrounding margin of normal tissue and sampling possibly involved lymph nodes in the draining nodal basin is recommended. Important exceptions to the rule of normal margins exist (e.g., tumors of the orbit and of the genitourinary region).[2,3] The principle of wide and complete resection of the primary tumor is less applicable to patients known to have metastatic disease at the initial operation, but it is a reasonable concept if easily accomplished.
Patients with microscopic residual tumor following their initial excisional procedure appear to have improved prognoses if a second operative procedure (primary re-excision) to resect the primary tumor bed before beginning chemotherapy can achieve complete removal of the tumor.[4]
Clinical and/or imaging evaluation of regional lymph nodes is an important part of pretreatment staging. Pathologic evaluation of regional nodes is currently required for all patients with extremity primary rhabdomyosarcoma and boys aged 10 years and older with paratesticular rhabdomyosarcoma, because microscopic tumor is often documented even when the nodes are not enlarged. (Refer to the Regional and in-transit lymph nodes section of this summary for more information.)
There is little evidence that debulking surgery (i.e., expected to leave macroscopic residual tumor) improves outcome, compared with biopsy alone.[5][Level of evidence: 2A] Second-look procedures (also known as delayed primary excision) can identify viable tumor that remains after initial chemotherapy; patients with viable tumor had shorter event-free survival (EFS) rates than did those without viable tumor, but there was no effect on overall survival (OS).[6] Thus, the exact role of delayed primary excision remains undefined in rhabdomyosarcoma and is most appropriate if it is anticipated that a complete resection is possible and that the modest reduction in radiation dose will substantially decrease the risk for late effects.
Because rhabdomyosarcoma can arise from multiple sites, surgical care decisions and radiotherapeutic options must be tailored to the specific aspects of each site, and should be discussed with a multidisciplinary team including representatives of those specialties, as well as pediatric oncologists. Surgical management of the more common primary sites is provided in the Local Control Management with Surgery and RT by Primary Sites of Disease section of this summary.
Local Control Management: Radiation Therapy (RT)
Only 15% of patients present with Group I, completely resected disease, so RT is used in the majority of cases.
RT is an effective method for achieving local control of the tumor for patients with microscopic or gross residual disease following biopsy, initial surgical resection, or chemotherapy. Patients with completely resected embryonal rhabdomyosarcoma (Group I) do well without RT.[7] An earlier study of Group I patients with alveolar rhabdomyosarcoma and undifferentiated soft tissue sarcoma found that omission of RT was followed by decreased local control.[8] A subsequent review of patients with only alveolar rhabdomyosarcoma found that the improvement in outcome with RT did not reach statistical significance for patients with Stage 1 and 2 tumors. There were very few patients (n = 4) with large tumors (Stage 3, >5 cm) who did not receive RT, but their outcome was poor.[9][Level of evidence: 3iiiDii]
In more than 50% of Group II rhabdomyosarcoma patients, local recurrence was due to noncompliance with guidelines or omission of RT.[10] A review of European trials conducted by the German Cooperative Weichteilsarkom Studien (CWS) Group between 1981 and 1998, in which RT was omitted for some Group II patients, demonstrated a benefit to using RT as a component of local tumor control for all Group II patient subsets, as defined by tumor histology, tumor size, and tumor site.[11]
The predominant type of relapse for patients with Group III disease is local failure. Patients with tumor-involved regional lymph nodes at diagnosis also have a higher risk of local and distant failure compared with patients whose lymph nodes are uninvolved.[12] As with the surgical management of patients with rhabdomyosarcoma, recommendations for RT depend on the site of primary tumor, the postsurgical (if performed) amount of residual disease (none vs. microscopic vs. macroscopic), and the presence of involved lymph nodes.
For optimal care of pediatric patients undergoing radiation treatments, it is imperative to have available a radiation oncologist, radiation technicians, and nurses who are experienced in treating children. An anesthesiologist may be necessary to sedate and immobilize young patients. Computerized treatment planning with a three-dimensional planning system should be available. Techniques to deliver radiation specifically to the tumor while sparing normal tissue (e.g., conformal radiation therapy, intensity-modulated radiation therapy [IMRT], proton-beam therapy [charged-particle radiation therapy], or brachytherapy) are appropriate.[13,14,15] Comparison of proton-beam and IMRT treatment plans has shown that proton-beam radiation can spare more normal tissue adjacent to the targeted volume than IMRT.[16,17] Follow-up remains relatively short, and there are no data available to determine if the reduction in dose to adjacent tissue will result in improved functional outcome or reduce the risk of secondary malignancy. Because patient numbers are small, it is not possible to determine if the risk of local recurrence might be increased by reducing radiation dose in tissue adjacent to the primary tumor.
Standard RT of children with rhabdomyosarcoma includes the following:
The IRS-IV trial included a randomized study that reported the administration of RT twice a day, 6 to 8 hours apart, at 1.1 Gy per dose (hyperfractionated schedule), 5 days per week, was feasible but difficult to accomplish in small children who required sedation twice daily. Patients with localized, gross residual tumors were randomly assigned to receive conventional, once-daily RT (total dose of 50.4 Gy) versus the twice-daily hyperfractionated schedule (total dose of 59.4 Gy). There was no demonstrated advantage in terms of local control.[24] Conventional RT remains the standard for treating patients who have rhabdomyosarcoma with gross residual disease.[25]
Brachytherapy, using either intracavitary or interstitial implants, is another method of local control and has been used in selected situations for children with rhabdomyosarcoma, especially those with primary tumors at vaginal or vulvar sites [26,27,28,29,30] and selected bladder/prostate sites.[31][Level of evidence: 3iiiA] In small series from one or two institutions, this treatment approach was associated with a high survival rate and with retention of a functional organ or tissue in most patients.[27,32] Other sites, especially head and neck, have also been treated with brachytherapy.[33] Patients with initial Group III disease, who subsequently have microscopic residual disease following chemotherapy with or without delayed surgery are likely to achieve local control with RT at doses of 40 Gy or more.[34]
Very young children (aged ≤36 months) diagnosed with rhabdomyosarcoma pose a therapeutic challenge because of their increased risk for treatment-related morbidity.[23] As suggested above, in older children, reduced radiation doses may be appropriate if delayed surgery can provide negative margins. However, for infants who are unable to undergo surgical resection, higher doses of RT remain appropriate.[35] Radiation techniques are designed to maximize normal tissue sparing, and should include conformal approaches, often with intensity-modulated techniques.
Local Control Management with Surgery and RT by Primary Sites of Disease
Head and neck
Rhabdomyosarcomas of the orbit should not undergo exenteration, but biopsy is needed for diagnosis.[36,37] Biopsy is followed by chemotherapy and RT, with orbital exenteration reserved for the small number of patients with locally persistent or recurrent disease.[38,39] RT and chemotherapy are the standard of care, with survival in excess of 90% to 95%. For patients with orbital tumors, precautions should be taken to limit the RT dose to the lens and cornea.
If the tumors are nonorbital and cranial parameningeal (arising in the middle ear/mastoid, nasopharynx/nasal cavity, paranasal sinus, parapharyngeal region, or pterygopalatine/infratemporal fossa), a magnetic resonance imaging (MRI) scan with contrast of the primary site and brain should be obtained to check for presence of base-of-skull erosion and possible extension onto or through the dura.[40,41,42] If skull erosion and/or transdural extension is equivocal, a computed tomography (CT) scan with contrast of the same regions is indicated. Also, if there is any suspicion of extension down the spinal cord, an MRI scan with contrast of the entire cord should be obtained. The cerebrospinal fluid (CSF) should be examined for malignant cells in all patients with parameningeal tumors. Because complete removal of these tumors is difficult, owing to their location, the initial surgical procedure for these patients is usually only a biopsy for diagnosis.
