text:
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, pediatric radiation oncologist, pediatric hematologist/oncologist, rehabilitation specialist, 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 Supportive and Palliative Care summaries 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. Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%.[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.
Pediatric soft tissue sarcomas (STSs) are a heterogenous group of malignant tumors that originate from primitive mesenchymal tissue and account for 7% of all childhood tumors.[3] Multidisciplinary evaluation in centers that have surgical and radiotherapeutic expertise is of critical importance to ensure the best clinical outcome for these patients. Although surgery with or without radiation therapy can be curative for a significant proportion of patients, the addition of chemotherapy might benefit subsets of children with the disease; therefore, enrollment into clinical trials is encouraged.
Rhabdomyosarcoma, a tumor of striated muscle, is the most common STS in children aged 0 to 14 years and accounts for 50% of tumors in this age group.[4] (Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.) The remaining STSs are commonly referred to as nonrhabdomyosarcomatous STSs and account for about 3% of all childhood tumors.[5] This heterogeneous group of tumors includes neoplasms of:[6]
In children, synovial sarcoma, fibrosarcoma, fibrohistiocytic tumors, and malignant peripheral nerve sheath tumors predominate.[7,8] The distribution of STSs by histology and age, based on the Surveillance Epidemiology and End Results (SEER) information from 1975 to 2008, is depicted in Table 1. The distribution of histologic types by age is shown in Figure 1.
Figure 1. The distribution of nonrhabdomyosarcomatous soft tissue sarcomas in children aged 0 to 19 years, as reported by the Surveillance Epidemiology and End Results program from 1975 to 2008.
Nonrhabdomyosarcomatous STSs are more common in adolescents and adults,[6] and most of the information regarding treatment and natural history of the disease in younger patients has been based on adult studies.
Risk Factors
Some genetic and environmental factors have been associated with the development of nonrhabdomyosarcomatous STS:
Clinical Presentation
Although nonrhabdomyosarcomatous STSs can develop in any part of the body, they arise most commonly in the trunk and extremities.[7,18,19] These neoplasms can present initially as an asymptomatic solid mass, or they may be symptomatic because of local invasion of adjacent anatomical structures.
Systemic symptoms (e.g., fever, weight loss, and night sweats) are rare. Hypoglycemia and hypophosphatemic rickets have been reported in cases of hemangiopericytoma, whereas hyperglycemia has been noted in patients with fibrosarcoma of the lung.[20]
When a suspicious lesion is identified, it is crucial that a complete workup, followed by adequate biopsy be performed. Generally, it is better to image the lesion prior to any interventions. Plain films can be used to rule out bone involvement and detect calcifications that may be seen in soft tissue tumors such as extraskeletal osteosarcoma or synovial sarcoma. Chest radiography and computed tomography (CT) of chest are essential to assess the presence of metastases. CT can be used to image intraabdominal tumors, such as liposarcoma, and magnetic resonance imaging (MRI) can be used for extremity lesions.
Nonrhabdomyosarcomatous soft tissue tumors are fairly readily distinguished pathologically from rhabdomyosarcoma and Ewing sarcoma; however, classification of childhood nonrhabdomyosarcomatous STS type is often difficult. A core-needle biopsy or small incisional biopsy that obtains adequate tumor tissue is crucial to allow for conventional histology, immunocytochemical analysis, and other studies such as light and electron microscopy, cytogenetics, fluorescence in situ hybridization, and molecular pathology,[21,22] given the diagnostic importance of translocations. Needle biopsy techniques must obtain an adequate tissue sample and usually require obtaining multiple cores of tissue. Image guidance using ultrasound, CT scan, or MRI may be necessary to ensure a representative biopsy.[23] Incisional biopsies are acceptable but should not compromise subsequent wide local excision, and excisional biopsy of the lesion must be avoided. Transverse extremity incisions should be avoided to reduce skin loss, as should extensive surgical procedures prior to definitive diagnosis. For these reasons, open biopsy or multiple core-needle biopsies are strongly encouraged so that adequate tumor tissue can be obtained to allow for crucial studies to be performed and to avoid limiting future treatment options.
A single-institution analysis of adolescents and adults compared patients with unplanned excision of STS to stage-matched controls. In this retrospective analysis, unplanned initial excision of STS resulted in increased risk for local recurrence, metastasis, and death, and this increase was greatest for high-grade tumors.[24][Level of evidence: 3iiA]
Many nonrhabdomyosarcomatous STSs are characterized by chromosomal abnormalities. Some of these chromosomal translocations lead to a fusion of two disparate genes. The resulting fusion transcript can be readily detected by using polymerase chain reaction-based techniques, thus facilitating the diagnosis of those neoplasms that have translocations. Some of the most frequent aberrations seen in nonrhabdomyosarcomatous soft tissue tumors are listed in Table 2.
The prognosis of nonrhabdomyosarcomatous STS tumors varies greatly depending on the histologic grade, invasiveness, tumor size, resectability, use of radiation therapy, site of primary tumor, and presence of metastases.[36,37,38] Some pediatric nonrhabdomyosarcomatous STSs are associated with a better outcome. For instance, infantile fibrosarcoma, presenting in infants and children younger than 4 years, has an excellent prognosis given that the tumor is highly chemosensitive and surgery alone can cure a significant number of these patients.[5]
Soft tissue sarcomas in older children and adolescents often behave similarly to those in adult patients.[5,21]
Pediatric patients with unresected localized nonrhabdomyosarcomatous STSs have a poor outcome. Only about one-third of patients treated with multimodality therapy remain disease free.[36,39]; [40,41][Level of evidence: 3iiiA]
In a pooled analysis from U.S. and European pediatric centers, outcome was better for patients who received radiation therapy than for patients who did not, and outcome was better for patients whose tumor-removal procedure was deemed complete than for patients whose tumor removal was incomplete.[40][Level of evidence: 3iiiA]
Because long-term related morbidity must be minimized while disease-free survival is maximized, the ideal therapy for each patient must be carefully and individually determined utilizing these prognostic factors before initiating therapy for these patients.[18,42,43,44,45,46]
Related Disease Summaries
Refer to the following PDQ summaries for information about other types of sarcoma:
World Health Organization (WHO) Classification of Soft Tissue Sarcomas (STSs)
The WHO lists the following cell types in its classification of STSs:[1,2]
This summary focuses on high-grade sarcomas and low-grade tumors that present special problems in the pediatric and adolescent population, including desmoid tumor and infantile fibrosarcoma. For many low-grade STSs, surgical resection is curative and there is no need for additional therapy.
a Not a high-grade tumor; b The category of fibrosarcoma can be inclusive of fibrosarcomatous differentiation in dermatofibrosarcoma protuberans; c Cutaneous angiosarcoma may be difficult to stage using the American Joint Committee on Cancer system.
Clinical staging has an important role in predicting the clinical outcome and determining the most effective therapy for pediatric soft tissue sarcomas (STSs). As yet, there is no well-accepted staging system that is applicable to all childhood sarcomas. The system from the American Joint Committee on Cancer (AJCC) that is used for adults has not been validated in pediatric studies.
Although a standardized staging system for pediatric nonrhabdomyosarcomatous STS does not exist, the last Children's Oncology Group (COG) trial used the sixth edition AJCC cancer staging manual for STSs (with central pathology review) (see Tables 3–6 below).[1]
Two systems are currently in use for staging pediatric nonrhabdomyosarcomatous STS tumors.
Intergroup Rhabdomyosarcoma Study Staging System
Nonmetastatic disease
Metastatic disease
Recurrent/progressive disease
TNM Staging System
The AJCC has designated staging by the four criteria of tumor size, nodal status, histologic grade, and metastasis.[4]
Soft Tissue Sarcoma Tumor Pathological Grading System
In most cases, accurate histopathologic classification of STSs alone does not yield optimal information about their clinical behavior. Therefore, several histologic parameters, including degree of cellularity, cellular pleomorphism, mitotic activity, degree of necrosis, and invasive growth, are evaluated in the grading process. This process is used to improve the correlation between histologic findings and clinical outcome.[5] In children, grading of STSs is compromised by the good prognosis of certain tumors, such as infantile fibrosarcoma and hemangiopericytoma, which have a good prognosis in children younger than 4 years, and also angiomatoid fibrous histiocytoma and dermatosarcoma protuberans, which may recur locally if incompletely excised, but usually do not metastasize.
Testing a grading system within the pediatric population is difficult because of the rarity of these neoplasms. In March 1986, the Pediatric Oncology Group (POG) conducted a prospective study on pediatric STSs other than rhabdomyosarcoma and devised the grading system that is shown below. Analysis of outcome for patients with localized STSs other than rhabdomyosarcoma demonstrated that patients with grade 3 tumors fared significantly worse than those with grade 1 or grade 2 lesions. This finding suggests that this system can accurately predict the clinical behavior of nonrhabdomyosarcomatous STS.[5,6,7]
The grading systems developed by the POG and the French Federation of Comprehensive Cancer Centers (Fédération Nationale des Centres de Lutte Contre Le Cancer [FNCLCC]) Sarcoma Group are described below. These grading systems are being compared by the central review pathologists on the COG-ARST0332 study. The study has closed and results are pending.
POG grading system
The POG grading system is described below:[5]
Grade I
Grade I lesions are based on histologic type, well-differentiated cytohistologic features, and/or age of the patient.
