Neoadjuvant Immunochemotherapy and Postoperative Acute Hypoxemic Respiratory Failure in Thoracic Surgery: A Multicenter Cohort Study

Objective: While immune checkpoint inhibitors (ICIs) continue to transform the neoadjuvant treatment, its association with postoperative acute hypoxemic respiratory failure (AHRF) remains unexplored. This study aimed to assess the association between neoadjuvant immunochemotherapy (nICT) and postoperative AHRF risk following thoracic tumor surgeries and identify the risk subgroups. Methods: This retrospective two-center cohort study included 327 patients receiving nICT (n=167) or nCT (n=160) before thoracic tumor surgeries from December 2017 to June 2023. Data were analyzed by using the propensity score matching (PSM) and multivariable logistic regressions. Subgroup and sensitivity analyses were performed to test the stability of the conclusions. Results: The nICT group demonstrated significantly higher postoperative AHRF incidence than the nCT group (19.8% vs. 8.1%, p=0.002). The inverse probability-weighting model (IPTW) confirmed elevated AHRF risk associated with nICT compared to nCT (OR=2.41, 95% CI: 1.2-4.82). In patients with non-small cell lung cancer (NSCLC), the binary logistic regression analysis showed that the history of nICT was significantly associated with postoperative AHRF (OR=4.12, 95% CI: 1.15-14.8) in patients with non-small cell lung cancer (NSCLC). Subgroup analyses revealed elevated AHRF risks with nICT versus nCT in patients with time interval between neoadjuvant therapy and surgery within 42 days (OR=6.68, 95% CI: 1.24-35.98), those with squamous cell carcinoma (SCC) (OR=3.64, 95% CI: 1.41-9.44), and those who did not achieve pathologic complete response (non-pCR) (OR=2.82, 95% CI: 1.14-6.98). Conclusions: nICT was associated with increased postoperative AHRF risk in thoracic surgical patients, necessitating rigorous perioperative monitoring.