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The Long-term Effect of D4 Lymphadenectomy for Gastric Cancer

Phase 2
Conditions
Gastric Cancer
Effects of Chemotherapy
Surgery
Interventions
Procedure: Radical Gastrectomy Plus D4 Lymphadenectomy
Procedure: Radical Gastrectomy Plus D2 Lymphadenectomy
Drug: S-1+Oxaliplatin
Registration Number
NCT02423278
Lead Sponsor
First Affiliated Hospital, Sun Yat-Sen University
Brief Summary

The main purpose of this study is to evaluate the effect of extensive lymphadenectomy procedure in treatment of gastric cancer. This study is designed as a open-label, multi-centers, randomized controlled trial. The overall survival and free disease survival are primary outcomes, with postoperative complication, hospital charges, and life quality as secondary outcomes.

Detailed Description

Background: Gastric cancer is the second leading cause of cancer-associated death worldwide, with high incidence in China. The prognosis of advanced gastric cancer is quite poor. Although perioperative chemotherapy may help to prolong survival in cases of advanced disease, radical tumor resection remains the most effective treatment for curable gastric cancer. Nowadays, radical gastrectomy with extended (D2) lymphadenectomy has become the standard for treatment of advanced gastric cancer. However, this surgical procedure cannot achieve a radical tumor resection for most cases with advanced disease. Hence, a more extensive (D2 plus para-aortic nodal dissection, D4) lymphadenectomy along with gastrectomy has been performed in Japan and other Asian countries. A recent study by Sasako et al. indicated that a prophylactic D4 lymphadenectomy did not improve the prognosis of curable gastric cancer, but increased the blood loss and operation time compared with single D2 procedure. We reviewed our database, which had collected almost 2,000 gastric cancer cases since its establishment in 1994, and found that the D4 surgical procedure actually improved the prognosis of T4 tumor and tumor with lymph node metastasis at the second stations. To further confirm the results from our retrospective analysis, we performed a prospective study with multicenter, open-label, and randomized design in the affiliated hospitals of Sun Yat-sen University. This study would be helpful to improve the prognosis of patients with advanced gastric cancer, and find more efficient management for curable gastric cancer.

Method: This study, which started from January, 2011 and planned to close after ten years, has been approved by the ethic committee of Sun Yat-sen University, with written inform consent obtained from all enrolled subjects. Patients who had histologically proven gastric adenocarcinoma and confirmed lymph node metastasis to para-aortic nodes (\<3 enlarged lymph nodes) were prospectively enrolled in this trial. A standard D2 lymphadenectomy or D4 procedure was randomly decided by a formal randomization program. The primary end point of this study was overall survival, defined as the time from randomization to death. The secondary end points were recurrence-free survival, postoperative complications, length of stay, and hospital charges. Recurrence-free survival was defined as the time from randomization to the first recurrence of cancer or death from any cause. The follow-up period would last for at least five years after the definitive operation.

Significance: This study would further confirm the efficacy of D2 plus para-aortic nodal dissection(PAND) procedure for management of advanced gastric cancer as compared with the classic D2 lymphadenectomy operation. Moreover, the therapeutic measures employed in current study may guide the future treatment of advanced gastric cancer in China.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
200
Inclusion Criteria
  • The informed consent has been obtained from the patient.
  • With confirmed pathological diagnosis of gastric cancer and visible para-aortic lymph nodes metastasis.
  • Endurable D2/D4 gastrectomy and neoadjuvant chemotherapy.
  • With moderate/good ECOG health rating (PS): 0-1 score.
Exclusion Criteria
  • Pregnant woman or lactating woman.
  • With confirmed distant metastasis in liver, lung, bones, or other organs.
  • Intolerable operation or neoadjuvant chemotherapy.
  • With severe comorbidities, such as cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and chronic renal dysfunction.
  • With bad compliance or contraindication to enrollment.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
D4 LymphadenectomyRadical Gastrectomy Plus D4 LymphadenectomyThis is the interventional group in which additional para-aortic lymph nodes are dissected meanwhile. Under this arm, main therapeutic measures are listed as follows: * three-cycle SOX chemo regimen (S-1+Oxaliplatin) as neoadjuvant chemotherapy * radical gastrectomy plus D4 lymphadenectomy * five-cycle SOX chemo as adjuvant chemotherapy * five-year follow-up program to evaluate the prognosis.
D4 LymphadenectomyS-1+OxaliplatinThis is the interventional group in which additional para-aortic lymph nodes are dissected meanwhile. Under this arm, main therapeutic measures are listed as follows: * three-cycle SOX chemo regimen (S-1+Oxaliplatin) as neoadjuvant chemotherapy * radical gastrectomy plus D4 lymphadenectomy * five-cycle SOX chemo as adjuvant chemotherapy * five-year follow-up program to evaluate the prognosis.
D2 LymphadenectomyRadical Gastrectomy Plus D2 LymphadenectomyThis is the control group in which a classic surgical procedure for gastric cancer is performed. Under this arm, main therapeutic measures are included as follows: * three-cycle SOX chemo regimen (S-1+Oxaliplatin) as neoadjuvant chemotherapy * radical gastrectomy plus D2 lymphadenectomy (Without para-aortic lymph nodes dissection) * five-cycle SOX chemo as adjuvant chemotherapy * five-year follow-up program to evaluate the prognosis.
D2 LymphadenectomyS-1+OxaliplatinThis is the control group in which a classic surgical procedure for gastric cancer is performed. Under this arm, main therapeutic measures are included as follows: * three-cycle SOX chemo regimen (S-1+Oxaliplatin) as neoadjuvant chemotherapy * radical gastrectomy plus D2 lymphadenectomy (Without para-aortic lymph nodes dissection) * five-cycle SOX chemo as adjuvant chemotherapy * five-year follow-up program to evaluate the prognosis.
Primary Outcome Measures
NameTimeMethod
Relapse-free Survivalfive years after surgery
Overall Survivalfive years after surgery
Secondary Outcome Measures
NameTimeMethod
Perioperative mortalitywithin the first 30 days after surgery
Life quality measured by HRQOL scorefive years after surgery

a questionnaire form would be sent to each enrolled patients after surgery.

Length of Hospital stayan expected average of 4 weeks after admission

The duration between admission and final discharge from hospital. An average of 4 weeks is expected.

Early complicationswithin the first 30 days after surgery

Rate of early postoperative events, such as anastomotic leak, intra-abdominal hemorrhage, adhesive intestinal obstruction and surgical site infection, in each arm.

Trial Locations

Locations (1)

The First Affiliated Hospital of Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

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