Nonorbital cranial parameningeal tumors are optimally managed by conformal RT and chemotherapy. Patients with parameningeal disease with intracranial extension in contiguity with the primary tumor, and/or cranial base bone erosion, and/or cranial nerve palsy do not require whole-brain irradiation or intrathecal therapy, unless tumor cells are present in the CSF at diagnosis.[40] Patients should receive RT to the site of primary tumor with a 1.5 cm margin to include the meninges adjacent to the primary tumor and the region of intracranial extension, if present, with a 1.5 cm margin.[41] In a retrospective trial, starting radiation therapy within 2 weeks of diagnosis for patients with signs of meningeal impingement was associated with lower rates of local failure. When no signs of meningeal impingement were present, delay of radiation therapy for more than 10 weeks did not impact local failure rates.[41]
Children who present with tumor cells in the CSF (Stage 4) may or may not have other evidence of diffuse meningeal disease and/or distant metastases. In a review of experience from IRSG Protocols II though IV, eight patients had tumor cells in the CSF at diagnosis; three of four without other distant metastases were alive at 6 to 16 years after diagnosis, as was one of four who had concomitant metastases elsewhere.[43] Patients may also have multiple intraparenchymal brain metastases from a distant primary tumor. They may be treated with central nervous system-directed RT in addition to treatment with chemotherapy/RT for the primary tumor. Spinal RT may also be indicated.[44,45]
For nonparameningeal and nonorbital head and neck tumors, wide excision of the primary tumor (when feasible) and ipsilateral neck lymph node sampling of clinically involved nodes are appropriate.[46] Narrow resection margins (<1 mm) are acceptable because of anatomic restrictions. Cosmetic and functional factors should always be considered, but with modern techniques, complete resection in patients with superficial tumors need not be inconsistent with good cosmetic and functional results. Specialized, multidisciplinary surgical teams also have performed resections of anterior skull-based tumors in areas previously considered inaccessible to definitive surgical management, including the nasal areas, paranasal sinuses, and temporal fossa. These procedures should only be considered, however, in children with recurrent locoregional disease or residual disease following chemotherapy and RT.
For patients with head and neck primary tumors that are considered unresectable, chemotherapy and RT with organ preservation are the mainstay of primary management.[38,42,47,48,49,50] Several studies have reported excellent local control in patients with rhabdomyosarcoma of the head and neck treated with IMRT, fractionated stereotactic radiation therapy, or protons and chemotherapy. Further study is needed, but the use of IMRT and chemotherapy in patients with head and neck rhabdomyosarcoma may result in less severe late effects.[51,52,53]; [54][Level of evidence: 3iiiA]
Extremity sites
Intensity-modulated radiation therapy (IMRT) can be used to spare the bone, yet provide optimal soft tissue coverage, and is used for the management of extremity rhabdomyosarcoma. Complete primary tumor removal from the hand or foot is not feasible in most cases because of functional impairment.[55][Level of evidence: 3iiA] For children presenting with a primary tumor of the hands or feet, Children's Oncology Group (COG) studies have shown 100% 10-year local control using RT along with chemotherapy, avoiding amputation in these children.[56][Level of evidence: 3iiiA]
Primary re-excision prior to beginning chemotherapy (i.e., not delayed) may be appropriate in patients whose initial surgical procedure leaves microscopic residual disease that is deemed resectable by a second procedure.[4]
Regional and in-transit lymph nodes
The Soft Tissue Sarcoma Committee of the COG (COG-STS) recommends systematic aggressive axillary node sampling for patients with upper-extremity primary tumors, even with clinically and radiographically negative nodes. The COG-STS also recommends inguinal and femoral triangle node sampling for patients with lower-extremity primary tumors, even with clinically and radiographically negative nodes. If clinically positive nodes are present, biopsy of more proximal nodes is recommended prior to sampling of the involved nodal region. Sentinel lymph node mapping is employed at some centers to identify the regional nodes that are the most likely to be involved.[57,58,59,60] However, the contribution of sentinel lymph node mapping is not yet clearly defined in pediatric patients.
Because of the significant incidence of regional nodal spread in patients with extremity primary tumors (often without clinical evidence of involvement) and because of the prognostic and therapeutic implications of nodal involvement, extensive pretreatment assessment of regional (and possibly in-transit) nodes is warranted.[57,61,62,63,64]; [65][Level of evidence: 3iiDi] In-transit nodes are defined as epitrochlear and brachial for upper-extremity tumors and popliteal for lower-extremity tumors. Regional lymph nodes for those tumor sites are axillary/infraclavicular nodes and inguinal/femoral nodes, respectively. In a review of 226 patients with primary extremity rhabdomyosarcoma, 5% had tumor-involved in-transit nodes, and over 5 years, the rate of in-transit node recurrence was 12%. Very few patients (n = 11) underwent in-transit node examination at diagnosis, but five of them, all with alveolar rhabdomyosarcoma, had tumor-involved nodes. However, the EFS rates were not significantly different among those evaluated initially and those not evaluated initially for in-transit nodal disease.[65]
Truncal sites
The surgical management of patients with lesions of the chest wall or abdominal wall should follow the same guidelines as those used for lesions of the extremities (i.e., wide local excision and an attempt to achieve negative microscopic margins). These resections may require use of prosthetic materials. Very large truncal masses should be biopsied initially. Chemotherapy, with or without RT, is then given. Initial surgery is performed if there is a realistic expectation of achieving negative margins. However, most patients who present with large tumors in these sites have localized disease that becomes amenable to complete resection with negative margins after preoperative chemoradiotherapy and those patients may have excellent long-term survival.[66,67,68,69]
Intrathoracic or intra-abdominal sarcomas may not be resectable at diagnosis because of the massive size of the tumor and extension into vital organs or vessels.[70] For patients with initially unresectable retroperitoneal/pelvic tumors, complete surgical removal following chemotherapy, with or without RT, offers a significant survival advantage (73% vs. 34%–44% without removal).[70]
With rhabdomyosarcoma of the biliary tree, total resection is rarely feasible and standard treatment includes chemotherapy and RT. Outcome for patients with this primary site is good despite residual disease after surgery. External biliary drains significantly increase the risk of postoperative infectious complications. Thus, external biliary drainage is not warranted.[71]
Patients with rhabdomyosarcoma arising from tissue around the perineum or anus usually have advanced disease. These patients have a high likelihood of regional lymph node involvement, and about half of the tumors have alveolar histology. The current recommendation is to sample the regional lymph nodes. When feasible and without unacceptable morbidity, removing all gross tumor prior to chemotherapy improves the likelihood of cure. In Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols I through IV, the OS rate after aggressive therapy for 71 patients with tumors in this location was 49%, best for patients in Stage 2 (small tumors, negative regional nodes), intermediate for those in Stage 3, and worst for those in Stage 4 at diagnosis.[72] However, with the goal of organ preservation, patients with tumors of the perineum/anus are preferentially managed with chemotherapy and RT without aggressive surgery, which may result in loss of sphincter control.
