Laparoscopic Versus Open Lower Mediastinal Lymphadenectomy for Esophagogastric Junction Cancer

Laparoscopic Versus Open Lower Mediastinal Lymphadenectomy for Siewert Type II/III Adenocarcinoma of Esophagogastric Junction: an Exploratory, Prospective, Observational, IDEAL Stage 2, Cohort Study

Mediastinal lymph node dissection has been adopted as standard treatment for adenocarcinoma of esophagogastric junction(AEJ). This multi-center, exploratory, prospective, cohort study aims at provide standard technical details of laparoscopic mediastinal lymph node dissection, and explore the potential clinical effects, gather key information for following study regarding sample size calculation, primary outcome and feasibility.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Procedure: Radical gastrectomy with dissection of lower mediastinal lymph node

Detailed Description

Introduction: Lower mediastinal lymph node dissection has been adopted as standard by treatment guideline for adenocarcinoma of esophagogastric junction(AEJ), but the effect of laparoscopic mediastinal lymph node dissection remains unknown. The aim of this study is to provide standard technical details of laparoscopic mediastinal lymph node dissection, and explore the potential clinical effects, gather key information for following study regarding sample size calculation, primary outcome and feasibility. This study report intervention development, governance procedures and selection and reporting of outcomes to optimize methods for using the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for surgical innovation that informs evidence-based practice.

Methods and analysis: This is an IDEAL stage II, prospective, parallel control, open label, multi-center and exploratory study. The inclusion criteria is Siewert II/ III, AEJ, cT2-4aN0-3M0(AJCC-8th Gastric Cancer TNM stage manual), decide to receive radical gastrectomy, without preoperative anti-neoplastic therapy. The individual included in the study is performed the radical total or proximal gastrectomy plus the lower mediastinal lymphadenectomy via either laparoscopic (trial arm) or open (control arm) TH approach. The surgical approach is determined by the investigator in each center before the operation and recorded in the electronic case report forms (CRF).

The primary outcome is the number of lower mediastinal lymph nodes retrieved. Secondary outcome include complication, surgery length, postoperative death, R0 resection rate, etc. Expected sample size is 518 in each group, thus has 80% power to detect a difference of 0.17 in the average number of lower mediastinal lymph node dissected in between two groups.

• Study Type: Observational
• Enrollment (Anticipated): 1036

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Fei Shan, MD; Phone Number: 010-88196598; Email: shanfei@hsc.pku.edu.cn
      • Contact: Zhemin Li, MD; Phone Number: 010-88196598; Email: tagzhemin@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pathologically Confirmed esophageal gastric adenocarcinoma, clinical stage cT2-4aN3M0(AJCC - 8th gastric cancer tumor TNM staging), Siewert Ⅱ/Ⅲ, receive surgical treatment without preoperative treatment.

Description

Inclusion Criteria:

• 18-80 years old;
• Karnofsky score ≥70%;Or ECOG score ≤2;
• Preoperative pathological biopsy confirmed adenocarcinoma.
• According to gastroscopy, abdominal CT or upper gastrointestinal angiography, the tumor site conforms to the definition of esophageal and gastric junction adenocarcinoma in the "Chinese expert consensus", that is, the tumor center is within 5cm above and below the esophagogastric anatomical junction and crosses or touches the esophagogastric junction;
• Length of esophageal invasion ≤2cm;
• By abdominal contrast-enhanced CT/MRI, the clinical stage was CT2-4aN0-3M0 (according to AJCC-8th TNM tumor stage);
• Subject's blood routine and biochemical indicators meet the following standards: hemoglobin ≥80g/L; Absolute count of neutrophils (ANC) ≥1.5×109/L; Platelet ≥75×109/L;ALT and AST≤2.5 times the normal upper limit; ALP≤2.5 times the normal upper limit; Serum total bilirubin ≤1.5 times the normal upper limit; Serum creatinine ≤ the normal upper limit; Serum albumin ≥30g/L;
• Obtain written informed consent.

