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

Published on Oct 30, 2020in Frontiers in Oncology4.848
· DOI :10.3389/FONC.2020.575909
Tim Rattay8
Estimated H-index: 8
(University of Leicester),
Petra Seibold27
Estimated H-index: 27
(DKFZ: German Cancer Research Center)
+ 116 AuthorsSheryl Green17
Estimated H-index: 17
Sources
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.
References55
Newest
#1Mélissa Roy (U of T: University of Toronto)H-Index: 6
#2Stephanie Sebastiampillai (UHN: University Health Network)H-Index: 4
Last. Anne C. O'Neill (U of T: University of Toronto)H-Index: 14
view all 6 authors...
BACKGROUND: Immediate breast reconstruction has many advantages but is associated with higher complication rates than delayed reconstruction. Complications can delay the delivery of adjuvant cancer treatments. This study aimed to develop and validate a risk stratification model for the prediction of perioperative complications in immediate microvascular breast reconstruction. METHODS: The association between patient and treatment variables and perioperative complications was evaluated in a retro...
4 CitationsSource
#1Petra Seibold (DKFZ: German Cancer Research Center)H-Index: 27
#2A Webb (University of Leicester)H-Index: 9
Last. William Li (The Queen's Medical Center)H-Index: 1
view all 128 authors...
Abstract Purpose REQUITE aimed to establish a resource for multi-national validation of models and biomarkers that predict risk of late toxicity following radiotherapy. The purpose of this article is to provide summary descriptive data. Methods An international, prospective cohort study recruited cancer patients in 26 hospitals in eight countries between April 2014 and March 2017. Target recruitment was 5300 patients. Eligible patients had breast, prostate or lung cancer and planned potentially ...
15 CitationsSource
#1Maysa Pouri (Mazandaran University of Medical Sciences)H-Index: 1
#2Zahra Shaghaghi (Mazandaran University of Medical Sciences)H-Index: 3
Last. Seyed Jalal Hosseinimehr (Mazandaran University of Medical Sciences)H-Index: 31
view all 4 authors...
OBJECTIVES: Gliclazide (GL) is widely used to reduce hyperglycemia in diabetic patients. The aim of this study was to investigate the protective effect of GL against chromosome damage induced by ionizing radiation in human blood lymphocytes. METHODS: In this experimental study, peripheral blood samples were collected from human volunteers and treated with GL at various concentrations (5, 25, 50 or 100 μM) for three hours. Then samples were irradiated to X-ray (1.5 Gy). Blood samples were culture...
2 CitationsSource
#1John Kang (URMC: University of Rochester Medical Center)H-Index: 7
#2Tiziana RancatiH-Index: 27
Last. Barry S. Rosenstein (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 35
view all 9 authors...
Due to the rapid increase in the availability of patient data, there is significant interest in precision medicine that could facilitate the development of a personalized treatment plan for each patient on an individual basis. Radiation oncology is particularly suited for predictive machine learning models due to the enormous amount of diagnostic data used as input and therapeutic data generated as output. An emerging field in precision radiation oncology that can take advantage of machine learn...
32 CitationsSource
#1Nima Khavanin (Johns Hopkins University)H-Index: 2
#1Nima Khavanin (Johns Hopkins University)H-Index: 17
Last. John Y.S. Kim (NU: Northwestern University)H-Index: 39
view all 7 authors...
Summary Introduction The Breast reconstruction Risk Assessment (BRA) Score estimates patient-specific risk for postsurgical complications using an individual's unique combination of preoperative variables. In this report, we externally validate the BRA Score models for surgical site infection, seroma, and explantation in a large sample of intra-institutional patients who underwent prosthetic breast reconstruction. Methods We reviewed all initiated tissue expander/implant reconstructions by the s...
8 CitationsSource
#1Mohsen Cheki (Tehran University of Medical Sciences)H-Index: 13
#2Alireza Shirazi (Tehran University of Medical Sciences)H-Index: 19
Last. Seyed Jalal Hosseinimehr (Mazandaran University of Medical Sciences)H-Index: 31
view all 5 authors...