Genitourinary system
Primary sites for childhood rhabdomyosarcoma within the genitourinary system include the paratesticular area, bladder, prostate, kidney, vulva, vagina, and uterus. Specific considerations for the surgical and radiotherapeutic management of tumors arising at each of these sites are discussed in the paragraphs below.[73]
Lesions occurring adjacent to the testis or spermatic cord and up to the internal inguinal ring should be removed by orchiectomy with resection of the spermatic cord, utilizing an inguinal incision with proximal vascular control (i.e., radical orchiectomy).[74] Resection of hemiscrotal skin is required when there is tumor fixation or invasion, or when a previous transscrotal biopsy has been performed. For patients with incompletely removed paratesticular tumors that require RT, temporarily repositioning the contralateral testicle into the adjacent thigh prior to scrotal radiation therapy may preserve hormone production.[75][Level of evidence: 3iiiC]
Paratesticular tumors have a relatively high incidence of lymphatic spread (26% in IRS-I and IRS-II),[61] and all patients with paratesticular primary tumors should have thin-cut abdominal and pelvic CT scans with contrast to evaluate nodal involvement. For patients who have Group I disease, are younger than 10 years, and in whom CT scans show no evidence of lymph node enlargement, retroperitoneal node biopsy/sampling is unnecessary, but a repeat CT scan every 3 months is recommended.[76,77] For patients with suggestive or positive CT scans, retroperitoneal lymph node sampling (but not formal node dissection) is recommended, and treatment is based on the findings of this procedure.[3,25,78] A staging ipsilateral retroperitoneal lymph node dissection is currently required for all children 10 years and older with paratesticular rhabdomyosarcoma on COG-STS studies. However, node dissection is not routine in Europe for adolescents with resected paratesticular rhabdomyosarcoma. Many European investigators rely on radiographic rather than surgical-pathologic assessment of retroperitoneal lymph node involvement.[74,76] It appears, however, that the ability of the CT scan to predict the presence of lymph node involvement needs further study.[79]
Bladder preservation is a major goal of therapy for patients with tumors arising in the bladder and/or prostate. Two important reviews provide information about the historical, current, and future treatment approaches for patients with bladder and prostate rhabdomyosarcomas.[80,81]
In rare cases, the tumor is confined to the dome of the bladder and can be completely resected. Otherwise, to preserve a functional bladder in patients with gross residual disease, chemotherapy and RT have been used to reduce tumor bulk,[82,83] followed, when necessary, by a more limited surgical procedure such as partial cystectomy.[84] Early experience with this approach was disappointing, with only 20% to 40% of patients with bladder/prostate tumors remaining alive and with functional bladders 3 years following diagnosis (3-year OS was 70% in IRS-II).[84,85] The later experience from IRS-III and IRS-IV, which used more intensive chemotherapy and RT, showed 55% of patients alive with functional bladders at 3 years postdiagnosis, with 3-year OS exceeding 80%.[83,86,87] Patients with a primary tumor of the bladder/prostate who present with a large pelvic mass resulting from a distended bladder caused by outlet obstruction at diagnosis receive RT to a volume defined by imaging studies following initial chemotherapy to relieve outlet obstruction. This approach to therapy remains generally accepted, with the belief that more effective chemotherapy and RT will continue to increase the frequency of bladder salvage.
The initial surgical procedure in most patients consists of a biopsy, which often can be performed using ultrasound guidance or cystoscopy, or by a direct-vision transanal route. In selected cases in one series, bladder-conserving surgery plus brachytherapy for boys with prostate or bladder-neck rhabdomyosarcoma led to excellent survival, bladder preservation, and short-term functional results.[31][Level of evidence: 3iiiB] For patients with biopsy-proven, residual malignant tumor following chemotherapy and RT, appropriate surgical management may include partial cystectomy, prostatectomy, or exenteration (usually approached anteriorly with preservation of the rectum). Very few studies have objective long-term assessments of bladder function, and urodynamic studies are important to obtain accurate evaluation of bladder function.[88]
In patients who have been treated with chemotherapy and RT for rhabdomyosarcoma arising in the bladder/prostate region, the presence of well-differentiated rhabdomyoblasts in surgical specimens or biopsies obtained after treatment does not appear to be associated with a high risk of recurrence and is not an indication for a major surgical procedure such as total cystectomy.[86,89,90] One study suggested that in patients with residual bladder tumors with histologic evidence of maturation, additional courses of chemotherapy should be given before cystectomy is considered.[86] Surgery should be considered only if malignant tumor cells do not disappear over time following initial chemotherapy and RT. Because of very limited data, it is unclear whether this situation is analogous for patients with rhabdomyosarcoma arising in other parts of the body.
The kidney is occasionally the primary site for rhabdomyosarcoma; six cases were identified from among 5,746 eligible patients enrolled on IRSG protocols. The tumors were large (mean widest diameter, 12.7 cm), and anaplasia was present in four (67%) patients. Three patients with grossly complete tumor removal at diagnosis survived; the three with incomplete removal and gross or metastatic disease died of infection or metastatic tumor.[91]
For patients with genitourinary primary tumors of the vulva/vagina/uterus, the initial surgical procedure is usually a vulvar or transvaginal biopsy. Initial radical surgery is not indicated for rhabdomyosarcoma of the vulva/vagina/uterus.[3] Conservative surgical intervention for vaginal rhabdomyosarcoma, with primary chemotherapy and adjunctive radiation (often brachytherapy) for residual disease (Group II or III), results in excellent disease-free survival.[92,93]
In the COG-ARST0331 study, there was an unacceptably high rate of local recurrences in girls with Group III vaginal tumors who did not receive RT.[93][Level of evidence: 3iiiDiii]
Because of the smaller number of patients with uterine rhabdomyosarcoma, it is difficult to make a definitive treatment decision, but chemotherapy with or without RT is also effective.[92,94] Exenteration is usually not required for primary tumors at these sites, but if needed, it may be done, with rectal preservation possible in most cases.
Girls with genitourinary primary tumors should have their ovaries shielded or possibly moved, in an effort to preserve fertility when they are receiving RT to the lower abdomen and pelvis.
Unusual primary sites
Rhabdomyosarcoma occasionally arises in sites other than those discussed above. Patients with localized primary rhabdomyosarcoma of the brain can occasionally be cured using a combination of tumor excision, RT, and chemotherapy.[95][Level of evidence: 3iiiDiii]
Patients with laryngeal rhabdomyosarcoma will usually be treated with chemotherapy and RT after biopsy in an attempt to preserve the larynx.[96]
Patients with diaphragm tumors often have locally advanced disease that is not grossly resectable initially because of fixation to adjacent vital structures such as the lung, great vessels, pericardium, and/or liver. In such circumstances, chemotherapy and RT should be initiated after diagnostic biopsy, with the intent to consider removal of residual tumor at a later date if feasible.[97]
Two well-documented cases of primary ovarian rhabdomyosarcoma (one Stage III and one Stage IV) have been reported to supplement the eight previously reported patients. These two patients were alive at 20 and 8 months after diagnosis. Six of the previously reported eight patients had died of their disease.[98][Level of evidence: 3iiiDiii] Treatment with combination chemotherapy followed by removal of the residual mass or masses can sometimes be successful.[98]
Metastatic sites
Primary resection of metastatic disease at diagnosis (Stage 4, M1, Group IV) is rarely indicated.
The CWS Group reviewed four consecutive trials and identified 29 patients with M1 embryonal rhabdomyosarcoma and metastasis limited to the lung at diagnosis. They reported approximately 38% 5-year EFS for the cohort and did not identify any benefit for local control of pulmonary metastasis, whether by lung irradiation (n = 9), pulmonary metastasectomy (n = 3), or no targeted pulmonary therapy (n = 19).[99][Level of evidence: 3iiiA]
The IRSG reviewed 46 IRS-IV (1991–1997) patients with metastatic disease at diagnosis confined to the lungs. Only 11 (24%) had a biopsy of the lung, including six at the time of primary diagnosis. They were compared with 234 patients with single non-lung metastatic sites or multiple other sites of metastases. The lung-only patients were more likely to have embryonal rhabdomyosarcoma and parameningeal primary tumors than the larger group of 234 patients, and were less likely to have regional lymph node disease at diagnosis. Failure-free survival (FFS) and OS rates at 4 years were 35% and 42%, respectively, better than for those with two or more sites of metastases (P = .005 and .002, respectively). Being younger than 10 years at diagnosis was also a favorable prognostic factor. Lung irradiation was recommended by the protocols for the lung-only group, but many did not receive it. Those who did receive lung irradiation had better FFS and OS at 4 years than those who did not (P = .01 and P = .039, respectively).[100][Level of evidence: 3iiiB]
Chemotherapy Treatment Options
All children with rhabdomyosarcoma should receive chemotherapy. The intensity and duration of the chemotherapy are dependent on the Risk Group assignment.[101] See Table 4 in the Stage Information section for more information about Risk Groups.
