BMJ Open (Oct 2019)
Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol
- Bonnie Ky,
- Justin E Bekelman,
- Hien Lu,
- Stephanie Pugh,
- Kaysee Baker,
- Christine D Berg,
- Amy Berrington de Gonzalez,
- Lior Z Braunstein,
- Walter Bosch,
- Cynthia Chauhan,
- Susan Ellenberg,
- L Christine Fang,
- Gary M Freedman,
- Elizabeth A Hahn,
- B G Haffty,
- Atif J Khan,
- Rachel B Jimenez,
- Christy Kesslering,
- Choonsik Lee,
- Hsiao-Ming Lu,
- Mark V Mishra,
- C Daniel Mullins,
- Robert W Mutter,
- Suneel Nagda,
- Mark Pankuch,
- Simon N Powell,
- Fred W Prior,
- Karen Schupak,
- Alphonse G Taghian,
- J Ben Wilkinson,
- Shannon M MacDonald,
- Oren Cahlon,
- David Gierga,
- Harald Paganetti,
- Daniel Soto,
- Aman Anand,
- Michele Halyard,
- Lisa A. McGee,
- Kimberly Corbin,
- Nicholas Remmes,
- Elizabeth Yan,
- Elizabeth S. Bloom,
- Karen E. Hoffman,
- Falk Poenisch,
- Benjamin Smith,
- Xiaorong Ronald Zhu,
- John Cuaron,
- Daphna Gelblum,
- Erin Gillespie,
- Linda Hong,
- Beryl McCormick,
- Borys Mychalczak,
- Preeti Parhar,
- Paul Romesser,
- Anne Marie Shepherd,
- Jaffa Bennouna,
- Marcio Fagundes,
- Alonso Gutierrez,
- Jennifer Yu,
- David Cella,
- Stephen Mihalcik,
- Michael Stutz,
- Tomas Dvorak,
- Omar Zeidan,
- Eugene Fourkal,
- David C. Weksberg,
- Dennis Mah,
- Henry Tsai,
- Jeffrey Campbell,
- Kiran Prabhu,
- Trevor Twyford,
- Allen Meek,
- Niek Schreuder,
- Sharad Goyal,
- Rihan Millevoi,
- Nisha Ohri,
- Chang Chang,
- Jared Sturgeon,
- William Bennet,
- Lawrence Tarbox,
- Jyoti Mayadev,
- Vitali Moiseenko,
- Dominique Rash,
- James Urbanic,
- Catheryn Yashar,
- Julie A. Bradley,
- Xiaoying Liang,
- Nancy Mendenhall,
- Michael Rutenberg,
- Chee-Wai Cheng,
- Janice Lyons,
- Katja Langen,
- Elizabeth Nichols,
- Abigail Berman,
- Steven Feigenberg,
- James Volker,
- Lilie Lin,
- Ann Marie Siegal,
- Neil Taunk,
- Tony Wong,
- Sasa Music,
- William Straube,
- Imran Zoberi,
- Peter Chen,
- Xuanfeng Ding,
- Phuong Daniella Dang,
- Sanford Katz,
- Lane R Rosen,
- Terry Wu
Affiliations
- Bonnie Ky
- Department of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Justin E Bekelman
- Penn Center for Cancer Care Innovation, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Hien Lu
- 1 Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Stephanie Pugh
- 2 American College of Radiology, Philadelphia, Pennsylvania, USA
- Kaysee Baker
- 3 Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, USA
- Christine D Berg
- 4 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
- Amy Berrington de Gonzalez
- 4 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
- Lior Z Braunstein
- 5 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York city, New York, USA
- Walter Bosch
- 6 Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri, USA
- Cynthia Chauhan
- 7 Mayo Clinic Minnesota, Rochester, Minnesota, USA
- Susan Ellenberg
- 8 Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- L Christine Fang
- 9 Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington, USA
- Gary M Freedman
- 1 Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Elizabeth A Hahn
- 10 Department of Medical Social Sciences, Northwestern University, Evanston, Illinois, USA
- B G Haffty
- 11 Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
- Atif J Khan
- 5 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York city, New York, USA
- Rachel B Jimenez
- 12 Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Christy Kesslering
- 13 Northwestern Medicine Chicago Proton Center, Warrenville, Illinois, USA
