A RANDOMIZED PHASE-III STUDY OF ACCELERATED HYPERFRACTIONATION VERSUSSTANDARD IN PATIENTS WITH UNRESECTED BRAIN METASTASES - A REPORT OF THE RADIATION-THERAPY-ONCOLOGY-GROUP (RTOG)9104

Purpose: To compare 1-year survival and acute toxicity rates between a n accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. Me thods and Materials: The Radiation Therapy Oncology Group (RTOG) accru ed 445 patients to a Phase III comparison of accelerated hyperfraction ation vs, standard fractionation from 1991 through 1995, All patients had histologic proof of malignancy at the primary site, Brain metastas is were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function class ification of 1 or 2, For AH, 32 Gy in 20 fractions over 10 treatment d ays (1.6 Gy twice daily) was delivered to the whole brain, A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margi n, Results: The average age in both groups was 60 years; nearly two-th irds of all patients had lung primaries, Of the 429 eligible and analy zable patients, the median survival time was 4.5 months in both arms, The 1-year survival rate was 19% in the AF arm vs, 16% in the AH arm, No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms, Recursive partitioni ng analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 ye ars of age, and brain metastases only (RPA class I), had a 1-year surv ival of 35% in the AF arm vs, 25% in the AH arm (p = 0.95), In a multi variate model, only age, KPS, extent of metastatic disease (intracrani al metastases only vs, intra-and extracranial metastases), and status of primary (controlled vs, uncontrolled) mere statistically significan t (at p < 0.05), Treatment assignment was not statistically significan t, Overall Grade III or TV toxicity was equivalent in both arms, and o ne fatal toxicity at 44 days secondary to cerebral edema was seen in t he AH arm, Conclusion: Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic dise ase, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demon strate any improvement in survival when compared to a conventional reg imen of 30 Gy in 10 fractions, Therefore, this accelerated hyperfracti onated regimen to 54.4 Gy cannot be recommended for patients with intr acranial metastatic disease, (C) 1997 Elsevier Science Inc.