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Impact of geography on prognostic outcomes of 21,509 patients with metastatic colorectal cancer enrolled in clinical trials: an ARCAD database analysis
Impact of geography on prognostic outcomes of 21,509 patients with metastatic colorectal cancer enrolled in clinical trials: an ARCAD database analysis
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Jun Yin*, Shaheenah Dawood*, Romain Cohen, Jeff Meyers, John Zalcberg, Takayuki Yoshino, Matthew Seymour, Tim Maughan, Leonard Saltz, Eric Van Cutsem, Alan Venook, Hans-Joachim Schmoll, Richard Goldberg, Paulo Hoff, J. Randolph Hecht, Herbert Hurwitz, Cornelis Punt, Eduard Diaz Rubio, Miriam Koopman, Chiara Cremolini, Volker Heinemann, Christophe Tournigard, Carsten Bokemeyer, Charles Fuchs, Niall Tebbutt, John Souglakos, Jean-Yves Doulliard, Fairooz Kabbinavar, Benoist Chibaudel, Aimery de Gramont, Qian Shi, Axel Grothey, Richard AdamsFirst Published June 30, 2021 Research Article
https://doi.org/10.1177/17588359211020547
Article information
Article has an altmetric score of 7 Open AccessCreative Commons Attribution, Non Commercial 4.0 License
Article Information
Volume: 13
Article first published online: June 30, 2021; Issue published: January 1, 2021
Received: December 29, 2020; Accepted: May 05, 2021
Jun Yin*
Department of Health Sciences Research, Mayo Clinic, 200 First Street, SW Rochester, MN 55905, USA
Shaheenah Dawood*
Mediclinic City Hospital: North Wing, Dubai Health Care City, Dubai UAE
Romain Cohen
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Jeff Meyers
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
John Zalcberg
School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia
Takayuki Yoshino
Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
Matthew Seymour
NIHR Clinical Research Network, Leeds, UK
Tim Maughan
CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, UK
Leonard Saltz
Memory Sloan Kettering Cancer Center, New York, NY, USA
Eric Van Cutsem
Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
Alan Venook
Department of Medicine, The University of California San Francisco, San Francisco, CA, USA
Hans-Joachim Schmoll
Klinik fur Innere Med IV, University Clinic Halle, Saale, Germany
Richard Goldberg
Department of Oncology, West Virginia University, Morgantown, WV, USA
Paulo Hoff
Centro de Oncologia de Brasilia do Sirio Libanes: Unidade Lago Sul, Siro Libanes, Brazil
J. Randolph Hecht
Ronald Reagan UCLA Medical Center, UCLS Medical Center, Santa Monica, CA, USA
Herbert Hurwitz
Duke Cancer Institute, Duke University, Durham, NC, USA
Cornelis Punt
Department of Medical Oncology, University of Amsterdam, Amsterdam, The Netherlands
Eduard Diaz Rubio
Department Oncology, Hospital ClÃnico San Carlos, Madrid, Spain
Miriam Koopman
Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands
Chiara Cremolini
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
Volker Heinemann
Department of Medical Oncology and Comprehensive Cancer Center, University of Munich, Munich, Germany
Christophe Tournigard
Hopital Henri Mondor, Creteil, France
Carsten Bokemeyer
Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Charles Fuchs
Director of Yale Cancer Center, Boston, MA, USA
Niall Tebbutt
Sydney Medical School, University of Sydney, Sydney, Australia
John Souglakos
University of Crete, Heraklion, Greece
Jean-Yves Doulliard
University of Nantes Medical School, Nantes, France
Fairooz Kabbinavar
UCLA Medical Center, Santa Monica, CA, USA
Benoist Chibaudel
Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France
Aimery de Gramont
Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France
Qian Shi
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Axel Grothey
West Cancer Center, Germantown, TN, USA
Richard Adams
Cardiff University and Velindre Cancer Center, Cardiff, UK
Corresponding Author:
[email protected]
*Co-first authors.
https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
Abstract
Background:
Benchmarking international cancer survival differences is necessary to evaluate and improve healthcare systems. Our aim was to assess the potential regional differences in outcomes among patients with metastatic colorectal cancer (mCRC) participating in international randomized clinical trials (RCTs).
Design:
Countries were grouped into 11 regions according to the World Health Organization and the EUROCARE model. Meta-analyses based on individual patient data were used to synthesize data across studies and regions and to conduct comparisons for outcomes in a two-stage random-effects model after adjusting for age, sex, performance status, and time period. We used mCRC patients enrolled in the first-line RCTs from the ARCAD database, which provided enrolling country information. There were 21,509 patients in 27 RCTs included across the 11 regions.
Results:
Main outcomes were overall survival (OS) and progression-free survival (PFS). Compared with other regions, patients from the United Kingdom (UK) and Ireland were proportionaly over-represented, older, with higher performance status, more frequently male, and more commonly not treated with biological therapies. Cohorts from central Europe and the United States (USA) had significantly longer OS compared with those from UK and Ireland (p = 0.0034 and p < 0.001, respectively), with median difference of 3–4 months. The survival deficits in the UK and Ireland cohorts were, at most, 15% at 1 year. No evidence of a regional disparity was observed for PFS. Among those treated without biological therapies, patients from the UK and Ireland had shorter OS than central Europe patients (p < 0.001).
Conclusions:
Significant international disparities in the OS of cohorts of mCRC patients enrolled in RCTs were found. Survival of mCRC patients included in RCTs was consistently lower in the UK and Ireland regions than in central Europe, southern Europe, and the USA, potentially attributed to greater overall population representation, delayed diagnosis, and reduced availability of therapies