Grade II
Grade II lesions are STSs not included in grade I or III by histologic diagnosis (with <5 mitoses/10 high-power fields or <15% necrosis):
Grade III
Grade III lesions are similar to Grade II lesions and include certain tumors known to be clinically aggressive by virtue of histologic diagnosis and non-Grade I tumors (with >4 mitoses per 10 high-power fields or >15% necrosis):
Any other sarcoma not included in grade I in which more than 15% of the surface area is necrotic or in which there are more than four mitotic figures per ten high-power fields (40X objective) is considered a grade III lesion. Marked atypia and cellularity are less predictive but may assist in placing tumors in this category.
FNCLCC grading system
The FNCLCC histologic grading system was developed for adults with STS. The purpose of the grading system is to predict which patients will develop metastasis and subsequently benefit from adjuvant chemotherapy.[8,9] The system is described in Tables 7 and 8.
Prognostic Significance of Tumor Grading
The two grading systems described above have proven to be of prognostic value in pediatric and adult nonrhabdomyosarcomatous STSs.[10,11,12,13,14] In a study of 130 tumors from children and adolescents with nonrhabdomyosarcomatous STS enrolled in three prospective clinical trials, a correlation was found between the POG-assigned grade and the FNCLCC-assigned grade. However, grading did not correlate in all cases; 44 tumors received discrepant grades and their clinical outcome was intermediate between those who were assigned grades 1 and 2 or 3 in both systems. A mitotic index of 10 or greater emerged as an important prognostic factor.[15] The recently completed COG-ARST0332 trial will analyze data comparing the POG and FNCLCC pathologic grading systems to determine which system better correlates with clinical outcomes.
In a review of a large adult series of nonrhabdomyosarcomatous STSs, superficial extremity sarcomas had a better prognosis than deep tumors. Thus, in addition to grade and size, the depth of invasion of the tumor should be considered.[16]
Several adult and pediatric series have shown that patients with large or invasive tumors have a significantly worse prognosis than do those with small, noninvasive tumors. A retrospective review of STSs in children and adolescents suggests that the 5 cm cutoff used for adults with STS may not be ideal for smaller children, especially infants. The review identified an interaction between tumor diameter and body surface area.[17] This relationship requires further study to determine the therapeutic implications of the observation.
Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas (STSs), all children, adolescents, and young adults with these tumors should have their treatment coordinated by a multidisciplinary team comprising pediatric oncologists, pathologists, surgeons, and radiation oncologists. To better define the tumors' natural history and response to therapy, children with rare neoplasms should be considered for entry into national or institutional treatment protocols. Information about ongoing clinical trials is available from the NCI Web site.
Every attempt should be made to resect the primary tumor with negative margins before or after chemotherapy. Involvement of a surgeon with special expertise in the resection of STSs in the decision is highly desirable.
The timing of surgery depends on an assessment of the feasibility and morbidity of surgery. If the initial operation fails to achieve pathologically negative tissue margins or if the initial surgery was done without the knowledge that cancer was present, a re-excision of the affected area should be performed to obtain clear, but not necessarily wide, margins.[1,2,3,4,5] This surgical tenet is true even if no mass is detected by magnetic resonance imaging after initial surgery.[6]; [7][Level of evidence: 3iiA]
Regional lymph node metastases at diagnosis are unusual and appear most likely with epithelioid and clear cell sarcomas.[8] Sentinel lymph node mapping is employed at some centers to identify the regional nodes that are the most likely to be involved, although its widespread contribution to the staging and management of these tumors has yet to be clearly defined.[9,10,11]
Radiation Therapy
Considerations for radiation therapy are based on the potential for surgery, with or without chemotherapy, to obtain local control without loss of critical organs, or significant functional, cosmetic or psychological impairment. This will vary according to patient variables, including age and gender, and tumor variables, including histopathology, site, size, and grade. Radiation therapy considerations include the same patient and tumor variables, surgical margin status, and expectations for radiation-induced morbidities such as impaired bone or muscle development, organ damage, or second malignancy. Radiation therapy can be given preoperatively or postoperatively, and the radiation field size and dose will again be based on patient and tumor variables and the operability of the tumor.
In general, radiation is indicated for patients with inadequate surgical margins and for larger, high-grade tumors.[12,13] This is particularly important in high-grade tumors with tumor margins smaller than 1 cm.[14,15]; [16][Level of evidence: 3iiDiv] With combined surgery and radiation therapy, local control of the primary tumor can be achieved in more than 80% of patients.[17,18] Preoperative radiation therapy has been associated with excellent local control rates.[19,20,21] This approach has the advantage of treating smaller tissue volumes because it does not necessitate treating a postsurgical bed; it also has the advantage of somewhat lower radiation doses because relative hypoxia from surgical disruption of vasculature and scarring is not present. Preoperative radiation therapy has been associated with an increased rate of wound complications in adults, primarily in lower extremity tumors, but the degree of this is questionable.[22] Conversely, preoperative radiation therapy may lead to less fibrosis than with postoperative approaches, perhaps due to the smaller treatment volume and dose.[23] Brachytherapy and intraoperative radiation may be applicable in select situations.[18,24,25]; [26][Level of evidence: 3iiiDii] In the recently closed COG-ARST0332 trial, preoperative radiation therapy was recommended for patients who presented with unresected tumor. The use of postoperative radiation therapy for patients who presented following primary resection was dependent on the tumor size, grade, and margin status.
Retroperitoneal sarcomas are a special issue since radiosensitivity of the bowel to injury makes postoperative radiation therapy less desirable. Reasons for this include the postoperative adhesions and bowel immobility that increase the risk of damage from any given radiation dose. This is in contrast to the preoperative approach in which the tumor often displaces bowel outside of the radiation field, and any exposed bowel is more mobile, which decreases exposure to specific bowel segments.
Radiation volume and dose depend on all patient, tumor, and surgical variables as noted above. Considerations include patient age and growth potential, the ability to avoid critical organs, epiphyseal plates, and lymphatics (but not the neurovascular bundles that are relatively radiation tolerant), and the functional/cosmetic outcome. Radiation margins are typically 2 cm to 4 cm longitudinally, and encompassing fascial planes axially. Radiation doses are typically 45 Gy to 50 Gy preoperatively, with consideration for postoperative boost of 10 Gy to 20 Gy if resection margins are microscopically or grossly positive, or planned brachytherapy if the resection is predicted to be subtotal. However, data documenting the efficacy of a postoperative boost are lacking.[27] The postoperative radiation dose is 55 Gy to 60 Gy, or rarely, higher in the situation where unresectable gross residual disease exists.
The role of adjuvant (postoperative) chemotherapy remains controversial.[28] A meta-analysis of updated data from adult STS patients from all available randomized trials concluded that recurrence-free survival was better with adjuvant chemotherapy for patients with high-grade tumors larger than 5 cm.[29] The largest prospective pediatric trial failed to demonstrate any benefit with adjuvant vincristine, dactinomycin, cyclophosphamide, and doxorubicin.[17]
Special Treatment Considerations for Children With STS
Many therapeutic strategies for children and adolescents with soft tissue tumors are similar to those for adult patients, although there are important differences. For example, the biology of the neoplasm in pediatric patients may differ dramatically from that of the adult lesion. Additionally, limb-sparing procedures are more difficult to perform in pediatric patients. The morbidity associated with radiation therapy, particularly in infants and young children, may be much greater than that observed in adults.[30]
Improved outcomes with multimodality therapy in adults and children with STSs over the past 20 years has caused increasing concern about the potential long-term side effects of this therapy in children, especially when considering the expected longer life span of children versus adults. Therefore, to maximize tumor control and minimize long-term morbidity, treatment must be individualized for children and adolescents with nonrhabdomyosarcomatous STS. These patients should be enrolled in prospective studies that accurately assess any potential complications.[31]
Adipocytic Tumors
Liposarcoma is rare in the pediatric population. In a review of 182 pediatric patients with adult-type sarcomas, only 14 had a diagnosis of liposarcoma.[1] One retrospective study identified 34 patients younger than 22 years from 1960 to 2011.[2] There were roughly equal numbers of male and female patients and the median age was 18 years. In an international clinicopathological review, the characteristics of 82 cases of pediatric liposarcoma were reported. The median age was 15.5 years and females were more commonly affected.[3] In both reports, the great majority of patients had myxoid liposarcoma.
Liposarcomas can be roughly divided into the following four large groups:
The great majority of liposarcomas in the pediatric and adolescent age range are low grade. Myxoid liposarcoma is typically low grade. Pleomorphic liposarcoma is typically high grade and much more likely to develop metastasis. Metastasis to lymph nodes is very uncommon, and the great majority of metastases are pulmonary. Tumors arising in the periphery are more likely to be low grade and myxoid. Tumors arising centrally are more likely to be high grade, pleomorphic, and present with metastasis or recur with metastasis.
