Although the incidence of gastric cancer has been substantially declining for several decades, it is still the sixth most common cancer and the fourth most frequent cause of cancer death worldwide. Surgery is still the only curative option for gastric cancer. However, most patients are unable to undergo surgery because of late stage, unresectable disease. The prognosis for these patients is very poor. Although the Magic trial showed that perioperative chemotherapy can increase the rate of curative surgery and significantly improve overall survival in patients with operable gastric or lower esophageal adenocarcinomas, no pCR events were reported in this trial. The intervention arm in PREACT consists of pre-operative chemotherapy, pre-operative radiochemotherapy, surgery and post-operative chemotherapy. The control arm consists of pre-operative chemotherapy, surgery, and post-operative chemotherapy. The primary purpose of PREACT is to investigate whether the addition of radiochemotherapy to chemotherapy is superior to chemotherapy alone in the pre-operative setting in improving disease free survival in patients with locally advanced gastric or esophagogastric junction adenocarcinoma.

Inclusion Criteria:

• Age >=18 years
• Female and male
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Life expectancy >=6 months
• Histologically proven adenocarcinoma of the stomach or gastroesophageal junction (GEJ) (excluding Siewert I) that is: Stage IIB (T3N1 only), IIIA (T2N3 not eligible), IIIB, and IIIC, i.e. T3 - T4a and node positive, or T4b and/ or node positive, according to American Joint Committee on Cancer (AJCC) 7th edition
• Considered operable following initial staging investigations or after pre-operative therapy Disease which can be radically treated with radiotherapy to 45 Gy with standard fractionation
• Adequate organ function defined as follows:
• Bone marrow: Haemoglobin >=90 g/L, Absolute neutrophil count (ANC) >=1.5 x 109 /L, Platelet count >=100 x 109 /L; Hepatic: Serum bilirubin <=1.5 x upper limit of normal, aspartate aminotransferase (AST) and/or alanine transaminase (ALT) <=2.5 x upper limit of normal; Renal: Serum creatinine <=1.0 x upper limit of normal
• Patients are willing to obey the treatment and provide blood and tissue specimens
• Written informed consent obtained before randomization

Exclusion Criteria:

• Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures
• Sexually active males or females refuse to practice contraception during the study until 30 days after end of study
• Evidence of metastatic disease
• Prior chemotherapy or radiotherapy
• Patients with a past history of cancer in the 5 years before randomization except for the squamous or basal cell carcinoma of the skin that has been effectively treated, and carcinoma in situ of the cervix that has been treated by operation
• Patients with other significant underlying medical conditions that may be aggravated by the study treatment or are not controlled
• Patients with central nervous system(CNS) disorder or peripheral nervous system disorder or psychiatric disease
• Known history of uncontrolled or symptomatic angina, uncontrolled arrhythmias and hypertension, or congestive heart failure, or cardiac infarction within 6 months prior to study enrollment, or cardiac insufficiency
• Concurrent severe infection
• Severe gastrointestinal bleeding, gastrointestinal perforation
• Unable to swallow
• Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety
• Known hypersensitivity reaction or metabolic disorder to S-1or oxaliplatin
• Renal impairment (GFR <=50ml/min)
• Linitis plastica