# Pretreatment emotional distress and peripheral biomarkers predict immune checkpoint inhibitor response in people with advanced inoperable gastroesophageal cancer

## TL;DR

High stress and inflammation before treatment worsen immunotherapy outcomes in advanced stomach/esophageal cancer patients.

## Contribution

This study identifies emotional distress and peripheral inflammatory markers as predictors of immunotherapy response in gastroesophageal cancer.

## Key findings

- Baseline emotional distress is linked to shorter progression-free survival and lower disease control rates.
- Peripheral inflammatory markers synergize with emotional distress to worsen immunotherapy outcomes.
- Psychological and inflammatory factors together suggest psycho-inflammatory mechanisms affecting treatment.

## Abstract

Emotional distress (ED) has been demonstrated to compromise immune responses against tumors; however, few clinical studies have explored its influence on the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients, especially those with gastroesophageal cancer (GEC). Additionally, reliable biomarkers for predicting the response to immunotherapy remain elusive. This study was aimed at investigating whether ED affects the outcomes of immunotherapy in advanced GEC patients and identifying potential biomarkers predictive of immunotherapy efficacy.

This prospective observational cohort study enrolled 84 patients with advanced, treatment-naïve, and inoperable GEC. ED was evaluated at baseline using the Patient Health Questionnaire-9 and the Generalized Anxiety Disorder 7-item Scale. The primary endpoint was Progression-Free Survival (PFS), while the secondary endpoint was Disease Control Rate (DCR).

Patients with baseline ED exhibit significantly shorter median PFS (7.8 months vs. 14.0 months, HR = 2.59, 95% CI: 1.35-4.97, P = 0.004) and a lower DCR (39.5% vs. 68.3%, OR = 3.21, 95% CI: 1.29–7.98, P = 0.012) compared to those without ED. Exploratory analyses further demonstrate that both pre- and post-treatment peripheral inflammatory markers (PIMs) are independently and jointly associated with survival outcomes in combination with ED.

This prospective study demonstrates that ED and elevated PIMs significantly impair ICI efficacy in advanced GEC. The synergistic interaction between ED and PIMs suggests underlying psycho-inflammatory mechanisms affecting treatment outcomes. These findings establish the clinical importance of integrating routine psychological assessment and PIMs monitoring in cancer patients receiving immunotherapy.

This study explored how stress and inflammation affect treatment outcomes in patients with advanced stomach or esophageal cancer receiving a type of treatment called immunotherapy. We aimed to understand why some patients respond better to these drugs and whether emotional health plays a role. We followed 84 patients, using questionnaires and blood tests to measure stress and inflammation before treatment. Patients with high stress before treatment saw faster cancer progression (7.8 vs. 14 months) and poorer responses to immunotherapy. High inflammation levels further worsened outcomes, especially when combined with stress. These results highlight that reducing stress and monitoring inflammation before treatment could help doctors tailor immunotherapy plans, potentially improving survival and quality of life for cancer patients.

Huang et al. examine the impact of emotional distress on immune checkpoint inhibitor efficacy in advanced gastroesophageal cancer patients. Baseline emotional distress and elevated peripheral inflammatory markers significantly impair treatment outcomes through synergistic psycho-inflammatory mechanisms.