@article{5b149f4929f249dab6fad2b96ebc2a76,
title = "External Validation of a Predictive Model for Acute Skin Radiation Toxicity in the REQUITE Breast Cohort",
abstract = "Background: Acute skin toxicity is a common and usually transient side-effect of breast radiotherapy although, if sufficiently severe, it can affect breast cosmesis, aftercare costs and the patient's quality-of-life. The aim of this study was to develop predictive models for acute skin toxicity using published risk factors and externally validate the models in patients recruited into the prospective multi-center REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve QUalITy of lifE in cancer survivors) study.Methods: Patient and treatment-related risk factors significantly associated with acute breast radiation toxicity on multivariate analysis were identified in the literature. These predictors were used to develop risk models for acute erythema and acute desquamation (skin loss) in three Radiogenomics Consortium cohorts of patients treated by breast-conserving surgery and whole breast external beam radiotherapy (n = 2,031). The models were externally validated in the REQUITE breast cancer cohort (n = 2,057).Results: The final risk model for acute erythema included BMI, breast size, hypo-fractionation, boost, tamoxifen use and smoking status. This model was validated in REQUITE with moderate discrimination (AUC 0.65), calibration and agreement between predicted and observed toxicity (Brier score 0.17). The risk model for acute desquamation, excluding the predictor tamoxifen use, failed to validate in the REQUITE cohort.Conclusions: While most published prediction research in the field has focused on model development, this study reports successful external validation of a predictive model using clinical risk factors for acute erythema following radiotherapy after breast-conserving surgery. This model retained discriminatory power but will benefit from further re-calibration. A similar model to predict acute desquamation failed to validate in the REQUITE cohort. Future improvements and more accurate predictions are expected through the addition of genetic markers and application of other modeling and machine learning techniques.",
keywords = "ADJUVANT RADIOTHERAPY, COMPLICATIONS, DNA-REPAIR, INTENSITY-MODULATED RADIOTHERAPY, NORMAL-TISSUE, PROSTATE-CANCER, RECEIVING RADIOTHERAPY, RECONSTRUCTION, RISK-FACTOR, THERAPY, breast cancer, early toxicity, prediction model, radiotherapy, validation",
author = "Tim Rattay and Petra Seibold and Aguado-Barrera, {Miguel E.} and Manuel Altabas and David Azria and Barnett, {Gillian C.} and Renee Bultijnck and Jenny Chang-Claude and Ananya Choudhury and Coles, {Charlotte E.} and Dunning, {Alison M.} and Elliott, {Rebecca M.} and {Farcy Jacquet}, Marie-Pierre and Sara Gutierrez-Enriquez and Kerstie Johnson and Anusha Mueller and Giselle Post and Tiziana Rancati and Victoria Reyes and Rosenstein, {Barry S.} and {De Ruysscher}, Dirk and {de Santis}, {Maria C.} and Elena Sperk and Hilary Stobart and Symonds, {R. Paul} and Begona Taboada-Valladares and Ana Vega and Liv Veldeman and Webb, {Adam J.} and West, {Catharine M.} and Riccardo Valdagni and Talbot, {Christopher J.} and {REQUITE consortium}",
note = "Funding Information: We sincerely thank all patients who participated in the REQUITE study and all REQUITE staff involved at the following hospitals: Belgium: Prof. Wilfried de Neve, Dr. Christel Monten, Dr. Pieter Deseyne at Ghent University Hospital; Gilles Defraene, Rita Aerts, Soumia Arredouani, Maarten Lambrecht at KU Leuven. France: ICM Montpellier, CHU N{\^i}mes (Department of Radiation Oncology, CHU N{\^i}mes, N{\^i}mes, France). Germany: Praxis f{\"u}r Strahlentherapie an der Stadtklinik Baden-Baden (Dr. Thomas Blaschke); Klinikum Darmstadt GmbH (PD Dr. Christian Wei{\ss}); Zentrum f{\"u}r Strahlentherapie Freiburg (Dr. Petra Stegmaier); ViDia Christliche Kliniken Karlsruhe (Prof. Dr. Johannes Cla{\ss}en); Klinikum der Stadt Ludwigshafen gGmbH (PD Dr. Thomas Schnabel); Universit{\"a}tsklinikum Mannheim; Strahlentherapie Speyer (Dr. J{\"o}rg Schnabel). The researchers at DKFZ also thank Irmgard Helmbold and Dr. Sabine Behrens. ES was previously supported by the Ministry of Science and Arts of the State of Baden-W{\"u}rttemberg (2017–19) through the Brigitte-Schlieben-Lange-Programme. Italy: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano. Spain: Santiago: Complexo Hospitalario Universitario de Santiago. AV was supported by Spanish Instituto de Salud Carlos III (ISCIII) funding, an initiative of the Spanish Ministry of Economy and Innovation partially supported by European Regional Development FEDER Funds (INT15/00070, INT16/00154, INT17/00133; PI16/00046; PI13/02030; PI10/00164), and through the Autonomous Government of Galicia (Consolidation and structuring program: IN607B); Barcelona: The authors acknowledge the Cellex Foundation for providing research facilities and equipment and thank the CERCA Programme/Generalitat de Catalunya for institutional support. SG-E was supported by the ISCIII Miguel Servet II Program (CP16/00034). UK: Cambridge: AD was supported by Cancer Research-UK C8197/A16565. Leicester: University Hospitals Leicester: Support from the HOPE Clinical Trials Unit and Leicester Experimental Cancer Medicine Center (ECMC), Theresa Beaver, Sara Barrows; Manchester: CW was supported by Cancer Research UK (C1094/A18504, C147/A25254). AC and CW are supported by the NIHR Manchester Biomedical Research Center. USA: Mount Sinai Hospital, New York. LeND cohort: We would like to thank all patients who participated in this study. Cambridge IMRT trial: We would like to acknowledge the work of Miss Jenny Wilkinson, research radiographer who was supported by funding from Breast Cancer Now (formerly Breast Cancer Campaign). We would also like to thank all the patients who participated in the trial. GB receives funding from the Cancer Research UK Radiation Research Unit at the University of Cambridge (CRUK RadNet: Cambridge, C17918/A28870). CEC was supported by the Cambridge NIHR Biomedical Research Center. German ISE cohort: The researchers at DKFZ thank Ursula Eilber and Irmgard Helmbold, all patients and staff at the participating clinics involved in the project. Funding Information: TRat is currently an NIHR Clinical Lecturer. He was previously funded by a National Institute of Health Research (NIHR) Doctoral Research Fellowship (DRF 2014-07-079). This publication presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The REQUITE study received funding from European Union{\textquoteright}s 7th Framework Programme for research, technological development and demonstration under grant agreement no. 601826. The ISE study was supported by the German Office for Radiation Protection, project number St. Sch. 4116 and 4233. The LeND study received funding from Breast Cancer Now (formerly Breast Cancer Campaign) under grant ref. 2007NovPR45. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Rattay, Seibold, Aguado-Barrera, Altabas, Azria, Barnett, Bultijnck, Chang-Claude, Choudhury, Coles, Dunning, Elliott, Farcy Jacquet, Guti{\'e}rrez-Enr{\'i}quez, Johnson, M{\"u}ller, Post, Rancati, Reyes, Rosenstein, De Ruysscher, de Santis, Sperk, Stobart, Symonds, Taboada-Valladares, Vega, Veldeman, Webb, West, Valdagni, Talbot and REQUITE consortium.",
year = "2020",
month = oct,
day = "30",
doi = "10.3389/fonc.2020.575909",
language = "English",
volume = "10",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media S.A.",
}