Surgery is the most important treatment for liposarcoma. After surgical resection of myxoid liposarcoma, event-free survival (EFS) and overall survival (OS) are roughly 90%. Local recurrences have been seen and are controlled with a second resection of the tumor. Higher grade or central tumors are associated with a significantly higher risk of death. In a retrospective review, 5-year survival for central tumors was 42%. In the international review, seven of ten patients with pleomorphic myxoid liposarcoma died because of their disease.[3] If initial surgery is incomplete, re-excision should be performed to achieve a wide margin of resection. There are reports of the use of chemotherapy to decrease the size of liposarcoma prior to surgery to facilitate complete resection, particularly in central tumors.[4,5] The role of adjuvant chemotherapy for liposarcoma is poorly defined. There does not appear to be a need for any adjuvant therapy for completely resected myxoid liposarcoma. Even with the use of adjuvant chemotherapy, the survival of pleomorphic liposarcoma remains poor.[6]
Chondro-osseous Tumors
Chondro-osseous tumors include the following tumor subtypes:
Extraskeletal chondrosarcoma (mesenchymal and other variants)
Mesenchymal chondrosarcoma is a highly malignant tumor with a propensity to spread to the lungs. A review of 15 patients younger than 26 years from the German Cooperative Soft Tissue Sarcoma Study Group (11 with soft-tissue lesions) and the German-Austrian-Swiss Cooperative Osteosarcoma Study Group (four with primary bone lesions) protocols suggests that complete surgical removal, or incomplete resection followed by radiation therapy, is necessary for local control.[7][Level of evidence: 3iiA]
Multiagent chemotherapy may decrease the likelihood of lung metastases: OS at 10 years was 67%, compared with approximately 20% in an earlier series of young patients.[8]
Extraskeletal osteosarcoma
Extraskeletal osteosarcoma is extremely rare in the pediatric and adolescent age range. A 2003 review identified only ten case reports in the medical literature.[9]
Extraskeletal osteosarcoma is associated with a high risk of local recurrence and pulmonary metastasis.[10]
The primary therapy for extraskeletal osteosarcoma is surgical resection of the primary tumor. Chemotherapy for extraskeletal osteosarcoma has not been well studied. It has been recommended that the treatment for extraskeletal osteosarcoma abide by the soft tissue sarcoma (STS) guidelines, rather than the guidelines for osteosarcoma of bone.[9] A report of a series of adult patients with extraskeletal osteosarcoma suggested that adjuvant chemotherapy reduced the risk of recurrence.[10] Extraskeletal osteosarcoma may be more chemosensitive in young patients than in adults.[9] A retrospective analysis of the German Cooperative Osteosarcoma Study identified a favorable outcome for extraskeletal osteosarcoma treated with surgery and conventional osteosarcoma chemotherapy.[11] (Refer to the PDQ summary on Osteosarcoma and Malignant Fibrous Histiocytoma of Bone Treatment for more information.)
Fibroblastic/Myofibroblastic Tumors
Fibroblastic/myofibroblastic tumors include the following tumor subtypes:
a Not a high-grade tumor.
Desmoid tumors
Desmoid tumors are also known as aggressive fibromatoses.
Desmoid tumors are low-grade malignancies with extremely low potential to metastasize. The tumors are locally infiltrating, and surgical control can be difficult because of the need to preserve normal structures. These tumors also have a high potential for local recurrence. Desmoid tumors have a highly variable natural history, including well documented examples of spontaneous regression.[12] Mutations in exon 3 of the beta-catenin gene are seen in over 80% of desmoid tumors and the mutation 45F has been associated with an increased risk of disease recurrence.[13] Repeated surgical resection can sometimes bring recurrent lesions under control.[14]
A small number of desmoid tumors may occur in association with a mutation in the familial adenomatous polyposis (FAP) gene (associated with intestinal polyps and a high incidence of colon cancer). Currently there are no general recommendations for genetic testing in children with desmoid tumors. A family history of colon cancer or the presence of congenital hyperplasia of the retinal pigment epithelium should prompt referral to a genetic counselor.
The treatment of choice is resection to achieve clear margins. If postoperative margins are positive, 70% of patients will have a recurrence of disease. Postoperative radiation therapy is a consideration when progression would entail additional surgery that might cause functional or cosmetic compromise and if radiation is considered acceptable in terms of morbidities. When the diagnosis is known and complete surgical excision is not feasible, and if the tumor poses significant potential for mortality or morbidity, preoperative strategies may include the following:[15,16]
Evaluation of the benefit of interventions for treatment of desmoid tumors has been extremely difficult, because desmoid tumors have a highly variable natural history.
Large adult series and a single pediatric series have reported long periods of disease stabilization and even regression without systemic therapy.[14,17] Combination chemotherapy using vinblastine and methotrexate produced objective responses in about one-third of patients with recurrent or unresectable desmoid tumors.[15] A small series of mainly adult patients (N = 19) with desmoid tumors were treated with imatinib mesylate and showed infrequent objective responses.[18] A series of mainly adult patients with familial adenomatous polyposis and unresectable desmoid tumors that were unresponsive to hormone therapy showed that doxorubicin plus dacarbazine followed by meloxicam (a nonsteroidal anti-inflammatory agent) can be safely administered and can induce responses.[19] Pegylated liposomal doxorubicin has also been used with some responses.[20]
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac have been used in single cases for desmoid tumors; the responses seen were usually disease stabilization. Similar results have been seen with antiestrogen treatment, usually tamoxifen. In some trials, these drugs were used in combination.[21]
Radiation has been used for unresectable desmoid tumors or adjuvantly for tumors with inadequate resections. The potential long-term complications of radiation therapy, especially subsequent neoplasms, makes use of this modality less appealing in a young population.[22]
Partially excised or recurrent lesions that do not pose a significant danger to vital organs may be monitored closely if other treatment alternatives are not available.[14,23,24,25,26] Whenever possible, however, the treatment of choice is complete resection.
There are two distinct types of fibrosarcoma in children and adolescents: infantile fibrosarcoma (also called congenital fibrosarcoma) and fibrosarcoma that is indistinguishable from fibrosarcoma seen in adults. These are two distinct pathologic diagnoses.
Infantile fibrosarcoma
Infantile fibrosarcoma usually occurs in children younger than 1 year. It occasionally occurs in children up to age 4 years. It usually presents with a rapidly growing mass, often noted at birth or even seen in prenatal ultrasound. The tumors are often quite large at the time of presentation. The tumor almost always has a characteristic cytogenetic translocation t(12;15)(ETV-NTRK3). Infantile fibrosarcoma shares this translocation and a virtually identical histologic appearance with mesoblastic nephroma. These tumors have a low incidence of metastases at diagnosis.
Complete resection is curative in the majority of patients with infantile fibrosarcoma. However the large size of the lesion frequently makes resection without major functional consequences impossible (for instance, tumors of the extremities often require amputation for complete excision). Preoperative chemotherapy has made a more conservative surgical approach possible; agents active in this setting include vincristine, dactinomycin, cyclophosphamide, and ifosfamide.[27,28,29]; [30][Level of evidence: 3iiA]; [31][Level of evidence: 3iiB]
Adult-type fibrosarcoma
These tumors lack the translocation seen in infantile fibrosarcomas. They present like the great majority of nonrhabdomyosarcomas and the management approach is similar.
Dermatofibrosarcoma protuberans
Dermatofibrosarcoma is a rare tumor, but many of the reported cases arise in children.[32] The tumor has a consistent chromosomal translocation t(17;22)(q22;q13) that juxtaposes the COL1A1 gene with the PDGF-beta gene.
Most dermatofibrosarcoma tumors can be cured by complete surgical resection. Radiation therapy has been used in the adjuvant setting after surgery.[33] When surgical resection cannot be accomplished or the tumor is recurrent, treatment with imatinib has been effective.[33,34]
Inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor is an incompletely characterized neoplasm of intermediate biologic potential. It recurs frequently but metastasizes rarely.[35,36] Roughly half of inflammatory myofibroblastic tumors exhibit a clonal mutation that activates the anaplastic lymphoma kinase (ALK)-receptor tyrosine kinase gene at chromosome 2p23.[37]
There are no well-documented responses to chemotherapy. A case report described a partial response in a patient with recurrent inflammatory myofibroblastic tumor who was treated with crizotinib, an ATP-competitive inhibitor of the ALK and MET tyrosine kinases.[38] There are case reports of response to either steroids or NSAIDs.[39,40]
Low-grade fibromyxoid sarcoma
Low-grade fibromyxoid sarcoma is somewhat misnamed, because its appearance is deceptively benign, but its behavior is malignant, although rather indolent.[41] In a review, 21 of 33 patients had local recurrences after intervals of up to 15 years (median, 3.5 years) and 15 had metastases, mostly in the lungs and pleura, after periods of up to 45 years (median, 5 years), indicating that follow-up must be lifelong.[41] Even after metastases occur, the course may be indolent.[42]
The limited treatment information for low-grade fibromyxoid sarcoma is summarized in the review above. This tumor is not very chemosensitive and there are little data regarding the use of chemotherapy and/or radiation therapy.
Myxofibrosarcoma, low grade
Myxofibrosarcoma, low grade, is a rare lesion, especially in childhood. It is typically treated with complete surgical resection.
Sclerosing epithelioid fibrosarcoma
Sclerosing epithelioid fibrosarcoma is another rare, usually low-grade, sarcoma. It is typically treated with complete surgical excision.
Skeletal Muscle Tumors
There are three forms of rhabdomyosarcoma:
Refer to the PDQ summary on Childhood Rhabdomyosarcoma Treatment for more information.
