A PHASE-II TRIAL EVALUATING SELECTIVE USE OF ALTERED RADIATION-DOSE AND FRACTIONATION IN PATIENTS WITH UNRESECTABLE RHABDOMYOSARCOMA

Purpose: Between 1987 and 1998, 25 children with advanced rhabdomyosar coma (20 with IRS Group 3 disease and 5 with Group 4 disease) were ent ered on a prospective study evaluating selective use of hyperfractiona ted irradiation (HFI) and reduced-dose conventionally fractionated irr adiation (CFI), based on disease status following induction chemothera py (ifosfamide or melphalan, followed by vincristine, adriamycin, and cyclophosphamide combination) with or without delayed surgery. Methods and Materials: Patients with gross disease following induction chemot herapy with or without delayed surgery, and whose primary tumor sites did not involve the central nervous system, received HFI (n = 12) at 1 .1 Gy twice-a-day to 59.4-63.8 Gy total. Patients with parameningeal p rimaries and intracranial disease extension received HFI with initiati on of therapy (n = 2). Those with microscopic disease following induct ion chemotherapy with or without delayed surgery (n = 11) received red uced-dose CFI to 40 Gy. Active follow-up ranges from 28-75 months (med ian = 43 months) with no patient lost to follow-up. Results: Eighteen patients (72%) are alive and without evidence of disease, including 8 of the children with gross residual disease postinduction therapy. The :absolute 2-year continuous local tumor control rate is 86% for all pa tients. Among the 14 who received HFI, the absolute 2-year continuous local tumor control rate is 75% at 33 to 67 months (median = 38 months ) postirradiation. Hyperfractionated irradiation was associated with e xpected enhancement of acute reactions, which all resolved with conser vative medical management. Grade 4 or 5 acute toxicities were not seen . Significant late radiation morbidity has; thus far, been minimal and limited to Grade 1 and 2 events. Among the 11 who received reduced-do se CFI, the absolute 2-year continuous local tumor control rate is 100 % at 25 to 70 months (median = 40 months) postirradiation. Conclusion: This limited experience suggests that HFI to a dose level of 60 Gy ca n be used selectively in children with advanced rhabdomyosarcoma left with gross disease following induction chemotherapy, with or without d elayed surgery, with an apparent improvement in local control, and min imization of potential late radiation toxicity, Concurrently, those le ft with microscopic disease following induction therapy can be selecti vely treated with reduced-dose CFI with excellent local control.