Prospective Randomized Controlled Trials on Clinical Outcomes of Indocyanine Green Tracer Using in Laparoscopic Gastrectomy with Lymph Node Dissection for Locally Advanced Gastric Cancer (CLASS-11)

1. Research purpose Patients with locally advanced gastric adenocarcinoma (cT2-4a, N0/+, M0) were selected as study subjects to investigate the safety, efficacy, and feasibility of ICG near-infrared imaging tracing in guiding laparoscopic D2 LND for GC by comparing an injection ICG group and a non-injection ICG group.
2. Research design Prospective, multicenter, randomized controlled, open-control, parallel assignment, superiority test. ClinicalTrials.gov: NCT04593615. IRB number: 2020YF028-01 2.1 multicenter This study was conducted in 15 centers, including Fujian Medical University Union Hospital; Peking University Cancer Hospital and Institute; Zhongshan Hospital, Fudan University; Teaching Hospital of Putian First Hospital of Fujian Medical University; Zhangzhou Affiliated Hospital of Fujian Medical University; The First Hospital of Jilin University; Southern Medical University Nanfang Hospital; The First Affiliated Hospital of Nanjing Medical University; Affiliated Hospital of Qinghai University; Qilu Hospital of Shandong University; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Tangdu Hospital, Fourth Military Medical University; Tianjin Medical University Cancer Institute and Hospital; Cancer Hospital, Chinese Academy of Medical Sciences; and Sun Yat-Sen University Cancer Center.

2.2 Case Group Group A (Study Group, 535 cases): Laparoscopic gastrectomy group with the use of near-infrared imaging (ICG group) Group B (Control Group, 535 cases): Laparoscopic gastrectomy group without the use of near-infrared imaging (Non-ICG group) 2.3 Estimate Sample Size The three-year disease-free survival (DFS) was this study's main effectiveness evaluation index. The study implemented a superiority test (unilateral), assuming that the study group's three-year DFS would be better than that of the control group,23, according to previous research results of laparoscopic surgery for locally advanced GC in which the three-year DFS was 65.2%; therefore, the 3-year DFS of the control group would be 65.2%, assuming that the 3-year DFS of the experimental group could be increased by 9% to 74.2%. With an inspection level of 0.025 (unilateral) and an inspection efficiency of 0.9 and using PASS 11 log-rank tests (Lakatos) [Proportion surviving] the calculated sample size was N=428; namely, each group needed 428 people, considering cases of possible exclusion and loss to follow-up (20% drop out rate). The final sample size for each group was 535 cases, for 1070 cases. Approximately 62-63 cases were initially assigned to each center.

2.4 randomization After laparoscopic exploration and confirmation that the cases complied with the standards, they were included in the randomized groups in this study. We adopted the central dynamic layered segment randomization method, with control factors including age, gender, tumor location, clinical staging, research center of the given seed number, and segment length. SAS 9.2 produced a serial number ranging from 0001 - 1070 corresponding to the treatment allocation, which was reserved in the data center and research center. Each center had a specialist who sent the patients' information (age, sex, tumor location, clinical staging, and research center) to the randomization implementation department of the data center via email, telephone call, or text message, and the central randomization department analyzed this information to determine the case enrollment and inform the research center.

2.5 Blinding Method: This research adopts an open design. 2.6 Research cycle: Estimated enrollment cycle: complete enrollment within 2 years. Follow-up period: Enrolling the first case was the starting point for follow-up. and the enrollment of the last case to the postoperative pathology report (generally 2 weeks after surgery) was the endpoint of follow-up for secondary outcomes. The follow-up endpoint for the main outcomes was three years after the last case was enrolled.

Estimated time: 2020.11-2022.10 (complete enrollment) to 2025.10 (complete follow-up) 3. Study Objects All patients who meet the inclusion criteria and do not conform to the exclusion criteria are qualified for this study. 4. Interim analysis: Safety and effectiveness of the interim analyses in the present study will be conducted when all of the patients had been enrolled, but there were no planned interim analyses for 3-year DFS rate.