A Multicenter Phase III Randomized Clinical Trial Comparing the Efficacy of an Adjuvant SOX Chemotherapy Regimen with SOX Combined with a Simultaneous Radiotherapy Regimen after D2 Radical Resection for Gastric Cancer

Purpose/Objective(s)

Adjuvant chemotherapy and chemoradiotherapy are both mainstream treatment modalities for gastric cancer, but whether to administer radiotherapy after gastric cancer D2 radical resection has been a focal point of discussion in recent years. This study compared the efficacy of chemotherapy alone and radiochemotherapy for adjuvant treatment in patients with stage T4 or positive lymph nodes after D2 resection.

Materials/Methods

Researchers randomly assigned patients in a 1:1 ratio to either the concurrent chemoradiotherapy arm (SOXRT) or the chemotherapy-alone arm (SOX). In the SOXRT arm, patients received one cycle of induction chemotherapy with the SOX regimen 21 days before starting radiotherapy; the radiotherapy was at a total dose of 50.4Gy in 28 fractions, 1.8Gy per day, 5 fractions per week, simultaneously with concurrent chemotherapy with S-1 at a dose of 50 mg, bid. Three to four weeks after the completion of radiotherapy, three cycles of chemotherapy with the SOX regimen were administered, with the same dosage as the induction chemotherapy. The SOX arm received a total of six cycles of chemotherapy with the SOX regimen. The specific dosages for the SOX regimen were: S-1 30-40mg/m2 bid on days 1-14, and oxaliplatin 130mg/m2 on day 1, every 3 weeks. The primary endpoint of the study was disease-free survival (DFS). The double significance level is 0.05. Assuming that higher DFS can be achieved with simultaneous radiotherapy, the sample size needed for this project is 516 patients. Assuming that 20% of the patients need to be excluded from the statistics, the total number of patients that need to be enrolled in this project is 620.

Results

A total of 620 patients were randomized up to 16 August 2022. Patients had a median age of 54 years, 64% were male, 43% were stage T4 patients, and 72% were stage III (the eighth edition of the Cancer Staging Manual of AJCC). The baseline patient characteristics were balanced across treatment arms. The median DFS follow-up period was 64 months, with 263 DFS events observed. The 3-year DFS rates were 71.7% and 71.4%, and the 5-year DFS was 60.2% and 59.2% in the SOXRT and SOX arms, respectively. The median overall survival (OS) follow-up period was 69 months, with 188 OS events observed. The 3-year OS rates were 81.1% and 79.8%, and 5-year OS survival rates were 74.9% and 73.2% in the SOXRT and SOX arms, respectively. There was no statistically significant difference between the SOX arm and the SOXRT arm in both DFS (HR 0.930; P=0.56) and OS (HR 1.003; P=0.99). The incidence of adverse events in each treatment arm was as expected, and overall it was well tolerated with manageable toxicity.

Conclusion

In T4 or lymph node-positive GC patients with D2 resection, the addition of radiation therapy to the postoperative adjuvant SOX regimen did not significantly improves the DFS or OS after D2 gastrectomy for patients with gastric cancer. This trial was registered at Clinicaltrials.gov (ChiCTR-TRC-12002919).