Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2019; 25(47): 6835-6846
Published online Dec 21, 2019. doi: 10.3748/wjg.v25.i47.6835
Trends in treatment and overall survival among patients with proximal esophageal cancer
Judith de Vos-Geelen, Sandra ME Geurts, Margreet van Putten, Liselot BJ Valkenburg-van Iersel, Heike I Grabsch, Nadia Haj Mohammad, Frank JP Hoebers, Chantal V Hoge, Paul M Jeene, Evelien JM de Jong, Hanneke WM van Laarhoven, Tom Rozema, Marije Slingerland, Vivianne CG Tjan-Heijnen, Grard AP Nieuwenhuijzen, Valery EPP Lemmens
Judith de Vos-Geelen, Sandra ME Geurts, Liselot BJ Valkenburg-van Iersel, Evelien JM de Jong, Vivianne CG Tjan-Heijnen, Department of Internal Medicine, Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6202 AZ, Netherlands
Margreet van Putten, Valery EPP Lemmens, Department of Research, Netherlands Comprehensive Cancer Organization (IKNL), Eindhoven 5612 HZ, Netherlands
Heike I Grabsch, Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6202 AZ, Netherlands
Heike I Grabsch, Pathology and Data Analytics, Leeds Institute of Medical Research at St James”s, University of Leeds, Leeds LS9 7TF, United Kingdom
Nadia Haj Mohammad, Department of Medical Oncology, University Medical Center Utrecht, Utrecht 3584 CX, Netherlands
Frank JP Hoebers, Department of Radiation Oncology (MAASTRO clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6229 ET, Netherlands
Chantal V Hoge, Department of Internal Medicine, Division of Gastroenterology, Maastricht University Medical Center, Maastricht 6202 AZ, Netherlands
Paul M Jeene, Department of Radiotherapy, Radiotherapiegroep, Deventer 7416 SE, Netherlands
Hanneke WM van Laarhoven, Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam 1105 AZ, Netherlands
Tom Rozema, Department of Radiotherapy, Insituut Verbeeten, Tilburg 5042 SB, Netherlands
Marije Slingerland, Department of Medical Oncology, Leiden University Medical Center, Leiden 2333 ZA, Netherlands
Grard AP Nieuwenhuijzen, Department of Surgery, Catharina Hospital Eindhoven, Eindhoven 5623 EJ, Netherlands
Valery EPP Lemmens, Department of Public Health, Erasmus Medical Center Rotterdam, Rotterdam 3015 GD, Netherlands
Author contributions: de Vos-Geelen J, Geurts SME, Tjan-Heijnen VCG, Nieuwenhuijzen GAP and Lemmens VEPP designed the study, interpreted the data, and wrote the first draft of the manuscript. de Vos-Geelen J, Geurts SME and Van Putten M collected and analysed the data; the other authors contributed to the interpretation of data and revised the manuscript for important intellectual content. All authors approved the final version of the manuscript.
Institutional review board statement: This study was approved by the Privacy Review Board of the Netherlands Cancer Registry and the need for a separate approval from an ethics committee in the Netherlands was waived.
Informed consent statement: Not applicable. The original anonymous dataset is available from the Netherlands Cancer Registry.
Conflict-of-interest statement: de Vos-Geelen J has received non-financial support from BTG, and Servier, and has served as a consultant for Shire and has received institutional research funding from Servier. van Laarhoven HWM has served as a consultant for BMS, Celgene, Lilly, Nordic, and Servier and has received unrestricted research funding from Bayer, BMS, Celgene, Lilly, Merck Serono, MSD, Nordic, Philips, Roche, and Servier, all outside the submitted work. Slingerland M has served as a consultant for BMS and Lilly. Tjan-Heijnen VCG has received honoraria/travel grants from Roche, Novartis, Pfizer, Lilly, and Accord Healthcare, and has received institutional research funding from AstraZeneca, Roche, Pfizer, Novartis, Eisai, and Lilly. All remaining authors have declared no conflicts of interest.
Data sharing statement: The original anonymous dataset is available on request from the Netherlands Cancer Registry. Data analysis syntax can be requested from corresponding author at judith.de.vos@mumc.nl.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Judith de Vos-Geelen, MD, Medical Oncologist, Department of Internal Medicine, Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P. Debyelaan 25, Maastricht 6202 AZ, Netherlands. judith.de.vos@mumc.nl
Received: October 16, 2019
Peer-review started: October 16, 2019
First decision: November 10, 2019
Revised: December 4, 2019
Accepted: December 14, 2019
Article in press: December 14, 2019
Published online: December 21, 2019
ARTICLE HIGHLIGHTS
Research background

Proximal esophageal cancer is a rare disease, accounting for only 10% of all esophageal cancers. Nearby vital structures are involved in almost all proximal esophageal cancers at diagnosis, and as such surgical treatment is mutilating with major implications for quality of life of patients. Definitive chemoradiation (CRT) is an alternative treatment option, but survival data are scarce, restricting patient counseling.

Research motivation

To optimize treatment strategies and counseling of patients with proximal esophageal cancer, it is therefore essential to gain more insight in patient characteristics, provided therapies and outcome through real-life studies.

Research objectives

The aim of this population-based cohort study was to establish the trends in treatment and overall survival (OS) in patients diagnosed with non-metastatic or metastatic proximal esophageal cancer in a nationwide registry between 1989 and 2014.

Research methods

All patients with a tumor located in the cervical or upper thoracic esophagus diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry (NCR). The NCR is a population-based cancer registry of all residents of the Netherlands. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect f period of diagnosis on OS, adjusted for adjust for patient, tumor, and treatment characteristics.

Research results

Median OS of patients with proximal esophageal cancer significantly increased by approximately two mo between 1989 and 2014. In patients with non-metastatic proximal esophageal cancer, 5-year OS almost tripled to 13% in 2010-2014, although the absolute longterm outcome remains poor. Multivariable analysis showed that improvements in treatment over time have led to this survival benefit. The improvement is likely to be attributable to the implementation of CRT in the late nineties, accounting for almost 50% of treatment choices in non-metastatic proximal esophageal cancer nowadays, as shown in the current study. In metastatic disease, median OS did not change significantly between 1989 and 2014.

Research conclusions

Surgical treatment for proximal esophageal cancer has been substituted by definitive CRT in the more recent years, and was likely to be associated with significant survival improvement of patients with non-metastatic proximal esophageal cancer. (Long-term) survival data of patients with (non-)metastatic proximal esophageal cancer are provided from a large national database, representing daily clinical practice.

Research perspectives

Our findings give insights in real-life survival of patients with proximal esophageal cancer, providing crucial support for patient counseling. Future research should focuss on outcome between different CRT regimens, to optimize non-surgical treatment.