Adjuvant SOX chemotherapy versus concurrent chemoradiotherapy after D2 radical resection of locally advanced esophagogastric junction (EGJ) adenocarcinoma: study protocol for a randomized phase III trial (ARTEG)

Jinwen Shen,Xiangdong Cheng,Yian Du,Zhiyuan Xu,Litao Yang,Luying Liu,Yunli Zhang,Xiu Zhu,Yanqiang Zhang,Yuan Zhu,Ling Huang,Pengfei Yu

doi:10.1186/s13063-021-05617-7

Abstract

BackgroundSurvival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. Esophagogastric junction (EGJ) adenocarcinoma, which is usually classified as gastric cancer in East Asia, often has a higher locoregional recurrence rate after operation because of its special anatomical characteristics. The aim of this study is to determine whether adjuvant radiotherapy can improve survival of locally advanced EGJ adenocarcinoma after D2 radical resection.MethodsIn this phase III, randomized, open label, controlled trial, we plan to recruit 378 patients with Siewert type II and III adenocarcinoma of EGJ, who had undergone transabdominal radical surgery and D2 lymphadenectomy, and were divided into pathological stage IIB to IIIC. All patients will be randomized 1:1 to receive either adjuvant chemotherapy alone (control group) or adjuvant chemotherapy plus chemoradiotherapy (experimental group). Patients allocated to control group will receive eight cycles of S-1 plus oxaliplatin (SOX), while the experimental group will receive two cycles of SOX followed by 45-Gy RT combined with S-1 and four additional cycles of SOX. The primary endpoint is 3-year disease-free survival rate (DFS). The secondary endpoints are 3-year overall survival rate (OS), 3-year locoregional recurrence-free survival rate (LRFS), 3-year distant metastasis-free survival rate (DMFS), and quality of life (QoL).DiscussionIn the past, the adjuvant treatment of EGJ adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma. In this study, EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection.Trial registrationClinicalTrials.govNCT03973008. Registered on 1 June 2019 (retrospectively registered), URL: https://clinicaltrials.gov/ct2/show/NCT03973008?term=NCT03973008&draw=2&rank=1

Highlights

Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial
In the past, the adjuvant treatment of Esophagogastric junction (EGJ) adenocarcinoma needs to draw on the experience of esophageal adenocarcinoma or gastric adenocarcinoma
EGJ adenocarcinoma is considered as an independent disease, and the conclusion will provide evidence for optimal adjuvant therapy of locally advanced EGJ adenocarcinoma after D2 radical resection

Summary

Introduction

Survival benefit of adjuvant radiotherapy for locally advanced gastric cancer following gastrectomy plus D2 lymphadenectomy has always been controversial. For locally advanced gastric cancer, the locoregional recurrence rate and distant metastasis rate are still high after D2 radical resection [3, 4], leading to poor prognosis of these patients. Adjuvant chemotherapy after radical surgery is currently recommended for all locally advanced gastric cancer. Pivotal CLASSIC trial, which was conducted in the East Asia, has demonstrated the superiority of adjuvant CAPOX chemotherapy in improving OS for postoperative patients with stage II/III gastric cancer [5]. ARTIST 2 trial has confirmed that adjuvant SOX can prolong DFS than S-1 monotherapy in D2-resected, node-positive gastric cancer patients [6]

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