External Validation of a Predictive Model for Acute Skin Radiation Toxicity in the REQUITE Breast Cohort

Tim Rattay*, Petra Seibold, Miguel E. Aguado-Barrera, Manuel Altabas, David Azria, Gillian C. Barnett, Renee Bultijnck, Jenny Chang-Claude, Ananya Choudhury, Charlotte E. Coles, Alison M. Dunning, Rebecca M. Elliott, Marie-Pierre Farcy Jacquet, Sara Gutierrez-Enriquez, Kerstie Johnson, Anusha Mueller, Giselle Post, Tiziana Rancati, Victoria Reyes, Barry S. RosensteinDirk De Ruysscher, Maria C. de Santis, Elena Sperk, Hilary Stobart, R. Paul Symonds, Begona Taboada-Valladares, Ana Vega, Liv Veldeman, Adam J. Webb, Catharine M. West, Riccardo Valdagni, Christopher J. Talbot, REQUITE consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article number575909
Number of pages14
JournalFrontiers in Oncology
Publication statusPublished - 30 Oct 2020


  • breast cancer
  • early toxicity
  • prediction model
  • radiotherapy
  • validation

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