MAGIC trial has shown the benefit of perioperative chemotherapy in the treatment of patients with potentially resectable or unresectable gastric cancer, but whether the addition of neoadjuvant chemoradiotherapy (NACRT) to surgery can improve outcomes better than neoadjuvant chemotherapy (NACT) followed by surgery is not clear.
This phase II study is designed to evaluate whether neoadjuvant chemoradiotherapy (NACRT) is superior to neoadjuvant chemotherapy(NACT) with both followed by surgery and postoperative chemotherapy for locally advanced gastric cancer. Patients with potentially resectable or unresectable gastric cancer(cT3-4NxM0 or cTxN1-3M0) will be randomized to either NACT arm or NACRT arm in a 1:1 ratio with stratiﬁcation by clinical T stage (cT1-3 vs cT4). NACT arm consists of neoadjuvant three cycles of SOX (S-1: 40 ∼ 60mg, orally twice daily on days 1 to 14, oxaliplatin 130mg/m2 intravenously on day 1, 21 days per cycle followed by radical surgery and another postoperative three cycles of SOX. NACRT arm receives intensity-modulated radiotherapy with a simultaneous integrated boost (SIB-IMRT) to primary tumor (45.1Gy and 40.04Gy in 22 fractions) concurrently with oral S-1(40mg/m2 orally twice daily, 5 days/week) followed by surgery and four to six cycles of SOX at the same dosage with NACT arm. Surgery is scheduled to begin within 6-8 weeks of NACRT or NACT. The interval between NACRT or NACT and surgery is 6-8 weeks. The primary endpoint is surgical resection rate, second points are pathological response rate, postoperative complications, 3-year local control rate, disease free survival and overall survival. The sample size for the primary endpoint is based on Simon's two-stage design. Based on NACT arm of the MAGIC trial, we are assuming a 70% of surgical resection rate. The primary hypothesis is that using NACRT will increase this rate by at least 20%. For each arm, with a sample size of 26 patients, type I error amounted to 5%, and the type II error was set to 20%. Taking into account a rate of 15% of ineligible/lost patients, a total of 60 patients have to be enrolled.
Clinical trial identification
All authors have declared no conflicts of interest.