The REQUITE-AB study: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality of life in breast cancer patients


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Tim Rattay1,Kerstie Johnson1,David Azria2,Jenny Chang-Claude3,Susan Davidson4,Alison Dunning5,Dirk de Ruyscher6,Sara Gutierrez-Enriquez7,Philippe Lambin8,Samuel Lavers1,Tiziana Rancati9,Barry Rosenstein10,Petra Seibold3,R Paul Symonds1,Christopher Talbot1,Hubert Thierens11,Ricardo Valdagni9,Ana Vega12,Adam Webb1,Frederik Wenz13,Catharine West14
1University of Leicester,2University of Montpellier,3German Cancer Research Centre (DKFZ), Heidelberg,4The Christie Hospital NHS Foundation Trust,5University of Cambridge,6University Hospitals Leuven/KU Leuven, Belgium,7Vall d'Hebron Institute of Oncology, Barcelona, Spain,8Maastro Clinic, Maastricht, Netherlands,9Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy,10Mount Sinai School of Medicine, New York, USA,11Universiteit Ghent,12Fundacion Publica Galega Medicina Xenomica, Santiago de Compostela, Spain,13University Medical Centre Mannheim, Germany,14University of Manchester

Abstract

Background

Clinically significant side-effects from radiotherapy affect around a quarter of breast cancer patients and may impact considerably on outcomes from breast surgery. An increasing number of replicated genetic associations for radiotherapy toxicity are being reported.[1],[2]  The EU-funded REQUITE consortium aims to validate genetic markers and clinical factors implicated in radiotoxicity.  The purpose of the REQUITE-AB project is to develop an integrated set of predictors for acute radiotherapy side-effects in breast cancer patients to be used as clinical decision-making tool.

Method

As part of the REQUITE prospective cohort study, 2,000 patients eligible for adjuvant breast radiotherapy will be recruited in nine centres across Europe and North America between April 2014 and August 2016, with centralised data management, biobanking and two years’ follow-up using a standardised protocol. Patient characteristics and treatment details being captured include dose-volume histograms and DICOM files.  Genotyping will take place in autumn 2016.  Primary endpoints are acute skin toxicity (CTC-AE v4.0) and quality-of-life (QoL) on completion of radiotherapy and at 3 months from start of radiotherapy.  Secondary endpoints are late side-effects including change in breast appearance.

Results

1,724 breast cancer patients have been recruited to May 2016 with standardized documentation of toxicity and QoL. On completion of radiotherapy, 21.6% of patients developed grade 2 skin toxicity (brisk erythema) and 1.3% grade 3 (moist desquamation).  The ability of patient, treatment and genetic variables to predict clinical outcomes and QoL will be examined. 

Conclusion

The REQUITE study includes the largest radiogenomics cohort of breast cancer patients to date recruited under a single standardised protocol. Findings of the REQUITE-AB project are likely to inform the development of interventional biomarker trials and personalise breast cancer care in the future. 

[1] Talbot et al, Br J Cancer, 2012; 107: 748-53.

[2] Seibold et al, Int J Radiat Oncol Biol Phys, 2015; 92: 1084-92