Follow the TRAIL: understanding the etiology of persistent fatigue and cognitive impairment following radiation therapy

Authors

• LR Feng
• K Filler
• A Espina
• M Renner
• LN Saligan

Abstract

Fatigue is one of the most debilitating side effects of cancer and cancer therapy, and it persists long after treatment completion. In this study, we aimed to investigate changes in immunological markers in fatigued men receiving external beam radiation therapy for non-metastatic prostate cancer. A sample of 34 men with prostate cancer scheduled to receive radiation therapy were followed at baseline and one year after treatment completion. Demographic and clinical data were obtained by chart review. The Functional Assessment of Cancer Therapy-Fatigue (FACT-F) was administered to measure fatigue levels. Gene expression profiles were determined using microarray analysis and analyzed using Partek Genomics Suite 6.6 as well as Ingenuity Pathway Analysis. At one year after EBRT completion, 34% of subjects continued to experience persistent fatigue. Microarray analysis of blood samples collected one year following radiation therapy revealed 44 genes that were differentially expressed between fatigued and non-fatigued subjects. The main disease networks identified by pathway analysis are related to cancer pathophysiology. Compared to non-fatigued subjects, there was an increase in expression levels of the decoy receptor TRAIL-R3 in the fatigued group. Interestingly, the ligand of this receptor, TRAIL, is also significantly upregulated in fatigued subjects. Evidence of the involvement of cancer disease networks as well as the concomitant upregulation of TRAIL and its decoy receptor suggest that fatigue and cognitive impairment may be more than distressing side effects of cancer treatment. Instead, these symptoms may serve as behavioral indicators of the underlying disease status in cancer patients.

Scientific Focus Area: Immunology

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