Multidisciplinary management of childhood sarcoma: time to expand

Abstract

"…our knowledge regarding different entities in sarcoma has considerably increased over the last two decades, and this information among others has helped to classify sarcomas more precisely and to identify new subgroups."Sarcomas are a heterogeneous group of tumors. In the last 20 years, the finding of specific acquired chromosomal alterations in sarcomas has helped, in many cases, to understand their underlying genetic basis. Each of the various recurrent chromosomal translocations in sarcomas ultimately results in the creation of a novel chimeric or fusion gene. With the discovery of these new chromosomal alterations in sarcomas, and subsequently of the fusion genes, it was believed that remarkable progress would be possible in the treatment approach for these tumors. Certainly, our knowledge regarding different entities in sarcoma has considerably increased over the last two decades, and this information among others has helped to classify sarcomas more precisely and to identify new subgroups. However, whether this information has also translated into a better treatment approach is questionable. In children, rhabdomyosarcoma (RMS) is the most common malignant soft-tissue tumor. Although combined treatment modalities including surgery, chemotherapy and/or radiotherapy have increased overall survival in many RMSs and other groups of soft-tissue sarcomas, conventional treatment has not yet resolved the problem of metastatic disease and many situations of disease relapse.Furthermore, another important concern is the side effects of conventional chemotherapy and especially radio therapy. Since most current therapies are not specifically targeted to tumor cells, a variety of normal cells in the body may also be affected by these therapeutic modalities, resulting in undesired and long-term side effects in the developing child."Although combined treatment modalities … have increased overall survival in many rhabdomyosarcomas and other groups of soft-tissue sarcomas, conventional treatment has not yet resolved the problem of metastatic disease and many situations of disease relapse."Optimization of chemotherapy has certainly brought some improvement but it is unlikely to deliver a real breakthrough in the therapeutic approach. Combination therapies including vincristine, dactinomycin and cyclophosphamide or ifosfamide can be considered as the backbone of current treatment protocols. Other antineoplastic agents including doxorubicin, cisplatin, carboplatin, etoposide, topotecan, irinotecan, melphalan and methotrexate are active against RMS and have been combined in various combinations with backbone drugs. The overall survival rate in non-metastatic RMS has reached approximately 70%. However, substantial differences can be observed according to tumor site and clinical stage, ranging from approximately 60%, for example, in RMS of the limbs, to 90% or higher in orbital RMS or in genitourinary and nonbladder