Symptomatic radiation necrosis after concurrent targeted therapy and stereotactic radiosurgery for brain metastases: a bicentric retrospective analysis.

PURPOSE/OBJECTIVE(S): Data describing the safety/efficacy of targeted therapies in combination with stereotactic radiotherapy (SRS/SRT) for brain metastases are limited. We leverage a bicentric cohort to evaluate rates of intracranial failure and radiation necrosis in patients receiving targeted therapy and SRS. MATERIALS/METHODS: Patients with intact brain metastases at two institutions treated with SRS/SRT and concurrent central nervous system (CNS)-active targeted therapy were identified. Concurrent targeted therapy was defined as receipt of targeted therapy starting before and continuing through receipt of radiation therapy, except for a brief washout interval of 3–7 days. Patients were followed for a minimum of 3 months after SRS/SRT with brain MRI. Kaplan-Meier analysis was performed to evaluate overall survival and cumulative rates of symptomatic radiation necrosis (sRN). Variables associated with radiation necrosis on univariable analysis (p < 0.2) were included in a multivariable logistic regression model for adjusted analysis. RESULTS: The study included 93 patients with 306 metastases, and median follow-up was 17 months. The overall rate of sRN per-metastasis and per-patient was 16/306 (5%) and 13/93 (13%), respectively. Symptomatic RN occurred in 6/28 (21%) of patients exposed to anti-HER2 agents overall and in 3/15 (20%) of those exposed to anti-HER2 antibody-drug conjugate agents (ADCs). Anti-HER2 demonstrated a trend toward significance (p = 0.107) and met the threshold for inclusion in the multivariable analysis. On adjusted analysis, exposure to anti-HER2 therapy was associated with increased odds of sRN, but this was non-significant (odds ratio 2.49, 95% CI[0.66–9.41], p = 0.180). Median overall survival for the cohort was 27.4 months with median intracranial progression-free survival of 12 months. CONCLUSIONS: Patients treated with a combination of SRS/SRT and targeted therapy demonstrated a median of 12 months of intracranial control with limited radiation necrosis.