PREACT Study: Locally Advanced Gastric Cancer, Chemoradiotherapy vs. Chemotherapy Followed by D2 Surgery and Adjuvant Chemotherapy

• Tegafur-Gimeracil-Oteracil Potassium (Drug), also known as S-1: The dose of S-1 is according to body-surface area (BSA): patients with a BSA of less than 1.25 m2 received 80 mg daily; those with a BSA of 1.25 m2 or more but less than 1.5 m2 received 100 mg daily; and those with a BSA of 1.5 m2 or more received 120 mg daily. oxaliplatin 130mg/m2, intravenously, on day 1.
• Chemoradiotherapy (Radiation), also known as radiochemotherapy: Chemotherapy: S-1 40-60mg/m2 orally, oral tablet twice daily, days 1-5 of each week of radiotherapy. Radiotherapy: 45 Gy of radiation in 25 fractions, five days per week for five weeks.
• Gastric resection (Procedure), also known as Gastrectomy: A standard D2 gastrectomy was recommended. The type of gastrectomy performed depended on the location and extent of the primary lesion. For middle third tumors, the gastric margin was recommended to be more than 5 cm, and a total gastrectomy was performed. For lower third tumors, a 2 cm duodenal margin was recommended and a subtotal or total gastrectomy was considered. For upper third tumors, a 3 cm esophageal margin was recommended and a total gastrectomy or esophagogastrectomy was performed. Billroth I or Roux-en-y gastrojejunostomy was performed for distal gastrectomy patients, Roux-en-y esophagojejunostomy was performed for total gastrectomy patients.
• Oxaliplatin (Drug): The dose of oxaliplatin is according to body-surface area (BSA): 130mg/m2, intravenously, on day 1.

Primary outcomes

• Disease free survival [up to 3 years]

Secondary outcomes

• Overall survival [up to 3 years]
• Surgical complete resection rate (R0) [at the time of surgery]
• Pathological response rate [at the time of surgery]
• Proportion of patients with toxicities [up to 3 years]
• Proportion of patients with surgery-related complication [at the time of surgery]

Sex: All, ages: 18 Years to any

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

• Results publication: Klute KA, Shah MA. Evolving Therapeutics for Resectable Esophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257044. doi: 10.6004/jnccn.2025.7044. PMID 40340830
• Results publication: Liu X, Jin J, Cai H, Huang H, Zhao G, Zhou Y, Wu J, Du C, Long Z, Fang Y, Ma M, Li G, Zhou M, Yin J, Zhu X, Zhu J, Sheng W, Huang D, Zhu H, Zhang Z, Lu Q, Xie L, Zhang Z, Wang Y. Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT. BMC Cancer. 2019 Jun 20;19(1):606. doi: 10.1186/s12885-019-5728-8. PMID 31221115
• Results publication: Liu X, Cai H, Sheng W, Huang H, Long Z, Wang Y. microRNAs expression profile related with response to preoperative radiochemotherapy in patients with locally advanced gastric cancer. BMC Cancer. 2018 Oct 29;18(1):1048. doi: 10.1186/s12885-018-4967-4. PMID 30373600

• Ya-nong Wang, M.D., Principal investigator, Fudan University
• Zhen Zhang, M.D., Principal investigator, Fudan University