Physiological and neurophysiological determinants of postcancer fatigue: design of a randomized controlled trial

BMC Cancer

Hetty Prinsen⁵  Gijs Bleijenberg¹  Machiel J Zwarts²  Maria T EHopman³  Arend Heerschap⁶  Hanneke W M van Laarhoven⁴ 

[1] Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

[2] Department of Clinical Neurophysiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

[3] Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

[4] Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

[5] Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

[6] Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

关键词: Physical activity;    Physical condition;    Brain metabolism;    Brain morphology;    Central fatigue;    Peripheral fatigue;    Cognitive behaviour therapy;    Postcancer fatigue;   

Others  :  1080351
DOI  :  10.1186/1471-2407-12-256

 received in 2012-05-09, accepted in 2012-06-18,  发布年份 2012

【 摘 要 】

Background

Postcancer fatigue is a frequently occurring, severe, and invalidating problem, impairing quality of life. Although it is possible to effectively treat postcancer fatigue with cognitive behaviour therapy, the nature of the underlying (neuro)physiology of postcancer fatigue remains unclear. Physiological aspects of fatigue include peripheral fatigue, originating in muscle or the neuromuscular junction; central fatigue, originating in nerves, spinal cord, and brain; and physical deconditioning, resulting from a decreased cardiopulmonary function. Studies on physiological aspects of postcancer fatigue mainly concentrate on deconditioning. Peripheral and central fatigue and brain morphology and function have been studied for patients with fatigue in the context of chronic fatigue syndrome and neuromuscular diseases and show several characteristic differences with healthy controls.

Methods/design

Fifty seven severely fatigued and 21 non-fatigued cancer survivors will be recruited from the Radboud University Nijmegen Medical Centre. Participants should have completed treatment of a malignant, solid tumour minimal one year earlier and should have no evidence of disease recurrence. Severely fatigued patients are randomly assigned to either the intervention condition (cognitive behaviour therapy) or the waiting list condition (start cognitive behaviour therapy after 6 months). All participants are assessed at baseline and the severely fatigued patients also after 6 months follow-up (at the end of cognitive behaviour therapy or waiting list). Primary outcome measures are fatigue severity, central and peripheral fatigue, brain morphology and function, and physical condition and activity.

Discussion

This study will be the first randomized controlled trial that characterizes (neuro)physiological factors of fatigue in disease-free cancer survivors and evaluates to which extent these factors can be influenced by cognitive behaviour therapy. The results of this study are not only essential for a theoretical understanding of this invalidating condition, but also for providing an objective biological marker for fatigue that could support the diagnosis and follow-up of treatment.

Trial registration

The study is registered at http://ClinicalTrials.gov webcite (NCT01096641).

