Long-Term Prognostic Analysis of Chemoradiotherapy vs. Chemotherapy after D2 Resection for High-Risk Gastric Cancer: Results from a Prospective Randomized Control Study

Abstract

Purpose/Objective(s)

To explore the prognosis value of postoperative chemoradiotherapy in patients with D2-resected, high-risk, node-positive gastric cancer.

Materials/Methods

This randomized clinical trial enrolled patients between October 1, 2011, and December 31, 2019. Patients with pathologically confirmed gastric cancer (stage any T, N+, M0) who underwent D2 gastrectomy were randomized (1:1) to receive postoperative chemoradiotherapy (CRT) or adjuvant chemotherapy. The interventions of the adjuvant chemotherapy group were 8 cycles of SOX (S-1+Oxaliplatin) chemotherapy. The radiotherapy was given after 4-6 cycles of SOX chemotherapy. Radiotherapy (RT) comprised 45 Gy in 25 fractions of 1.8 Gy over 5 weeks by the intensity modulated radiation therapy (IMRT) technique concurrently with S-1 chemotherapy. The primary endpoint was 3-year disease-free survival (DFS). Acute toxic effects were assessed and graded according to the Common Terminology Criteria for Adverse Events version 4.0.

Results

The trial closed in June 2022 due to slow patient enrollment. A total of 308 patients (median [IQR] age, 58 [23-74] years; 221 [71.8%] men and 87 [28.8%] women) were enrolled, including 157 patients randomized to the adjuvant chemotherapy group and 151 patients to the adjuvant chemoradiotherapy group. One hundred and twenty-one (46.5%) patients had stage III disease. Three-year DFS was 67.2% for the control arm and 67.5% for the experimental arm (hazard ratio [HR] = 1.08; 95% CI = 0.69-1.70; P = 0.74). There was no significant difference between groups in overall survival (HR = 0.81; 95% CI = 0.49-1.33; P = 0.40) or local recurrence (HR = 1.58; 95% CI = 0.66-3.82; P = 0.31). After analyzing the number of positive lymph nodes and the location of lymph node metastasis in the patients, we defined pN staging ≥ N2 patients with extra-perigastric lymph node metastasis as the high-risk group and the remaining patients as the low-risk group. The three-year DFS for the high-risk group and the low-risk group was 59.8% and 76.2%, respectively (HR = 2.05; 95% CI = 1.30-3.25; P < 0.05). For high-risk patients, the three-year DFS in the adjuvant chemotherapy and adjuvant chemoradiotherapy group were 54.0% and 71.2%, respectively (P < 0.05). More grade 3 and 4 acute toxic effects were observed in the adjuvant chemotherapy group than in the chemoradiotherapy group (42 patients [26.8%] vs 18 patients [17.5%]; P = 0.08), but the difference was not significant.

Conclusion

The result of the subgroup analysis from the randomized clinical trial found that high-risk patients could benefit from the adjuvant chemoradiotherapy.