Introduction: Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non-small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICI in patients with NSCLC excluded patients with untreated brain metastases (BM). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, we sought to define the safety, radiologic/clinical outcomes for patients with NSCLC-BM treated with concurrent ICI/SRS.

Methods: A retrospective, matched cohort study was performed on patients who underwent SRS to one or more NSCLC-derived BM. Two matched cohorts were identified: one who received ICI within 3-months of SRS (concurrent-ICI) and one who did not (ICI-naive). Locoregional tumor control, peritumoral edema, and central nervous system adverse events were compared.

Results: Seventeen patients (45-BMs) and 34 patients (92-BMs) comprised the concurrent-ICI and ICI-naive cohorts, respectively. Per RANO criteria, there was no difference in overall-survival (HR 0.99, 95%-CI: 0.39-2.52) or CNS progression-free-survival (HR 2.18, 95%-CI 0.72-6.62) between both groups. Similarly, the 12-month local tumor control rate was 84.9% and 76.3% for tumors in the concurrent-ICI and ICI-naive cohorts, respectively (p=0.94). Nevertheless, patients receiving concurrent-ICI had increased rates of complete response for BMs treated with SRS (50% versus 15.6%; p=.012) per RANO criteria. There was a shorter median time to BM regression in the concurrent-ICI cohort (2.5-months versus 3.1-months, p<.001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in patients receiving concurrent-ICI (concurrent-ICI: 5.9%; ICI-naive: 2.9%, p=0.99). There was no difference in the rate of peritumoral edema progression across both groups (concurrent-ICI: 11.1%, ICI-naive: 21.7%; p=0.162).

Conclusions: The use of ICI/SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent-ICI did not increase rates of peritumoral edema, radiation necrosis or intratumoral hemorrhage. Further studies are needed to evaluate whether concurrent ICI/SRS improves PFS/OS for patients with metastatic NSCLC.

Patient Care: The use of checkpoint inhibitors has recently been shown to increase survival for patients with advanced non-small cell lung cancer (NSCLC). Patients with untreated brain metastases, however, were excluded from the initial clinical trials that examined the efficacy of nivolumab, pembrolizumab and atezolizumab. As many patients with NSCLC will develop brain metastases and ultimately undergo stereotactic radiosurgery, understanding the safety and efficacy of concurrent stereotactic radiosurgery and immune checkpoint inhibitors is imperative. In this study, we retrospectively analyzed the clinical and radiographic outcomes of patients with NSCLC with brain metastases who were treated with stereotactic radiosurgery with or without concurrent checkpoint inhibitors. While our results do not show improved OS or PFS when combining ICI/SRS, patients treated with ICI/SRS were more likely to have complete response per RANO criteria. Similarily, more rapid BM regression was noted in the ICI/SRS cohort. Furthermore, the combination of ICI/SRS did not increase rates of radiation necrosis, intratumoral hemorrhage or peritumoral edema. While further prospective studies are needed to verify these results, we feel that this data will be hypothesis generating and aids in the management of patients with NSCLC brain metastases undergoing SRS and concurrent immunotherapy.

Learning Objectives: (1) Describe the role of immune checkpoint inhibitors (ICIs) in the management of non-small cell lung cancer (NSCLC) brain metastases (2) Discuss whether or not combining ICIs and stereotactic radiosurgery improve progression free survival in patients with NSCLC. (3) Explain the abscopal effect and the rational behind combining radiation and immune checkpoint inhibitors

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