Adolescents treated with therapy for rhabdomyosarcoma experience less hematologic toxicity and more peripheral nerve toxicity than do younger patients.[102]
Low-risk patients
Standard treatment options
The COG-D9602 study stratified 388 patients with low-risk embryonal rhabdomyosarcoma into two groups.[103] Treatment for subgroup A patients (n = 264; Stage 1 Group I/IIA, Stage 2 Group I, and Stage 1 Group III orbit) consisted of VA with or without RT for 48 weeks. Patients with subgroup B disease (n = 78; Stage 1 Group IIB/C, Stage I Group III nonorbit, Stage 2 Group II, and Stage 3 Group I/II disease) received VA plus cyclophosphamide (total cumulative dose of 28.6 g/m2). Radiation doses were reduced from 41.4 Gy to 36 Gy for Stage 1 Group IIA patients and from 50 Gy or 59 Gy to 45 Gy for Group III orbit patients. For subgroup A patients, the 5-year overall FFS rate was 88% and the OS rate was 97%. For subgroup B patients, the 5-year FFS rate was 85% and the OS rate was 93%.
Other subgroups of low-risk patients have achieved survival rates of at least 90% with three-drug chemotherapy with VA and cyclophosphamide ([VAC], total cyclophosphamide dose of 28.6 g/m2) plus RT for residual tumor. See Table 6 below.
Intermediate-risk patients
Standard treatment options
A comparison of survival in patients with tumors of embryonal histology treated on IRS-IV (who received higher doses of alkylating agents) compared with similar patients treated on IRS-III (who received lower doses of alkylating agents) suggested a benefit with the use of higher doses of cyclophosphamide for certain groups of intermediate-risk patients. These included patients with tumors at favorable sites and positive lymph nodes, patients with gross residual disease, or patients with tumors at unfavorable sites who underwent grossly complete resections, but not patients with unresected embryonal rhabdomyosarcoma at unfavorable sites.[104] For other groups of intermediate-risk patients, an intensification of cyclophosphamide was feasible but did not improve outcome.[105]
Treatment options under clinical evaluation
The following is an example of a national and/or international clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
High-risk patients
A pooled analysis of 788 high-risk rhabdomyosarcoma patients treated with multiagent chemotherapy (all regimens used cyclophosphamide or ifosfamide plus dactinomycin and vincristine with or without additional chemotherapeutic agents), followed by local therapy (surgery with or without RT) within 3 to 5 months of starting chemotherapy, identified several adverse prognostic factors. These were age younger than 1 year, age 10 years or older, unfavorable primary site, bone and/or bone marrow involvement, and three or more different metastatic sites. The EFS rate at 3 years was 50% for patients without any of these adverse prognostic factors. The EFS rates were 42% for patients with one adverse prognostic factor, 18% for patients with two adverse prognostic factors, 12% for patients three adverse prognostic factors, and 5% for patients with four adverse prognostic factors (P < .0001).[116][Level of evidence: 3iiiA]
The standard systemic therapy for children with metastatic rhabdomyosarcoma is the three-drug combination of VAC. Despite many clinical trials attempting to improve outcome by adding additional agents to standard VAC chemotherapy (or substituting new agents for one or more components of VAC chemotherapy), to date, no chemotherapy regimens have been shown to be more effective than VAC, including the following:
Alternative Therapies
The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with previously untreated childhood rhabdomyosarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Although patients with recurrent or progressive rhabdomyosarcoma sometimes achieve complete remission with secondary therapy, the long-term prognosis is usually poor.[1,2] The prognosis is most favorable (50% to 70% 5-year survival rates) for children who initially present with Stage 1 or Group I disease and embryonal histology and who have small tumors, and for those who have a local or regional nodal recurrence.[1,2,3] The small number of children with botryoid histology who relapse have a similarly favorable prognosis.[1] Most other children who relapse have an extremely poor prognosis.[1] A retrospective review of rhabdomyosarcoma patients from German soft tissue sarcoma trials identified time to recurrence as an important independent prognostic factor. Shorter time to recurrence was associated with higher risk of mortality from recurrent rhabdomyosarcoma.[4][Level of evidence: 3iiB] European investigators performed a retrospective review of patients with rhabdomyosarcoma enrolled on cooperative group trials who experienced recurrence. They identified metastatic (as opposed to local) recurrence, prior radiation therapy, initial tumor size (>5 cm), and time to relapse (<18 months) as unfavorable prognostic features for survival after recurrence.[5]
The selection of further treatment depends on many factors, including the site(s) of recurrence, previous treatment, and individual patient considerations. Treatment for local or regional recurrence may include wide local excision or aggressive surgical removal of tumor, particularly in the absence of widespread bony metastases.[6,7] Some survivors have also been reported after surgical removal of only one or a few metastases in the lung.[6] Radiation therapy should be considered for patients who have not already received radiation therapy in the area of recurrence, or rarely for those who have received radiation therapy but for whom surgical excision is not possible. Previously unused, active, single agents or combinations of drugs may also enhance the likelihood of disease control.
The following standard chemotherapy regimens have been used to treat recurrent rhabdomyosarcoma:
Treatment options under clinical evaluation for recurrent rhabdomyosarcoma:
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood rhabdomyosarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information
Revised text to state that childhood rhabdomyosarcoma is a soft tissue malignant tumor of mesenchymal origin.
Revised text about the incidence of each histologic subtype of rhabdomyosarcoma.
Added text to state that infants younger than 1 year, who may be less likely to receive radiation therapy for local control, have a relatively high rate of local failure.
Added Gupta et al. as reference 37.
Added text about a report from the AIEOP Soft Tissue Sarcoma Committee that suggested that adolescents may have more frequent unfavorable tumor characteristics including alveolar histology, regional lymph node involvement, and metastatic disease involvement, accounting for their poor prognosis when compared with children (cited Bisogno et al. as reference 38).
Revised text to state that a statistically significant difference in 5-year survival by histopathologic subtype (82% for embryonal rhabdomyosarcoma vs. 65% for alveolar rhabdomyosarcoma), was not noted when 1,258 IRS-III and IRS-IV patients with rhabdomyosarcoma were analyzed.
Added text to state that anaplasia was not shown to be an independent prognostic variable in a multivariate analysis.
Cellular Classification
Added text to state that in some earlier studies, any alveolar focus was sufficient, but that criterion was later abandoned.
Revised text to state that unique translocations between the FOXO1 (previously called FKHR) gene on chromosome 13 and either the PAX3 gene on chromosome 2 (t(2;13)(q35;q14)) or the PAX7 gene on chromosome 1 (t(1;13)(p36;q14)) are found in 70% to 80% of patients with alveolar histology tumors.
Stage Information
Revised text about the process of assigning a Stage, Group, and Risk Group for rhabdomyosarcoma.
Revised text to state that current Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG-STS) protocols for rhabdomyosarcoma use the TNM-based pretreatment staging system that incorporates the primary tumor site, presence or absence of tumor invasion of surrounding tissues, tumor size, regional lymph node status, and the presence or absence of metastases.
Revised Table 2 to include the definitions for T1, T2a, and T2b staging.
Revised Table 3 to update the definition for each surgical-pathologic Group.
Treatment Option Overview
Revised text to state that surgical resection may be performed prior to chemotherapy if it will not result in disfigurement, substantial functional compromise, or organ dysfunction. Also added text to state that the majority of patients have Group III (gross residual) disease; after initial chemotherapy, Group III patients receive definitive radiation therapy (RT) for control of the primary tumor.
Added text to state that the primary COG-STS objective has been to employ local therapy soon after the initial operation or biopsy (except in patients with metastatic disease), using RT for patients with residual disease. Event-free survival is the target endpoint, attempting to avoid relapse and subsequent salvage therapy.
Added text to state that the COG-ARST0332 trials has now been closed.