Abstract Metformin is a widely prescribed drug used in the treatment of patients with type 2 diabetes. In this study, the radioprotective effect of metformin was investigated against cytotoxicity and genotoxicity induced by ionizing radiation (IR) in human peripheral blood lymphocytes. Human lymphocytes were treated with metformin at concentrations 10 and 50 μM for 2 h and irradiated with 6 MV X-rays. The radiation antagonistic potential of metformin was assessed by MTT [3-(4,5-dimethyl-2-thiaoz...
27 CitationsSource
#1Chamberlain Mbah (UGent: Ghent University)H-Index: 3
#2Hubert Thierens (UGent: Ghent University)H-Index: 61
Last. Kim De Ruyck (UGent: Ghent University)H-Index: 23
view all 9 authors...
Purpose To identify the main causes underlying the failure of prediction models for radiation therapy toxicity to replicate. Methods and Materials Data were used from two German cohorts, Individual Radiation Sensitivity (ISE) (n=418) and Mammary Carcinoma Risk Factor Investigation (MARIE) (n=409), of breast cancer patients with similar characteristics and radiation therapy treatments. The toxicity endpoint chosen was telangiectasia. The LASSO (least absolute shrinkage and selection operator) log...
6 CitationsSource
#1A. Murray Brunt (Keele University)H-Index: 6
#2Duncan Wheatley (Royal Cornwall Hospital)H-Index: 22
Last. Judith M. Bliss (ICR: Institute of Cancer Research)H-Index: 77
view all 15 authors...
Abstract Background and purpose FAST-Forward is a phase 3 clinical trial testing a 1-week course of whole breast radiotherapy against the UK standard 3-week regimen after primary surgery for early breast cancer. Two acute skin toxicity substudies were undertaken to test the safety of the test schedules with respect to early skin reactions. Material and methods Patients were randomly allocated to 40Gy/15 fractions (F)/3-weeks, 27Gy/5F/1-week or 26Gy/5F/1-week. Acute breast skin reactions were gra...
69 CitationsSource
#1Francesco PastoreH-Index: 1
#2Manuel Conson (National Research Council)H-Index: 18
Last. Roberto Pacelli (National Research Council)H-Index: 26
view all 10 authors...
AbstractBackground: Severe acute radiation-induced skin toxicity (RIST) after breast irradiation is a side effect impacting the quality of life in breast cancer (BC) patients. The aim of the present study was to develop normal tissue complication probability (NTCP) models of severe acute RIST in BC patients.Patients and methods: We evaluated 140 consecutive BC patients undergoing conventional three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery in a prospective study...
24 CitationsSource
#1Robin Wijsman (Radboud University Nijmegen)H-Index: 7
#2Frank J. W. M. Dankers (Radboud University Nijmegen)H-Index: 8
Last. Johan Bussink (Radboud University Nijmegen)H-Index: 40
view all 7 authors...
Abstract Background and purpose The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to distinct dosimetric characteristics of intensity-modulated radiation therapy (IMRT), 3D-CRT based models need revision. We established a multivariable NTCP model for AET in 149 AS-NSCLC patient...
34 CitationsSource
Cited By1
Newest
#1Rainer J. KlementH-Index: 27
#2Michael M. WeigelH-Index: 3
Last. Reinhart A. SweeneyH-Index: 20
view all 3 authors...
Summary Background & Aims Ketogenic diets (KDs) have been proposed as complementary nutritional treatments for cancer patients. Because it is important to gain knowledge about the safety of KDs adopted during cancer therapy, we studied the effects of KDs on quality of life and blood parameters in women with early-stage breast cancer undergoing radiotherapy. Methods A total of 29 patients consuming a KD were compared to 30 patients consuming their standard diet (SD) with respect to EORTC-QLQ30 qu...
2 CitationsSource