RADT-06. IMPACT OF STEREOTACTIC RADIOSURGERY TIMING RELATIVE TO IMMUNE CHECKPOINT BLOCKADE ADMINISTRATION ON BRAIN METASTASIS DISEASE AND RADIONECROSIS OUTCOMES

Abstract Stereotactic radiosurgery (SRS) and immune checkpoint blockade (ICB) for brain metastases (BrMs) may have desirable combinatorial effects, but whether a time window exists for synergistic efficacy and toxicity is unclear. We examined this in a large, contemporary cohort of patients who received concurrent SRS+ICB. Patients who received SRS to intact BrMs within 1 month before to 6 months after an ICB cycle between 2018-2023 at a single centre, without prior whole-brain radiotherapy or prior SRS to the same BrMs, were retrospectively analysed. Intracranial progression-free survival (icPFS), local control (LC), distant brain control (DBC), overall survival (OS), extracranial disease control (ECDC), and radionecrosis were analysed by Kaplan-Meier. Cox regression was used for uni/multivariable analysis (UVA/MVA). A frailty model accounted for intra-patient correlation of BrM events. 419 BrMs, 170 treatment episodes, and 134 patients were analysed. 43% and 40% of patients had melanoma and non-small cell lung cancer. A shorter SRS-ICB interval significantly correlated with improved icPFS (1-year rates for 0-7 vs 8-30 vs 30+ days: 36.8% vs 23.8% vs 25.0%, p=0.022), LC (88.7% vs 56.7% vs 67.4%, p<0.0001) and OS (67.5% vs 47.0% vs 33.3%, p=0.041), but not DBC or ECDC. On MVA, SRS-ICB interval as continuous factor (per day) outperformed other factors including histology, ICB type, and de novo BrM status in predicting icPFS (p=0.030), LC (p=0.042) and OS (p=0.033). The LC impact was most prominent for melanoma BrMs with ipilimumab-nivolumab. Dexamethasone use correlated with poorer OS (p=0.039). In its absence, pre-SRS lymphocyte counts correlated with improved LC (p=0.020). Radionecrosis was associated with BrM size but not SRS-ICB interval. This cohort represents the largest-to-date on concurrent SRS+ICB for BrMs. Proximity of SRS to ICB administration was associated with improved intracranial and survival outcomes without affecting radionecrosis. This may present an opportunity to optimise BrM treatment strategies.