A PHASE I II STUDY TO EVALUATE THE EFFECT OF FRACTIONATED HEMIBODY IRRADIATION IN THE TREATMENT OF OSSEOUS METASTASES - RTOG-88-22/

Purpose: The present study was initiated to determine the maximum tole rated total dose that can be delivered by fractionated hemibody irradi ation (HBI), as defined by the acute hematological and nonhematologica l toxicity. Although it was designed as a dose searching trial, the in fluence of higher doses on occult and overt disease were considered eq ually important. The study was not designed to evaluate pain relief. T he results were compared to Radiation Therapy Oncology Group (RTOG) 82 -06, which employed single high-dose HBI, to determine if either singl e or fractionated HBI is more effective in controlling occult or overt disease. Methods and Materials: A total of 144 patients were entered from September 1989 to April 1993. Only patients with a single symptom atic bone metastases from either prostate or breast cancer primaries a nd a KPS greater than or equal to 60 were eligible. All patients initi ally received 30.0 Gy in 10 fractions to the symptomatic area followed by HBI in 2.50 Gy fractions to one of five arms: I-10.0 Gy (37 patien ts); II-12.5 Gy (23 patients); III-15.0 Gy (18 patients); IV-17.5 Gy ( 40 patients), and V-20.0 Gy (26 patients). A dose limiting toxicity wa s defined as an observed toxicity of greater than or equal to Grade 3 lasting more than 30 days postcompletion of HBI. If three or more dose -limiting toxicities occurred at any dose level, the previous dose was considered as the maximum tolerable dose. Results: Thirty-six of 142 patients experienced greater than or equal to Grade 3 hematological to xicity at some time following HBI. The distribution of dose-limiting h ematological toxicity in each arm was: I-two patients; II-one patient; III-zero patients; IV-one patient; and V-three patients. The major no nhematological toxicity was gastrointestinal and occurred in 10 patien ts, None were dose limiting. At 12 months from the initiation of treat ment, the percent of patients with new disease were: Arms I-19%; II-9% ; III-17%; IV-19%; V-13%; the percent of patients requiring additional treatment in the hemibody field were: Arms I-36%; II-30%; III-33%; IV -32%; and V-19%. When compared to single high dose HBI the estimated r eduction in the failure rate was 36% after fractionated HBI which pote ntially represents a modest improvement. Conclusions: The maximum tole rated dose of fractionated (2.50 Gy) HBI was found to be 17.5 Gy, The major dose limiting toxicity was hematological (thromboleukopenia). Th ere was not a significant dose response effect on occult disease (appe arance of new disease) or in the requirement for additional treatment, although certain trends were noted for the higher doses, When only pa tients completing assigned HBI from RTOG 82-06 and 88-22 were compared , there was no difference in the time to new disease or additional tre atment in the treated field. Based on the investigative parameters of this study, single high-dose HBI was as effective as fractionated HBI. The incorporation of cytokines, to ameliorate hematological toxicity, should allow for the delivery of higher doses of fractionated HBI and sequential HBI as a means of delivering systemic irradiation.