An Explorative Study on Physiological and Neurophysiological Determinants of Fatigue in Cancer Survivors

Postcancer fatigue is a severe and invalidating problem, impairing quality of life. About 20 to 40% of the patients remain fatigued, at least one year after successful cancer treatment. Fortunately, there is an effective treatment for postcancer fatigue; cognitive behavior therapy. However, no cause for postcancer fatigue has been identified yet. The aim of the study is to identify factors that (partly) cause postcancer fatigue to improve the theoretical understanding of fatigue and to improve the diagnostics of fatigue, predict therapy outcome, and facilitate other treatment options. In this study, disease-free fatigued cancer patients, who finished treatment for cancer at least one year and maximally ten years ago, will be approached for this study. They will be compared to non-fatigued patients. First, a baseline assessment will take place. Magnetic resonance imaging of the brains will be performed to assess brain volume and magnetic resonance spectroscopy will be performed to measure the concentrations of specific substances in the brains. Changes in the volume of parts of the brains have been observed in (non-cancer) patients with the chronic fatigue syndrome (CFS), in comparison with healthy controls. In addition, abnormal concentrations of specific substances have been observed in patients with CFS compared to healthy controls. To assess muscle fatigue, a two-minute endurance test of the upper arm will be administered at maximal voluntary contraction. Next to differences in the brains, CFS patients showed (central) muscle fatigue. A maximal exercise test on a bicycle will be performed to assess physical fitness. Physical activity in fatigued cancer survivors is decreased, compared to healthy controls. It is not known whether physical deconditioning originated during the cancer treatment is the reason why these patients are still less active. In addition, patients and controls will wear an actometer for two weeks to register baseline daily physical activity and for an additional 5 days after the maximal exercise test, to assess the effect of exercise on the daily physical activity. Finally, patients and controls will complete standardized questionnaires and will perform neurological/psychological tests, like a reaction time test and a short time memory task, at baseline. The results of the non-fatigued and the fatigued patients will be compared at baseline. For the non-fatigued participants, the study will be finished after the baseline measurements. The fatigued participants will start with cognitive behavior therapy immediately after the baseline measurements or after 6 months, depending on the randomization. At the end of the therapy, after six months, or after 6 months of waiting for cognitive behavior therapy, a second assessment will take place, comparable to the baseline measurements. These results will be compared with the baseline situation to analyze the effect of cognitive behavior therapy on the (possible) causes of postcancer fatigue.

Sex

All

Minimum age

19 Years

Maximum age

65 Years

Inclusion Criteria:

* Treated for a malignant solid tumour.
* Completion of treatment for cancer minimal 1 year ago
* Single treatment modality surgery permitted
* Current hormonal therapy permitted
* Disease-free, as defined by the absence of somatic disease activity parameters.
* Age between 19 and 65.
* Age at disease onset minimal 18 years

Exclusion Criteria:

* Brain tumour in the past
* Current psychological or psychiatric treatment.
* Physical comorbidity which could explain the fatigue.
* Contra-indication for MR examinations (e.g. claustrophobia).
* Treatment with anti-depressive drugs, anti-epileptic drugs, benzodiazepines.
* Insufficient command of the Dutch language to fill out questionnaires.

• DERIVEDMuller F, Wijayanto F, Abrahams H, Gielissen M, Prinsen H, Braamse A, van Laarhoven HWM, Groot P, Heskes T, Knoop H. Potential mechanisms of the fatigue-reducing effect of cognitive-behavioral therapy in cancer survivors: Three randomized controlled trials. Psychooncology. 2021 Sep;30(9):1476-1484. doi: 10.1002/pon.5710. Epub 2021 May 3. PMID 33899978
• DERIVEDTer Veer E, Prinsen H, Sprangers MAG, Zwinderman KAH, Bleijenberg G, van der Pouw Kraan TCTM, de Vries IJM, Wierenga EA, van Laarhoven HWM. Interferon Gamma-Induced Protein (IP-10) as Potential Biomarker for Cancer-Related-Fatigue: Results from a 6-month Randomized Controlled Trial. Cancer Invest. 2018;36(7):371-377. doi: 10.1080/07357907.2018.1499933. Epub 2018 Sep 6. PMID 30188739
• DERIVEDPrinsen H, Heerschap A, Bleijenberg G, Zwarts MJ, Leer JW, van Asten JJ, van der Graaf M, Rijpkema M, van Laarhoven HW. Magnetic resonance spectroscopic imaging and volumetric measurements of the brain in patients with postcancer fatigue: a randomized controlled trial. PLoS One. 2013 Sep 11;8(9):e74638. doi: 10.1371/journal.pone.0074638. eCollection 2013. PMID 24040301
• DERIVEDPrinsen H, Bleijenberg G, Heijmen L, Zwarts MJ, Leer JW, Heerschap A, Hopman MT, van Laarhoven HW. The role of physical activity and physical fitness in postcancer fatigue: a randomized controlled trial. Support Care Cancer. 2013 Aug;21(8):2279-88. doi: 10.1007/s00520-013-1784-9. Epub 2013 Mar 22. PMID 23519566
• DERIVEDPrinsen H, Bleijenberg G, Zwarts MJ, Hopman MT, Heerschap A, van Laarhoven HW. Physiological and neurophysiological determinants of postcancer fatigue: design of a randomized controlled trial. BMC Cancer. 2012 Jun 18;12:256. doi: 10.1186/1471-2407-12-256. PMID 22708881