Smooth Muscle Tumors
A 24-year retrospective analysis of the Italian cooperative group identified one child with leiomyosarcoma.[5] A retrospective analysis of the St. Jude Children's Research Hospital (SJCRH) experience from 1962 to 1996 identified 40 children with nonrhabdomyosarcomatous STS; none had leiomyosarcoma.[43] Among 43 children with HIV/AIDS who developed tumors, eight developed Epstein-Barr virus–associated leiomyosarcoma.[44] Survivors of hereditary retinoblastoma have a statistically significant increased risk of developing leiomyosarcoma and 78% of these were diagnosed 30 or more years after the initial diagnosis of retinoblastoma.[45]
So-called Fibrohistiocytic Tumors
So-called fibrohistiocytic tumors include the following tumor subtypes:
Plexiform fibrohistiocytic tumor
Plexiform histiocytic tumor is a rare, low- to intermediate-grade tumor that most commonly affects children and young adults. Depending on the series, the median age at presentation ranges from 8 to 14.5 years; however, the tumor has been described in patients as young as 3 months.[46,47]
The tumor commonly arises as a painless mass in the skin or subcutaneous tissue and most often involves the upper extremities, including the fingers, hand, and wrist.[48,49,50] There are rare reports of spread to regional lymph nodes or the lungs.[46,50,51]
No consistent chromosomal anomalies have been detected but a t(4;15)(q21;q15) has been reported.[52]
Surgery is the treatment of choice but local recurrence has been reported in 12% to 50% of cases.[53]
Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (high-grade)
At one time, malignant fibrous histiocytoma was the single most common histiotype among adults with STSs. Since it was first recognized in the early 1960s, malignant fibrous histiocytoma has been plagued by controversy in terms of both its histogenesis and its validity as a clinicopathologic entity. The latest World Health Organization classification no longer includes malignant fibrous histiocytoma as a distinct diagnostic category but rather as a subtype of an undifferentiated pleomorphic sarcoma.[54]
This entity accounts for 2% to 6% of all childhood STSs.[55] These tumors can arise in previously irradiated sites or as a second malignancy in patients with retinoblastoma.
These tumors occur mainly in the second decade of life. In a series of ten patients, the median age was 10 years and the tumor was most commonly located in the extremities. In this series, all tumors were localized and five of nine (for whom follow-up was available) were alive in first remission.[55] In another series of 17 pediatric patients with malignant fibrous histiocytoma, the median age at diagnosis was 5 years and the extremities were involved in eight cases.[56] All patients with metastatic disease died and two patients experienced a clinical response to a doxorubicin-based regimen.
Tumors of Peripheral Nerves
Malignant peripheral nerve sheath tumor (malignant schwannoma)
Malignant peripheral nerve sheath tumor arises in children with type 1 neurofibromatosis (NF1), and it arises sporadically.[57]
Features with favorable prognosis include the following:[57,58,59,60]
It is not clear whether the absence of NF1 is a favorable prognostic factor as it has been associated with both favorable [58] and unfavorable outcomes.[57,58,60]
There is agreement that complete surgical removal of the tumor, whenever possible, is the mainstay of treatment. The role of radiation therapy is difficult to assess, but durable local control of known postsurgical microscopic residual tumor is not assured after radiation therapy. Chemotherapy has achieved objective responses in childhood malignant peripheral nerve sheath tumor. A large retrospective analysis of the German and Italian experience with malignant peripheral nerve sheath tumor reported that 65% of measurable tumors had objective responses to ifosfamide-containing chemotherapy regimens, but the analysis did not conclusively demonstrate improved survival for chemotherapy.[57] This retrospective analysis also noted a trend toward improved outcome with adjuvant radiation therapy.[57] A series of 37 young patients with malignant peripheral nerve sheath tumor and NF1 showed that most patients had large invasive tumors that were poorly responsive to chemotherapy; progression-free survival was 19% and 5-year OS was 28%.[61] The role of adjuvant chemotherapy following resection of malignant peripheral nerve sheath tumor has not been prospectively evaluated.
Tumors of Uncertain Differentiation
Tumors of uncertain differentiation include the following tumor subtypes:
Alveolar soft part sarcoma
This is a tumor of uncertain histogenesis. A consistent chromosomal translocation t(X;17)(p11.2;q25) juxtaposes the ASPSCR1 gene with the TFE3 gene.[62,63] In children, alveolar soft part sarcoma often presents with metastases [64] and sometimes has a very indolent course. A subset of renal tumors found in young people was previously considered to be renal cell carcinoma, but the subset now appears to be genetically related to alveolar soft part sarcoma.[65]
Pediatric alveolar soft part sarcoma seems to have a better outcome than its adult counterpart.[66] In a series of 19 treated patients, one group reported a 5-year OS rate of 80%, a 91% OS rate for patients with localized disease, a 100% OS rate for patients with tumors 5 cm or smaller, and a 31% OS rate for patients with tumors larger than 5 cm.[67] In another series of 33 patients, OS was 68% at 5 years from diagnosis and 53% at 10 years from diagnosis. Survival was better for smaller tumors (≤5 cm) and completely resected tumors.[68][Level of evidence: 3iiA]
The standard approach is complete resection of the primary lesion.[67] If complete excision is not feasible, radiation therapy should be administered.
The value of adjuvant chemotherapy in completely resected alveolar soft part sarcoma remains unproven, particularly because patients with unresected or metastatic tumors failed to respond to chemotherapeutic agents frequently used to treat STSs.[69] Alveolar soft part sarcoma is considered a chemoresistant tumor.[70] There are sporadic reports of objective responses to interferon-alpha, bevacizumab, and sunitinib.[71,72,73,74]
Patients with alveolar soft part sarcoma may relapse several years after a prolonged period of apparent remission.[75] Because these tumors are rare, all children with alveolar soft part sarcoma should be considered for prospective clinical trials.
Treatment options under clinical evaluation for alveolar soft part sarcoma
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
Clear cell sarcoma of soft tissue
Clear cell sarcoma (formerly and inappropriately called malignant melanoma of soft parts), also called clear cell sarcoma of tendons and aponeuroses, is somewhat similar to cutaneous malignant melanoma but is cytogenetically distinct; most cases have a t(12;22)(q13;q12) translocation that has not been reported in melanoma.[76] In one series, clear cell sarcoma demonstrated a propensity to metastasize to regional lymph nodes (12%–43%).[77]
Patients who have small, localized tumors with low mitotic rate and intermediate histologic grade fare best.[78]
The primary treatment for clear cell sarcoma is complete surgical resection, with the addition of radiation therapy for uncertain or involved margins. Chemotherapy is rarely effective.[79]
Desmoplastic small round cell tumor
Desmoplastic small round cell tumor is a primitive sarcoma that most frequently involves the abdomen, pelvis, or tissues around the testes.[80,81,82] The tumor occurs more commonly in males and invades locally but may spread to the lungs and elsewhere.
Cytogenetic studies of these tumors have demonstrated the recurrent translocation t(11;22)(p13;q12), which has been characterized as a fusion of the WT1 and EWS genes.[83]
There is no standard approach to the treatment of desmoplastic small round cell tumor. Complete surgical resections are rare, and the overall prognosis for desmoplastic small round cell tumor remains extremely poor, with reported rates of death at 90%. A small series of patients who were treated with hyperthermic intraperitoneal chemotherapy with acceptable toxicity has been reported.[84]
Greater than 90% tumor resection either at presentation or after neoadjuvant chemotherapy may be a favorable prognostic factor for overall survival.[85,86] Treatment may include chemotherapy, surgery, and radiation therapy. Multiagent chemotherapy analogous to that used for sarcomas has been used, as well as total abdominal radiation therapy.[80,81,85,87,88]
Epithelioid sarcoma
Epithelioid sarcoma is a rare mesenchymal tumor of uncertain histogenesis which displays multilineage differentiation.[89] It is characterized by inactivation of the SMARC gene, which is present in both conventional and proximal types of epithelioid sarcoma.[90]
Epithelioid sarcoma commonly presents as a slowly growing firm nodule based in the deep soft tissue; the proximal type predominantly affects adults and involves the axial skeleton and proximal sites. The tumor is highly aggressive and has a propensity for lymph node metastases.
In a review of 30 pediatric patients with epithelioid sarcoma (median age at presentation, 12 years), responses to chemotherapy were reported in 40% of patients using sarcoma-based regimens, and 60% of patients were alive at 5 years following initial diagnosis.[91]
Perivascular epitheloid cell tumors (PEComas)
PEComas (tumors showing perivascular epithelioid cell differentiation) include the following:
Benign PEComas are common in tuberous sclerosis, an autosomal dominant syndrome that also predisposes to renal cell cancer and brain tumors. Tuberous sclerosis is caused by germline inactivation of either TSC1 (9q34) or TSC2 (16p13.3), and the same tumor suppressor genes are inactivated somatically in sporadic PEComas.[92] Inactivation of either gene results in stimulation of the mTOR pathway, providing the basis for the treatment of nonsurgically curable PEComas with mTOR inhibitors.[93,94]
PEComas occur in various rare gastrointestinal, pulmonary, gynecologic, and genitourinary sites. Soft tissue, visceral, and gynecologic PEComas are more commonly seen in middle-aged female patients and are usually not associated with the tuberous sclerosis complex.[95] Most PEComas have a benign clinical course, but malignant behavior has been reported and can be predicted based on the size of the tumor, mitotic rate, and presence of necrosis.[96]
Extrarenal (extracranial) rhabdoid tumor
Malignant rhabdoid tumors were first described in children with renal tumors in 1981 (refer to the Wilms Tumor and Other Childhood Kidney Tumors Treatment summary for more information) and were later found in a variety of extrarenal sites. They are uncommon and highly malignant, especially in children younger than 2 years. The first sizeable series of 26 childhood patients with extrarenal extracranial malignant rhabdoid tumor of soft tissues came from patients enrolled on the Intergroup Rhabdomyosarcoma Studies (IRS) I through III during a review of pathology material. Only five patients (19%) were alive without disease.[97] Later, investigation of children with atypical teratoid/rhabdoid tumors of the brain, as well as those with renal and extrarenal malignant rhabdoid tumors, found germline and acquired mutations of the SMARCB1 gene in all 29 tumors tested.[98] Rhabdoid tumors may be associated with germline mutations of the SMARCB1 gene and may be inherited from an apparently unaffected parent.[99] This observation was extended to 32 malignant rhabdoid tumors at all sites in patients whose mean age at diagnosis was 12 months.[100] The disease can occur congenitally [101] and is uncommon in older children and adults.
