Background
Open-label, phase 3 RCT; N=620; 5 tertiary hospitals in China (2012–2022); gastric adenocarcinoma with pathologic T4 or node-positive disease after R0 resection with D2 lymphadenectomy. Tests whether adding postoperative radiotherapy to adjuvant S-1 + oxaliplatin (SOX) chemotherapy improves disease-free survival.
Results
Interventions and follow up: Arm A: SOX + RT — 1 cycle induction SOX, then RT 50.4 Gy/28 fx with concurrent S-1 (50 mg BID), then 3 cycles SOX, n=309
Arm B: SOX — 6 cycles S-1 + oxaliplatin (130 mg/m2 day 1, q3w), n=311
Primary endpoint: 3-year DFS
mFollow up: long-term (5-year outcomes reported)
Results: 3-yr DFS: 70.5% vs 69.3%; HR 0.98 (95% CI 0.73–1.33); P=.93
3-yr OS: 80.8% vs 78.4%; HR 0.86 (95% CI 0.60–1.23)
5-yr DFS: 60.0% vs 57.3%; P=.76
5-yr OS: 73.7% vs 71.4%; P=.55
Arm B: SOX — 6 cycles S-1 + oxaliplatin (130 mg/m2 day 1, q3w), n=311
Primary endpoint: 3-year DFS
mFollow up: long-term (5-year outcomes reported)
Results: 3-yr DFS: 70.5% vs 69.3%; HR 0.98 (95% CI 0.73–1.33); P=.93
3-yr OS: 80.8% vs 78.4%; HR 0.86 (95% CI 0.60–1.23)
5-yr DFS: 60.0% vs 57.3%; P=.76
5-yr OS: 73.7% vs 71.4%; P=.55
Adverse events
Treatment-related AEs: similar between groups
Tolerability: adding concurrent chemoradiotherapy did not meaningfully increase overall toxicity (grouped grade ≥3 rates NR in abstract)
Tolerability: adding concurrent chemoradiotherapy did not meaningfully increase overall toxicity (grouped grade ≥3 rates NR in abstract)
Conclusions
Adding postoperative radiotherapy to adjuvant SOX chemotherapy did not improve DFS or OS in T4/node-positive gastric cancer after D2 gastrectomy. The findings do not support routine adjuvant chemoradiotherapy in adequately D2-resected patients.
Key Limitations
Open-label; few centers in a single country; SOX backbone rather than contemporary perioperative FLOT; no central radiotherapy quality-assurance detail in the report; a negative result may reflect adequate local control from D2 surgery rather than radiotherapy inefficacy per se; no biomarker- or margin-selected subgroup (e.g., R1) in which radiotherapy might still benefit.
Clinical Context
Reinforces ARTIST, ARTIST-2, and CRITICS, which showed no DFS benefit from adding radiotherapy to chemotherapy after D2 dissection. NCCN, ASCO, and ESMO favor perioperative or adjuvant chemotherapy (not routine chemoradiotherapy) after adequate D2 resection, with postoperative chemoradiotherapy generally reserved for D0/D1 or R1 settings. Confirms adjuvant chemotherapy alone as the standard after D2 gastrectomy.