J Korean Neurosurg Soc.  2021 Mar;64(2):271-281. 10.3340/jkns.2020.0135.

Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer with Brain Metastasis : The Role of Gamma Knife Radiosurgery

• Lee MH
• Cho KR
• Choi JW
• Kong DS
• Seol HJ
• Nam DH
• Jung HA
• Sun JM
• Lee SH
• Ahn JS
• Ahn MJ
• Park K
• Lee JI

• KMID: 2513858
• DOI: http://doi.org/10.3340/jkns.2020.0135

Abstract

Objective
: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1–77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5–27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

Keyword

Programmed cell death 1 receptor; Carcinoma, Non-small-cell lung; Radiosurgery; Neoplasm metastasis

Figure

• 

  Fig. 1. Flow chart of the study. ICI : immune checkpoint inhibitor, GKS : Gamma Knife radiosurgery.

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  Fig. 2. Survival curve according to the treatment group. A : Overall survival. B : Intracranial disease progression-free survival. C : Local progression-free survival according to the treatment group (group A, ICI alone without GKS; group B, ICI with concurrent GKS within 14 days of prescribing ICI; and group C, ICI with non-concurrent GKS after 14 days of prescribing ICI). ICI : immune checkpoint inhibitor, GKS : Gamma Knife radiosurgery.

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  Fig. 3. Leptomeningeal progression-free survival curve according to the treatment group duration from the start of ICI treatment (A) and diagnosis of brain metastasis (B) to the development of leptomeningeal seeding (ICI alone without GKS, treatment with GKS before ICI treatment or within 14). ICI : immune checkpoint inhibitor, GKS : Gamma Knife radiosurgery.

Reference

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