In a Surveillance Epidemiology and End Results study of 229 patients with renal, central nervous system, and extrarenal malignant rhabdoid tumor, patients aged 2 to 18 years, limited extent of tumor, and delivery of radiation therapy were shown to affect the outcome favorably compared with other patients (P < .002 for each comparison). Site of the primary tumor was not prognostically significant. Overall survival at 5 years was 33%.[102]
Treatment includes surgical removal when possible, chemotherapy as used for STSs (but no single regimen is currently accepted as best), and radiation therapy.[103][Level of evidence: 3iA]; [104,105][Level of evidence: 3iiiB]
Extraskeletal myxoid chondrosarcoma
Extraskeletal myxoid chondrosarcoma is relatively rare among STSs, representing only 2.3% of all STSs.[106] It has been reported in children and adolescents.[107]
Extraskeletal myxoid chondrosarcoma is a multinodular neoplasm. The rounded cells are arranged in cords and strands in a chondroitin sulfate myxoid background. Several cytogenetic abnormalities have been identified (see Table 2), with the most frequent being the translocation t(9;22)(q22;q12), involving the EWSR1/NR4A3 genes.[108] The tumor has traditionally been considered of low-grade malignant potential.[109] However, recent reports from large institutions showed that extraskeletal myxoid chondrosarcoma has significant malignant potential, especially if patients are followed for a long time.[110,111] Patients tend to have slow protracted courses. Nodal involvement has been well described. Local recurrence (57%) and metastatic spread to lungs (26%) have been reported.[111]
The therapeutic benefit of chemotherapy has not been established. Aggressive local control and aggressive resection of metastases led to OS of 87% at 5 years and 63% at 10 years.[110] There may be potential genetic targets for small molecules, but these should be studied as part of a clinical trial.
Primitive neuroectodermal tumor (PNET)/extraskeletal Ewing tumor
(Refer to the PDQ summary on Ewing Sarcoma Treatment for more information.)
Synovial sarcoma
Synovial sarcoma is one of the most common nonrhabdomyosarcomatous STSs in children and adolescents. In a Surveillance Epidemiology and End Results review from 1973 to 2005, 1,268 patients with synovial sarcoma were identified. Approximately 17% of these patients were children and adolescents and the median age at diagnosis was 34 years.[112] The most common location is the extremities, followed by trunk and head and neck.[112] Patients younger than 10 years have more favorable outcomes and clinical features, including extremity primaries, smaller tumors, and localized disease, than do older patients.[112]
Synovial sarcoma can be subclassified as the following types:
The diagnosis of synovial sarcoma is made by immunohistochemical analysis, ultrastructural findings, and demonstration of the specific chromosomal translocation t(x;18)(p11.2;q11.2). This abnormality is specific for synovial sarcoma and is found in all morphologic subtypes. Synovial sarcoma results in rearrangement of the SYT gene on chromosome 18 with one of the subtypes (1, 2, or 4) of the SSX gene on chromosome X.[114,115] It is thought that the SYT/SSX18 transcript promotes epigenetic silencing of key tumor suppressor genes.[116]
The most common site of metastasis is the lung.[117,118] The risk of metastases is highly influenced by tumor size; it is estimated that patients with tumors that measure greater than 5 cm have a 32-fold risk of developing metastases when compared with other patients.
In a retrospective analysis of synovial sarcoma in children and adolescents who were treated in Germany and Italy, tumor size (>5 cm or ≤5 cm in greatest dimension) was an important predictor of EFS.[119] In this analysis, local invasiveness conferred an inferior probability of EFS, but surgical margins were not associated with clinical outcome. A multicenter analysis of 219 children from various treating centers including Germany, SJCRH, Instituto Tumori, and MD Anderson Cancer Center reported an estimated 5-year OS of 80% and EFS rate of 72%. In this analysis, an interaction between tumor size and invasiveness was observed; in multivariate analysis, patients with large or invasive tumors or with Intergroup Rhabdomyosarcoma Study (IRS) Clinical Group III and IV disease had decreased OS. Treatment with radiation therapy was related to improved OS (hazard ratio, 0.4; 95% confidence interval, 0.2–0.7). In IRS Group III patients, objective response to chemotherapy (18 of 30 [60%]) correlated with improved survival. In adults, factors such as International Union Against Cancer/American Joint Committee on Cancer stage III and stage IVA, tumor necrosis, truncal location, elevated mitotic rate, age, and histologic grade have been associated with a worse prognosis.[120,121,122]
Synovial sarcoma appears to be more sensitive to chemotherapy than many other STSs, and children with synovial sarcoma seem to have a better prognosis when compared with adults.[5,118,122,123,124,125,126,127,128] The most commonly used regimens for the treatment of synovial sarcoma incorporate ifosfamide and doxorubicin.[126,129,130] Response rates to the ifosfamide and doxorubicin regimen are higher than in other nonrhabdomyosarcomatous STSs.[131] A meta-analysis also suggested that response to chemotherapy was correlated with improved survival.[130]
Several treatment centers advocate adjuvant chemotherapy following resection and radiation therapy of synovial sarcoma in children and young adults.[119,127,130,132,133,134] The International Society of Pediatric Oncology-Malignant Mesenchymal Tumors studies showed that select patients (young age, < 5 cm resected tumors) with nonmetastatic synovial sarcoma can have excellent outcome in the absence of radiation, but it is still unclear whether or not that obviates an advantage of radiation for local or regional control.[133] A German trial suggested a benefit for adjuvant chemotherapy in children with synovial sarcoma.[134] A meta-analysis also suggested that chemotherapy may provide benefit.[130] However, unequivocal proof of the value of adjuvant chemotherapy from prospective, randomized clinical trials is lacking and the results of COG-ARST0332 are pending. Survival following relapse is poor (30% at 5 years). Factors associated with outcome after relapse include duration of first remission (> or ≤ 18 months) and lack of a second remission.[135]
Undifferentiated sarcoma; sarcoma, NOS
Patients with undifferentiated STS had been eligible for participation in rhabdomyosarcoma trials coordinated by the Intergroup Rhabdomyosarcoma Study Group and the Children's Oncology Group (COG) from 1972 to 2006. The rationale was the observation that patients with undifferentiated STS had similar sites of disease and outcome as those with alveolar rhabdomyosarcoma. Therapeutic trials for adults with STS include patients with undifferentiated STS and other histologies, which are treated similarly, using ifosfamide and doxorubicin, and sometimes with other chemotherapy agents, surgery, and radiation therapy. Currently in the COG, they are treated on clinical trials for patients with nonrhabdomyosarcomatous STSs.
Vascular Tumors
Vascular tumors vary from hemangiomas, which are always considered benign, to angiosarcomas, which are highly malignant.[136] Vascular tumors include the following tumor subtypes:
Angiosarcoma (deep)
Complete surgical excision appears to be crucial for angiosarcomas and lymphangiosarcomas despite evidence of tumor shrinkage in some patients in response to local or systemic therapy.[137,138,139,140] A review of 222 patients (median age, 62 years; range, age 15–90 years) showed an overall disease-specific survival (DSS) rate of 38% at 5 years. Five-year DSS was 44% in 138 patients with localized, resected tumors but only 16% in 43 patients with metastases at diagnosis.[140]
A review of 20 years of experience in the Italian and German Soft Tissue Sarcoma Cooperative Group identified 12 children with angiosarcoma.[139] One objective response to chemotherapy was observed, and the overall behavior of this tumor was identical to angiosarcoma in adults. A subsequent retrospective study of 14 children with angiosarcoma performed by the Polish and German Cooperative Paediatric Soft Tissue Sarcoma Study Groups identified four chemotherapy responses in ten children.[141] Another review of 15 patients demonstrated a 33% survival rate.[142]
Anti-angiogenesis therapy may prove useful in the treatment of this group of neoplasms.[143]
Epithelioid hemangioendothelioma
Hemangioendotheliomas are tumors found in infants that arise within the liver or elsewhere and usually remain benign.[144,145] However, not all liver hemangiomas remain benign. A report from France presents five girls with angiosarcoma. Three of them were aged newborn to 3 months with cutaneous hemangiomas, two of whom also had simultaneous hepatomegaly. After variable treatments, liver size decreased, but at age 2.5 to 5 years, liver enlargement was noted and all three died of liver angiosarcoma (type 2 malignant hemangioendothelioma). The other two girls presented with vascular liver tumors at age 2 and 3.5 years, with no prior history. The younger child had a benign (type 1) hemangioendothelioma on initial biopsy, but 3 months later another biopsy showed both type 1 and type 2 histology, and she died. The older girl had type 2 histology but no metastases and underwent liver transplantation. She was alive and receiving tacrolimus 2 years later, without recurrence. Alpha-fetoprotein determinations were normal in all five patients. Because chemotherapy and radiation therapy are usually ineffective for angiosarcoma, the authors recommend periodic liver ultrasound surveillance of all infants with multinodular liver hemangiomas and liver transplantation if feasible to clear the tumor(s), provided that no metastases are found.[145]
The tumors are sometimes associated with consumptive coagulopathy, also known as the Kasabach-Merritt syndrome (or phenomenon).[146,147,148]; [149][Level of evidence: 3iiiDiv] Chemotherapy and interferon have had some benefit in isolated cases.[147,148] In older children and adults, hemangioendotheliomas may occur elsewhere in the body and can metastasize to lungs, lymph nodes, bones, and within the pleural or peritoneal cavities. The preferred pathologic designation for these lesions in older persons is epithelioid hemangioendothelioma, which connotes the possibility of distant spread. These latter lesions are considered to be of intermediate malignant potential, between benign hemangioma and angiosarcoma.[150,151] In more extensive hemangioendothelioma, inhibition of mTOR pathway may be helpful.[152] However, this should be investigated as part of a clinical trial before use in the clinical setting.
