Does radiation increase the risk of immunotherapy related pneumonitis in cancer patients with thorax radiotherapy combined immune checkpoint inhibitors: A meta-analysis

Abstract

Background: Thorax radiotherapy (TRT) combined with immunotherapy has shown promising results. However, it remains unclear whether TRT would increases the risk of immunotherapy related pneumonitis (IRP). Here, we performed a meta-analysis to compare the rates of IRP in patients treated with TRT to patients treated without TRT. Methods: A meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Two individual researchers conducted the platform searches on the PubMed upto Nov. 4th, 2019. Quality of studies was assessed independently by two researchers using the Cochrane Collaboration's tool for randomized clinical trials, and the Newcastle-Ottawa Scale for cohort studies. Any disagreements encountered were settled through senior authors. The single rate of pneumonitis along with the corresponding 95% confidence interval (CI) was estimated. The odds ratio (OR) and its 95% CI were computed using random-effects model after checking the heterogeneity across studies using the Cochran Q chi-square test and the I2 statistic. Data analyses were performed using R version 3.6.2, meta and metafor packages. Results: A total of 62 studies including 14648 patients on IRP were first selected. Thirteen studies had two arms data, 501 patients were in TRT arm, 1185 patients were in non-TRT arm. Two studies including 557 patients were treated with immunotherapy and concurrent/sequential TRT. The remaining 47 studies had no TRT patients or TRT data were unavailable. The pooled rate of any grade IRP of all 62 studies (14648 patients) was 6% (95% CI: 5%-8%). All grades IRP was significantly higher among patients treated with immunotherapy and TRT arm when compared to the non-TRT arm (OR = 1.44, 95% CI: 1.04-2.00, P = 0.030). In the subgroup analysis, no significance difference in IRP rate was found between patients with various cancer types or various types of immune checkpoint inhibitors (p = 0.7033, p = 0.7522, respectively). The rate of IRP in all TRT patients was 18% (95% CI: 13%-24%), comparing to 5% (95% CI: 4%-6%) in control group. Conclusions: This meta-analysis demonstrates that TRT combined immunotherapy had an elevated incidence of IRP compared to non-TRT (OR = 1.44, 95% CI: 1.04-2.00, P = 0.030). There remains a lack of data on risk factors of IRP in TRT patients, and future large-scale studies are warranted. To our knowledge, this is the first comprehensive meta-analysis of IRP for TRT patients. © 2020 American Society of Clinical Oncology