Correlation of Psychological Distress With Efficacy of Immune Checkpoint Inhibitors in Patients With Advanced Gastric Cancer
Objective: Evaluate the association between chronic stress and tumor response (via Tumor Regression Grade, TRG) in advanced gastric cancer patients undergoing neoadjuvant immunotherapy. Secondary
Objectives: Assess the effect of chronic stress on post-gastrectomy quality of life (QoL). Analyze correlations between chronic stress biomarkers and survival outcomes (PFS, OS). 3. Study Endpoints Primary Endpoint: Pathological response assessed by TRG (Mandard criteria). Secondary Endpoints: QoL (EORTC QLQ-C30/STO22 questionnaires). PFS and OS. Exploratory Endpoints: Dynamic changes in chronic stress biomarkers (serum cortisol, ACTH, epinephrine, norepinephrine, serotonin). Correlation of biomarker levels with TRG and survival. 4. Study Design Type: Single-center, prospective observational study. Duration: 36 months. Sample Size: 268 patients (134 high chronic stress, 134 low chronic stress). Inclusion Criteria: Age 18-75 years. Histologically confirmed gastric adenocarcinoma (per Japanese Gastric Cancer Guidelines, 2017). Scheduled for neoadjuvant immunotherapy + radical gastrectomy. Informed consent. Exclusion Criteria: Pregnancy/breastfeeding. Prior upper abdominal surgery (excluding cholecystectomy). Active infection, autoimmune disease, or corticosteroid use within 1 month. Psychiatric disorders or investigator-deemed unsuitability. Withdrawal Criteria: Patient request, loss to follow-up, or safety concerns. 5. Methods Chronic Stress Assessment: Validated psychological questionnaires (e.g., Hospital Anxiety and Depression Scale) at baseline and treatment milestones. Biomarker analysis: Serum cortisol, ACTH, epinephrine, norepinephrine, serotonin at key timepoints (pre-treatment, post-neoadjuvant therapy, post-surgery). Clinical Data Collection: TRG evaluation post-surgery. QoL assessments at 1, 3, 6, 12, 18, 24, and 36 months post-surgery. Survival tracking via hospital records and follow-up visits. Statistical Analysis: Stratification by baseline stress scores (high/low). Cox regression for survival outcomes; logistic regression for TRG-QoL correlations. Significance threshold: \*p\* \< 0.05. 6. Significance This study addresses a critical gap in understanding how psychological factors modulate ICI efficacy. By identifying chronic stress as a predictor of treatment response, results may guide personalized interventions (e.g., beta-blockers, behavioral therapy) to improve outcomes in advanced gastric cancer.
• Voluntary signing of informed consent;
• 18≦ age ≦75 years;
• Sex: no limitation;
• Patients with gastric adenocarcinoma diagnosed according to the 15th edition of the Japanese gastric cancer statute, 2017, after endoscopic biopsy of the primary lesion;
• Patients requiring preoperative immune checkpoint inhibitor therapy at the discretion of the treating physician, followed by radical gastrectomy.