Prevalence of neurologic death in NSCLC patients with brain metastases treated with radiosurgery in the modern treatment era.

Abstract

e20698 Background: Immune checkpoint blockade (ICB) and molecularly targeted therapies are increasingly integrated into the management of patients with non-small-cell lung cancer (NSCLC)in parallel with higher utilization of radiosurgery (SRS) for brain metastases. We report our experience with SRS for NSCLC brain metastases, contrasting the rate of post-treatment neurologic death in earlier versus recent years. Methods: We conducted a retrospective cohort study of patients treated with gamma knife (GK) SRS for NSCLC brain metastases at a single institution. Patients were grouped by treatment period: Period 1 (2013-2015), when early use of ICB and blood-brain-barrier (BBB) crossing molecular therapies was minimal, and SRS was more conservative; and Period 2 (2019-2021), when upfront ICB, BBB-crossing agents and SRS were increasingly utilized. The primary outcome was neurologic death, using cumulative incidence technique, treating non-neurologic death as a competing event. Cumulative incidence functions were estimated using the Aalen-Johansen estimator and compared at 6, 12, and 24 months. Absolute risk differences with 95% confidence intervals were estimated using nonparametric bootstrap resampling. A cause-specific Cox proportional hazards model was used as a secondary analysis. Results: A total of 125 patients were included (48 in Period 1; 77 in Period 2). Median follow-up among surviving patients was 51.1 months in Period 1 and 26.8 in Period 2. Neurologic death occurred more frequently in Period 1 than Period 2. At 12 months, the cumulative incidence was 11.7% and 1.5% in Period 1 and Period 2, respectively; at 24 months, the absolute risk difference widened to-−15.6 percentage points: 17.3% versus 1.5% (95% CI, -28.7 to -4.4). In cause-specific Cox analysis, treatment in Period 2 was associated with a significantly lower hazard of neurologic death (HR 0.09, 95% CI 0.01-0.72) p = 0.024. Conclusions: Patients treated with GK SRS during the modern period (2019-2021) of improved systemic therapy and increased SRS utilization experienced a substantially lower cumulative incidence and hazard of neurologic death compared with moderately earlier era (2013-2015). While causality cannot be concluded, these findings are consistent with emerging evidence supporting improved intracranial control with contemporary systemic therapies and SRS. Absolute risk differences in cumulative incidence of neurologic death at 6, 12, and 24 months. Time (months) CIF Period 1 (%) CIF Period 2 (%) ARD (%) 95% CI (%) p-value 6 6.5 0 -6.1 (-13.8, 0) 0.09 12 11.7 1.5 -10 (-20.6, -1.1) 0.023 24 17.3 1.5 -15.6 (-28.7, -4.4) 0.002 CIF: Cumulative Incidence Function. ARD: Absolute Risk Difference. CI: Confidence Interval. Absolute risk differences are reported as percentage-point differences between Period 2 and Period 1. 95% CI and p-values were estimated using nonparametric bootstrap resampling.