Early Immune Checkpoint Inhibitor Administration Increases the Risk of Radiation-Induced Pneumonitis in Patients with Stage III Unresectable NSCLC Undergoing Chemoradiotherapy.

Abstract

<h4>Background/objectives</h4>The PACIFIC trial showed that immune checkpoint inhibitors (ICI) administered after concurrent chemoradiotherapy (cCRT) significantly improve survival in stage III unresectable non-small cell lung cancer (NSCLC). However, the optimal timing of ICI administration with cCRT is still debated, with concerns about increased risks of adverse effects, particularly radiation-induced pneumonitis (RP), from combining radiotherapy and immunotherapy.<h4>Methods</h4>A search of multiple databases identified studies on stage III unresectable NSCLC patients receiving cCRT and ICI. A meta-analysis was performed utilizing the meta package in R software. Furthermore, data from 170 patients treated at Shandong Cancer Hospital and Institute between 2019 and 2023 were analyzed to assess RP following cCRT and ICI treatment.<h4>Results</h4>The meta-analysis revealed that the incidences of ≥grade 2 RP were 25.3%, 24.3%, and 45.3% in the ICI following cCRT group, the ICI concurrent with cCRT group, and the ICI prior to cCRT group, respectively. The ICI prior to cCRT group exhibited significantly elevated rates. In the clinical retrospective study, ≥grade 2 RP was more prevalent in the ICI concurrent with cCRT group (HR: 2.258, 95% CI: 1.135-4.492, <i>p</i> = 0.020) and the ICI prior to cCRT group (HR: 2.843, 95% CI: 1.453-5.561, <i>p</i> = 0.002) compared with the ICI following cCRT group. Furthermore, a shorter interval between treatments correlates with an increased incidence of RP.<h4>Conclusions</h4>Advancing the timing of ICI administration is associated with an increased incidence of ≥grade 2 RP following cCRT in patients with stage III unresectable NSCLC.