Treatment of asymptomatic liver hemangioendothelioma in a child younger than 1 year may include close observation, because some tumors will regress. Symptomatic lesions require urgent medical or surgical management, especially if coagulopathy is present.[144,146,147,148] Epithelioid hemangioendothelioma of the liver should be managed surgically. Some patients may need orthotopic liver transplantation because this disease does not respond to radiation therapy or chemotherapy.[150]
Hemangiopericytoma (infantile)
Hemangiopericytoma is a highly vascularized tumor of uncertain origin. Hemangiopericytoma in children younger than 1 year seems to have a better prognosis than in children older than 1 year.[153,154,155] Histologically, hemangiopericytomas are composed of packed round or fusiform cells that are arranged around a complex vasculature, forming many branch-like structures. Hyalinization is often present. Infantile hemangiopericytomas have similar histology but many are multilobular with vasculature outside the tumor mass.[156]
In a series of 17 children, the differences in metastatic potential and response to treatment were clearly demonstrated for adult and infantile hemangiopericytomas.[29] Eleven children were older than 1 year. Several of these patients had disease in the lymph nodes or lungs. Six patients with stage II and III disease progressed and died. Three patients with stage I disease survived, although one had recurrence in the lungs. Six patients had infantile hemangiopericytoma, most were greater than stage I (5 of 6). All six survived and three had good responses to vincristine, actinomycin, and cyclophosphamide.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with nonmetastatic childhood soft tissue sarcoma. 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.
Standard treatment options for metastatic childhood soft tissue sarcoma (STS) include the following:
The prognosis for children with metastatic STSs is poor,[1,2,3,4,5,6] and these children should receive combined treatment with chemotherapy, radiation therapy, and surgical resection of pulmonary metastases. In a prospective randomized trial, chemotherapy with vincristine, dactinomycin, doxorubicin, and cyclophosphamide, with or without dacarbazine, led to tumor responses in one-third of patients with unresectable or metastatic disease. The estimated 4-year survival rate, however, was poor, with fewer than one-third of children surviving.[6,7,8]
Pulmonary Metastases
Children with isolated pulmonary metastases should undergo a surgical procedure in an attempt to resect all gross disease. For patients with multiple or recurrent pulmonary metastases, additional surgical procedures can be performed if the morbidity is deemed acceptable. An alternative approach is focused radiation therapy (fractionated stereotactic radiation therapy), which has been successfully used in adults to sterilize lesions. The estimated 5-year survival rate after thoracotomy for pulmonary metastasectomy has ranged from 10% to 58% in adult studies. Emerging data suggest a similar outcome following the use of focused radiation therapy in adults.[9] Formal segmentectomy, lobectomy, and mediastinal lymph node dissection are unnecessary.[10]
Treatment Options Under Clinical Evaluation
The following agents are being studied for the treatment of certain metastatic STSs:
The Children's Oncology Group COG-ARST0332 trial entered 552 eligible patients younger than 30 years with localized and metastatic nonrhabdomyosarcoma STSs from 2007 until 2012. The study is now closed and awaits analysis as the first risk-based treatment program for nonrhabdomyosarcoma STS in this age group.
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.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with metastatic childhood soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
With the possible exception of infants with infantile fibrosarcoma, the prognosis for patients with recurrent or progressive disease is poor. No prospective trial has been able to prove that enhanced local control of pediatric soft tissue sarcomas (STSs) will ultimately improve survival. Therefore, treatment should be individualized for the site of recurrence and biologic characteristics (e.g., grade, invasiveness, and size) of the tumor.
Decisions about treatment options for progressive or recurrent childhood STS are based on many factors, including the following:
Standard treatment options for recurrent or progressive disease include the following:
Resection is the standard treatment for recurrent pediatric nonrhabdomyosarcomatous STSs. If the patient has not yet received radiation therapy, adjuvant radiation should be considered after local excision of the recurrent tumor. Limb-sparing procedures with adjuvant brachytherapy have been evaluated in adults but have not been studied extensively in children. For some children with extremity sarcomas who have received previous radiation therapy, amputation may be the only therapeutic option.
Pulmonary metastasectomy may achieve prolonged disease control for some patients.[5] A large, retrospective analysis of patients with recurrent STS showed that isolated local relapse had a better prognosis and that resection of pulmonary metastases improved the probability of survival.[6] All patients with recurrent tumors should be considered for current clinical trials.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood soft tissue sarcoma. 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
Added text to state that multidisciplinary evaluation in centers that have surgical and radiotherapeutic expertise is of critical importance to ensure the best clinical outcome for these patients. Although surgery with or without radiation therapy can be curative for a significant proportion of patients, the addition of chemotherapy might benefit subsets of children with the disease; therefore, enrollment into clinical trials is encouraged.
Revised Table 1 to include the percentage of the total number of soft tissue sarcoma (STS) cases in children younger than 20 years for all subtypes and to state that dermatofibrosarcoma accounts for 75% of fibrohistiocytic tumor cases.
Added text about the use of plain films, computed tomography, and magnetic resonance imaging to diagnose STSs.
Added text to state that a single-institution analysis of adolescents and adults compared patients with unplanned excision of STS to stage-matched controls. In this retrospective analysis, unplanned initial excision of STS resulted in increased risk for local recurrence, metastasis, and death, and this increase was greatest for high-grade tumors (cited Qureshi et al. as reference 24 and level of evidence 3iiA).
Treatment Option Overview
Added Delaney et al. as reference 13.
Added text to state that in the recently closed COG-ARST0332 trial, preoperative radiation therapy was recommended for patients who presented with unresected tumor. The use of postoperative radiation therapy for patients who presented following primary resection was dependent on the tumor size, grade, and margin status.
Revised text to state that radiation doses are typically 45 Gy to 50 Gy preoperatively, with consideration for postoperative boost of 10 Gy to 20 Gy if resection margins are microscopically or grossly positive, or planned brachytherapy if the resection is predicted to be subtotal. Also added text to state that data documenting the efficacy of a postoperative boost are lacking; the postoperative radiation dose is 55 Gy to 60 Gy, or rarely, higher in the situation where unresectable gross residual disease exists (cited Al Yami et al. as reference 27).
Treatment of Newly Diagnosed Childhood Soft Tissue Sarcoma
Added text about the possible association between desmoid tumors and a mutation in the familial adenomatous polyposis (FAP) gene.
Added text to state that radiation therapy has been used in the adjuvant setting after surgery (cited Miller et al. as reference 33).
Added Extrarenal (extracranial) rhabdoid tumor as a new subsection.
Revised text to state that the International Society of Pediatric Oncology-Malignant Mesenchymal Tumors studies showed that select patients (young age, < 5 cm resected tumors) with nonmetastatic synovial sarcoma can have excellent outcome in the absence of radiation, but it is still unclear whether or not that obviates an advantage of radiation for local or regional control.
Added text about the presentation, treatment, and outcome of five children with angiosarcoma (type 2 hemangioendothelioma).
Treatment of Metastatic Childhood Soft Tissue Sarcoma
Revised Table 9 to include imatinib as an agent with selective activity against dermatofibrosarcoma protuberans (cited Rutkowski et al. as reference 17).
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 soft tissue sarcoma. 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 Soft Tissue Sarcoma 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.
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The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Childhood Soft Tissue Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/child-soft-tissue-sarcoma/HealthProfessional. Accessed <MM/DD/YYYY>.
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Busan Neighborhoods • Nampo-dong
Nampo-dong Pictures
The Gwangbok-dong, Nampo-dong, and Jungang-dong areas form the old central business district with many offices, cafes, bars, shops and restaurants. Some of the restaurants in this district are locally famous with family recipes passed down the generations. Jagalchi Market(pics) (near part of the very active port) is an area of narrow street stalls and is well known for its fish market. The Gukje Market(pics) is also located nearby. Jungang-dong is the home of many international law offices, the old Immigation Office, and the international ferry terminal serving Japanese routes. Lotte World II is currently under construction along the water between Jungang-dong 7-Ga and 8-Ga. When completed, Lotte World II will house a hotel, department store, entertainment complex, and a skyscraper that will be one of the tallest buildings in the world.
How to get to Nampo-dong Neighborhood
Nampo-dong subway station.
Last edited by Parent on Sun Aug 10, 2008 9:27 am, edited 5 times in total.
