Immunotherapy may promote the occurrence of radiation-induced brain injury in NSCLC patients with brain metastases undergoing radiotherapy: a retrospective propensity score-matching and inverse probability of treatment weighting study.

Purpose: The combination of radiotherapy (RT) and immunotherapy can significantly improve the prognosis of non-small cell lung cancer (NSCLC) patients. However, concerns about whether the synergistic effect may increase the risk of radiation-induced brain injury (RIBI) remain controversial. This study aims to explore the impact of immune checkpoint inhibitors (ICIs) on the occurrence of RIBI in patients with NSCLC brain metastases (BMs).

Methods: This study retrospectively enrolled NSCLC patients with BMs undergoing RT between January 2017 and December 2023. Patients were stratified into groups based on PD-1/PD-L1 checkpoint inhibitors, administration, with confounding factors controlled via propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Final cohorts included an RT-only group (n = 54) and an RT + ICIs group (n = 28). RIBI incidence and progression-free survival (PFS) were compared between groups.

Results: After 1:1 PSM analysis, the incidence of RIBI in the RT + ICIs group was significantly higher than that in the RT-only group (17.9% vs 42.9%, P = 0.042). Further IPTW analysis showed that the incidence of RIBI in the RT + ICIs group was significantly higher than that in the RT-only group (24.8% vs 47.8%, P = 0.033). Regarding the impact on PFS, there was no statistical difference between the two groups in both PSM and IPTW (P > 0.05).

Conclusions: Immunotherapy combined with RT may increase the occurrence of RIBI in patients with NSCLC BMs. The mechanism underlying this phenomenon requires further investigation.