Abstract P3-15-07: Cutaneous toxicity and recovery: Is there a difference between breast cancer patients treated with daily radiotherapy in the morning versus the afternoon?
Authors: Lee A , Yang X , Mister D , Liu T , Torres MA 
Published: August 2014

Abstract
Background: The human body is most immunologically primed to respond to injury one hour after awakening when peak cortisol levels are achieved. Previous studies have shown that acute stressors like surgery induce a redistribution of immune cells within the body and immediate leukocyte trafficking to the skin in response to cutaneous injury. When surgery is performed during peak cortisol levels (AM), recovery is significantly shorter due to the rapid immunologic response. However, no study has assessed whether the timing of daily radiotherapy (RT) treatment (AM vs. PM) impacts cutaneous healing in breast cancer patients undergoing whole breast RT. The purpose of this study is to compare cutaneous toxicity and recovery in breast cancer patients treated in the morning vs. those treated in the afternoon with standard breast RT.
Methods: Forty post-lumpectomy breast cancer patients were enrolled in a prospective, longitudinal ultrasound imaging study to objectively quantify RT-induced cutaneous toxicity and recovery. Twenty-two women received treatment before 9am and eighteen were treated after 3pm for the duration of their treatment course. All subjects received standard whole breast RT (50 Gy plus a 10 Gy boost in 30 total fractions). Patients were assessed 1 week prior to RT (baseline, T1), week 6 of RT (T2), and 6 weeks (T3), 3 months (T4), 6 months (T5) and 1 year (T6) post-RT. All four quadrants of the affected and unaffected breast were imaged with a 10-MHz ultrasound. Epidermal thickness was measured as a proxy for cutaneous toxicity. A skin thickness ratio (STRA) was generated by normalizing the epidermal thickness measurements to the corresponding contralateral breast measurements. RT-induced skin toxicity was assessed by measuring the change in STRA from baseline to T2, T3, T4, T5 and T6. The recovery time point was determined by identifying the STRA ratio measured after RT most closely approximating that of baseline. Differences in STRA for each patient was assessed at each time point and subsequently compared between patients treated daily before 9am vs. those treated after 3pm.
Results: A total of 138 ultrasound scans were examined. Regardless of treatment time (AM vs. PM), the STRA returned to near normal levels at T6 as indicated by non-significant STRA differences when compared to baseline. Skin thickness change maximized at T5 for the pre-9am group (0.380, 95%CI 0.118-0.641) and at T4 for the post-3pm group (0.487, 95%CI 0.162-0.813). Comparison of STRA changes between subjects treated before 9am and after 3pm showed significantly better recovery at T4 for the morning group (p = 0.049), but were not conclusively different at all other time points.
Conclusions: This study is the first of its kind to objectively document the development of skin toxicity in breast cancer patients treated with daily RT in the AM vs. PM using quantitative ultrasound. Our findings suggest that morning treatment with RT may result in less skin toxicity 3 months post-RT but timing of daily RT did not impact cutaneous toxicity during RT or recovery by 6 months and 1 year post-RT. Further investigation is warranted with a larger cohort and consistent follow up to better ascertain the effect size.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-15-07.