Exclusion Criteria:

• Any anti-cancerous treatment received prior to surgery.
• Multiple malignant lesions in the stomach.
• Suspicious lymph node metastasis in the middle and/or upper mediastinum.
• Surgical history in the upper abdomen (laparoscopic cholecystectomy excluded).
• Pregnant or breastfeeding women.
• Uncontrolled epilepsy, central nervous system disease or mental disorder.
• The Bulky N2 status.
• The emergency surgery.
• Severe heart disease.
• History of cerebral infarction or cerebral hemorrhage within 6 months.
• Organ transplant recipients who need immunosuppressive therapies.
• Other malignancy diagnosed within 5 years (cured dermoid caner and cervical cancer excluded).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Laparoscopic Surgery; Lower Mediastinal Lymphadenectomy should be finished via laparoscopic method.	Procedure: Radical gastrectomy with dissection of lower mediastinal lymph node; Radical gastrectomy for gastric cancer should be consistent with Japanese gastric cancer treatment guideline.
Open Surgery; Lower Mediastinal Lymphadenectomy should be finished via open method.	Procedure: Radical gastrectomy with dissection of lower mediastinal lymph node; Radical gastrectomy for gastric cancer should be consistent with Japanese gastric cancer treatment guideline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of lower mediastinal lymph nodes retrieved	The number of lower mediastinal lymph nodes retrieved	immediately after the pathology report issued

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complication during Lower Mediastinal Lymphadenectomy	Complication during Lower Mediastinal Lymphadenectomy & anastomosis, including damage of pericardium, esophagus, etc.	immediately after the surgery
Rate of postoperative complication after Lower Mediastinal Lymphadenectomy	Postoperative complication after Lower Mediastinal Lymphadenectomy, including leakage, bleeding, etc, complication related with Lower Mediastinal Lymphadenectomy	Day 30 after surgery
Time length of Lower Mediastinal Lymphadenectomy	Time length of Lower Mediastinal Lymphadenectomy	immediately after the surgery
Rate of Postoperative complication	Any complication within 30d after surgery	Day 30 after surgery
Rate of postoperative death	death within 30 days after surgery	Day 30 after surgery
Rate of unscheduled reoperation	reoperation within 30 days after surgery	Day 30 after surgery
Rate of unscheduled readmission	unscheduled readmission within 30 days after surgery	Day 30 after surgery
R0 resection rate	R0 resection rate	immediately after the pathology report issued
Proximal margin length	from proximal tumor margin to proximal margin	30minutes after removal of tumor
Local recurrence of lower mediastinal area in 3 years	Local recurrence of lower mediastinal area in 3 years	Year 3 after surgery
Rate of cancer specific death in 3 years	Rate of cancer specific death in 3 years	Year 3 after surgery
Recurrence free survival in 3 years	Recurrence free survival in 3 years	Year 3 after surgery
Overall survival in 3 years	Overall survival in 3 years	Year 3 after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality evaluation index of Lower Mediastinal Lymphadenectomy	surgical characteristics that are directly related to the safety outcome of surgery	through study completion, an average of 3 years
Learning curve of Lower Mediastinal Lymphadenectomy	refers to the number of surgical cases corresponding to the transition point	through study completion, an average of 3 years
Treatment tendency of surgeons and patients	the proportion of persons willing to receive treatment in randomization	through study completion, an average of 3 years
Number of patients that can be screened and successfully recruited	The number of patients that can be screened, excluded, successfully recruited, intervented, and followed up throughout each phase of the study.	through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Zhejiang Cancer Hospital; Shanxi Province Cancer Hospital; Guangdong Provincial Hospital of Traditional Chinese Medicine; Sun Yat-sen University; Fudan University; Beijing Friendship Hospital; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Shanghai Zhongshan Hospital; Chinese PLA General Hospital; RenJi Hospital; West China Hospital; Peking University Cancer Hospital & Institute; First Affiliated Hospital Xi'an Jiaotong University; The Affiliated Hospital of Qingdao University; Nanfang Hospital of Southern Medical University; Ruijin Hospital; Shandong Provincial Hospital; Tianjin Medical University Cancer Institute and Hospital; Guangdong Provincial People's Hospital; The First Hospital of Jilin University; Wuhan Union Hospital, China; Fujian Medical University Union Hospital; Hebei Medical University Fourth Hospital; First Hospital of China Medical University; The First Affiliated Hospital of Dalian Medical University; Affiliated Hospital of Qinghai University; The First Affiliated Hospital of Xiamen University; Changzhi People's Hospital; Xijing hospital of air force Medical University

