Soft Tissue Sarcoma in Children

Abstract

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.

The serum levels of soluble interleukin-2 receptor α and lactate dehydrogenase but not of B2-microglobulin correlate with selected clinico-pathological prognostic factors and response to therapy in childhood soft tissue sarcomas

“…Soft tissue sarcomas (STS) in children are a group of malignant tumours that originate from primitive mesenchymal tissue and account for approximately 7% of all childhood neoplasms (Koscielniak et al 2002). Rhabdomyosarcomas (RMS) and RMS-like sarcomas constitute more than 55% of all STS; the remaining cases comprise a heterogeneous group of non-rhabdomyosarcoma STS (NRSTS) (Spunt et al 2008).…”

“…Rhabdomyosarcomas (RMS) and RMS-like sarcomas constitute more than 55% of all STS; the remaining cases comprise a heterogeneous group of non-rhabdomyosarcoma STS (NRSTS) (Spunt et al 2008). STS can develop in any part of the body and the prognosis depends on their histological subtype, patient's age, stage of disease, localisation and feasibility of complete resection of the primary tumour, response to chemo-and radiotherapy and others (Koscielniak et al 2002). These clinical variables imply the choice of therapeutic strategy which in Poland is based on the protocols of the German Paediatric STS Study Group (CWS) (Klingebiel et al 2008).…”

Effects of standard chemotherapy on tumor growth and regulation of multidrug resistance genes and proteins in childhood rhabdomyosarcoma

“…Investigations on single cytotoxic agents in animal models have been only described in a few cases [19,20]. Most data exist from multicenter studies such as the German Cooperative Soft Tissue Sarcoma Study (CWS) [21] or from Intergroup Studies on RMS [22]. Treatment with cytotoxic agents is complicated by poor response to chemotherapy and metastatic disease.…”

Rhabdomyosarcoma in Children: A SEER Population Based Study

“…Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal extra-skeletal malignancies that account for 8% of all neoplasms in children and adolescents [1]. Rhabdomyosarcoma (RMS) is the most common STS of childhood, accounting for over 50% of all cases and with the overwhelming majority of patients presenting by 14 y of age [2,3].…”