A Comparison of Laparoscopic With Open Distal Gastrectomy in Advanced Gastric Cancer After Neoadjuvant Chemotherapy

The study is an open-label, controlled, randomized Phase II clinical trial. The protocol has been approved by the Ethics Committee of Beijing Cancer Hospital.

The primary endpoint is the 3-year progression-free survival (PFS) rate. The secondary endpoints are the overall survival, surgical morbidity and mortality.

• Neoadjuvant Chemotherapy (Drug), also known as NACT: XELOX: Oxaliplatin 130mg/m2,iv.,d1;Capecitabine 1000mg/m2,po.,Bid,d1-14; Repeat every 21 days for 3 courses.
• Laparoscopic gastrectomy (Procedure), also known as LDG: Laparoscopic distal gastrectomy with D2 lymph node dissection
• Open gastrectomy (Procedure), also known as ODG: Open distal gastrectomy with D2 lymph node dissection
• Adjuvant Chemotherapy (Drug), also known as ACT: XELOX: Oxaliplatin 130mg/m2,iv.,d1;Capecitabine 1000mg/m2,po.,Bid,d1-14; Repeat every 21 days for 5 courses.

Primary outcomes

• 3-year progression-free survival [36 months]: In terms of locally advanced gastric cancer, to evaluate the disease free survival rate in laparoscopic subtotal gastrectomy with D2 lymph node dissection at postoperative 3 years compared with open subtotal gastrectomy with D2 lymph node dissection

Secondary outcomes

• Overall survival [36 months]: In terms of locally advanced gastric cancer, to evaluate the overall survival rate in laparoscopic subtotal gastrectomy with D2 lymph node dissection at postoperative 3 years compared with open subtotal gastrectomy with D2 lymph node dissection
• Surgical morbidity [30 days]: Surgical morbidity is defined as the events which occurs with-in postoperative 30 days, extension of hospitalization and re-hospitalization. It is necessary to evaluate the complication and if it occurs during the hospitalization, it is required to record complication name, date of on-set (postoperatively), grade on Clavien-Dindo Classification and treatment for complication.
• Surgical mortality [30 days]: It is defined as the death within postoperative 30 days regardless of postoperative reason. If the patient is transferred to other medication institutes with impossible condition for recovery before death, it is regarded as death.
• Postoperative recovery index [2 weeks]: Postoperatively, the investigator evaluates the patient's recovery condition once a day. Evaluation items for patient's recovery condition: the pain score, the leaving bed time, postoperative gastrointestinal function recovery time and hospital stay.
• Postoperative quality of life [Up to 1 year post-operative]: In pre-therapy <7 days, pre-operative <7 days, and post-operative at 12 months after surgery, both the European Organisation for Research and Treatment of Cancer (EORTC) C30 and STO22 are analyzed with quality of life by following methods. In case of EORTC-C30, the analysis is undergone by classifying into 5 functional scales (physical, role, emotional, cognitive, and social functioning), 3 symptom scales (fatigue, pain and nausea, and vomiting), 1 global health status and 6 single items.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* Histologically proven adenocarcinoma of the stomach.
* Clinical cT2N+M0,or cT3-4a/N+M0 disease, confirmed by upper gastrointestinal endoscopy and abdominal computed tomography (CT) and laparoscopy. The T and N stages are determined by the method of Habermann et al.
* The gastric tumors are located in the middle to lower third of the stomach, are macroscopically resectable by distal gastrectomy with D2 lymph node dissection, and R0 or R1 resection can be achieved.
* No bulky lymph node metastasis is detected by abdominal CT.
* No pleural effusion, no ascites exceeding the pelvis and no metastasis to the peritoneum, liver or other distant organs are confirmed by abdominal pelvic CT.
* No clinically apparent distant metastasis.
* Karnofsky performance status ≥70%.
* Sufficient oral intake.
* No previous treatment with chemotherapy or radiation therapy for any tumors.
* No previous surgery for the present disease.
* Sufficient organ function, as evaluated by laboratory tests 7 days or more after the date when the anticancer drugs were given. When patients are recovering from myelosuppression,the revised criteria are shown in parentheses.

White blood cell count≥3000/mm3 (2000/mm3) Platelet count≥10.0*104/mm3 (5.0*104/mm3) Aspartate aminotransferase≤100 IU/l Alanine aminotransferase≤100 IU/l Total bilirubin≤2.0 mg/dl Serum creatinine≤1.5 mg/dl

* No need for emergency surgery due to bleeding or perforation of the primary tumor.
* No mechanical obstruction.
* Written informed consent.

Exclusion Criteria:

* Past history of upper abdominal surgery.
* Past history of surgery for the gastrointestinal tract.
* Body mass index exceeding 30 kg/m2.

• Li Z, Shan F, Ying X, Zhang L, Ren H, Li S, Jia Y, Miao R, Xue K, Li Z, Wang Y, Yan C, Zhang Y, Pang F, Ji J. Laparoscopic or open distal gastrectomy after neoadjuvant chemotherapy for advanced gastric cancer: study protocol for a randomised phase II trial. BMJ Open. 2018 Aug 10;8(8):e021633. doi: 10.1136/bmjopen-2018-021633. PMID 30099396
• Li Z, Shan F, Wang Y, Li S, Jia Y, Zhang L, Yin D, Ji J. Laparoscopic versus open distal gastrectomy for locally advanced gastric cancer after neoadjuvant chemotherapy: safety and short-term oncologic results. Surg Endosc. 2016 Oct;30(10):4265-71. doi: 10.1007/s00464-015-4739-z. Epub 2016 Jun 10. PMID 27287914
• Results publication: Li Z, Shan F, Ying X, Zhang Y, E JY, Wang Y, Ren H, Su X, Ji J. Assessment of Laparoscopic Distal Gastrectomy After Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: A Randomized Clinical Trial. JAMA Surg. 2019 Dec 1;154(12):1093-1101. doi: 10.1001/jamasurg.2019.3473. PMID 31553463

• Study Protocol (PDF, 2018-07-13)
• Informed Consent Form (PDF, 2015-02-26)

• Ziyu Li, M.D., Principal investigator, Peking University Cancer Hospital & Institute