【 授权许可】

   
2012 Prinsen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Bower JE, Ganz PA, Desmond KA, Bernaards C, Rowland JH, Meyerowitz BE, Belin TR: Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer 2006, 106(4):751-758.
• [2]Servaes P, van der Werf S, Prins J, Verhagen S, Bleijenberg G: Fatigue in disease-free cancer patients compared with fatigue in patients with chronic fatigue syndrome. Support Care Cancer 2001, 9(1):11-17.
• [3]Irvine D, Vincent L, Graydon JE, Bubela N, Thompson L: The prevalence and correlates of fatigue in patients receiving treatment with chemotherapy and radiotherapy. A comparison with the fatigue experienced by healthy individuals. Cancer Nurs 1994, 17(5):367-378.
• [4]Smets EM, Garssen B, Schuster-Uitterhoeve AL, de Haes JC: Fatigue in cancer patients. Br J Cancer 1993, 68(2):220-224.
• [5]Hjermstad MJ, Fossa SD, Oldervoll L, Holte H, Jacobsen AB, Loge JH: Fatigue in long-term Hodgkin's Disease survivors: a follow-up study. J Clin Oncol 2005, 23(27):6587-6595.
• [6]Nieboer P, Buijs C, Rodenhuis S, Seynaeve C, Beex LV, van der Wall E, Richel DJ, Nooij MA, Voest EE, Hupperets P, et al.: Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study. J Clin Oncol 2005, 23(33):8296-8304.
• [7]Servaes P, Gielissen MF, Verhagen S, Bleijenberg G: The course of severe fatigue in disease-free breast cancer patients: a longitudinal study. Psychooncology 2007, 16(9):787-795.
• [8]Servaes P, Verhagen S, Schreuder HW, Veth RP, Bleijenberg G: Fatigue after treatment for malignant and benign bone and soft tissue tumors. J Pain Symptom Manage 2003, 26(6):1113-1122.
• [9]Bartsch HH, Weis J, Moser MT: Cancer-related fatigue in patients attending oncological rehabilitation programs: prevalence, patterns and predictors. Onkologie 2003, 26(1):51-57.
• [10]Dimeo F, Schmittel A, Fietz T, Schwartz S, Kohler P, Boning D, Thiel E: Physical performance, depression, immune status and fatigue in patients with hematological malignancies after treatment. Ann Oncol 2004, 15(8):1237-1242.
• [11]Gielissen MF, Schattenberg AV, Verhagen CA, Rinkes MJ, Bremmers ME, Bleijenberg G: Experience of severe fatigue in long-term survivors of stem cell transplantation. Bone Marrow Transplant 2007, 39(10):595-603.
• [12]Okuyama T, Akechi T, Kugaya A, Okamura H, Shima Y, Maruguchi M, Hosaka T, Uchitomi Y: Development and validation of the cancer fatigue scale: a brief, three-dimensional, self-rating scale for assessment of fatigue in cancer patients. J Pain Symptom Manage 2000, 19(1):5-14.
• [13]Woo B, Dibble SL, Piper BF, Keating SB, Weiss MC: Differences in fatigue by treatment methods in women with breast cancer. Oncol Nurs Forum 1998, 25(5):915-920.
• [14]Gielissen MF, Verhagen S, Witjes F, Bleijenberg G: Effects of cognitive behavior therapy in severely fatigued disease-free cancer patients compared with patients waiting for cognitive behavior therapy: a randomized controlled trial. J Clin Oncol 2006, 24(30):4882-4887.
• [15]Bigland-Ritchie B, Jones DA, Hosking GP, Edwards RH: Central and peripheral fatigue in sustained maximum voluntary contractions of human quadriceps muscle. Clin Sci Mol Med 1978, 54(6):609-614.
• [16]Van Engelen BG, Kalkman JS, Schillings ML, Van Der Werf SP, Bleijenberg G, Zwarts MJ: Fatigue in neuromuscular disease. Ned Tijdschr Geneeskd 2004, 148(27):1336-1341.
• [17]Zwarts MJ, Stegeman DF: Multichannel surface EMG: basic aspects and clinical utility. Muscle Nerve 2003, 28(1):1-17.
• [18]Schillings ML, Hoefsloot W, Stegeman DF, Zwarts MJ: Relative contributions of central and peripheral factors to fatigue during a maximal sustained effort. Eur J Appl Physiol 2003, 90(5–6):562-568.
• [19]Gandevia SC: Neural control in human muscle fatigue: changes in muscle afferents, motoneurones and motor cortical drive [corrected]. Acta Physiol Scand 1998, 162(3):275-283.
• [20]Schillings ML, Kalkman JS, Janssen HM, van Engelen BG, Bleijenberg G, Zwarts MJ: Experienced and physiological fatigue in neuromuscular disorders. Clin Neurophysiol 2007, 118(2):292-300.
• [21]Schillings ML, Kalkman JS, van der Werf SP, van Engelen BG, Bleijenberg G, Zwarts MJ: Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome. Clin Neurophysiol 2004, 115(11):2518-2524.
• [22]Yavuzsen T, Davis MP, Ranganathan VK, Walsh D, Siemionow V, Kirkova J, Khoshknabi D, Lagman R, LeGrand S, Yue GH: Cancer-related fatigue: central or peripheral? J Pain Symptom Manage 2009, 38(4):587-596.
• [23]Kalkman JS, Schillings ML, van der Werf SP, Padberg GW, Zwarts MJ, van Engelen BG, Bleijenberg G: Experienced fatigue in facioscapulohumeral dystrophy, myotonic dystrophy, and HMSN-I. J Neurol Neurosurg Psychiatry 2005, 76(10):1406-1409.
• [24]Buchwald D, Cheney PR, Peterson DL, Henry B, Wormsley SB, Geiger A, Ablashi DV, Salahuddin SZ, Saxinger C, Biddle R, et al.: A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection. Ann Intern Med 1992, 116(2):103-113.