- Choonsik Lee
- 4 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
- Hsiao-Ming Lu
- 12 Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Mark V Mishra
- 3 Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, USA
- C Daniel Mullins
- 15 PHSR, University of Maryland School of Pharmacy, Baltimore, Maryland, USA
- Robert W Mutter
- 16 Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA
- Suneel Nagda
- 1 Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Mark Pankuch
- 13 Northwestern Medicine Chicago Proton Center, Warrenville, Illinois, USA
- Simon N Powell
- 5 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York city, New York, USA
- Fred W Prior
- 17 Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
- Karen Schupak
- 5 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York city, New York, USA
- Alphonse G Taghian
- 12 Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- J Ben Wilkinson
- 18 Provision Proton Therapy Center, Knoxville, Tennessee, USA
- Shannon M MacDonald
- 12 Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Oren Cahlon
- 5 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York city, New York, USA
- David Gierga
- Harald Paganetti
- Daniel Soto
- Aman Anand
- Michele Halyard
- Lisa A. McGee
- Kimberly Corbin
- Nicholas Remmes
- Elizabeth Yan
- Elizabeth S. Bloom
- Karen E. Hoffman
- Falk Poenisch
- Benjamin Smith
- Columbia University, New York, New York, USA
- Xiaorong Ronald Zhu
- John Cuaron
- Daphna Gelblum
- Erin Gillespie
- Linda Hong
- Beryl McCormick
- Borys Mychalczak
- Preeti Parhar
- Paul Romesser
- Anne Marie Shepherd
- Jaffa Bennouna
- Marcio Fagundes
- Alonso Gutierrez
- Jennifer Yu
- 1Centre Armand-Frappier Santé Biotechnologie, Institut national de la recherche scientifique, Laval, QC, Canada
- David Cella
- Northwestern University, Chicago, United States of America
- Stephen Mihalcik
- Michael Stutz
- Tomas Dvorak
- Omar Zeidan
- Eugene Fourkal
- David C. Weksberg
- Dennis Mah
- Henry Tsai
- 2Neogenomics Laboratories, Fort Myers, FL, USA
- Jeffrey Campbell
- Kiran Prabhu
- Poole Hospital NHS Foundation Trust, Poole, UK
- Trevor Twyford
- Allen Meek
- Niek Schreuder
- Sharad Goyal
- Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
- Rihan Millevoi
- Nisha Ohri
- Chang Chang
- Jared Sturgeon
- William Bennet
- consultant in endocrinology
- Lawrence Tarbox
- Jyoti Mayadev
- 2 Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA
- Vitali Moiseenko
- Dominique Rash
- 2 Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA
- James Urbanic
- Catheryn Yashar
- 2 Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California, USA
- Julie A. Bradley
- Xiaoying Liang
- Nancy Mendenhall
- Michael Rutenberg
- Chee-Wai Cheng
- Janice Lyons
- Katja Langen
- Elizabeth Nichols
- Abigail Berman
- Steven Feigenberg
- James Volker
- Lilie Lin
- Ann Marie Siegal
- Neil Taunk
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Tony Wong
- Sasa Music
- William Straube
- Imran Zoberi
- Peter Chen
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Xuanfeng Ding
- Phuong Daniella Dang
- Sanford Katz
- Lane R Rosen
- Terry Wu
- DOI
- https://doi.org/10.1136/bmjopen-2018-025556
- Journal volume & issue
-
Vol. 9,
no. 10
Abstract
Introduction A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer.Methods We are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events.Ethics and dissemination The RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets.Trial registration number NCT02603341
