3121 - Pathological Response and Locoregional Control in Gastric Cancer Patients after Preoperative Chemoradiation Versus Preoperative Chemotherapy: Data from the Neo-Crag Clinical Trial

M. Jing¹, Y. J. Zhang¹, H. Shao¹, J. J. Wang¹, Y. Ling², N. Li², Y. Fang¹, and Z. W. Zhou³; ¹Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China, ²Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China, ³Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China

Purpose/Objective(s): The multicentric randomized phase III clinical trial (Neo-CRAG, NCT01815853) comparing preoperative chemoradiation (CRT) with preoperative chemotherapy (ChT) in patients with locally advanced gastric cancer has finished patients recruitment of 620 cases in July,2022,and is in the course of data collection. The clinical stage of enrollment need to be cT3N2-3, cT4aN+, or cT4bNany, and M0. Preoperative treatments included of 1 XELOX cycle followed by 2 dose-reduced XELOX cycles plus concurrent IMRT 45Gy/25f in the CRT arm, or 3 XELOX cycles in the ChT arm. This study is to report the pathological response and locoregional control in patients enrolled in our single institute. Materials/

Methods: 272 patients aged 26-75 years (median 61yrs) were included. there were 197 males and 75 females, from June, 2013 till July, 2022. After randomization,135 patients were assigned to the CRT group and 137 patients to the ChT group, respectively. The radiation target volume delineation chiefly included moderate mucosal CTV expansion (3cm) in a fasting stomach, and elective regional LN stations irradiation (including 16a2 LN as the lower border).
Results: 211 patients fulfilled the assigned preoperative treatment and D2 radical gastrectomy for further analyses, with 105 (77.8%) patients in the CRT group and 106 (77.4%) patients in the ChT group. 27 patients got pathological complete remission (pCR), 22 (21.0%) in the CRT group, and 5 (4.7%) in the ChT group (p<0.001). The rates of ypT0 were 23.8% (25/105) and 4.7% (5/106) in CRT and ChT groups, and the rates of ypN0 were 61.0% (64/105) and 26.4% (28/106) in CRT and ChT groups (both p<0.001), respectively. Primary NCCN-TRG also favored the CRT group significantly, with TRG0-1 in 53 (50.5%) patients in the CRT group, and 21 (19.8%) patients in the ChT group(?²=21.782,p<0.001), respectively. Each of 1st to 12th LN group got obvious reduced positive rates in the CRT group vs. the ChT group. Addition of radiotherapy didn’t increase perioperative complications. Overall incidence of perioperative complications of grade 3 or higher were 5% (5/105) in the CRT group, and 8% (8/106) in the ChT group, respectively. After a median follow-up of 46.7 months, in the 203 patients with data of failure pattern, 82 (40.4%) patients suffered from recurrence, most of which (79.3%) were distant or/and peritoneal metastases. The CRT group had lower rate of locoregional recurrence (LRR) (10.7%) than the ChT group (22.0%, P=0.046). Patients with TRG3 (28.6% vs 12.3%, P=0.003), ypT4(29.4% vs 13.3%, P=0.002), and ypN1-3(22.3% vs 8.0%, P=0.001) had higher risk of LRR than the rest of patients, respectively.
Conclusion: The pathological regression of both primary tumor and regional LN suggested the superiority of preoperative CRT to preoperative ChT. Perioperative complication and locoregional recurrence comparisons further proved the feasibility of the proposal target volume delineating protocol and the entire CRT scheme in this clinical trial.