• [25]Greco A, Tannock C, Brostoff J, Costa DC: Brain MR in chronic fatigue syndrome. AJNR Am J Neuroradiol 1997, 18(7):1265-1269.
• [26]Lange G, DeLuca J, Maldjian JA, Lee H, Tiersky LA, Natelson BH: Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci 1999, 171(1):3-7.
• [27]Schwartz RB, Komaroff AL, Garada BM, Gleit M, Doolittle TH, Bates DW, Vasile RG, Holman BL: SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression. AJR Am J Roentgenol 1994, 162(4):943-951.
• [28]de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I: Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage 2005, 26(3):777-781.
• [29]Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N: Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol 2004, 4(1):14. BioMed Central Full Text
• [30]de Lange FP, Koers A, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I: Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome. Brain 2008, 131(Pt 8):2172-2180.
• [31]Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, Davey NJ: Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand 2002, 106(3):224-226.
• [32]Chaudhuri A, Condon BR, Gow JW, Brennan D, Hadley DM: Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Neuroreport 2003, 14(2):225-228.
• [33]Tomoda A, Miike T, Yamada E, Honda H, Moroi T, Ogawa M, Ohtani Y, Morishita S: Chronic fatigue syndrome in childhood. Brain Dev 2000, 22(1):60-64.
• [34]Brooks JC, Roberts N, Whitehouse G, Majeed T: Proton magnetic resonance spectroscopy and morphometry of the hippocampus in chronic fatigue syndrome. Br J Radiol 2000, 73(875):1206-1208.
• [35]Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, Otcheretko V, Coplan JD, Shungu DC: Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed 2009, 22(3):251-258.
• [36]Servaes P, Prins J, Verhagen S, Bleijenberg G: Fatigue after breast cancer and in chronic fatigue syndrome: similarities and differences. J Psychosom Res 2002, 52(6):453-459.
• [37]Irwin ML, Crumley D, McTiernan A, Bernstein L, Baumgartner R, Gilliland FD, Kriska A, Ballard-Barbash R: Physical activity levels before and after a diagnosis of breast carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer 2003, 97(7):1746-1757.
• [38]Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G: Dimensional assessment of chronic fatigue syndrome. J Psychosom Res 1994, 38(5):383-392.
• [39]VanderZee KI, Sanderman R, Heyink JW, de Haes H: Psychometric qualities of the RAND 36-Item Health Survey 1.0: a multidimensional measure of general health status. Int J Behav Med 1996, 3(2):104-122.
• [40]Beck AT, Guth D, Steer RA, Ball R: Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care. Behav Res Ther 1997, 35(8):785-791.
• [41]Ashburner J, Friston KJ: Voxel-based morphometry–the methods. Neuroimage 2000, 11(6 Pt 1):805-821.
• [42]Patenaude B, Smith SM, Kennedy DN, Jenkinson M: A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage 2011, 56(3):907-922.
• [43]Scheenen TW, Klomp DW, Wijnen JP, Heerschap A: Short echo time 1 H-MRSI of the human brain at 3 T with minimal chemical shift displacement errors using adiabatic refocusing pulses. Magn Reson Med 2008, 59(1):1-6.
• [44]Cox NJ, Hendriks JC, Binkhorst RA, Folgering HT, van Herwaarden CL: Reproducibility of incremental maximal cycle ergometer tests in patients with mild to moderate obstructive lung diseases. Lung 1989, 167(2):129-133.
• [45]Vercoulen JH, Bazelmans E, Swanink CM, Fennis JF, Galama JM, Jongen PJ, Hommes O, Van der Meer JW, Bleijenberg G: Physical activity in chronic fatigue syndrome: assessment and its role in fatigue. J Psychiatr Res 1997, 31(6):661-673.
• [46]Vercoulen JH, Swanink CM, Galama JM, Fennis JF, Jongen PJ, Hommes OR, van der Meer JW, Bleijenberg G: The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model. J Psychosom Res 1998, 45(6):507-517.
• [47]Bleijenberg G, Kuijpers HC: Biofeedback treatment of constipation: a comparison of two methods. Am J Gastroenterol 1994, 89(7):1021-1026.
• [48]Wiborg JF, Knoop H, Frank LE, Bleijenberg G: Towards an evidence-based treatment model for cognitive behavioral interventions focusing on chronic fatigue syndrome. J Psychosom Res 2012, 72(5):399-404.
• [49]van Sonderen E: Het meten van sociale steun met de Sociale Steun Lijst - Interacties (SSL-I) en Sociale Steun Lijst - Discrepancies (SSL-D), een handleiding. Noorderlijk Centrum voor Gezondheidsvraagstukken, Groningen; 1993.
• [50]Bazelmans E, Bleijenberg G, Van Der Meer JW, Folgering H: Is physical deconditioning a perpetuating factor in chronic fatigue syndrome? A controlled study on maximal exercise performance and relations with fatigue, impairment and physical activity. Psychol Med 2001, 31(1):107-114.
• [51]Bazelmans E, Bleijenberg G, Voeten MJ, van der Meer JW, Folgering H: Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome. J Psychosom Res 2005, 59(4):201-208.