A phase [formula omitted] study to evaluate the effect of fractionated hemibody irradiation in the treatment of osseous metastases—RTOG 88-22

Abstract

Purpose : The present study was initiated to determine the maximum tolerated total dose that can be delivered by fractionated hemibody irradiation (HBI), as defined by the acute hematological and nonhematological toxicity. Although it was designed as a dose searching trial, the influence of higher doses on occult and overt disease were considered equally important. The study was not designed to evaluate pain relief. The results were compared to Radiation Therapy Oncology Group (RTOG) 82-06, which employed single high-dose HBI, to determine if either single 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 symptomatic bone metastases from either prostate or breast cancer primaries and a KPS ≥ 60 were eligible. All patients initially 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 patients); 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 was defined as an observed toxicity of ≥ Grade 3 lasting more than 30 days postcomplementation 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 ≥ Grade 3 hematological toxicity at some time following HBL The distribution of dose-limiting hematological toxicity in each arm was: I—two patients; II—one patient; III—zero patients; IV—one patient; and V—three patients. The major nonhematological toxicity was gastrointestinal and occurred in 10 patients. None were dose limiting. At 12 months from the initiation of treatment, 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 reduction in the failure rate was 36% after fractionated HBI which potentially represents a modest improvement. Conclusions : The maximum tolerated dose of fractionated (2.50 Gy) HBI was found to be 17.5 Gy. The major dose limiting toxicity was hematological (thromboleukopenia). There was not a significant dose response effect on occult disease (appearance of new disease) or in the requirement for additional treatment, although certain trends were noted for the higher doses. When only patients completing assigned HBI from RTOG 82-06 and 88-22 were compared, there was no difference in the time to new disease or additional treatment 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 alow for the delivery of higher doses of fractionated HBI and sequential HBI as a means of delivering systemic irradiation.