Previously Untreated Childhood Rhabdomyosarcoma
Added text to state that clinical and/or imaging evaluation of regional lymph nodes is an important part of pretreatment staging. Pathologic evaluation of regional nodes is currently required for all patients with extremity primary rhabdomyosarcoma and boys aged 10 years and older with paratesticular rhabdomyosarcoma, because microscopic tumor is often documented even when the nodes are not enlarged.
Added text to state that an earlier study of Group I patients with alveolar rhabdomyosarcoma and undifferentiated soft tissue sarcoma found that omission of RT was followed by decreased local control. A subsequent review of patients with only alveolar rhabdomyosarcoma found that the improvement in outcome with RT did not reach statistical significance for patients with Stage 1 and 2 tumors; there were very few patients with large tumors who did not receive RT, but their outcome was poor (cited Raney et al. as reference 9 and level of evidence 3iiiDii).
Revised text to state that as with the surgical management of patients with rhabdomyosarcoma, recommendations for RT depend on the site of primary tumor, the postsurgical amount of residual disease, and the presence of involved lymph nodes.
Added text about how treatment plans show that proton-beam radiation can spare more normal tissue adjacent to the targeted volume than intensity-modulated radiation therapy (IMRT); however, follow-up remains short and there are no data available to determine if the reduction in dose to adjacent tissue will result in improved functional outcome or reduce the risk of secondary malignancy (cited Cotter et al. and Childs et al. as references 16 and 17, respectively).
Revised text to state that in general, patients with microscopic residual disease (Group II) receive RT to 36 Gy if they do not have involved lymph nodes and 41 Gy in the presence of involved nodes. Also added text to state that experience supports using a somewhat reduced dose of RT in patients with Group III disease who have delayed gross total resection with negative margins. In the recent COG-D9602 study, these patients had a greater than 85% likelihood of local control with 36 Gy (cited Breneman et al. as reference 23).
Revised text to state that in older children, reduced radiation doses may be appropriate if delayed surgery can provide negative margins; however, for infants who are unable to undergo surgical resection, higher doses of RT remain appropriate.
Revised text to state that for patients with orbital tumors, precautions should be taken to limit the RT dose to the lens and cornea.
Added text to state that because complete removal of these tumors is difficult, owing to their location, the initial surgical procedure for patients with parameningeal tumors is usually only a biopsy for diagnosis.
Added text to state that in a retrospective trial, starting RT within 2 weeks of diagnosis for patients with signs of meningeal impingement was associated with lower rates of local failure. When no signs of meningeal impingement were present, delay of RT for more than 10 weeks did not impact local failure rates.
Added Wharam and Raney as references 44 and 45, respectively.
Revised text to state that several studies have reported excellent local control in patients with rhabdomyosarcoma of the head and neck treated with IMRT, fractionated stereotactic RT, or protons and chemotherapy.
Added text to state that primary re-excision prior to beginning chemotherapy may be appropriate in patients whose initial surgical procedure leaves microscopic residual disease that is deemed resectable by a second procedure.
Added text to state that two important reviews provide information about the historical, current, and future treatment approaches for patients with bladder and prostate rhabdomyosarcomas (cited Rodeberg et al. as reference 81).
Added text to state that adolescents treated with therapy for rhabdomyosarcoma experience less hematologic toxicity and more peripheral nerve toxicity than do younger patients (cited Gupta et al. as reference 102).
Recurrent Childhood Rhabdomyosarcoma
Added text to state that at 1 year after initiation of treatment for recurrence, the failure-free survival (FFS) rate was 37% and the overall survival (OS) rate was 55% for Regimen 1A; the FFS rate was 38% and OS was 60% for Regimen 1B. The COG-STS Committee recommended the more convenient Regimen 1B for further investigation.
Added text to state that in another trial investigating single-agent vinorelbine, 6 of 12 young patients had a partial response.
Added text to state that rapamycin and the combination of topotecan, vincristine, and doxorubicin are standard chemotherapy regimens that have been used to treat recurrent rhabdomyosarcoma.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood rhabdomyosarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Rhabdomyosarcoma Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Childhood Rhabdomyosarcoma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/childrhabdomyosarcoma/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2012-08-17
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One week and counting until Texas' largest wine and food festival
HOUSTON, TEXAS, April 16, 2014 – The 11th Annual Sugar Land Wine & Food Affair (sugarlandwineandfoodaffair.
2014 Participants – Grand Tasting
John Signorelli, Remington at St. Regis
Manual Pucha, TABLE on Post Oak
Maurizio Ferrarese, Quattro
Danny Jacob, Brasserie 19
Kenneth Burke, Ibiza Food & Wine Bar Jacques Fox, Artisans
Randy Evans, Haven
Jean Phillipe Gaston, Cove at Haven
Rebecca Masson, Fluff Bake Bar
Kevin Williamson, Ranch 616
Neal Cox, Olivette @ The Houstonian Hotel Club & Spa Frederick Perrier, Aura Brasserie & Coco Pazzo
Brian & Shanna O'Hea, Acadame @ The Kennebunk Inn Taylor Salazar, Veritas Steak & Seafood
Visiting Chefs of Mexico
Arturo García Mogollón, Mexico City
Yolanda Yanar, Puerto Vallarta
Isaac Esparza, Riviera Maya
Deemed Texas's largest wine and food festival, this five-day event celebrates all that is good, gooey, sweet, savory, bubbly, hoppy and simply irresistible. In addition to interactive seminars, this year's affair will add even more food and chefs, tastings, bartender's challenge, pop-up book spot, beer garden and much more.
The Sugar Land Wine & Food Affair has become one of the most anticipated culinary attractions of the year. Located in historic Sugar Land just minutes from Houston proper, its dinners, tastings and demos and have gained a well-deserved reputation for a rollicking good time where chefs share secrets, sommeliers get un-corked and attendees have exclusive access to incredible food, wine, spirits and beer.
The Fort Bend Chamber of Commerce produces the event in collaboration with the University of Houston's Conrad N. Hilton College of Hotel and Restaurant Management. Proceeds benefit a permanent scholarship endowment for Houston's finest hospitality students. Since its inception, the event has given more than 45 scholarships to students, with a record-breaking eight scholarships awarded to students in 2013. A handpicked team of 15 students will assist in this year's event in areas such as production, marketing and social media campaigns.
The five-day wine and food affair kicks off with a VIP dinner, followed by four days of events and tastings. New attractions include an outdoor beer garden, pavilion for chef demonstrations and cookware, and a pop-up book spot sponsored by My Table magazine.
Adding to the international flair will be a cadre of celebrated chefs from Mexico. Representing the diversity of fine Mexican cuisine, the chefs will create dishes that reflect indigenous ingredients and technique. Chefs will be paired with wine producers from Mexico and makers of small-batch tequilas, many of which are highly sought after by tequila connoisseurs and difficult to find stateside.
2014 Event Schedule
VIP Kick-Off Dinner – April 23 – SOLD OUT!
6 – 9:30 p.m.
Museum of Natural Science – Sugar Land
Kicking off the 11th annual event will be a seated VIP dinner at the Houston Museum of Natural Science – Sugar Land. "The Judgment of Paris" will recreate the famous tasting held in Paris in 1976, during which the judges awarded winning scores to California wines over French wines and sent shock waves around the wine world. Guests will feel as if they have gone back in time as they dine on a five-course meal and participate in blind tastings of French and Californian wines. Guests and media judges will determine who wins: old world or new world.
Hendrick's Gin On the Rocks Bartender's Challenge – April 24
6:30 – 9:00 p.m.
Anson Aviation – Sugar Land Regional Airport
Mingling in the shadows of the hangar's private planes, guests will be able to sample all of the Hendrick's-fueled tipples and nibble on delectable dishes while the bartenders ply their titillating trade. One competitor will be awarded $1,000, with the winning recipe being named the official cocktail of the 11th Annual Sugar Land Wine & Food Affair, which will be served at the Grand Tasting, Sip & Stroll and Bistro Brunch.
Wine, Herradura Tequila, Tullamore Dew Irish Whiskey Seminars – April 25
5:30 – 6:30 p.m.