Neighborhoods Nearby Nampo-dong - Pictures by Parent
Busan Tower Neighborhood by Parent. A few pictures of the park nearby Busan.. Distance from Nampo-dong: 0.1km NE, 8 pictures.
Gukje Market Neighborhood by Parent. Some pictures taken within the Gukje market area, a couple of hundred meters west of Nampo-dong. The Gukje market abounds with all sorts of brick-a-brac with lots of russian, japanese, chinese, and south-east asian.. Distance from Nampo-dong: 0.2km NW, 14 pictures.
Jagalchi Market Neighborhood by Parent. The Jagalchi fish market is a small market nearby.. Distance from Nampo-dong: 0.2km S, 5 pictures.
Busan Station Neighborhood by Parent. A few pictures nearby the Busan high-speed train station and the nearby chinese/russian.. Distance from Nampo-dong: 1.9km NNE, 9 pictures.
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subset: commoncrawl


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Cocaine, Amphetamine, Marijuana, Opiate, Methamphetamine, and Benzodiazepine
Built-In Adulteration Strips Test For:pH, Specific Gravity, and Oxidants/Bleach
This FDA Cleared cup is Collector Controlled vs. Donor Controlled, meaning that the collector is the only person who has complete control of the device and can activate the test at their convenience. Afterward, once the test is performed and the results are displayed, the collector can make a photocopy of the result simply by placing the flat front side onto a copy machine or scanner.
If you are looking for a very effective pre-employment screening kit, the split specimen cup can help. Employees who test positive in pre-employment drug tests are 66% more likely to be absent and 77% more likely to be discharged within 3 years than those who tested negative. Employers, the court system, police departments, and schools have used urine drug testing for the drugs of abuse detection.
With this drug test cup kit, you'll receive 27 security seals, 1 package insert, and 2 procedure cards, all included when you place your order. One important feature the split specimen cup 6 panel drug test offers is a temperature strip that is conveniently located on the back of the mechanism to help ensure specimen sample integrity for accuracy and reliable results.
The split specimen cup 6 panel drug test with AD utilizes a patented key operated trigger system that allows the collector to transfer 2ml of the urine specimen into the separate testing chamber. The reason for this is that if the test reports a non-negative result, the cup can then be sent to a laboratory with the remaining untouched specimen for GC/MS confirmation. However, it does include a quality control device built into the drug test cup, and a red line in the control region (C) is considered an internal procedural control. It confirms sufficient specimen volume, adequate membrane wicking, and correct procedural technique.
Does a faint line indicate a negative result?Yes, faint lines DO indicate negative results. The shade of color in the test region (Drug/T) will vary, but it should be considered a negative result whenever there is even a faint colored line. Any indication of a line (even faint) is a negative result.
Is there specific training required to administer these drug tests?Although there is no official training required to administer the tests, procedure cards are provided as well as, instructional videos, and drug test interpretation quizzes free of charge.
Are any of your drug tests FDA Cleared?All of our urine tests have an FDA 510k clearance except for the new K2 Test Kit, which is waiting for FDA 510 (k) clearance.
Are there products that can be used in the tests to give a false negative? What can be done to avoid this?Although there are only a small handful of products that can be used to change the result of an impending test, there are validity screens available which can detect these adulterants. Some are integrated into the tests, which are built-in adulteration, and we also have individual adulteration strips.
Does the product need to be disposed of in any special way, such as a bio hazard bag?Urine and oral drug screens do not pose a bio hazard risk and can be disposed of in regular waste receptacles.
What is the minimum amount of specimen needed for a conclusive test result?It is always important to collect a sufficient amount of specimen in case of a non-negative result. The confirmation laboratory requires a minimum of 15mL of the specimen but prefers 30mL for urine testing.
Is there any specific way these products need to be stored? Do they have to be refrigerated?All drug test devices can be stored at room temperature up to the date of expiration printed on the individual foil pouch. They cannot be stored in extreme heat or cold and must remain sealed in the foil pouch until use.
How accurate are the test results?Laboratory test results for drugs of abuse have indicated a greater than 97% accuracy when used according to the step-by-step instructions that are provided with the test.
Are there any legal medications that can trigger positive results?Yes.
The most common problem is the pseudoephedrine in many over-the-counter sinus and cold medications, which can cause a positive result for methamphetamine. A GC/MS confirmation, as well as an MRO review, is necessary to determine the source of the positive result. Some forms of the drugs we test for may be available legally under prescription as well.
Where is the "key" for my "Split Specimen cup"?The "key" is located in the lid of the cup.


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North Carolina - Morganton Bail Bonds
Switchlanes Bail Bonding & Recovery(704) 915-2173
Jeff Fuller Bail Bonds(828) 452-5452
Jeff Fuller Bail Bonds is available to assist your family and friends with all your bail bonding needs. We frequently bond the following charges: D...
Morganton Bail Bonds
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DuPont has reached a regulatory milestone and the final step of the U.S. regulatory process with confirmation from the USDA that its Plenish high oleic soybean trait has been approved for cultivation in the U.S.
"Obtaining USDA deregulation for Plenish high oleic soybeans is an example of Pioneer's increased focus and capability in moving biotech traits through global regulatory systems and into farmers' fields," says Paul E. Schickler, president – Pioneer Hi-Bred, a DuPont business. "This is a significant milestone as we work to develop biotech traits that provide direct consumer benefits and solid results in the fields."
Plenish high oleic soybeans from Pioneer contain the highest oleic acid content (more than 75 percent) of any soybean product under commercial development. This significantly increases the stability of the oil and provides greater flexibility in food applications, and yields a product with 0g trans fat. Plenish high oleic soybean oil also has 20 percent less saturated fat than commodity soybean oil, making it a more attractive ingredient for consumer food products.
"We continue to see solid results and strong interest from food companies looking for a soybean oil with consumer benefits and functionality," says Craig F. Binetti, president – DuPont Nutrition & Health. "This announcement allows our partners to move to the next phase of product testing and development with Plenish high oleic soybean oil."
High oleic soybean oil also presents opportunities for industrial applications. The high heat stability of this oil in industrial settings allows companies to develop renewable, environmentally enhanced alternatives to petroleum-based products such as lubricants, foams and adhesives.
"Growing Plenish high oleic soybeans adds value to the bottom line of my farming operation with comparable yields and demand for the improved oil produced," said Rob Roettger, a contract Plenish high oleic soybean grower from Dysart, IA.
Pioneer will launch the high oleic soybean trait in its industry-leading lineup of Pioneer brand Y Series soybean varieties, and field testing has confirmed yields on par with elite commercial products. Plenish high oleic soybeans will be grown under contract for ongoing field and oil testing in the U.S. and Canada in 2010 and 2011. Full commercialization of the trait is anticipated in 2012, upon global regulatory approvals and ongoing field testing.
Canada and Mexico were the first countries to complete regulatory reviews of the Plenish high oleic soybean trait. The U.S. Food and Drug Administration (FDA) completed its review of PlenishTM high oleic soybeans in 2009 and this announcement from the USDA allows Plenish high oleic soybeans to be grown under contract for ongoing field testing in the U.S. and additional oil testing by major oil processors and food companies. Regulatory submissions for the trait also have been submitted to key soybean-importing countries around the world.


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Shropshire Dawn 15"x10"
Shropshire Dawn 15"x10"
All prints are archival giclée fine art prints using Canson Baryta Photographique paper. This museum-grade paper perfectly conveys contrast and colour and will last a lifetime. All print sizes are approximate, the exact final size will depend on the aspect ratio of the photograph chosen – please contact me prior to ordering if you would like to know the exact dimensions.
Add To Cart


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Mountain Lions
Mountain Lion Publications
For more info see:
- Mountain Lions of Texas(PDF 294.5 KB)
- Mountain Lions of Texas (Spanish version)(PDF 305.6 KB)
- Field Guide to the Mountain Lions of Texas(PDF 888.6 KB)
Mountain lions are native to Texas and classified as nongame species. They occur in the Trans Pecos in primarily large undeveloped tracts of land. TPWD has records of mountain lions occurring in every county of Texas except for the northernmost counties of the Panhandle.
The average mountain lion home ranges in the Trans Pecos are 50,000 to 80,000 acres. Lions are reclusive by nature. You should consider yourself fortunate if you ever get the opportunity to see one of these big cats.
TPWD has collected mountain lion sighting and mortality data for the past 18 years. If you have a verifiable sighting or kill a mountain lion please contact your local biologist or game warden or call Texas Parks and Wildlife headquarters at 1-800-792-1112.
Because lions are secretive by nature it is rare to see a mountain lion; however, as we encroach upon their habitat conflict is bound to occur. It is wise to know what to do if you ever find yourself confronting a mountain lion.
What To Do If You Encounter A Mountain Lion
- Pick all children up off the ground immediately.
- Do NOT approach the lion
- Stay calm. Talk calmly and move slowly.
- Face the lion and remain in an upright position.
- Do not turn your back on the lion. Back away slowly.
- Do NOT run.
- Do all you can to enlarge your image. Do NOT crouch down or try to hide
- IF the lion is aggressive, throw rocks, sticks, or anything you can get your hands on.
- If the lion attacks, fight back. Fighting back can drive off lions.
Confrontation information and more can be found in TPWD publications: Mountain Lions in Texas and A Field Guide to Texas Mountain Lions.


