Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project

Shelley Potter; Kerry Avery; Rosina Ahmed; Jana de Boniface; Sanjoy Chatterjee; David Dodwell; Peter Dubsky; Hiroji Iwata; Michael Jiang; Han-Byoel Lee; Mairead MacKenzie; Fiorita Poulakaki; Andrea L Richardson; Karla Sepulveda; Andrew Spillane; Alastair M Thompson; Gustavo Werutsky; Jean L Wright; Nicholas Zdenkowski; Katherine Cowan; Stuart McIntosh

doi:10.1136/bmjopen-2024-084488

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project

BMJ Open. 2024 Apr 19;14(4):e084488. doi: 10.1136/bmjopen-2024-084488.

Authors

Shelley Potter^#^{1

2}, Kerry Avery^{1

3

4}, Rosina Ahmed⁵, Jana de Boniface^{6

7}, Sanjoy Chatterjee⁵, David Dodwell⁸, Peter Dubsky^{9

10}, Hiroji Iwata¹¹, Michael Jiang¹, Han-Byoel Lee^{12

13}, Mairead MacKenzie¹⁴, Fiorita Poulakaki^{15

16}, Andrea L Richardson¹⁷, Karla Sepulveda¹⁸, Andrew Spillane¹⁹, Alastair M Thompson²⁰, Gustavo Werutsky²¹, Jean L Wright²², Nicholas Zdenkowski²³, Katherine Cowan²⁴, Stuart McIntosh^#²⁵

Affiliations

¹ Bristol Surgical and Perioperative Care Complex Intervention Collaboration, Bristol Medical School, University of Bristol, Bristol, UK.
² Bristol Breast Care Centre, North Bristol NHS Trust, Bristol, UK.
³ Centre for Surgical Research, Bristol Medical School, University of Bristol, Bristol, UK.
⁴ NIHR Bristol Biomedical Research Centre, Bristol, UK.
⁵ Tata Medical Center, Kolkata, West Bengal, India.
⁶ Breast Unit, Capio St. Göran's Hospital, Stockholm, Sweden.
⁷ Department of Molecular Medicine and Surgery, Karolinska Instituet, Stockholm, Sweden.
⁸ University of Oxford, Oxford, UK.
⁹ Hirslanden Klinik St Anna, Lucerne, Switzerland.
¹⁰ University of Lucerne, Luzern, Switzerland.
¹¹ Aichi Cancer Center, Nagoya, Japan.
¹² Breast Care Centre, Dept. of Surgery, Seoul National University Hospital, Seoul, South Korea.
¹³ Cancer Research Institute, Seoul National University, Seoul, South Korea.
¹⁴ Independent Cancer Patients' Voice, London, UK.
¹⁵ Breast Surgery Department, Athens Medical Centre, Athens, Greece.
¹⁶ Europa Donna The European Breast Cancer Coalition, Milan, Italy.
¹⁷ Johns Hopkins University, Baltimore, Maryland, USA.
¹⁸ Baylor College of Medicine, Houston, Texas, USA.
¹⁹ University of Sydney, Sydney, New South Wales, Australia.
²⁰ Department of Surgical Oncology, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
²¹ Latin American Cooperative Oncology Group, Porto Alegre, Brazil.
²² Johns Hopkins Medicine, Baltimore, Maryland, USA.
²³ The University of Newcastle, Newcastle, New South Wales, Australia.
²⁴ Katherine Cowan Consulting Limited, St. Leonards-on-Sea, UK.
²⁵ Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK s.mcintosh@qub.ac.uk.

^# Contributed equally.

Abstract

Introduction: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved.

Methods and analysis: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance.

Ethics and dissemination: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely.

Registration: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).

Keywords: Clinical Trial; RADIOTHERAPY; SURGERY.

MeSH terms

Breast Neoplasms* / therapy
Delphi Technique
Endpoint Determination
Female
Humans
Neoadjuvant Therapy*
Neoplasm Recurrence, Local / therapy
Outcome Assessment, Health Care / methods
Quality of Life
Research Design
Systematic Reviews as Topic
Treatment Outcome