Sugar Land Marriott Town Square
Learn from experts representing many of the world's top brands. These lively, interactive sessions provide new insight into what makes your drink of choice so special.
- Join award-winning wine professionals Monique Studak and James Watkins for an in-depth look at whether women an men's preferences are guided by gender rather than grapes at the Fred Parks Wine Seminar: Battle of Sexes.
- If whiskey is your drink of choice, Tullamore Dew Irish Whiskey Brand Ambassador, Maurice "Mossie" Power, will teach you all there is to know about this signature spirit from the Emerald Isle in a tasty and insightful seminar.
- Transport your taste buds to the beautiful agave fields of Mexico at the Herradura Tequila Seminar as you sample some of the finest tequilas in the world.
The Grand Tasting – April 25
7:00 – 9:30 p.m.
Sugar Land Marriott Town Square
Get up close and personal with a who's who of culinary superstars. Held in the elegant ballroom of the Sugar Land Marriott, the Grand Tasting showcases mouthwatering creations alongside craft beer, wines and spirits.
Sip and Stroll – April 26
1:00 – 4:00 p.m.
Imperial Sugar Land
Sip and stroll your way across the grounds of the historic Imperial Sugar Factory showcasing chefs, restaurants and wines. The Sip and Stroll will also include a new outdoor beer garden featuring more than 100 beers from 25 different breweries and a pop-up book spot sponsored by My Table magazine. Houston-area cookbook authors including Paul Galvani, Erin Hicks, Gracie Cavnar, Shubhra Ramineni, Efisio Farris, Ken Hoffman, Teresa Byrne-Dodge, "Peace Meals"/Junior League, John DeMers and Michael & David Cordúa will be on hand to sign books in a chic lounge setting in the old Char House.
Bistro Brunch – April 27
11:00 a.m. – 2 p.m.
Sugar Land Town Square
Bloody Marys, mimosas, wine, beer and much more await attendees at the Bistro Brunch. Partake in delicious foods from around the world —Mexico, France, Spain, Germany, Italy — and stateside — California, Texas, Oregon and Washington.
Tickets are priced from $40 – $150. A three-day VIP Grand Pass with access to The Grand Tasting, Sip & Stroll and Bistro Brunch is specially priced at $200. Special hotel packages are available at the official sponsor hotel, the Sugar Land Marriott Town Square.
Ticket purchases and additional information are available at sugarlandwineandfoodaffair.com or 713.SIP-WINE(713.747.9463). Listings of attending chefs, presenting wine, beer and spirits providers —updated frequently—are showcased on Facebook at facebook.com/

subset: commoncrawl


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buffetbuster Never Ending Pie Buffet?!?!?! This is the best idea since pie happy hour! I sure do wish I could attend. love2bake- Any chance you could take some photos and report back on the event? Actually, we'd love to hear about it even if there aren't any photos.
buffetbuster I think this is the one where loves2bake acts as a judge. As much as I would love to go, Cousin Johnny and I will be on our Northern California vacation at that time.


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Sexy lingerie can definitely help boost your confidence and make you ooze femininity as Adriana Lima demonstrates by posing like a true diva for Victoria's Secret May 2012 lookbook. The new designs place a heavy accent on both comfort and sexiness, so no wonder that they manage to steal plenty of attention and positive comments. Adriana Lima sizzles donning some of the sexiest and newest designs of the renowned lingerie label, so check out the fabulous lingerie styles worn by the Brazilian hottie and pick the ones that suit your personality ... Read More


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The All Blacks spluttered into life in the second half to hold off England 28-27 in the second Test in Dunedin and clinch their three-Test series.
The mistake-ridden hosts trailed 10-0 after eight minutes and were still down 10-6 at halftime before powering clear with three tries in a decisive third quarter.
They conceded two late tries but were never in danger of losing after skipping 28-13 ahead entering the final 10 minutes.
It was far from a perfect performance from either side, with mistakes prominent despite perfect conditions at the indoor stadium.
As happened in last week's 20-15 first Test win in Auckland, the All Blacks were squeezed into early errors by the bigger, more-disciplined visitors.
However, they began unfurling their best rugby soon before halftime and broke a tiring English defensive line repeatedly during a thrilling period after the break, crossing through fullback Ben Smith, winger Julian Savea and inside centre Ma'a Nonu.
It was the All Blacks' 16th successive win and they can move level with the world-record streak for a tier-one nation if successful in the third Test at Hamilton next weekend.
All Blacks coach Steve Hansen said his team improved considerably in the space of a week despite the tighter final scoreline.
"I don't think we played as well as we possibly can but, as a group, it was about believing in what we were doing and, eventually, if we stuck with it, it would come right."
England counterpart Stuart Lancaster was disappointed to cede the Hillary Shield but accepted New Zealand deserved to win.
"We have set ourselves high expectations on this tour but you've got some high-quality opposition there," Lancaster said.
"They've had an extra week's preparation and you could see the improvement in their performance."
England's early dominance resulted in a penalty to five-eighth Owen Farrell and his conversion of a try to winger Marland Yarde.
All Blacks No.10 Aaron Cruden responded with penalties in the 12th and 40th minutes, the latter coming after arguably the most important play of the game.
England winger Manu Tuilagi scooped a loose ball and powered 80 metres before being run down five metres out by Smith, who also effected a turnover.
Smith, revelling in the first of his 28 Tests at his favoured fullback position, opened the floodgates soon after halftime, following some slick work from Cruden and Savea.
Savea crossed for his 20th try in 21 Tests shortly afterwards to put the hosts 18-13 clear.
England's discipline began to unravel, resulting in a yellow card to Farrell in the 60th minute for persistent offending.
Nonu was rewarded for a bright attacking performance with his try when following up a Conrad Smith break.
The tourists finally were able to get some possession and sent fullback Mike Brown across with eight minutes to play and reserve winger Chris Ashton in the final minute to complete an encouraging finish.


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fifthteen years ago my next door neighbor had been
killed a few weeks after the funeral i saw him
walking down the road, he went into his drive way and disappeared!!!!!!!!!!!!!
see a ghost?????????
Started by booberry , Sep 29 2010 02:04 PM
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Autobiography of Alice B. Toklas, The
[ tok-luh s, tohk-luh s ]
/ ˈtɒk ləs, ˈtoʊk ləs /
a memoir (1933) by Gertrude Stein.
Content related to Autobiography of Alice B. Toklas, The
The Letter B Once Had A Much Longer NameThe letter B was part of the Phoenician alphabet more than 3000 years ago in 1000 BCE. At that time, the letter was called beth and looked a little different, but it made the sound of b and was second in the alphabet. The shape of the letter resembled the floor plan of a house, and the word beth meant "house." This is pictured below. In Hebrew, the letter was called beth, bet, or bayt which also …
Dictionary.com Unabridged Based on the Random House Unabridged Dictionary, © Random House, Inc. 2019


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Osso Buco
By á-2778
Who ate all the Osso Buco
- 1 cup olive oil
- 1/2 cup flour
- 4 each veal shanks, about 1 1/2-inches thick and each tied tightly around the middle
- 2 cups medium diced onions
- 1 cup medium diced carrots
- 1 cup medium diced celery
- 2 tablespoons chopped garlic
- 3 bay leaves
- 2 tablespoons chopped fresh thyme
- 1 cup red wine
- 1 pound new potatoes, quartered and cooked until tender
- 2 quarts veal or dark stock
- 1/4 cup parsley
Step 1
In a large stock pot or braising pot, add the olive oil. Season the veal shanks with salt and pepper. Season the flour with Essence.
Dredge the veal shanks in the seasoned flour, coating each side completely.
When the oil is hot, sear the shanks for 2 to 3 minutes on each side, or until very brown on all sides. Remove the shanks and set aside.
Add the onions to the pan and saute for 2 minutes. Add the carrots and celery and continue to saute for 1 minute.
