Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial

Object. After conventional doses of 55 to 65 Gy of fractionated irradiation , glioblastoma multiforme (GBM) usually recurs at its original location. Th is institutional phase II study was designed to assess whether dose escalat ion to 90 cobalt gray equivalent (CGE) with conformal protons and photons i n accelerated fractionation would improve local tumor control and patient s urvival. Methods. Twenty-three patients were enrolled in this study. Eligibility cri teria included age between 18 and 70 years, Karnofsky Performance Scale sco re of greater than or equal to 70, residual tumor volume of less than 60 mi , and a supratentorial, unilateral tumor. Actuarial survival rates at 2 and 3 years were 34% and 18%, respectively. T he median survival time was 20 months, with four patients alive 22 to 60 mo nths postdiagnosis. Analysis by Radiation Therapy Oncology Group prognostic criteria or Medical Research Council indices showed a 5- to 11-month incre ase in median survival time over those of comparable conventionally treated patients. All patients developed new areas of gadolinium enhancement durin g the follow-up period. Histological examination of tissues obtained at bio psy, resection, or autopsy was conducted in 15 of 23 patients. Radiation ne crosis only was demonstrated in seven patients, and their survival was sign ificantly longer than that of patients with recurrent tumor (p = 0.01). Tum or regrowth occurred most commonly in areas that received doses of 60 to 70 CGE or less; recurrent tumor was found in only one case in the 90-CGE volu me. Conclusions. A dose of 90 CGE in accelerated fractionation prevented centra l recurrence in almost all cases. The median survival time was extended to 20 months, likely as a result of central control. Tumors will usually recur in areas immediately peripheral to this 90-CGE volume, but attempts to ext end local control by enlarging the central volume are likely to be limited by difficulties with radiation necrosis.