Journal Article

Immune checkpoint inhibitor therapy may increase the incidence of treatment-related necrosis after stereotactic radiosurgery for brain metastases: a systematic review and meta-analysis

Aizer, Ayal A., Huang, Raymond Y., Rahman, Rifaquat, Suh, Chong Hyun, Kim, Dong Yeong, Kim, Ho Sung, Guenette, Jeffrey P., Kim, Pyeong Hwa, Kim, Kyung Won

2021

Overview

Objectives To compare the incidence of treatment-related necrosis between combination SRS+ICI therapy and SRS therapy alone in patients with brain metastases from melanoma and non-small cell lung cancer (NSCLC). Methods A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to August 10, 2020. The difference in the pooled incidence of treatment-related necrosis after SRS+ICI or SRS alone was evaluated. The cumulative incidence of treatment-related necrosis at the specific time point after the treatment was calculated and plotted. Subgroup and meta-regression analyses were additionally performed. Results Sixteen studies (14 on melanoma, 2 on NSCLC) were included. In NSCLC brain metastasis, the reported incidences of treatment-related necrosis in SRS+ICI and SRS alone ranged 2.9–3.4% and 0–2.9%, respectively. Meta-analysis was conducted including 14 studies on melanoma brain metastasis. The incidence of treatment-related necrosis was higher in SRS+ICI than SRS alone (16.0% vs. 6.5%; p = 0.065; OR, 2.35). The incidence showed rapid increase until 12 months after the SRS when combined with ICI therapy (14%; 95% CI, 8–22%) and its pace of increase slowed thereafter. Histopathologic diagnosis as the reference standard for treatment-related necrosis and inclusion of only symptomatic cases were the source of heterogeneity in SRS+ICI. Conclusions Treatment-related necrosis tended to occur 2.4 times more frequently in the setting of combination SRS+ICI therapy compared with SRS alone in melanoma brain metastasis showing high cumulative incidence within the first year. Treatment-related necrosis should be considered when SRS+ICI combination therapy is used for melanoma brain metastasis, especially in the first year. Key Points • Treatment-related necrosis occurred 2.4 times more frequently in the setting of combination SRS+ICI therapy compared with SRS alone in melanoma brain metastasis. • Treatment-related necrosis more frequently occurred in brain metastases from melanoma than NSCLC. • Reference standard for treatment-related necrosis and inclusion of only symptomatic treatment-related necrosis were a significant source of heterogeneity, indicating varying definitions of treatment-related necrosis in the literature need to be unified.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Brain / Brain cancer / Diagnostic Radiology / Heterogeneity / Imaging / Immune checkpoint / Immune checkpoint inhibitors / Immunotherapy / Internal Medicine / Interventional Radiology / Lung cancer / Medicine / Medicine & Public Health / Melanoma / Meta-analysis / Metastases / Metastasis / Necrosis / Neuro / Neuroradiology / Non-small cell lung carcinoma / Radiology / Radiosurgery / Small cell lung carcinoma / Subgroups / Therapy / Ultrasound