Peripheral blood inflammatory markers as predictive and prognostic indicators in neoadjuvant immunotherapy for...

Neoadjuvant immunotherapy has demonstrated favorable efficacy in patients with resectable non-small cell lung cancer (NSCLC). However, its clinical application remains limited by the lack of reliable and non-invasive biomarkers. Although existing histological biomarkers such as programmed death-ligand 1 (PD-L1) and tumor mutation burden (TMB) can be used for reference, they rely on invasive sampling and are susceptible to tumor heterogeneity. This study evaluated a series of peripheral blood inflammation-related indicators, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and interleukin-6 (IL-6), to explore their potential as non-invasive predictive and prognostic biomarkers for NSCLC. Furthermore, a prediction model based on the above indicators was constructed to provide a practical and feasible tool for optimizing individualized clinical management in patients with resectable NSCLC.

A retrospective analysis was conducted on 144 patients with resectable (stage IB-IIIB) NSCLC who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at the Second Xiangya Hospital, Central South University, between 2019 and 2022. Peripheral blood-related indicators at baseline and before surgery were collected. Clinical data that might influence treatment efficacy were also recorded, including age, sex, body mass index, smoking history, pathological type, clinical stage, and use of immune checkpoint inhibitors. The relationships between peripheral blood inflammatory indicators (NLR, LMR, PLR, SII, and IL-6) and objective response rate (ORR), pathological complete response (pCR), major pathological response (MPR), and disease-free survival (DFS) were analyzed. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values for each indicator. A prediction model for the efficacy of neoadjuvant immunotherapy in NSCLC was constructed using least absolute shrinkage and selection operator (LASSO) regression combined with a multivariate Cox proportional hazards model.

The median age of included patients was 58 years, and 91.0% (131/144) were male. Among pathological types, squamous cell carcinoma accounted for 74.3% (107/144), adenocarcinoma for 22.9% (33/144), and other types for 4 cases. The overall ORR, pCR, and MPR rates were 69.2%, 42.4%, and 61.5%, respectively. Univariate analysis showed that patients with squamous cell carcinoma had significantly higher ORR (P=0.007), pCR (P=0.027), and MPR (P=0.019). Lower baseline LMR was associated with a higher ORR. Elevated baseline PLR was significantly associated with pCR (P=0.014) and MPR (P=0.043). Increased baseline SII (P=0.015) and IL-6 (P=0.043) were associated with higher MPR rates. Multivariate analysis showed that squamous cell carcinoma was an independent predictor of MPR (OR=7.34, 95% CI 1.02 to 52.51, P=0.047), and lower baseline LMR was an independent predictor of ORR in NSCLC (OR=0.21, 95% CI 0.05 to 0.92, cutoff value 3.12; P=0.04). Further survival analysis indicated that low baseline NLR (HR=0.363, P=0.014), low preoperative LMR (HR=0.260, P=0.018), and high preoperative SII (HR=0.278, P=0.003) significantly reduced the risk of DFS. A prediction model including 9 factors (age, pathological type, baseline NLR, baseline neutrophils, baseline IL-6, baseline monocytes, preoperative lymphocytes, preoperative SII, and preoperative LMR) was established for predicting the efficacy of neoadjuvant immunotherapy in NSCLC, with an AUC of 0.818.

Neoadjuvant immunotherapy demonstrates favorable clinical efficacy in patients with NSCLC, particularly in those with squamous cell carcinoma. Meanwhile, peripheral blood inflammation-related indicators may serve as important biomarkers for predicting the efficacy and prognosis of neoadjuvant immunotherapy in NSCLC.