10.3389/fpsyg.2012.00132

Vollständiger Abstract

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<h4>Background</h4>Durable benefit from first-line PD-1/PD-L1 inhibitor-based therapy remains heterogeneous in advanced non-small cell lung cancer (NSCLC). Baseline biomarkers, including PD-L1 tumor proportion score, tumor mutational burden, and static inflammatory indices, only partly capture this heterogeneity and may not reflect host response. We evaluated whether a cycle 2 immune-inflammatory and nutritional recovery signature from blood markers was associated with durable clinical benefit (DCB), early progression, and survival.<h4>Methods</h4>This single-center retrospective cohort included 420 patients with advanced NSCLC treated with first-line PD-1/PD-L1 inhibitor-based therapy at Chengdu Third People's Hospital between January 2019 and September 2025, with data cutoff on March 31, 2026. The primary analytic cohort comprised 409 patients with a rule-derived cycle 2 dynamic recovery signature: favorable recovery, intermediate, or persistent failure. DCB at 6 months and early progression within 3 months were the primary endpoints. Associations were estimated using Firth-type penalized logistic regression and Cox models adjusted for clinical covariates and baseline NLR, PNI, and ALI. Model performance was assessed using discrimination, calibration, decision curves, and bootstrap optimism correction.<h4>Results</h4>Among 409 classifiable patients, 141 (34.5%), 115 (28.1%), and 153 (37.4%) had favorable recovery, intermediate, and persistent failure signatures. DCB occurred in 61.7, 43.5, and 33.3%, and early progression occurred in 11.3, 18.3, and 23.5%, respectively. Compared with favorable recovery, persistent failure was associated with lower DCB (adjusted odds ratio [OR], 0.34; 95% CI, 0.21-0.56), higher early progression (adjusted OR, 2.15; 95% CI, 1.13-4.07), and shorter progression-free survival (adjusted hazard ratio [HR], 3.34; 95% CI, 2.40-4.64). Its adjusted association with overall survival was weaker (HR, 1.22; 95% CI, 0.86-1.72). The clinical plus dynamic signature model had optimism-corrected AUCs of 0.619 for DCB and 0.562 for early progression. The composite signature did not outperform individual continuous dynamic biomarkers.<h4>Conclusion</h4>A rule-derived cycle 2 immune-inflammatory and nutritional recovery signature was independently associated with DCB and progression-free survival, but discrimination was modest, early-progression performance was weak, and no robust adjusted overall survival association was observed. It should be interpreted as an exploratory risk-stratification summary, not a clinically ready prediction tool. External validation and prospective evaluation are required before clinical use.

Abstract: PubMed · Datensatz