Publications and helpful links

General Publications

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313.
• Hu Y, Huang C, Sun Y, Su X, Cao H, Hu J, Xue Y, Suo J, Tao K, He X, Wei H, Ying M, Hu W, Du X, Chen P, Liu H, Zheng C, Liu F, Yu J, Li Z, Zhao G, Chen X, Wang K, Li P, Xing J, Li G. Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial. J Clin Oncol. 2016 Apr 20;34(12):1350-7. doi: 10.1200/JCO.2015.63.7215. Epub 2016 Feb 22.
• Kim W, Kim HH, Han SU, Kim MC, Hyung WJ, Ryu SW, Cho GS, Kim CY, Yang HK, Park DJ, Song KY, Lee SI, Ryu SY, Lee JH, Lee HJ; Korean Laparo-endoscopic Gastrointestinal Surgery Study (KLASS) Group. Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01). Ann Surg. 2016 Jan;263(1):28-35. doi: 10.1097/SLA.0000000000001346.
• Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy-assisted Billroth I gastrectomy. Surg Laparosc Endosc. 1994 Apr;4(2):146-8. Erratum In: Surg Laparosc Endosc. 2013 Oct;23(5):480.
• Markar SR, Dabakuyo-Yonli TS, Piessen G. Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer. Reply. N Engl J Med. 2019 Apr 25;380(17):e28. doi: 10.1056/NEJMc1901650. No abstract available.
• Yu J, Huang C, Sun Y, Su X, Cao H, Hu J, Wang K, Suo J, Tao K, He X, Wei H, Ying M, Hu W, Du X, Hu Y, Liu H, Zheng C, Li P, Xie J, Liu F, Li Z, Zhao G, Yang K, Liu C, Li H, Chen P, Ji J, Li G; Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group. Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial. JAMA. 2019 May 28;321(20):1983-1992. doi: 10.1001/jama.2019.5359.
• Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2021 Jan;24(1):1-21. doi: 10.1007/s10120-020-01042-y. Epub 2020 Feb 14. No abstract available.
• Kurokawa Y, Takeuchi H, Doki Y, Mine S, Terashima M, Yasuda T, Yoshida K, Daiko H, Sakuramoto S, Yoshikawa T, Kunisaki C, Seto Y, Tamura S, Shimokawa T, Sano T, Kitagawa Y. Mapping of Lymph Node Metastasis From Esophagogastric Junction Tumors: A Prospective Nationwide Multicenter Study. Ann Surg. 2021 Jul 1;274(1):120-127. doi: 10.1097/SLA.0000000000003499.
• Sugita S, Kinoshita T, Kaito A, Watanabe M, Sunagawa H. Short-term outcomes after laparoscopic versus open transhiatal resection of Siewert type II adenocarcinoma of the esophagogastric junction. Surg Endosc. 2018 Jan;32(1):383-390. doi: 10.1007/s00464-017-5687-6. Epub 2017 Jun 27.
• Sugita S, Kinoshita T, Kuwata T, Tokunaga M, Kaito A, Watanabe M, Tonouchi A, Sato R, Nagino M. Long-term oncological outcomes of laparoscopic versus open transhiatal resection for patients with Siewert type II adenocarcinoma of the esophagogastric junction. Surg Endosc. 2021 Jan;35(1):340-348. doi: 10.1007/s00464-020-07406-w. Epub 2020 Feb 5.
• Huang CM, Lv CB, Lin JX, Chen QY, Zheng CH, Li P, Xie JW, Wang JB, Lu J, Cao LL, Lin M, Tu RH. Laparoscopic-assisted versus open total gastrectomy for Siewert type II and III esophagogastric junction carcinoma: a propensity score-matched case-control study. Surg Endosc. 2017 Sep;31(9):3495-3503. doi: 10.1007/s00464-016-5375-y. Epub 2016 Dec 15.
• Li S, Ying X, Shan F, Jia Y, Li Z, Xue K, Miao R, Wang Y, Bu Z, Su X, Li Z, Ji J. Laparoscopic vs. open lower mediastinal lymphadenectomy for Siewert type II/III adenocarcinoma of esophagogastric junction: An exploratory, observational, prospective, IDEAL stage 2b cohort study (CLASS-10 study). Chin J Cancer Res. 2022 Aug 30;34(4):406-414. doi: 10.21147/j.issn.1000-9604.2022.04.08.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2020
• Primary Completion (ANTICIPATED): July 1, 2023
• Study Completion (ANTICIPATED): July 1, 2026

Study Registration Dates

• First Submitted: June 17, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (ACTUAL): June 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 2, 2021
• Last Update Submitted That Met QC Criteria: November 21, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: esophagogastric junction; laparoscopic gastrectomy; lower mediastinal lymphadenectomy; IDEAL framework
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: CLASS-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared after the publication of the results.
• IPD Sharing Time Frame: After the publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No