Prognostic immune markers for recurrence and survival in locally advanced esophageal adenocarcinoma.

Laila Babar,Nobel Chowdhury,Vida Jahangiri,Juliann E Kosovec,Ashten N Omstead,Blair A Jobe,Ajay Goel,Ali H Zaidi,Madison S Salvitti,Matthew A Smith,Ronan J Kelly,Ping Zheng

doi:10.18632/oncotarget.27052

Laila Babar, Nobel Chowdhury + Show 10 more

Open Access

https://doi.org/10.18632/oncotarget.27052

Copy DOI

Abstract

Treatment options and risk stratification for esophageal adenocarcinomas (EAC) currently rely on pathological criteria such as tumor staging. However, with advancement in immune modulated treatments, there is a need for accurate predictive biomarkers that will help identify high-risk patients and provide novel therapeutic targets. Hence, we analyzed as prognostic classifiers a host of histopathological parameters in conjunction with novel immune biomarkers. Specifically, gene expression levels for CXCL9, IDO1, LAG3, and TIM3 were established in treatment naïve samples. Additionally, PD-L1 and CD8 positivity was determined by immunohistochemical staining. Based on our finding, a Cox model consisting of pathological complete response (CR), LAG3, and CXCL9 provided improved predictability for disease-free survival (DFS) compared to CR alone, and it demonstrated statistical significance for predictability of recurrence (p=0.0001). Likewise, for overall survival (OS), a Cox model constituted of TIM3, CR, and IDO1 performed better than CR alone, and it demonstrated statistical significance for predictability of survival (p = 0.0004). TIM3 was identified as the best predictor for OS (HR=4.43, p=0.0023). In conclusion, given the paucity of treatment options for EAC, evaluation of these biomarkers early in the disease course will lead to better risk stratification of patients and much needed alternatives for improved therapy.

Highlights

Esophageal cancer is the 8th most common cancer worldwide, with esophageal adenocarcinoma (EAC) being the dominant subtype in the western hemisphere. [1] The prognosis of esophageal cancer is dismal, with an overall five-year survival rate of less than 20%. [2, 3] This rate falls even more dramatically for those patients presenting with metastatic disease, with a fiveyear survival less than 5%.[4]
Data for eight potential predictors
The tumor immune microenvironment plays a dynamic role in the development, prognosis, and resistance of esophageal adenocarcinomas (EAC) to standard chemoradiation therapy (CRT) therapeutics

Summary

Introduction

Esophageal cancer is the 8th most common cancer worldwide, with esophageal adenocarcinoma (EAC) being the dominant subtype in the western hemisphere. [1] The prognosis of esophageal cancer is dismal, with an overall five-year survival rate of less than 20%. [2, 3] This rate falls even more dramatically for those patients presenting with metastatic disease, with a fiveyear survival less than 5%.[4]. [2, 3] This rate falls even more dramatically for those patients presenting with metastatic disease, with a fiveyear survival less than 5%.[4]. In the United States, the preferred treatment for patients presenting with locally advanced EAC is neoadjuvant chemoradiation therapy (CRT) followed by surgical resection. 25-30% of these patients demonstrate a pathological complete response (CR) to neoadjuvant therapy, which is a proxy for favorable outcome, as this subset of responders has a five-year survival rate of approximately 60%.[5–7]. The utilization of CR on its own as a prognostic tool is mired in controversy, as there are not any universally agreed upon standards to capture survival benefit afforded to patients with a major but not complete pathological response.[8, 9]

Objectives

Methods

Results

Conclusion