Update on the analysis of operability parameter changes in neoadjuvant treatment with chemotherapy and anti-PD-1/PD-L1

BackgroundThe NA landscape for NSCLC has evolved with combined CT and IO, but data on functional effects are limited. This study examines and updates respiratory function impact with neoadjuvant NSCLC therapy.MethodsFrom Jan 2020 to Apr 2024, we studied NSCLC patients receiving CT or CT with IO. We updated comparative analysis of respiratory function tests (DLCO, FEV1, FVC) between CT and CT-IO subgroups pre and post-NA treatment, with a larger case series. Clinical, pathological, surgical data were collected. Univariate regression was updated to identify variables influencing DLCO, FEV1, FVC changes.ResultsStudied 186 patients, median age 68, 66.6% men, 93% smokers/ex-smokers. Squamous and adenocarcinoma common (46% each), balanced PD-L1 expression. Non-G12C KRAS mutation prevalent (15%). Pre-NA stages analyzed: IIIA N2 52.6%, IIIA non-N2 18.8%, IIIB 8.6%. In this update, CT usage increased to 29%, CT-IO higher (70%). Surgery rate 85.7%, mainly lobectomy (83.3%). Downstaging 58.5%, ypTNM: cPR (37%), mPR (27%), ypN1/ypN2 (7% each). 31 pts didn’t undergo surgery: persistent N2 (35.4%), M1 (6%), complications (27%), functional inoperability (32%) Median pre-NA DLCO, FEV1, and FVC similar between CT and CT-IO. However, CT-IO led to greater DLCO decline than CT (12.6% vs. 7.8%, p 0.007). Also, significant increases in FEV1 (3.8% vs. -2.5%, p 0.001) and FVC (3.7% vs. -0.7%, p 0.003) noted. Complications during NA showed no significant differences, except for more immune-mediated adverse events in CT-IO (p 0.28). Ten patients weren’t eligible for surgery, with more functional deterioration in CT-IO (6/10), though not statistically significant (p 0.1). Conversions to thoracotomy more common in CT vs CT-IO (17% vs 10%, p 0.19), but CT-IO had more reinterventions within 90 days (4.2% vs 3.9%, p 1.0). Univariate regression showed significant relationship with DLCO decline, smoking (p 0.037), CT-IO treatment (P=0.03), and trend with COPD (p 0.058).ConclusionsIn this update on the impact of the type of NA on operability parameters, we found a significant difference between patients treated with CT-IO and CT subgroups, including lower DLCO and higher FEV1/FVC in the CT-IO group. Prospective validation is essential to confirm these findings.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.