Operability changes in patients with NSCLC after neoadjuvant chemotherapy and anti-PD-1/PD-L1.
Authors: Garitaonaindia Yago , Baena Espinar Javier , Aguado Carlos , Cruz Patricia , López Castro Rafael , Rubio Jaime , Gomez Ana , Lopez Martin ANA , Traseira Cristina , Mielgo Rubio Xabier , Losada Beatriz , Rogado Revuelta Jacobo , Romano Irene , Campo-cañaveral Jose Luis , Gómez de Antonio David , Falagan Sandra , Rubio Gustavo , Montoro Francisco Javier , Sereno Maria 
Published: June 2024

8055 Background: The neoadjuvant (NA) treatment for non-small cell lung cancer (NSCLC) has evolved with the emergence of chemotherapy (CT) and immunotherapy (IO) combinations as the standard of care. However, limited data exist on the impact of these treatments on functional parameters. This is a multicenter retrospective study, focuses on respiratory function in NSCLC patients (pts) undergoing NA therapy. Methods: We conducted a multicenter study of NSCLC pts undergone NA from January 2021 to December 2023 with pre- and post-NA respiratory tests. They were treated with CT or CT-IO. Clinical, pathological and surgical variables were collected. Comparative analysis between DLCO (Diffusing Capacity for Carbon Monoxide), FEV1 (Forced Espiratory Volume in first second) and FVC (Forced Vital Capacity) pre- and post-NA in CT/CT-IO subgroups were studied. We performed a regression univariate analysis with variables influencing DLCO, FEV1 and FVC variations. Results: We included 159 patients from 13 hospitals. Median age was 70, with 67% men, 72% ECOG 0, and 93% smokers or ex-smokers. Squamous histology was present in 50.3%, and PD-L1 expression was balanced. Non-G12C KRAS mutation was the most common molecular finding (15%). Pre-NA treatment stages included IB (0.6%), IIA (0.6%), IIB (1.8%), IIIA (89%), and IIIB (6.9%). NA treatment comprised CT in 25% and CT-IO in 75%. Surgery was performed in 88.5% pts, with lobectomy as the most common procedure (82%). After surgery, ypTNM: cPR (35%); mPR (28.7%); ypN1 (10 %); ypN2 (7.9%). 20 pts did not surgery: persistent N2 (25%), M1 (10%), complications (15%) and functional inoperability (50%). No significant differences were found in median pre-NA DLCO, FEV1, and FVC between CT and CT-IO subgroups. However, post-NA DLCO showed a reduction in CTIO (69.7% vs. CT 77%, p=0.003), while post-NA FEV1 and FVC increased in CT-IO (FEV1: 88% vs. CT 81.8%, p=0.029; FVC: 100.6% vs. CT 91%, p=0.003). Variation rates from pre- to post-NA values indicated a trend towards DLCO reduction in CT-IO (13% vs. CT 8%, p=0.08), and an increase in FEV1 (5% vs. CT 0%, p=0.002) and FVC (4% vs. CT -1.2%, p=0.001). Complications during NA treatment showed no significant differences. 10 patients were ineligible for surgery, with functional deterioration more prominent in the CT-IO subgroup, though without statistical significance (p=0.091). Conversions to thoracotomy were more common in CT-IO (66.6% vs. CT 33.3%, p=0.49). Univariate regression analysis revealed trends towards significance between FVC and liver disease, renal disease, and type of NA, as well as between FEV1 and liver disease, BMI, type of NA, and patient outcomes. Conclusions: Significant differences in post-NA functional variables were observed between 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.