Association of digital pulse diagnostic indices with survival in patients with advanced non-small cell lung cancer receiving immunotherapy

Non-small cell lung cancer (NSCLC) is associated with poor survival, and evaluating quality of life (QoL) and clinical outcomes has become increasingly important in assessing the treatment efficacy of immune checkpoint inhibitors (ICIs). Given the limited predictive value of existing biomarkers in NSCLC immunotherapy, this study aimed to assess the association between digital pulse diagnostic indices and survival and QoL in patients with advanced NSCLC receiving immunotherapy. This study enrolled patients with stage IIIB–IV NSCLC who had failed first-line platinum chemotherapy and were scheduled to receive ICI monotherapy (pembrolizumab or atezolizumab) across 10 university hospitals in Korea. Pulse diagnostic indices collected every 9 weeks over a 45-week follow-up were analyzed for their association with overall survival (OS), progression-free survival (PFS), treatment response, and QoL using regression analyses with Benjamini–Hochberg false discovery rate adjustment for multiple comparisons. Of the 170 patients enrolled, 91 were included in the analysis. The median PFS and OS periods were 107 and 406 days, respectively. In unadjusted analyses, higher body mass index (BMI) and estimated cardiac output (ECO) and lower heart rate (HR) were nominally associated with longer OS. HR showed the most consistent association with OS; each 10-beat/min increase was associated with higher mortality after clinical adjustment (hazard ratio 1.487; 95% CI 1.192–1.854; p = 0.0004). No robust associations were observed between baseline pulse indices and PFS, durable clinical benefit, or QoL changes after adjustment for multiple comparisons. Among patients with NSCLC receiving ICIs, several pulse indicators showed nominal associations with OS and QoL changes. Notably, baseline HR showed the most consistent association with OS after clinical adjustment and FDR correction. These findings are exploratory and require validation in larger cohorts.