Background
Phase II trial (RTOG 9904). 49 patients enrolled, 43 assessable, with localized gastric adenocarcinoma at 20 institutions. Required negative diagnostic laparoscopy. Treatment: induction chemotherapy × 2 cycles → concurrent chemoradiotherapy → surgery 5–6 weeks post-CRT. Primary hypothesis: preoperative CRT would achieve ≥20% pathologic complete response (pCR).
Interventions and follow up
Arm A: Induction 5-FU 200 mg/m²/day (continuous) + leucovorin 20 mg/m²/day × 5 days + cisplatin 20 mg/m²/day × 5 days q28d × 2 cycles → RT 45 Gy + infusional 5-FU 300 mg/m²/day + weekly paclitaxel 45 mg/m² → gastrectomy
Primary endpoint: Pathologic complete response rate
mFollow up: Median follow-up not specified; 1-year survival reported
Primary endpoint: Pathologic complete response rate
mFollow up: Median follow-up not specified; 1-year survival reported
Results
pCR: 26% (exceeded 20% hypothesis)
R0 resection: 77%
1-year OS (pCR patients): 82% vs 69% (<pCR)
R0 resection: 77%
1-year OS (pCR patients): 82% vs 69% (<pCR)
Adverse events
Main adverse events: Grade 4 toxicity 21%. Radiotherapy delivered per protocol in only 44% (17 major RT variations, nearly all due to omission of mandated L3-4 interphase coverage). D2 dissection achieved in 50% (improved vs historical rates).
Conclusions
Preoperative chemoradiotherapy with induction FLC followed by concurrent 5-FU/paclitaxel + 45 Gy achieved a 26% pCR rate — exceeding the hypothesized 20% threshold — demonstrating that preoperative CRT is feasible in a cooperative group setting and warrants phase III evaluation.
Key Limitations
Key Limitations: Small phase II study — underpowered for survival endpoints. Poor radiotherapy protocol adherence (only 44% per protocol) due to contouring guideline complexity. Survival comparison between pCR and non-pCR groups is confounded (pCR is a selected favorable biology group). Preoperative chemoradiotherapy for gastric cancer never advanced to positive phase III — perioperative chemotherapy (FLOT) has become the dominant strategy.
Clinical Context
RTOG 9904 established the feasibility benchmark for preoperative CRT in gastric cancer and informed subsequent contouring guidelines and QA requirements. It demonstrated improved D2 dissection rates when surgery was part of a structured trial. Preoperative CRT remains investigational for gastric cancer; perioperative chemotherapy with FLOT is the established standard. Selected patients with proximal gastric/GEJ tumors may still receive preoperative CRT at some centers, particularly in the context of the CROSS regimen.
References
References: Ajani JA et al, J Clin Oncol 2006 (RTOG 9904)