Emotional distress and clinical response to neoadjuvant chemoimmunotherapy in resectable non-small-cell lung cancer: a protocol for the prospective observational NeoFUSE-Lung cohort study

Background: Neoadjuvant chemoimmunotherapy (NACI) has improved pathological and survival outcomes in patients with resectable non-small-cell lung cancer (NSCLC), yet marked heterogeneity in treatment response persists. Emotional distress (ED) may modulate antitumor immunity through neuroendocrine and immune-related mechanisms, but its association with response to NACI in patients with resectable NSCLC remains insufficiently explored. This study aims to prospectively evaluate the relationship between ED and clinical outcomes in patients with resectable NSCLC receiving NACI, with exploratory analyses of stress-related biomarkers and gut microbiome profiles.

Methods: This single-center, prospective observational cohort study will enroll patients with treatment-naïve, resectable stage II–IIIB NSCLC scheduled to receive first-line NACI at Fujian Medical University Union Hospital. All participants will receive NACI as part of routine clinical care, and no experimental intervention will be assigned. ED will be assessed using the Hospital Anxiety and Depression Scale (HADS) at baseline and after two cycles of NACI, and participants will be classified according to baseline ED status and longitudinal ED trajectories. Clinical, psychological, quality-of-life, biochemical, and fecal microbiome data will be collected at prespecified time points. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Secondary outcomes include objective response rate (ORR), pathological complete response (pCR), major pathological response (MPR), and quality of life (QoL). Associations between ED and clinical outcomes will be analyzed using appropriate regression and survival models, with exploratory analyses of stress-related biomarkers and gut microbiome profiles.

Discussion: This trial aims to provide prospective data on the association between ED and response to NACI in patients with resectable NSCLC, while exploring potential neuroimmune-microbiome pathways underlying this association.

Trial Registration: Chinese Clinical Trial Registry (ChiCTR) identifier: ChiCTR2600119872.