Season with salt and pepper.
Stir in the garlic, bay leaves, and thyme.
Cook for 1 minute.
Deglaze the pan with the red wine, scrapping the bottom and sides to loosen the browned particles. Add the stock.
Bring the liquid up to a boil and reduce to a simmer.
Add the shanks and continue to cook for about 2 hours, basting the shanks often, or until the sauce is stew-like and the meat falls of the bone.
Season with salt and pepper.


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Move from One Web Page to Another with Internet Explorer 10
To move from one web page to another, use Internet Explorer 10 from the Windows 8 Start screen or desktop — or even a competing web browser such as Firefox or Chrome. Web pages come with specific addresses, just as houses do. Any web browser lets you move among those addresses.
No matter which browser you use, they all let you move from one page to another in any of three different ways:
By pointing and clicking a button or link that automatically whisks you away to another page
By typing a complicated string of code words (the web address) into the Address Bar of the web browser and pressing Enter
By clicking the navigation buttons on the browser's toolbar, which is usually at the top of the screen
How to click links in Internet Explorer
The first way is by far the easiest. Look for links — highlighted words or pictures on a page — and click them.
For example, see how the mouse pointer turned into a hand as it pointed at the word Books in the figure? Click that word to see a web page with more information about that subject. The mouse pointer morphs into a hand whenever it's over a link. Click any linked word to see pages dealing with that link's particular subject.
How to type web addresses in the IE Address Bar
The second method is more difficult. If a friend gives you a napkin with a cool web page's address written on it, you need to type the website's address into your browser's Address Bar — the text-filled bar across the top. You'll do fine, as long as you don't misspell anything.
See the address for my website along the top of the figure? Type www.andyrathbone.com into the Address Bar. When you press Enter, Internet Explorer scoots you to this web page. (You don't need to type the http:// part, thank goodness.)
How to use Internet Explorer's toolbar
Finally, you can maneuver through the Internet by clicking various buttons on Internet Explorer's newly stripped-down toolbar, which sits at the top of the screen.
Hover your mouse pointer over a confusing Internet Explorer button to see its purpose in life.
For more information about Windows 8 and its features, explore Windows 8 For Dummies, available online.


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Chapel Hill Project Night
Chapel Hill Project Night meets on second Wednesdays. Have a project you want to show off, share, seek help with, or just get some work done surrounded by like minded Python lovers? Join us for our monthly project night and do just that! Don't have something to work on? Just need some help with Python? Show up and enjoy the energy, sprint on an open source project, find something interesting to contribute to or be inspired by! The setting is informal and there is no schedule, so don't worry if you show up past the start time. Whether you are a Python newbie needing help or have an open source project you want to share, come hang out and hack. Plenty of free after hours parking is available in the RENCI parking deck.
For more information, visit
- What
- Project Night
- When
- 2016-07-13 from 18:00 to 21:00
- Where
- Renaissance Computing Institute (RENCI), Biltmore Conference Room, 5th Floor, Europa Center, 100 Europa Drive, Suite 590, Chapel Hill
- Name
- Chris Calloway
- Contact Email
- email@example.com
- Contact Phone
- 599-3530


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October means reds, trout under Sabine Lake birds
Ah, sweet October – cooler weather and all the reds and trout you want to catch under the birds on Sabine Lake. It's doesn't get much better than that.
Our first really good cold front moved through Southeast Texas this week, and it's the icing on the cake if you're into chasing trout and reds under the birds on Sabine Lake, or even East Galveston Bay and Louisiana's Lake Calcasieu. Actually the action under the birds has been coming to life for the past couple of weeks. Each cool front has been dropping the water temperature a couple of degrees, and that's been enough to move shrimp and shad out of the marshes. But this week's cold front, our best yet, is the one that's going to really drop the water temperature and move lots of shrimp out of the marsh. And it's a sure bet that it won't take long for the word to spread, either. With that you can expect to see lots of boats in pursuit of two of the greatest game fish on the Texas coast – speckled trout and red fish.
I recently talked with Mike Cooper who lives on the lower end of Sabine Lake. If anybody's got the scoop on what's happening there from one day to the next, it's him. He'll be fishing from his boat during the day and off his lighted pier at night.
"Fishing all over the lake has been good for reds, specks and sand trout," said Cooper. "The best action under the birds has been good in the morning up until about 10 a.m., then it'll slow a little bit. With this week's cold weather, I think it'll kick into high gear. Aside from reds and trout, we've got a lot of good sized sand trout under the birds, too. They are also feeding under the lights at night."
Some of the best catches of trout and reds have been on the lower end of the lake. That was before this week's cold front. If we get a three to four degree drop in the water temperature some of the best action will move up to the northeast areas Sabine.
Catches of solid specks have been good while fishing soft plastics rigged on 1/4-ounce jig heads. The trick has been to let the jigs settle to bottom before beginning your retrieve. Lots of smaller trout are holding just under the birds. That's especially true during the hours of high sun. Early and late, the larger trout, fish in the 2-1/2 to 4 pound class, will be feeding directly under the birds. That's when topwater plugs like a Super Spook Jr. or She Dog will draw some better trout.
One of the all-time best lures for catching both trout and reds under the birds is a 1/2-ounce Rattle-Trap or a Cotton Cordell Super Spot. The 1/2-ounce lures are best because you can cast 'em from Beaumont to the SGS bait and tackle shop on Pleasure Island. Best colors will be blue/chrome or chartreuse/chrome. The Traps or Spots can be fished at any level on a fast retrieve.
East Galveston Bay guide Jim West says the action under the birds there is great for numbers of trout. But the only glitch is that most are in the 14 to 14-3/4 inch range, just shy of being a legal keeper.
"There are lots of 'em under the birds, but they aren't holding any size right now," said West.
Capt. Buddy Oaks with Hackberry Rod and Gun Club says the fishing under the birds is excellent on Calcasieu.
"Fishermen that fish Lake Calcasieu on a regular basis call October 'meat month' here is southwest Louisiana," said Oaks. "We call it a great opportunity to get out on the water and experience some of the best light-tackle saltwater fishing in the world. Huge flocks of working seagulls are pointing the way to fast and quick action in big schools of fish. It seems like every day limits of speckled trout and redfish come to the dock for our anglers. It ought to be great for at least the next four weeks."
Robert Sloan can be reached by e-mail at sloan288 [at] aol [dot] com.


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CORAL GABLES, Fla. (AP) With a steady din coming from the sea of orange behind the visitors' basket, No. 1-ranked Duke had a tough time making a shot.
The Blue Devils went more than 8 minutes without a field goal in the first half Wednesday night, and a sellout became a blowout for No. 25 Miami, which delighted a boisterous crowd with a 90-63 victory.
The defeat was the third-worst ever for a No. 1 team, and Duke's worst in nearly five years.
Durand Scott scored a season-high 25 points for the Hurricanes (14-3, 5-0 Atlantic Coast Conference), Kenny Kadji added a season-high 22, and Shane Larkin had 18 points, 10 rebounds and five assists.
Miami beat a No. 1 team for the first time, taking control with a stunning 25-1 run midway through the opening half. The Blue Devils (16-2, 3-2) missed 13 consecutive shots despite numerous good looks during the Hurricanes' run that transformed a 14-13 deficit into a 38-15 lead.
Seth Curry, Tyler Thornton and Quinn Cook went a combined 1 for 29 for the Blue Devils, who shot a season-low 30 percent. Rasheed Sulaimon led them with 16 points.
PHILADELPHIA (AP) - Ramon Galloway went the length of the court for the winning basket with 2.7 seconds left to send La Salle past Butler.
Fans stormed the court in a wild celebration for the biggest win for La Salle (13-5, 3-2 Atlantic 10) in 33 years. There was some confusion after Galloway's basket and fans were ordered off the court. Butler had attempted a last-second heave that was way off the mark. Officials huddled with both coaches and they decided the final score stood. It was mayhem again as fans rushed the court for the second time in minutes.
