Soft tissue sarcoma in children: prognosis and management.

Soft tissue sarcomas (STS) account for approximately 7% of malignant neoplasms in children. The heterogeneity of STS makes the diagnosis and therapy particularly difficult and should be reserved for specialized centers with expertise in treating cancer in children. Major progress in the accuracy of diagnosis and classification has been made by the identification of specific, recurring genetic alterations t(2;13)(q35;q14) and t(1;13)(p36;q14) in alveolar rhabdomyosarcomas (RMS), t(X;18)(p11;q11) for synovial sarcoma (SS) and t(11;22)(q24;q12) or t(21;22)(q22;q12) for Ewing's tumor family. As a result of large multicenter STS studies, such as the North-American Intergroup Rhabdomyosarcoma Study, the German Pediatric Soft Tissue Sarcoma Study Group (CWS), Italian Gruppo Cooperativo Italiano study and Sociètè Internationale d'Oncologie Pèdiatrique (SIOP) Malignant Mesenchymal Tumors study, the identification of more effective treatment strategies and improvement in prognosis have been made in the last 30 years. Prognostic variables were identified and, by exploring novel therapeutic strategies, criteria were established for the use of preoperative chemotherapy and radiotherapy, and primary and delayed second-look surgery. As a result of evaluation of different drugs active in STS, refinements in the utilization of chemotherapy have been made possible. Clinical trials have also been instrumental in defining the late effects of treatment. In STS the following drugs have proven to be useful: dactinomycin, vincristine, alkylating agents such as cyclophosphamide and ifosfamide, as well as anthracyclines such as doxorubicin (adriamycin) and epi-doxorubicin. Recommendations for radiation are dependent on the primary site and size of the tumour, histology, patient age and the extent of disease before and after surgical resection. In general, with conventional fractionation (1 x 1.8 to 2 Gy/day) radiotherapy doses between 40 and 50 Gy should be administered. The German CWS group explored the effectiveness of 32 Gy when accelerated and hyperfractionated, and given simultaneously to chemotherapy, and found it adequate for local tumor control in patients with selected favorable prognostic factors. When treated with a combination of chemotherapy and local therapy, STS showed an event-free survival between 50 and 80% [RMS 70%, extraskeletal Ewing sarcoma (EES) and peripheral neuroectodermal tumor (PNET) circa 50%, and SS 70 to 80%]. About one-fifth of patients with newly diagnosed RMS-like STS have metastatic disease. The 5-year survival rate among these patients is low (20 to 30%). Age (>10 years), bone, and/or bone marrow metastases are associated with a very poor prognosis (survival rate of about 5%). The value of high dose chemotherapy with hematopoietic stem cell rescue in patients with poor prognostic STS remains unclear and should be performed in controlled studies only.