Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: A selective review of Intergroup Rhabdomyosarcoma Study Group experience and rationale for intergroup rhabdomyosarcoma study V

Purpose: To review the importance of prognostic factors in developing new p rotocols for children with rhabdomyosarcoma (RMS). Patients and Methods: Four studies conducted by the Intergroup Rhabdomyosar coma Study (IRS) Group from 1972 through 1991. Results: Favorable prognostic factors are: (1) undetectable distant metasta ses at diagnosis; (2) primary sites in the orbit and nonparameningeal head/ neck and genitourinary nonbladder/prostate regions; (3) grossly complete su rgical removal of localized tumor at the time of diagnosis; (4) embryonal/b otryoid histology; (5) tumor size less than or equal to5 cm; and (6) age yo unger than 10 years at diagnosis. The IRS-V protocols are risk-based and re fine therapy by reducing exposure to cyclophosphamide and radiation therapy (XRT) in patients at low risk while adding new, active agents such as topo tecan or irinotecan to the standard therapy of vincristine, actinomycin D, and cyclophosphamide (VAC) plus XRT for patients with unfavorable histology or advanced disease. Collection of biologic specimens from patients with n ewly diagnosed disease continues to identify other factors that may disting uish patients with favorable features from those who need more intensive th erapy. A new protocol that takes into account their previous treatment is n eeded for patients with recurrent disease. This program (being planned) doe s not include bone marrow/stem cell reconstitution because this strategy ha s thus far failed to improve Survival rates of patients with metastases at diagnosis. Conclusion: Better understanding of biologic differences and new, active ag ents are needed to improve outcome of patients with unfavorable features at presentation.