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 fraction radiosurgery in patients with recurrent previously irradiated primary 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 of whom had recurrent brain metastases (median prior dose 30 Gy) less than or equal to 40 mm in maximum diameter. Unacceptable toxicity was defined as irreversible Grade 3, any Grade 4, or Grade 5 central nervous 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. Twelve 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 arm 6, 31-40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebral edema occurred in 0, 7, and 5% of patients on Arms 1, 2, and 3, respectively, 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 equal to 2 were significantly associated unacceptable toxicity. Of 15 patients with both tumor volume greater than or equal to 8200 mm(3) and MD/PD greater than or equal to 2, unacceptable toxicity occurred in 2 of 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, previously irradiated primary brain tumors or brain metastases less than or equal to 40 mm in maximum diameter treated according to the protocol described.