# Impact of Neoadjuvant Induction Chemotherapy Prior to Chemoradiation on Survival and Surgical Outcomes in Real-World Esophageal Adenocarcinoma Cohort

## TL;DR

This study examines whether giving chemotherapy before radiation therapy improves survival and surgery outcomes in esophageal cancer patients who may not have surgery.

## Contribution

The study provides real-world data on the impact of induction chemotherapy before chemoradiation in esophageal adenocarcinoma patients.

## Key findings

- Patients who received induction chemotherapy had a median survival of 3.5 years versus 2.2 years without it, though not statistically significant.
- There was no difference in surgical outcomes, pathologic complete response, or downstaging between the groups.
- Many patients in the study did not undergo esophagectomy, suggesting non-operative approaches are common.

## Abstract

The current standard of care for esophageal cancer is typically peri-operative chemotherapy and surgery. However, there are patients who prefer not to receive surgery or are not candidates for surgery or certain chemotherapies. Thus, non-operative approaches to esophageal cancer should continue to be studied. Chemoradiation can be part of non-operative approaches, and the role for chemotherapy before chemoradiation is not well-defined. The purpose of this study is to report outcomes of those who received induction chemotherapy (as compared to those who did not) prior to chemoradiation with or without surgery in a real-world population.

Background/objectives: Improvements in esophageal adenocarcinoma (EAC) treatment have reduced mortality. While chemoradiation before surgery was previously a standard of care, updated guidelines recommend peri-operative chemotherapy without chemoradiation. Continued investigation into optimal non-operative treatment paradigms for patients who defer surgery or are not candidates for surgery and certain chemotherapy regimens is needed. The impact of induction chemotherapy prior to chemoradiation on survival and surgical outcomes remains unclear. This study assessed survival and surgical outcomes in a real-world cohort of EAC patients receiving induction chemotherapy before chemoradiation. Methods: This single-institution, IRB-approved, retrospective cohort study included patients with newly diagnosed stage II-IVb (oligometastatic for IVb) EAC who received definitive chemoradiation (radiation ≥ 40 Gy and two cycles of chemotherapy) +/− esophagectomy from 2007 to 2022. Patients receiving induction chemotherapy were compared to those who did not. Endpoints included survival and surgical outcomes. Results: A total of 141 EAC patients received definitive chemoradiation; 83 received induction chemotherapy before chemoradiation. Patients receiving induction chemotherapy were younger (p < 0.01) with slightly lower performance status (p = 0.27) and presented at a more advanced stage (p < 0.001). Median OS was 3.5 years in the induction chemotherapy group compared to 2.2 years (p = 0.10). There was no difference in pathologic complete response (p = 0.81), esophagectomy frequency (p = 0.87), or surgical downstaging between treatment groups (p = 0.84). Conclusions: In this real-world, single-institutional patient cohort investigating induction chemotherapy prior to chemoradiation in EAC, patients receiving induction chemotherapy did well but did not have a statistically significant improvement in survival outcomes or surgical outcomes. This study showed that significant numbers of real-world patients may not receive esophagectomy. Thus, prospective, randomized clinical trials are warranted to better delineate the efficacy and selection of patients for induction chemotherapy when non-operative approaches are favored.