Impact of stereotactic radiosurgery timing relative to immune checkpoint blockade administration on brain metastasis disease and radionecrosis outcomes

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Abstract
Background: Whether stereotactic radiosurgery (SRS) and immune checkpoint blockade (ICB) for brain metastases (BrM) have a time window for synergistic efficacy and toxicity is unclear. We examined this question in a large, contemporary cohort of patients who received concurrent SRS and ICB. Methods: Patients who received SRS for intact BrM within 1 month before to 6 months after an ICB cycle at a single center from 2018 to 2023 were included if they had no prior whole-brain radiotherapy or SRS to the same BrM. Intracranial progression-free survival (icPFS), local control (LC), distant brain control (DBC), overall survival (OS), and radionecrosis were analyzed by Kaplan–Meier and log-rank methods. Cox regression was used for uni/multivariable analysis (UVA/MVA). Results: A total of 419 BrM, 170 treatment episodes, and 134 patients were analyzed. In total, 43% and 40% of patients had melanoma and non-small cell lung cancer. A shorter SRS-ICB interval significantly correlated with improved icPFS, LC, and OS, but not DBC. This was true when analyzed as either a categorical or continuous factor. On MVA, SRS-ICB interval outperformed all factors including histology, ICB type, and de novo BrM status in predicting icPFS (P = .030), LC (P = .042), and OS (P = .033). In the absence of corticosteroids, pre-SRS lymphocyte counts correlated with improved LC (P = .02). Radionecrosis was not associated with SRS-ICB interval, but with BrM size and number of ICB cycles received prior to SRS. Conclusion: Delivering SRS closer to ICB cycles was associated with improved icPFS, LC, and OS without affecting radionecrosis rates. This may present a therapeutic opportunity to improve BrM outcomes.
Funding Information
  • Peter Mac Foundation Discovery Partner Fellowship

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