Immune checkpoint inhibition in patients treated with stereotactic radiation for brain metastases

Emily S Kowalski, Jill S Remick, Kai Sun, Gregory S Alexander, Rahul Khairnar, Emily Morse, Hua-Ren Cherng, Lars J Berg, Yannick Poirier, Narottam Lamichhane, Stewart Becker, Shifeng Chen, Jason K Molitoris, Young Kwok, William F Regine, Mark V Mishra, Emily S Kowalski, Jill S Remick, Kai Sun, Gregory S Alexander, Rahul Khairnar, Emily Morse, Hua-Ren Cherng, Lars J Berg, Yannick Poirier, Narottam Lamichhane, Stewart Becker, Shifeng Chen, Jason K Molitoris, Young Kwok, William F Regine, Mark V Mishra

Abstract

Purpose: Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI.

Methods and materials: Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed.

Results: One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC.

Conclusion: These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.

Conflict of interest statement

MVM reports receiving an honorarium from Varian, outside of the scope of the present work.

Figures

Fig. 1
Fig. 1
Kaplan Meier comparison between SRS or SRT alone (blue) and SRS/SRT-ICI (red) in terms of a Local control, b Radiation necrosis-free survival
Fig. 2
Fig. 2
Subset analysis of NSCLC patients. Kaplan Meier comparison between SRS or SRT alone (blue) and SRS/SRT-ICI (red) in terms of a Local control, b Radiation necrosis-free survival
Fig. 3
Fig. 3
Subset analysis of timing of administration of ICI. Kaplan Meier comparison between administration of ICI within 3 months after SRS/SRT (blue) or administration of ICI within 3 months before SRS/SRT (red) in terms of a Local control, b Radiation necrosis-free survival

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