Abstract P1-10-07: Prospective longitudinal study of epidermal thickening in breast cancer patients treated with conventional versus hypofractionated radiotherapy
Authors: Torres MA , Yang X , Mister D , Ali A , Kahn S , Liu T 
Published: May 2019

Abstract
Purpose: We conducted two prospective longitudinal studies of epidermal thickening in breast cancer (BRCA) patients treated with either conventional (CRT) or hypofractionated radiotherapy (HRT) using ultrasound images to objectively measure radiotherapy (XRT)-induced skin changes. Methods: Following breast conserving surgery, 105 consenting Stage 0-IIIA BRCA patients were enrolled on two studies of whole breast XRT without regional nodal irradiation. In the first, 66 subjects were treated with conventional fractionation (50 Gy plus a sequential 10 Gy boost at 2 Gy per fraction). In the second, subsequent study, 39 patients with characteristics under-represented in trials of HRT were treated to 39.9 Gy at 2.66 Gy per fraction with a simultaneous integrated boost of 8.1 Gy at 0.54 Gy per fraction. Inclusion criteria for this trial included breast separation &gt;25cm, age &lt;50 years, chemotherapy treatment, or non-Caucasian race. Prior to XRT, the last week of XRT, and 12 weeks and 1 year post XRT, subjects underwent objective ultrasound measurements of epidermal thickness over all four quadrants of the treated breast. A skin thickness ratio (STRA) was generated normalizing for corresponding measurements taken of the untreated breast. Pertinent patient, tumor, and treatment characteristics were collected at all time points, as well as peripheral blood for gene expression assays and assessment of inflammatory markers. Results: HRT patients were significantly younger than CRT patients [mean age 52 (38-73) versus (vs.) 56 years (26-75), p=0.03]. There were no other significant differences in patient, tumor, or treatment characteristics. Baseline measurements indicated 68% of CRT (mean increase 27%, SD 0.30) vs. 71% of HRT patients (mean increase 23%, SD 0.29) had skin thickening in the treated versus untreated breast prior to XRT (p=0.50). At all subsequent time points, CRT patients had significantly higher mean STRA than HRT patients [1.53, SD 0.48 vs. 1.33, SD 0.34 during RT (p=0.03); 1.62, SD 0.48 vs. 1.31, SD 0.45 at 12 weeks post RT (p=0.002); and 1.45, SD 0.39 vs. 1.27, SD 0.40 at 1 year post RT (p=0.03), respectively]. At 1 year, 31% of CRT and 38% of HRT patients had an STRA which was either less than or equal to baseline, indicating full recovery. In multivariable analysis, baseline STRA (p&lt;0.001), BMI (p=0.002), chemotherapy (p=0.004) and CRT treatment (p=0.02) predicted for higher STRA 1 year post XRT. Dmax and breast volume receiving 107% of the dose did not predict for STRA. Gene ontology analysis revealed an over-representation of genes, differentially regulated among patients with high and low STRA, involved in the immune and defense responses. Tumor necrosis factor 2 receptor levels were also significantly higher in CRT than HRT treated patients at 1 year (p=0.03). Conclusions: Our findings indicate that CRT is associated with higher and more severe changes in STRA up 1 year after XRT than HRT, even among patients perceived to be at high risk for XRT-induced skin toxicity and who were not well-represented in the original HRT trials. An increase in peripheral markers of inflammation may be one mechanism by which CRT, BMI, and chemotherapy are associated with higher STRA 1 year post XRT.
Citation Format: Torres MA, Yang X, Mister D, Ali A, Kahn S, Liu T. Prospective longitudinal study of epidermal thickening in breast cancer patients treated with conventional versus hypofractionated radiotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-07.