AUTHOR=Rattay Tim , Seibold Petra , Aguado-Barrera Miguel E. , Altabas Manuel , Azria David , Barnett Gillian C. , Bultijnck Renée , Chang-Claude Jenny , Choudhury Ananya , Coles Charlotte E. , Dunning Alison M. , Elliott Rebecca M. , Farcy Jacquet Marie-Pierre , Gutiérrez-Enríquez Sara , Johnson Kerstie , Müller Anusha , Post Giselle , Rancati Tiziana , Reyes Victoria , Rosenstein Barry S. , De Ruysscher Dirk , de Santis Maria C. , Sperk Elena , Stobart Hilary , Symonds R. Paul , Taboada-Valladares Begoña , Vega Ana , Veldeman Liv , Webb Adam J. , West Catharine M. , Valdagni Riccardo , Talbot Christopher J. , REQUITE consortium , Lievens Yolande , van Eijkeren Marc , Ost Piet , Fonteyne Valérie , Monten Christel , De Neve Wilfried , Peeters Stephanie , Haustermans Karin , Weltens Caroline , Defraene Gilles , Lambrecht Maarten , van Limberghen Erik , Briers Erik , Bourgier Celine , Brengues Muriel , Draghici Roxana , Bons Francoise , Blaschke Thomas , Weiß Christian , Helmbold Irmgard , Weißenberger Christian , Stegmaier Petra , Claßen Johannes , Giesche Ulrich , Sautter-Bihl Marie-Luise , Neu Burkhard , Schnabel Thomas , Ehmann Michael , Gauter-Fleckenstein Benjamin , Herskind Carsten , Veldwijk Marlon , Schäfer Jörg , Giandini Tommaso , Franceschini Marzia , Sangalli Claudia , Avuzzi Barbara , Morlino Sara , Lozza Laura , Pietro Gabriele , Delmastro Elena , Garibaldi Elisabetta , Cicchetti Alessandro , Vanneste Ben , Piqué-Leiva Bibiana , Molla Meritxel , Giraldo Alexandra , Ramos Monica , Lobato-Busto Ramon , Sosa-Fajardo Paloma , Moya Laura Torrado , Dominguez-Rios Isabel , Fajardo-Paneque Irene , Calvo-Crespo Patricia , Carballo Ana , Peleteiro Paula , Olivia-Fuentes-Rios , Gomez-Caamano Antonio , Harrop Victoria , Payne Debbie , Keni Manjusha , Lavers Samuel , Wright Simon , Thiagarajan Sridhar , Aznar-Garcia Luis , Kancherla Kiran , Kent Christopher , Vasanthan Subramaniam , Appleton Donna , Kaushik Monika , Kenny Frances , Khout Hazem , Krupa Jaroslaw , Lambert Kelly V. , Pilgrim Simon , Shokuhi Sheila , Valassiadou Kalliope , Bioangiu Ion , Sampson Kufre , Osman Ahmed , Faivre-Finn Corinne , Foweraker Karen , Pascoe Abigail , Esler Claire P. , Ward Tim , Higginson Daniel S. , Stock Richard G. , Green Sheryl
TITLE=External Validation of a Predictive Model for Acute Skin Radiation Toxicity in the REQUITE Breast Cohort
JOURNAL=Frontiers in Oncology
VOLUME=10
YEAR=2020
URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.575909
DOI=10.3389/fonc.2020.575909
ISSN=2234-943X
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.