Abstract OT2-1-01: A personalized approach to understanding the development of radiation-induced fatigue
Authors: Mulay S , Grady J , Dowsett R , Liang B , Kamath J , Tannenbaum S 
Published: August 2014

Abstract
Background
Fatigue, a common complication of radiation therapy, can impact patients’ quality of life and ability to engage in their cancer treatments. The pathogenesis of radiation-induced fatigue is unclear. This lack of clear understanding has hindered the development of treatment strategies to overcome this morbidity. The purpose of our exploratory, non-randomized, prospective study is to investigate the factors associated with development of radiation-induced fatigue in women with early breast cancer. Our study is based on the hypotheses that adjuvant radiation therapy given to women with breast cancer for local disease control causes tissue damage by apoptosis and inflammation. This leads to increased levels of inflammatory cytokines and biomarkers of apoptosis. This inflammatory cascade differentially induces fatigue in patients depending on their baseline psychological profile.
Trial design
Existing patient flow in the radiation oncology division will be utilized to screen eligible subjects. All subjects will assessed at five different time points, beginning immediately before radiation therapy through 1 year after completion of therapy. Detailed clinical evaluation of skin toxicity (RTOG acute toxicity criteria) and laboratory parameters assessing anemia, cardiac and hepatic toxicity will be performed. Comprehensive psychological assessment will be done using questionnaires for fatigue, distress, depression, sleep, quality of life and pain. Buccal mucosa swabs will be obtained for genetic analysis in future studies.
Selection criteria
Inclusion: Women with breast cancer undergoing radiation therapy for breast conservation
Exclusion: Prior non-breast malignancy with active treatment (radiation or chemotherapy) within 1 year of enrolment on the study
Specific aims
1. To measure the severity of radiation-induced tissue damage
2. To measure circulating markers of apoptosis (caspase 3 p17) and inflammation
3. To establish a baseline psychological profile for each subject prior to start of radiation and determine temporal changes during the course of radiation therapy.
4. To determine the correlation between goals 1, 2 and 3.
5. To propose interventions for reducing radiation-induced fatigue which will be evaluated in a future study.
Statistical methods
The association between fatigue and severity of tissue toxicity (Yes vs. No) will be assessed using chi-square tests (eg, row mean score test). ANOVA will be used to compare mean visual analogue scales (VAS) and psychological questionnaire scores across the levels of the tissue toxicity scale. Mean log cytokine levels will be compared across levels of the dermatitis scale using ANOVA. The association between cytokines and fatigue will be assessed using correlation (eg, VAS) and two-group t-tests (eg, Yes vs. No) depending on which fatigue outcome is used. Two statistical models will be used to assess fatigue and its relationship to dermatitis, cytokine level, and their interactive effects using logistic regression (for dichotomous) and OLS regression (for VAS) approaches.
Present accrual: 0; Study initiation planned for July 1, 2013
Target accrual : 100.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-1-01.