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Friday, Nov. 30
New Hampshire hostage taker identified
Mending mortgages
Courting black women voters
God has 4,235,843 friends on MySpace
We've got mail
Hope for AIDS orphans
More on the 'Hoops for Hope' program
Hoops of Hope Web site
Hip-hop and black women
An interview with Pastor Tadd Grandstaff
Thursday, Nov. 29
FDA considers salt warning labels
Latest health hardship: The night shift
White House lowers growth projections
Republicans square off on immigration
Giuliani: Stretching the stats?
Hot copper
Hugo Chavez: President for life?
Black women and heart disease
Heart disease more prevalent in African-Americans
Wednesday, Nov. 28
Are we overscanning?
A rebound on Wall Street
Talking peace with Tony Blair
Harsh punishment for British teacher
Redefining black relationships
U.S. aid arrives in Bangladesh
Good Samaritan, but not American
Clinton's revisionist history
Full Tony Blair interview
Table Talk: An extended interview on African American women's series
Escape from Antarctic cruise
Tuesday, Nov. 27
Free ticket to Baghdad
'No more Mr. Nice Guy'
Israelis and Palestinians start talking again
Celebs star in political spotlight
More 'For Sale' signs
The comeback of key deer
Black women and breast cancer
Monday, Nov. 26
E-mapping the human body
Post-thanksgiving market down
Travel wasn't a holiday nightmare
More black women taking care of business
Gloves come off for GOP hopefuls
President prepares for peace summit
Cheney to undergo more tests
Putin plays for keeps
Sunday, Nov. 25
Development threatens Galapagos Islands
Saving the Smithsonian
Exiled Sharif returns to Pakistan
Residents return after Malibu blaze
A big weekend for holiday shoppers
Relief for survivors of nightmare cruise
Time running out for cyclone survivors
Delayed U.S. relief effort begins in Bangladesh
Saturday, Nov. 24
Malibu fire dashes dreams
Retailers cash in on sales
Taliban attacks provoke Pakistan
Saving Kenya one tree at a time
Devastating blaze in Malibu
Bangladesh bridge collapses
New generation of bosses
Candidates looking for momentum
Friday, Nov. 23
Women suffer in Iraq
Abandon ship!
Disaster recovery
Guarding against tainted toys
Shop while the economy drops?
Treating family war wounds
Senate stays in session
Wednesday, Nov. 21
Inside Delta's flight control center
Gov. Huckabee surging in Iowa polls
More Europeans coming to U.S. to shop
Desperate days in Bangladesh
Jehovah's Witnesses' abuse allegations
Eye on Iowa race
Renters feeling mortgage crunch
Tuesday, Nov. 20
Stem cell breakthrough
A young boy's brave decision
McClellan's book raises questions
A shift in Obama's favor?
Reporter on life in Baghdad
Countrywide changes some terms
'Right to bear arms' in spotlight
Monday, Nov. 19
Study: Heart trouble killing more women
Skivvies, the new civic duty
Help for neglected Serbians?
Broadway dark for holiday tourists
45 days to Iowa
Extent of Bangladesh disaster emerges
Celebrating a royal marriage
Ripple effect of housing decline
Sunday, Nov. 18
Goodbye paper route, hello Brangelina!
A crucial week for the economy
Wife's disappearance raises questions
Musharraf weathers storm of criticism
Cyclone death toll rises
Controversy and influence on the campaign
When grownups become cyber bullies
U.S. watching Pakistan carefully
Saturday, Nov. 17
Understanding parents' immunization motives
Volunteer firefighters a smoldering issue
Staggering toll in Bangladesh
U.S. envoy meets with Musharraf
Gridiron glory sparks passion
Bill Clinton on the campaign trail
Strong warming warning
Parents' choice: Immunization or imprisonment
Friday, Nov. 16
Letters, we get letters ...
The struggle against hyperemesis
A Giant headache for baseball
Army desertions skyrocket
Democratic slugfest in Vegas
Bumps and bruises
Economic trouble brewing
Hockey knight in Canada
Homeowners sue mortgage company
Thursday, Nov. 15
Clearing the air
'The Average American'
Direct hit in Bangladesh
Barry Bonds indicted
Deal or no deal?
Special needs cheerleaders
Close call in the Midwest
Wednesday, Nov. 14
Baghdad weddings, other good signs
Development in future of cloning
Emotional homecoming for soldier, sons
Delta and United deny merger reports
Disturbing conditions for Serbia's disabled
More on agent's secret past
$229,000 FEMA trailers
Foreclosure rate jumps
Text Stories
Disgraced CIA officer had key Iraq job
$229,000 FEMA trailers
Disabled kids abused in Serbia
Tuesday, Nov. 13
Detroit's economy struggles to recover
Chrysler turning around
British Airways flying on empty
Power struggle in Pakistan
Ex-FBI agent pleads guilty
New chapter for O'Connor
Vet stays on patrol
Monday, Nov. 12
Clinic's employees get healthy, too
Airlines bracing for travel surge
A hero among us
Bhutto's other side
Clinton and Obama race heats up
Crack cocaine review
Cleveland feels foreclosure crunch
Sunday, Nov. 12
Anxiety over economy
Holiday consumer concerns
Bush courts European allies
Musharraf on the defense
Baghdad grows quieter
Why Iowa matters
Saddam's secrets
A 'veteran' student
Saturday, Nov. 11
LAPD under fire
Lights out on Broadway
Pressure builds in Pakistan
Medal of honor
Eating green
Trouble for Kerik
Friday, Nov. 10
Unrest in Pakistan
Merck pays price for Vioxx
Stocks plunge again
Oil Spill in S.F. bay
Re-thinking nuclear power
Health insurance nightmare
The real Forest Gump
Thursday, Nov. 8
Full Mel Brooks interview
Bernanke: Slower growth ahead
U.S. agency recalls Aqua Dots
Pakistan elections delayed
Giuliani: Look at my record
Reporting from the bottom of the Earth
Medal of Honor: Still seeking peace
Another monster hit for Mel Brooks
Links and Extras
Toys linked to a date-rape drug recalled
--Sign up for the Consumer Product Safety Commission's simple listserv
that sends an email about every recall CPSC orders
Wednesday, Nov. 7
Col. Jacobs' courage and sacrifice
Danger signs in economy
Pakistan nearing meltdown
Giuliani gets endorsement from Pat Robertson
New presidential poll reveals surprises
Is it really OK to carry a few extra pounds?
Seeing an energy solution in empty fields
Medal of Honor: Jack Jacobs profiles Ted Rubin
Links and Extras
Benefits of being a little heavy?
-- Calculate your Body Mass Index
Tuesday, Nov. 6
Oil approaching $100 a barrel
Yahoo execs questioned for role in Chinese dissident's arrest
Rudy Giuliani on Hillary, 9/11 and more
The pill linked to heart disease risk
Riding a wave to energy independence?
Col. Bud Day recalls over five years in North Vietnamese prison
Monday, Nov. 5
Dangerous nation in state of emergency
A lot at stake for U.S. in Pakistan
Strike has Hollywood on hold
Oprah: A 'devastating experience'
Female explorers at the bottom of the world
Kids' lack of sleep can lead to obesity
Learning about wind power from Denmark
First act of bravery in World War II
Sunday, Nov. 4
Pakistani activists arrested amid crisis
Musharraf's crackdown creates crisis for U.S.
Thompson breaks out of character
Writer's strike looms on Hollywood horizon
Global warming threatens polar bears
Ann Curry calls in from Antarctica
Over thirty years later, the search continues
Unveiling the face of ancient Egypt
Links and Extras
Did you watch Brian host SNL? Tell us what you think
Click here to see an excerpt of one of the skits
Click here for Brian's 'new' Nightly News intro
Click here to see someo fhte highlights from the TODAY show
Watch the promotional spot
Brian and the SNL cast preview the show
Brian blogs
Fun on a night off
At rehearsals and behind-the-scenes, on multi-tasking
In whose footsteps?
Behind-the-scenes at rehearsals
Saturday, Nov. 3
State of emergency declared in Pakistan
White House reacts to Pakistan emergency
Pakistan's state of emergency
Hire-wire act fixes space station
Obama under fire for Iran remarks
Farming goes green
NYC Marathon I-ban irks runners
Friday, Nov. 2
Noel strikes out of nowhere
Devastating floods in Mexico
Free trips for safety chiefs under scrutiny
Tracking down the Clinton papers
Tapped out in Tennessee
Making a Difference: Rock star with a heart
Links and extras
Web extra: Watch the complete Bono interview
Bono vlogs
Watch previous reports, travels to Africa with Bono
How you can help: Join Red| Global Fund
Thursday, Nov. 1
Bono thanks you
Grim day for Wall Street
Foreclosures number soar
Attorney general fight reignites torture debate
Chrysler cuts 12,000 jobs
Clinton plays the 'woman' card
Steam pipe explosion victim stays positive
Easy for truckers to cheat drug tests
Dealing with boy who played with fire
Are we too soft on kids?
Links and extras
'Kids Now'
Web-extra: Government taking fun out of playgrounds?
Nov. 1: David Harsanyi, author of "Nanny State," looks at today's playgrounds and says that they aren't as intuitive or fun for kids who are learning about risk.
Video: Cupcakes vs. cantelope
Video: Are we pushing our kids too far?
More on finance, the economy
Latest on stocks
Foreclosures up 30%
Chrylser to cut 12,000 jobs
More on story reported by Lisa Myers
GAO: Easy to cheat on trucker drug tests
Calif. wildfires
Boy admits to starting Calif. blaze, police say
MORE 2007 archives