Pragmatic randomised clinical trial of proton versus photon therapy for patients with non-metastatic breast cancer: the Radiotherapy Comparative Effectiveness (RadComp) Consortium trial protocol

Justin E Bekelman, Hien Lu, Stephanie Pugh, Kaysee Baker, Christine D Berg, Amy Berrington de González, 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, Bonnie Ky, 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, RadComp (Radiotherapy Comparative Effectiveness Consortium), 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, Suneel Nagda, 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, Justin E Bekelman, Hien Lu, Stephanie Pugh, Kaysee Baker, Christine D Berg, Amy Berrington de González, 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, Bonnie Ky, 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, RadComp (Radiotherapy Comparative Effectiveness Consortium), 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, Suneel Nagda, 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

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.

Keywords: breast tumours; clinical trials; protocols & guidelines; radiation oncology.

Conflict of interest statement

Competing interests: JEB, SE, CDM and BK report grants from PCORI, during the conduct of the study. SNP, WB, L-MF, BGH, CK, MVM, RWM, FWP, SMM and OC report grants from University of Pennsylvania subcontracts as study investigator, during the conduct of the study.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Conceptual framework for randomised pragmatic clinical trial of proton versus photon therapy for locally advanced breast: generating patient centric, real-word evidence.
Figure 2
Figure 2
Study stratification schema.

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