96: Serum IL-6 level predicts survival and treatment response in gastric and gastroesophageal junction cancer

Friday, March 24, 2023

10:01 AM – 10:11 AM

Location: Ballroom A

Abstract Presenter(s)

John D. Karalis, MD

Resident
University of Texas Southwestern Medical Center
Dallas, Texas, United States

Disclosure(s): No financial relationships to disclose

First Author(s)

John D. Karalis, MD

Resident
University of Texas Southwestern Medical Center
Dallas, Texas, United States

Disclosure(s): No financial relationships to disclose

Author(s)

Michelle Ju, MD

General Surgery Resident
UT Southwestern
Dallas, Texas, United States

Disclosure information not submitted.
LY

Lynn Y. Yoon, BS

Medical Student
University of Texas Southwestern Medical Center, United States

Disclosure information not submitted.
EC

Esther C. Castro-Dubon, BS

Research Associate
University of Texas Southwestern Medical Center, United States

Disclosure information not submitted.
SH

Suntrea Hammer, MD

Associate Professor
University of Texas Southwestern Medical Center, United States

Disclosure information not submitted.
Matthew Porembka, MD

Associate Professor
UT Southwestern Medical Center
Dallas, Texas, United States

Disclosure information not submitted.
Sam C. Wang, MD

Associate Professor
UT Southwestern Medical Center
Dallas, Texas, United States

Disclosure information not submitted.

Disclosure(s):

John D. Karalis, MD: No financial relationships to disclose

Introduction: There are few biomarkers to guide treatment for gastric and gastroesophageal junction adenocarcinoma (G+GEJ). The systemic inflammatory response, which is reflected by circulating serum cytokine levels, of G+GEJ patients is associated with survival. In this study, we evaluated the relationship of circulating serum cytokine levels with overall survival (OS) and pathologic tumor regression grade (TRG) in G+GEJ patients.

Methods: A retrospective review of a prospectively maintained biobank was performed to identify patients diagnosed with G+GEJ from 2016-2022. Pre-treatment serum was collected at the time of diagnosis. For patients who received neoadjuvant therapy, an additional serum sample was collected immediately prior to surgical resection. A multivariable Cox proportional hazards model was used to assess the association of cytokine concentration with OS. In patients who received neoadjuvant therapy, we assessed whether the change in IL-6 (ΔIL-6) after therapy was associated with TRG.

Results: We first measured the pre-treatment levels of 17 different cytokines in a 67-patient cohort to determine if certain circulating cytokines were prognostic for OS. In a multivariable analysis adjusted for clinical stage and the expression level of the other cytokines, the only circulating cytokine level that was independently associated with OS was IL-6 (HR: 1.06 per 1 pg/ml increase, 95% CI: 1.04-1.08). We then analyzed the serum IL-6 level in an additional 134 patients, resulting in a final cohort of 201 patients. Serum IL-6 level ranged from 0.3-196.7 pg/ml. In a multivariable analysis adjusted for age, sex, clinical stage, pathologic differentiation, Lauren classification, H. pylori status and neutrophil-to-lymphocyte ratio, IL-6 level was independently associated with OS (HR: 1.012 per 1 pg/ml increase, 95% CI: 1.006-1.019). Patients in the top tercile of pre-treatment IL-6 level had worse median OS (10.6 months) compared to patients in the intermediate (17.4 months) and bottom tercile (35.8 months, p < 0.0001). Among patients who received neoadjuvant therapy (n = 50), ΔIL-6 ≤ 0 had a sensitivity of 80% and specificity of 80% for predicting complete or near-complete pathologic tumor regression (TRG 1).

Conclusions: Pre-treatment serum level of IL-6 is a promising prognostic biomarker for patients with G+GEJ. ΔIL-6 may predict response to neoadjuvant therapy.

Learning Objectives:

Upon completion, participants will be able to describe the potential use of serum IL-6 as a prognostic biomarker for gastric and gastroesophageal cancer.
Upon completion, participants will be able to describe the potential use of the change of serum IL-6 as a biomarker to predict response to neoadjuvant therapy in gastric cancer.
Upon completion, participants will be able to describe the sensitivity and specificity of ΔIL-6 ≤ 0 for predicting a complete or near-complete pathologic tumor response in gastric and gastroesophageal cancer.