Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 24, 2020; 11(4): 205-216
Published online Apr 24, 2020. doi: 10.5306/wjco.v11.i4.205
Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours
Jaseela Chiramel, Rose Almond, Astrid Slagter, Adeel Khan, Xin Wang, Kok Haw Jonathan Lim, Melissa Frizziero, Bipasha Chakrabarty, Annamaria Minicozzi, Angela Lamarca, Wasat Mansoor, Richard A Hubner, Juan William Valle, Mairéad Geraldine McNamara
Jaseela Chiramel, Adeel Khan, Kok Haw Jonathan Lim, Melissa Frizziero, Angela Lamarca, Wasat Mansoor, Richard A Hubner, Juan William Valle, Mairéad Geraldine McNamara, Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
Jaseela Chiramel, Royal Free London NHS Foundation Trust, London NW3 2QG, United Kingdom
Rose Almond, Xin Wang, Statistics Group, Digital Services, The Christie NHS Foundation Trust, Manchester, M20 4BX, United Kingdom
Astrid Slagter, Antoni van Leeuwenhoek/Netherlands Cancer Institute, Amsterdam 1066 Cx, Netherlands
Bipasha Chakrabarty, Department of Pathology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
Annamaria Minicozzi, Department of Surgery, Barts Health NHS Trust, London EC1A 7BE, United Kingdom
Richard A Hubner, Juan William Valle, Mairéad Geraldine McNamara, Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, United Kingdom
Author contributions: Chiramel J wrote the manuscript, drafted conception and designed the study; Almond R and Xin W were in charge of statistical analysis of data; Slagter A, Khan A, and Lim KHJ collected and analysed the data; Frizzero M, Chakrabarty B, Minicozzi A, Lamarca A, Mansoor W, Hubner RA, Valle JW and McNamara MG editing and review the manuscript.
Institutional review board statement: This study was approved by the Quality Improvement and Clinical Audit Committee of The Christie NHS Foundation Trust, Manchester, United Kingdom (reference SE17/2065).
Informed consent statement: Patients were not required to give informed consent to the study. We used anonymous clinical data for the analysis.
Conflict-of-interest statement: The authors report no conflict of interest in this work.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Mairéad Geraldine McNamara, BM BCh, MD, MSc, PhD, Attending Doctor, Senior Lecturer, Senior Researcher, Department of Medical Oncology, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom. mairead.mcnamara@christie.nhs.uk
Received: December 24, 2019
Peer-review started: December 24, 2019
First decision: February 20, 2020
Revised: February 29, 2020
Accepted: April 8, 2020
Article in press: April 8, 2020
Published online: April 24, 2020
Processing time: 119 Days and 17 Hours
ARTICLE HIGHLIGHTS
Research background

The prognostic significance of lymph nodes (LNs) metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours (GEP NETs) undergoing curative resection is still debatable. Many studies have demonstrated that resection of the primary tumour and regional lymphadenectomy results in a high cure rate for patients with GEP NETs.

Research motivation

LN positivity and LN ratio (LNR) are independent prognostic factors for survival in patients with resected NETs, but limited evidence is available on the optimal predictive number of resected LNs required. Several retrospective studies in Pancreatic NETs (PanNETs) and Small Bowel NETs (SiNETs) have emphasized the importance of adequate resection of regional LNs in patients undergoing curative resection. The current guidelines (AJCC TNM staging 8th edition and ENETS) for the management of GEPNETs do not provide a recommendation regarding LN yield. The main purpose of the study was to identify a cut off value for LN retrieval in resected GEP NETs.

Research objectives

This retrospective study was conducted to identify the optimal number of LNs that should be harvested in patients with GEP NETS undergoing curative surgery and to evaluate the association between LN metastases and survival (relapse-free and overall) in patients with resected well differentiated GEP NETs.

Research methods

Data on patients who underwent curative surgery for GEP NETs between January 2002 and March 2017 were identified and analysed retrospectively. Univariate Cox proportional hazard (CPH) models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS. LN cut-point value was determined using the cut-point determination methods in survival analysis, using R. This is an outcome-oriented method providing a value of a cut-point that corresponds to the most significant relationship with survival.

Research results

The result of univariate analysis suggested perineural invasion (P = 0.0023), LN positivity (P = 0.033), LN retrieval of ≥ 8 (P = 0.047) and localisation (P = 0.0049) have a statistically significant association with shorter RFS, but there was no effect of LN ratio (median 1.8) on RFS: P = 0.1 or OS: P = 0.75. LN cut-point value associated with RFS was 8. Tumour necrosis (P = 0.021) and perineural invasion (P = 0.016) were the only two variables significantly associated with worse OS. Retrieval of ≥ 8 LNs (HR = 2.70, 95%CI: 1.07-6.84, P = 0.036), tumour localisation: pancreas (HR = 27.33, P = 0.006) and small bowel (HR = 32.44, P = 0.005) were independent prognostic factors for shorter RFS on multivariable analysis.

Research conclusions

The study has concluded that an outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery. A prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.