Mitochondrial Bioenergetics Profile Indicates Likelihood of Radiation-Induced Fatigue in Prostate Cancer
Fatigue, a common symptom of cancer treatment, can adversely affect a patients quality of life.
|The following article features coverage from the 2017 Oncology Nursing Society's Annual Conference in Denver, Colorado. Click here to read more of Oncology Nurse Advisor's conference coverage.|
Mitochondrial oxidative phosphorylation rate in lymphocytes of patients with nonmetastatic prostate cancer decreased at midpoint and endpoint of radiation therapy, causing an increase in fatigue at midpoint of therapy that persisted through completion of radiation therapy, according to study results presented at the 2017 Oncology Nursing Society Annual Congress.
Fatigue is a common and burdensome symptom of cancer treatment that has the greatest impact on quality of life. However, the physiological mechanisms of the symptom and its increased severity in patients with nonmetastatic prostate cancer undergoing localized radiation therapy remain unknown. Therefore, a team of researchers at Case Western Reserve University in Cleveland, Ohio, sought to determine the association between mitochondrial bioenergetics and fatigue in this patient population.
The researchers proposed a mitochondrial bioenergetics mechanism linking impaired ATP production as a result of radiation therapy led to radiation-induced fatigue via a molecular-genetic approach.
Based on preliminary findings, they hypothesize that decreased BCS1L leads to a decrease of Rieske iron-sulfur protein incorporation into complex III, leading to a defect in complex III activity that impairs mitochondrial oxidative phosphorylation resulting in decreased ATP production, contributing to fatigue.
This was an ongoing clinical research project involving prospective hypothesis-testing with a longitudinal research design. Fatigue was measured using Patient Reported Outcomes Measurement Information System for Fatigue (PROMIS-F). Lymphocytes harvested from patients' peripheral blood using an Oxygraph-2k (O2k) high-resolution respirometry system were used to measure mitochondrial bioenergetics. Data were collected at 3 points: baseline, midpoint, and endpoint; then analyzed using paired t-tests and linear mixed models.
For this analysis, data from 15 patients with prostate cancer undergoing localized radiation therapy were completed. Results showed fatigue score increased at the midpoint of radiation therapy and persisted until treatment was completed (P =.01). Mitochondrial oxidative phosphorylation rate, coupled and uncoupled rates of complex I and III, decreased in lymphocytes of patients with nonmetastatic prostate cancer at midpoint and endpoint of radiation therapy. Furthermore, higher fatigue scores appear to be associated with decreased mitochondrial oxidative phosphorylation in this patient population reporting fatigue.
“This project is an essential step in pursuing a novel hypothesis designed to reveal the physiologic mechanisms of cancer-related fatigue,” explained Chao-Pin Hsiao, PhD, RN, of the School of Nursing, Case Western Reserve University. “Our results identify potential targets for pharmacological and, in particular, nutraceutical interventions and initiate a new direction for design of nursing interventions for cancer-related fatigue.”
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1. Hsiao CP, Daly B, Hoppel C. Decreased mitochondrial bioenergetics profile in fatigued men with prostate cancer undergoing radiation therapy. Oral presentation at: Oncology Nursing Society 42nd Annual Congress; May 4-7, 2017; Denver, CO.