Respiratory adverse effects in patients treated with immune checkpoint inhibitors in combination with radiotherapy: a systematic review and meta-analysis

We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy.

We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials (https://clinicaltrials.gov/). The data was analyzed by using Rstudio.

Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1–5 cough, 0.176 (95%CI: 0.113–0.274, I2 = 92.36%); grades 1–5 pneumonitis, 0.118 (95%CI: 0.067–0.198, I2 = 88.64%); grades 1–5 upper respiratory tract infection, 0.064 (95%CI: 0.049–0.080, I2 = 0.98%); grades 3–5 cough, 0.050 (95%CI: 0.012–0.204, I2 = 8.90%); grades 3–5 pneumonitis, 0.052 (95%CI: 0.031–0.078, I2 = 83.86%); grades 3–5 upper respiratory tract infection, 0.040 (95%CI: 0.007–0.249, I2 = 45.31%).

Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients.