Preliminary report of a phase I study of combined fractionated stereotactic radiosurgery and conventional external beam radiation therapy for unfavorable gliomas.

PURPOSE: To determine the tolerance and toxicities of fractionated stereotactic radiosurgery (FSRS) given in combination with conventional external beam radiation therapy (CEBRT). METHODS AND MATERIALS: From March 1995 to September 1998, 14 patients with previously unirradiated and unfavorable glioma (malignant glioma, n = 8; unfavorable low-grade glioma, n = 5; and recurrent glioma, n = 1) were stratified into 3 groups according to tumor volume (TV) to determine the initial FSRS dose schedule: Group A (n = 3): TV </= 5 cc (7 Gy x 2 pre- and post-CEBRT]; Group B (n = 6): 5 cc < TV </= 15 cc [7 Gy x 2 pre- and 7 Gy x 1 post-CEBRT]; and Group C (n = 5): 15 cc < TV </= 30 cc (7 Gy x 1 pre- and post-CEBRT). All patients received CEBRT to 59.4 Gy at 1.8 Gy/fraction. Dose escalation was planned, if toxicity was acceptable.
RESULTS: All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity has been limited to patients in groups B (grade 4, n = 2/6) and C (grade 4, n = 2/5). Eight patients required reoperation, with 3 (38%) having necrosis without evidence of tumor. Eleven patients (79%) have had objective partial (>/=50% reduction, n = 2) or minor (>20% reduction, n = 9) imaging response. Follow-up ranged from 9 to 51 months (median 15 months), with 7 patients alive at 22-51 months.
CONCLUSIONS: Imaging response and the ability of these patients with unfavorable intracranial gliomas to complete therapy without interruption or experiencing disease progression is very encouraging. Excessive toxicity of combined FSRS and CEBRT as evaluated thus far in this study was seen for patients with group B/C lesions. Evaluation of this novel treatment strategy with dose modification is ongoing.