Let them celebrate twice: La Salle hadn't defeated a top 10 team since 1980.
Butler's leading scorer Rotnei Clarke missed his third straight game with a severely sprained neck. No decision has yet been made about Saturday's home game against Temple. Clarke was hurt when he crashed head-first into a padded basket support at Dayton on Jan. 12.
BLOOMINGTON, Ind. (AP) - Victor Oladipo scored 19 points, and Yogi Ferrell added a season-high 15 to help Indiana rout Penn State.
The Hoosiers (17-2, 5-1 Big Ten) survived a sluggish shooting first half with strong defense and used a fast second-half start to reassert their dominance in this series.
D.J. Newbill had 18 points and Jermaine Marshall finished with 12 to lead the Nittany Lions (8-11, 0-7), who have lost seven straight overall and 12 straight on the road in league play.
While limiting Penn State to 29.6 percent shooting in the first half, Indiana used runs of 7-0, 8-2 and 12-5 to take a 33-19 lead.
The Hoosiers wasted no time taking control in the second half, going on an 8-0 spurt in the first 65 seconds to extend the lead to 41-19. Penn State couldn't get closer than 17 points the rest of the way.
ATHENS, Ga. (AP) - Scottie Wilbekin scored 17 points to help Florida shake off a sluggish first half and romp past another Southeastern Conference opponent.
The Gators (15-2, 5-0) trailed 27-24 at halftime, making just 1 of 9 attempts beyond the 3-point arc. But Florida quickly turned things around after the break. Wilbeken and Mike Rosario hits back-to-back 3s and forced Georgia into three straight turnovers.
The Gators led the rest of way, holding Georgia (7-11, 1-4) to only one field goal in the first 11 1/2 minutes of the second half.
Despite never leading in the first half, Florida added to its run of dominance in conference play. The Gators have won their first five SEC games by an average of nearly 25 points.
EVANSTON, Ill. (AP) - Jared Swopshire scored 16 points to lead Northwestern past Minnesota.
In a game where baskets were hard to come by at times, the Wildcats (12-8, 3-4 Big Ten) made just enough shots down the stretch to beat a ranked opponent for the second time in three games while sending the Gophers (15-4, 3-3) to their third straight loss.
Alex Marcotullio made a 3-pointer midway through the second half to give Northwestern a one-point lead and start the decisive 13-2 run.
Reggie Hearn scored 13 points after averaging 21 in the previous two games. Tre Demps added 10 points, and the Wildcats shook off a loss to Indiana and took out another ranked team to go with their victory over then-No. 23 Illinois last week.
They prevailed despite getting outrebounded 45-31 because they held Minnesota to its lowest point total of the season.
ALBUQUERQUE, N.M. (AP) - Tony Snell scored 23 points and New Mexico held off a late Colorado State rally.
The Lobos (17-2, 4-0 Mountain West) led 54-32 with 12:26 left before the Rams (15-4, 2-2) began a comeback behind Dorian Green. He scored 11 points in a 20-5 run that cut the lead to 59-52.
Colorado State's Wes Eikmeier hit a 3-pointer with 8.2 seconds left that made it 64-61, but Snell converted two free throws to preserve the victory.
Snell scored six points in a pivotal 10-0 run that turned a 27-25 lead with 4 minutes left in the first half into a 37-25 advantage early in the second half.
Eikmeier led Colorado State with 20 points and Green finished with 14.
EUGENE, Ore. (AP) - E.J. Singler scored 19 points and Oregon rallied from a 10-point halftime deficit to beat Washington State.
Singler scored 14 points in the second half for the Ducks (17-2, 6-0 Pac-12), who trailed 39-29 at halftime before pulling out their eighth straight victory.
Arsalan Kazemi added 16 points for Oregon and Damyean Dotson had 10 points and nine rebounds.
Mike Ladd had 19 points and Brock Motum scored 14 for the Cougars (10-9, 1-5).
Singler took over 5 minutes into the second half with the Ducks trailing 44-38. The senior forward scored 10 straight points, tying the score at 46-all with the second of his consecutive 3-pointers. His free throws at the 11:45 mark gave the Ducks their first lead, 48-46.
The Cougars went back up 53-52 on a layup by Royce Woolridge with 7:38 to play, but Kazemi answered with a dunk off a pass from Singler, and Dominic Artis made a 3 as the Ducks took a 57-53 lead. They led the rest of the way.
DES MOINES, Iowa (AP) - Richard Carter scored 20 points and Drake handed Creighton consecutive losses for the first time this season.
Ben Simons added 13 for the Bulldogs (9-10, 3-5 Missouri Valley Conference), who blew a 16-point lead before rallying for their first win over a ranked opponent in five years.
Grant Gibbs brought Creighton within 71-69 with 32 seconds left, and the Bluejays got the ball back on a steal. But Gibbs missed a layup and Simons sealed the win with a steal and two free throws with 0.5 seconds left.
Doug McDermott had 21 points to lead Creighton, which shot just 24 percent from 3-point range. But McDermott had just four points in the second half and didn't touch the ball on Creighton's last two possessions.
SPRINGFIELD, Mo. (AP) - Cleanthony Early scored 17 points, Carl Hall added 15 and Wichita State rallied past Missouri State.
The Bears, behind freshman Gavin Thurman, used a 19-1 run to take a 33-25 lead with 16:13 remaining in the game.
The Shockers came away empty on their first five possessions of the second half then Early and Hall got more active in the offense, scoring all but two of the points in a 16-2 run that gave Wichita State a 41-35 lead with 10:53 to go.
The Shockers (18-2, 7-1 Missouri Valley Conference), who were playing just days after upsetting then-No. 12 Creighton, remained in first place in the conference.
Thurman had 21 points to lead Missouri State (5-15, 3-5), which lost its fourth straight.


text: Going gray? Scientists uncover the root cause Finding may lead to better products to prevent, reverse the process As hydrogen peroxide in our hair builds up as we age, we go gray, British researchers concluded. featurepics By Irene Klotz updated 2:36 p.m. CT, Mon., March. 2, 2009 Attention parents: It's not your kids that are making you go gray. Your hair is simply building up too much hydrogen peroxide. Bottle-blondes may be a fan, but hydrogen peroxide, which is produced naturally in the human body, interferes with melanin, the pigment that colors our hair and skin. The body also produces the enzyme catalase, which breaks down hydrogen peroxide into water and oxygen. Or at least it does for a while. As we age, catalase production tails off, leaving nothing to transform the hydrogen peroxide into chemicals the body can release. So, as hydrogen peroxide builds up, we go gray, concluded researchers at the University of Bradford in the United Kingdom, who last week published the results of a study in the Federation of American Societies for Experimental Biology's online journal. Reversing the process "This new insight could open new strategies for intervention and reversal of the hair graying process," wrote the study's lead author John Wood, who died last month. The studies were based on analysis of cell cultures of human hair follicles. In addition to lacking catalase, the follicles of gray-haired people also had far fewer hair-repair enzymes, which in turn drove down production of melanin, the scientists found. Genetics play a role as well, causing some people, such as Caucasians, to gray earlier than others, like Asians. Scientists suspect the same mechanism also may be responsible for a condition known as vitiligo, where white spots appear in the skin. "It gives you insight into how we age in general," Gerald Weissmann, professor of medicine at New York University, told Discovery News. "They got the molecular basis of aging down pat." Skin cells produce small amounts of hydrogen peroxide as part of the body's oxygen cycle. The chemical serves to kill bacteria. Scientists are hopeful there may be a way to remix the chemical soup to keep color in our hair, which no doubt is of interest to a hair-care industry that will be worth about $42.5 billion worldwide by 2010, according to a market report published last year by Global Industry Analysts. Weissmann predicts it won't be long before products to remove hydrogen peroxide from the hair — and the body in general — are created. "The rule goes when basic science is discovered it is quickly followed by a product," he said. MSN.Com