Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

Object. This investigation was performed to determine the tolerance and tox icities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated be tween March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, an d one with a recurrent glioma. They were stratified into three groups accor ding to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm(3) or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm(3) but less than or equal to 15 cm(3) (7 G y twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV gre ater than 15 cm(3) but less than or equal to 30 cm(3) (7 Gy oncepre- and on ce post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable . All patients were able to complete CEBRT without interruption or experien cing disease progression. Unacceptable toxicity was observed in two Grade 4 /Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (greater than or equal to 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9-60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with i ntracranial gliomas to complete therapy without interruption or experiencin g disease progression is encouraging. Excessive toxicity derived from combi ned FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.