Progress in the diagnosis and treatment of rhabdomyosarcoma and related soft tissue sarcomas

Advances in the diagnosis and treatment of rhabdomyosarcoma and related sof t tissue sarcomas continue in the Intergroup Rhabdomyosarcoma Study Group ( IRSG) and European cooperative groups. The use of molecular biology techniq ues in soft tissue! sarcomas are redefining the classic pathology of these small blue cell tumors. Improvements in imaging, radiotherapy, and surgery, in part, deserve credit for the better survival seen in all cooperative tr ials. These advances confound the interpretation of consecutively run chemo therapy trials using historical comparisons. The IRSG has reported improvem ent in the prognosis of both nonmetastatic and metastatic embryonal rhabdom yosarcoma as attributable to three, three-drug regimens that use cyclophosp hamide at 2.2 g/m(2) in either maintenance or induction and maintenance the rapy. Patients of any age with metastatic, nonembryonal, and those over 10 years of age with metastatic embryonal rhabdomyosarcoma continue to have a poor prognosis, which even megatherapy has failed to change. The doublet of ifos-famitie and etoposide in combination with vincristine, actinomycin D, and cyclophosphamide at 2.2 g/m(2) achieved a remarkable 3-year survival o f 58% in patients with metastatic rhabdomyosarcoma and undifferentiated sof t tissue sarcoma. The topoisomerase I inhibitor, topotecan, has recently be en found by the IRSG to have a 57% overall response rate in patients with m etastatic alveolar rhabdomyosarcoma. Topotecan has completed testing with c yclophosphamide in a phase II window study in newly diagnosed patients with metastatic disease and has been incorporated into a randomized trial in in termediate risk patients in IRSG-V. Molecular studies in IRSG-V will be app lied in the detection of occult bone marrow metastases and the evaluation o f resection margins at initial and second-leak surgery. Long-term follow-up will be required in patients with gross residual sarcoma randomized to con ventional and hyperfractionated radiotherapy in IRSG-IV to assess late effe cts. Although older patients with unfavorable histology and metastatic dise ase continue to have a poor prognosis, the overall 5-year survival of child ren and adolescents with nonmetastatic and metastatic rhabdomyosarcama is a pproaching 80%. As molecular discoveries advance the diagnosis and defectio n of rhabdomyosarcoma, it is hoped that the futuristic molecular based trea tment strategies in development and early testing will further improve surv ival in high-risk patients with metastatic soft tissue sarcoma.