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Cancer-related fatigue is an extremely common and debilitating psychiatric symptom that affects up to 80% of cancer patients. Despite its negative impact on the patient's quality of life, there is no well-established biomarker or mechanisms associated with this debilitating condition. The functional brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with a variety of psychiatric illnesses. We hypothesized that Val66Met may influence the risk for developing cancer-related fatigue. BDNF Val66Met was analyzed by polymerase chain reaction in 180 patients with confirmed cancer diagnoses. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACIT-Fatigue) questionnaire. Depression was measured using the Hamilton Depression Scale (HAM-D). Data were transformed when necessary and regression models were constructed to access the association between genotype and symptom severity. Participants carrying the Met allele reported significantly less fatigue compared to the Val/Val genotype group. The presence of the Met allele did not influence depression levels. The results suggest that the BDNF Val66Met polymorphism confers protective advantage against cancer-related fatigue; whereas having the Val/Val genotype may be a genetic risk factor. Findings from this study not only provide clues to the neural basis of cancer-related fatigue, but also allow for symptom severity prediction and patient education with the goal to improve symptom management.

Following the publication of the article, the authors realized that they have overlooked acknowledging the assistance they received from the Murine Phenotyping Core at NHLBI. Therefore, the Acknowledgements section of the Declarations should also have stated the following: 'We would like to thank the Murine Phenotyping Core at NHLBI for all their help with the mouse experiments, including Dr Danielle Springer, Audrey Noguchi, Michele Allen, Heather Potts and Morteza Peiravi.' The authors regret their oversight in failing to include this information in the Acknowledgements section of their paper. [the original article was published in International Journal of Molecular Medicine 45: 485‑496, 2020; DOI: 10.3892/ijmm.2019.4435].

Cancer-related fatigue (CRF) is commonly reported by patients both during and after receiving treatment for cancer. Current CRF diagnoses rely on self-report questionnaires which are subject to report and recall biases. Objective measurements using a handheld dynamometer, or handgrip device, have been shown in recent studies to correlate significantly with subjective self-reported fatigue scores. However, variations of both the handgrip fatigue test and fatigue index calculations exist in the literature. The lack of standardized methods limits the utilization of the handgrip fatigue test in the clinical and research settings. In this study, we provide detailed methods for administering the physical fatigue test and calculating the fatigue index. These methods should supplement existing self-reported fatigue questionnaires and help clinicians assess fatigue symptom severity in an objective and quantitative manner.

Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is the standard of care treatment for non‑metastatic prostate cancer (NMPC). Despite the efficacy, treatment‑related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. A total of 64 participants with NMPC were enrolled. Fatigue was assessed using the Functional Assessment of Cancer Therapy‑Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMCs) extracted from participants' whole blood. An ADT/RT‑induced fatigue mouse model was developed, with fatigue measured as a reduction in voluntary wheel‑running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the ADT/RT mouse brains using western blot analysis of glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). The results demonstrated that fatigue in the ADT group was exacerbated during RT compared with the non‑ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMCs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non‑fatigued subjects, indicative of mitochondrial dysfunction. The ADT/RT mice demonstrated the synergistic effect of ADT and RT in decreasing VWRA. Brain tissues of ADT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. In conclusion, these findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (CNS). The synergistic effect of ADT/RT is behaviorally reproducible in a mouse model and its mechanism may be related to bioenergetics in the CNS.

Background: Cancer-related fatigue (CRF) is a debilitating symptom frequently reported by patients during and after treatment for cancer. CRF is a multidimensional experience and is often solely assessed by self-report measures. The goal of the study is to examine the physical and cognitive aspects of self-reported CRF using a cognitive function test and a physical fatigue index in order to provide objective measures that can characterize the CRF phenotype., Methods: A total of 59 subjects with nonmetastatic prostate cancer receiving external beam radiation therapy were included in the study. Fatigue was measured using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire. Cognitive characteristics of CRF was measured using the Stroop Color-Word Interference computerized test and the motor aspect of fatigue was measured using the static fatigue test using a handgrip dynamometer., Findings: Functional Assessment of Cancer Therapy-Fatigue scores significantly correlated with the Stroop Interference score, but not performance accuracy in all test conditions. Fatigued subjects exhibited a more rapid decline to 50% of maximal strength and increased static fatigue index in the handgrip test, whereas maximal grip strength was not affected., Conclusions: The results suggest that CRF exhibits both cognitive and physical characteristics. Subjective fatigue was associated with increased time required to overcome cognitive interference, but not cognitive performance accuracy. Fatigued patients exhibited decreased physical endurance and the ability to sustain maximal strength over time. These objective measures may serve as valuable tools for clinicians to detect cognitive and physical impairment associated with CRF., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Cancer Medicine published by John Wiley & Sons Ltd.)