RADIOSURGERY FOR THE TREATMENT OF PREVIOUSLY IRRADIATED RECURRENT PRIMARY BRAIN-TUMORS AND BRAIN METASTASES - INITIAL REPORT OF RADIATION-THERAPY ONCOLOGY GROUP PROTOCOL-90-05

Purpose: To determine the maximum acutely tolerable dose of single fra ction radiosurgery in patients with recurrent previously irradiated pr imary brain tumors or brain metastases. Methods and Materials: Between August 1990 and September 1993, 102 analyzable patients were entered on Radiation Therapy Oncology Group (RTOG) protocol 90-05, 38 of whom had recurrent primary brain tumors (median prior dose 60 Gy), and 64 o f whom had recurrent brain metastases (median prior dose 30 Gy) less t han or equal to 40 mm in maximum diameter. Unacceptable toxicity was d efined as irreversible Grade 3, any Grade 4, or Grade 5 central nervou s system (CNS) toxicity according to the RTOG CNS criteria, occurring in > 20% of patients per treatment arm within 3 months of radiosurgery . Results: Patients were initially entered onto one of three treatment arms according to the maximum diameter of the recurrent lesion. Twelv e to 22 patients were entered on each arm. The dose levels were: arm 1 , less than or equal to 20 mm, 18 Gy; arm 2, 21-30 mm, 15 Gy; and arm 3, 31-40 mm, 12 Gy. Subsequently, doses were escalated as follows: arm 4, less than or equal to 20 mm, 21 Gy; arm 5, 21-30 mm, 18 Gy; and ar m 6, 31-40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebra l edema occurred in 0, 7, and 5% of patients on Arms 1, 2, and 3, resp ectively, and in no patients on arms 4, 5, or 6. Multivariate analysis revealed that tumor volume greater than or equal to 8200 mm(3) and a ratio of maximum dose to prescription dose (MD/PD) greater than or equ al to 2 were significantly associated unacceptable toxicity. Of 15 pat ients with both tumor volume greater than or equal to 8200 mm(3) and M D/PD greater than or equal to 2, unacceptable toxicity occurred in 2 o f 4 treated with a single isocenter and 1 of 11 treated with multiple isocenters. Subsequently, operation for symptomatic radionecrosis was required in 6% of patients. Conclusion: We found that the incidence of acute toxicity was acceptable at 0-7% in patients with recurrent, pre viously irradiated primary brain tumors or brain metastases less than or equal to 40 mm in maximum diameter treated according to the protoco l described.