Minimum Esophageal Resection Length to Ensure Negative Proximal Margin in Total Gastrectomy for Gastric Cancer

Objective:. To identify the minimum length of esophageal resection to ensure a pathologically negative proximal margin (PM) in total gastrectomy for gastric cancer. Background:. In total gastrectomy, a certain esophageal length is resected to obtain a pathologically negative PM because of the possibility of unexpected pathological esophageal invasion. However, a recommendation regarding the esophageal transection site in total gastrectomy has not been established. Methods:. The data of patients who underwent total gastrectomy for gastric cancer from 2005 to 2018 were collected. We evaluated the length of unexpected pathological esophageal invasion (esophageal ΔPM) in each type of disease and each location of the gross proximal tumor boundary (PB) using the length between the PB and the esophagogastric junction (PB-EGJ length). Results:. Of the 1005 patients eligible for this study, 277, 196, and 532 had cT1, cT2–4 expansive (Exp), and cT2–4 infiltrative (Inf) growth patterns, respectively. In cT1 and Exp, no unexpected pathological esophageal invasion occurred when the PB-EGJ length was >1 cm, whereas pathological esophageal invasion occurred in 20.0% of cT1 and 32.7% of Exp when the PB-EGJ length was ≤1 cm. The esophageal ΔPM was 3 cm, whereas pathological esophageal invasion occurred in 17.4% of patients when the PB-EGJ length was ≤3 cm. The esophageal ΔPM was <2 cm. Conclusions:. New recommendations regarding the esophageal resection length required to ensure a pathologically negative PM in total gastrectomy are herein proposed

Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).

BackgroundIn Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection.MethodsThis study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events.DiscussionTo our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes

The treatment discontinuation and interruption criteria for nivolumab using National Cancer Institute Terminology Criteria for Adverse Events version 5.0.

The treatment discontinuation and interruption criteria for nivolumab using National Cancer Institute Terminology Criteria for Adverse Events version 5.0.</p

The time schedule of enrolment, administration of nivolumab, and assessments for the PENTAGON trial.

The time schedule of enrolment, administration of nivolumab, and assessments for the PENTAGON trial.</p

Recommended items to address in a clinical trial protocol and related documents.

Recommended items to address in a clinical trial protocol and related documents.</p

The time schedule of enrollment, administration of nivolumab, and follow-up for the PENTAGON trial.

The time schedule of enrollment, administration of nivolumab, and follow-up for the PENTAGON trial.</p