The Intergroup INT-0016 trial randomised 566 patients with resected stage IB-IVM0 disease to observation or adjuvant chemoradiation (CRT) consisting of induction fluorouracil and leucovorin followed by CRT (45Gy in 25 fractions plus concurrent fluorouracil and leucovorin) followed by 2 additional cycles of fluorouracil and leucovorin.r With a median follow-up of >10 years a significant benefit was demonstrated for adjuvant CRT over observation alone in terms of overall survival (HR 1.32; 95% CI, 1.10 to 1.60) and relapse free survival (HR 1.51: 95% CI, 1.25 to 1.83) in addition to improved locoregional control. The trial has been criticised for poor surgical quality assurance and suboptimal nodal dissections (only 36% and 10% of patients underwent D1 and D2 dissections respectively) with the hypothesis that radiotherapy may have compensated for inadequate surgery.r
The MAGIC trial randomised potentially resectable gastric or gastro-oesophageal adenocarcinomas to surgery or surgery plus peri-operative chemotherapy (Epirubicin-Cisplatin-5FU). The trial demonstrated survival benefit and the regimen was widely adopted in Australia and New Zealand.r More recently, the German FLOT-4 study which compared taxane-based chemotherapy (5FU-leucovorin-oxaliplatin-docetaxel) to MAGIC regimen reported improved R0 resection and survival benefit and is now the new standard of care.r
The indications for adjuvant CRT and the optimal management of patients with involved surgical margins or nodal disease burden remain controversial. A meta-analysis of postoperative CRT versus chemotherapy in resected gastric cancer analysed six trials comparing the two approaches and reported improved overall and disease-free survival with CRT.r There have been conflicting reports on the impact of D2 lymph node dissection on survival.r
The ARTIST and CRITICS trials have provided further guidance on the indications for CRT and the future direction of clinical research in the modern era. The CRITICS trial has failed to demonstrate a benefit of postoperative CRT over postoperative chemotherapy in patients with resectable gastric cancer treated with adequate preoperative chemotherapy and surgery.r The benefit of integrating neoadjuvant CRT into peri-operative chemotherapy protocols is being examined.
The ARTIST trial, however, reported a disease-free survival benefit in patients with node-positive disease following D2 dissection treated with CRT.r The ARTIST trial randomised 458 patients with completely resected stage IIA-IIIC gastric adenocarcinoma (with D2-dissection) to adjuvant capecitabine and cisplatin (n=228) or CRT (45Gy in 25 fractions with concurrent capecitabine and cisplatin) (n=230). With a median follow up of 7 years, outcomes were similar between the two arms in terms of disease-free survival and overall survival. A subgroup analysis in 396 patients with node-positive disease showed significantly improved 3-year disease free survival with CRT (76%) vs chemotherapy only (72%) (P = 0.04). The ARTIST-II trial (NCT01761461) is recruiting to randomise patients with node-positive disease to adjuvant chemotherapy or CRT.
Figure 2. Disease free survival outcomes from ARTIST trialr
© JCO 2012