Concurrent Radiosurgery and Immune Checkpoint Inhibition

Murphy, Blair; Walker, Joshua M.; Bassale, Solange; Monaco, D.; Jaboin, Jerry J.; Ciporen, Jeremy N.; Taylor, Mercedes K.; Kubicky, Charlotte Dai

doi:10.1097/coc.0000000000000509

Cited by 36 publications

(16 citation statements)

References 22 publications

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“…The efficacy of radiosurgery with ICI remains unclear. Several reports have revealed that brain metastasis from melanoma and NSCLC has a favorable survival outcome when treated with ICI and SRS 8,30,31,40,43,[46][47][48] ; however, some studies have https://doi.org/10.3340/jkns.2020.0135…”

Section: Discussionmentioning

confidence: 99%

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

Lee

Cho

Choi

et al. 2021

J Korean Neurosurg Soc

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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.

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Section: Discussionmentioning

confidence: 99%

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

Lee

Cho

Choi

et al. 2021

J Korean Neurosurg Soc

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“…Two studies [32,43] reported no grade 4 or 5 toxicities. Following the encouraging safety outcome from their previous study, Anderson et al [32] conducted a later study involving 21 patients.…”

Section: Resultsmentioning

confidence: 99%

The Combination of Radiotherapy with Pembrolizumab in the Treatment of Metastatic Melanoma Patients: a Systematic Review

Anahid

Afra

2020

SN Compr. Clin. Med.

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Melanoma is a severe form of skin cancer arising from melanocytes. In recent years, immunotherapy in particular, immune checkpoint inhibitor (ICI), has revolutionized the treatment of metastatic melanoma. Recent studies have explored the potential of treatment of metastatic melanoma using the combination of ICI with radiotherapy (RT). In present study, we systematically review available clinical studies involving the combination of RT with pembrolizumab. A systematic search using the electronic databases including PubMed, Scopus, and Embase was conducted to retrieve relevant clinical studies investigating the use of RT+ pembrolizumab on metastatic melanoma patients. Results showed that a total of 16 studies involving 612 metastatic melanoma patients were included. Furthermore, the treatment combination was generally safe with grade 3 or higher toxicities ranging from 1 to 11%. In conclusion, this therapeutic modality is promising. However, gray areas such as limited prospective studies and optimal timing will need to be addressed in future studies.

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“…Therefore, a dose-escalation study is warranted to maximize clinical efficacy with acceptable toxicities for prospective clinical trials. Encouraging results from preclinical and clinical studies support the synergistic effect of SBRT and ICI therapy against brain metastases from melanoma [68, 69]. Marrow-derived suppressor cells (MDSC) and immunosuppressive B cells could impede the antitumor activity induced by SBRT and immune therapy [70, 71].…”

Section: Discussionmentioning

confidence: 99%

Combination with Stereotactic Body Radiotherapy Offers a Promising Strategy to Overcome Resistance to Immunotherapy in Advanced Renal Cell Cancer

Sun

Gan

Aru

et al. 2019

Journal of Oncology

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Immunotherapy for renal cell cancer (RCC) has witnessed several developments for more than two decades. Checkpoint inhibitors, including anti-CTLA-4 and anti-PD-1/PD-L1 blockers, have changed the treatment landscape for patients with advanced RCC in the past 3 years. Despite these advances, more than 55% RCC patients become resistant to different immunotherapies without other treatment combination. Among various attempts at overcoming resistance to immunotherapy, stereotactic body radiotherapy (SBRT) has been found to potentiate the activity of immunotherapy agents through several potential mechanisms, including normalization of microvessels to alleviate tumor hypoxia, improvement in efficient delivery of drugs, abundant neoantigen exposure, and recruitment of antitumor immune cells to alter the immunosuppressive tumor microenvironment. Preclinical studies and clinical case reports have predicted that the combination of SBRT, an immunotherapy, may lead to remarkable results. This review aims to provide the biological basis for the feasibility of combining SBRT to overcome immunotherapy resistance and to review the currently available clinical evidence of this combination therapy in patients with advanced RCC.

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Concurrent Radiosurgery and Immune Checkpoint Inhibition

Cited by 36 publications

References 22 publications

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

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

The Combination of Radiotherapy with Pembrolizumab in the Treatment of Metastatic Melanoma Patients: a Systematic Review

Combination with Stereotactic Body Radiotherapy Offers a Promising Strategy to Overcome Resistance to Immunotherapy in Advanced Renal Cell Cancer

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