Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05

Purpose: To determine the maximum tolerated dose of single fraction radiosu rgery in patients with recurrent previously irradiated primary brain tumors and brain metastases. Methods and Materials: Adults with cerebral or cerebellar solitary non-brai nstem tumors less than or equal to 40 mm in maximum diameter were eligible. Initial radiosurgical doses were 18 Gy for tumors less than or equal to 20 mm, 15 Gy for those 2130 mm, and 12 Gy for those 31-40 mm in maximum diame ter. Dose was prescribed to the 50-90% isodose line. Doses were escalated i n 3 Gy increments providing the incidence of irreversible grade 3 (severe) or any grade 4 (life threatening) or grade 5 (fatal) Radiation Therapy Onco logy Group (RTOG) central nervous system (CNS) toxicity (unacceptable CNS t oxicity) was < 20% within 3 months of radiosurgery. Chronic CNS toxicity wa s also assessed. Results: Between 1990-1994, 156 analyzable patients were entered, 36% of wh om had recurrent primary brain tumors (median prior dose 60 Gy) and 64% rec urrent brain metastases (median prior dose 30 Gy). The maximum tolerated do ses were 24 Gy, 18 Gy, and 15 Gy for tumors less than or equal to 20 mm, 21 30 mm, and 31-40 mm in maximum diameter, respectively. However, for tumors < 20 mm, investigators' reluctance to escalate to 27 Gy, rather than excess ive toxicity, determined the maximum tolerated dose. In a multivariate anal ysis, maximum tumor diameter was one variable associated with a significant ly increased risk of grade 3, 4, or 5 neurotoxicity. Tumors 21-40 mm were 7 .3 to 16 times more likely to develop grade 36 neurotoxicity compared to tu mors < 20 mm. Other variables significantly associated with grade 3-5 neuro toxicity were tumor dose and Karnofsky Performance Status. The actuarial in cidence of radionecrosis was 5%, 8%, 9%, and 11% at 6, 12, 18, and 24 month s following radiosurgery, respectively. Forty-eight percent of patients dev eloped tumor progression within the radiosurgical target volume. A multivar iate analysis revealed two variables that were significantly associated wit h an increased risk of local progression, i.e. progression in the radiosurg ical target volume. Patients with primary brain tumors (versus brain metast ases) had a 2.85 greater risk of local progression. Those treated on a line ar accelerator (versus the Gamma Knife) had a 2.84 greater risk of local pr ogression. Of note, 61 % of Gamma Knife treated patients had recurrent prim ary brain tumors compared to 30% of patients treated with a linear accelera tor. Conclusions: The maximum tolerated doses of single fraction radiosurgery we re defined for this population of patients as 24 Gy, 18 Gy, and 15 Gy for t umors less than or equal to 20 mm, 2130 mm, and 31-40 mm in maximum diamete r. Unacceptable CNS toxicity was more likely in patients with larger tumors , whereas local tumor control was most dependent on the type of recurrent t umor and the treatment unit. (C) 2000 Elsevier Science Inc.