Abstract
Purpose
Treatment for head and neck cancer is associated with multiple side effects, including loss of body mass, impaired physical function and reduced health-related quality of life. This study aimed to investigate the impact of treatment (radiation therapy ± concurrent chemotherapy) on (i) muscle strength, muscle cross-sectional area and patient-reported outcomes, and (ii) central and peripheral alterations during a whole-body exercise task.
Methods
Ten people with head and neck cancer (4 female; 50 ± 9 years) completed a lab visit before and after (56 ± 30 days) completion of treatment. Participants performed a neuromuscular assessment (involving maximal isometric voluntary contractions in the knee extensors and electrical stimulation of the femoral nerve) before and during intermittent cycling to volitional exhaustion. Anthropometrics and patient-reported outcomes were also assessed.
Results
From before to after treatment, maximal isometric muscle strength was reduced (P = 0.002, d = 0.73), as was potentiated twitch force (P < 0.001, d = 0.62), and muscle cross-sectional area (e.g., vastus lateralis: P = 0.010, d = 0.64). Exercise time was reduced (P = 0.008, d = 0.62) and peripheral processes contributed to a reduction in maximal force due to cycling. After treatment, the severity of self-reported fatigue increased (P = 0.041, r = − 0.65) and health-related quality of life decreased (P = 0.012, r = − 0.79).
Conclusion
Neuromuscular function was impaired in patients with head and neck cancer after treatment. Whole-body exercise tolerance was reduced and resulted in predominantly peripheral, rather than central, disturbances to the neuromuscular system. Future research should evaluate strength training after treatment for head and neck cancer, with the overall aim of reducing fatigue and improving health-related quality of life.
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Abbreviations
- ANOVA:
-
Analysis of variance
- BF%:
-
Body fat percent
- BMI:
-
Body mass index
- CNS:
-
Central nervous system
- CSA:
-
Cross-sectional area
- EMG:
-
Electromyography
- FACIT-F:
-
Functional assessment of chronic illness therapy—fatigue
- FACT-H&N:
-
Functional assessment of cancer therapy—head & neck
- FNES:
-
Femoral nerve electrical stimulation
- HRQL:
-
Health-related quality of life
- HPV:
-
Human papillomavirus
- HNC:
-
Head and neck cancer
- IQR:
-
Interquartile range
- M-wave:
-
Compound muscle action potential
- MIVC:
-
Maximal isometric voluntary contraction
- PAR-Q+:
-
The Physical Activity Readiness Questionnaire for Everyone
- Qpot :
-
Potentiated twitch amplitude
- RF:
-
Rectus femoris
- RPE:
-
Rating of perceived exertion
- RPM:
-
Revolutions per minute
- RMS-EMG:
-
Root means square of electromyography
- SD:
-
Standard deviation
- SIT:
-
Superimposed twitch
- VA:
-
Voluntary activation
- VL:
-
Vastus lateralis
- ηp2 :
-
Partial eta squared
References
Adelstein DJ, Saxton JP, Lavertu P et al (1997) A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck J Sci Spec Head Neck 19:567–575. https://doi.org/10.1002/(sici)1097-0347(199710)19:7%3c567:aid-hed2%3e3.0.co;2-5
Adelstein D, Gillison ML, Pfister DG et al (2017) NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017. J Natl Compr Canc Netw 15:761–770. https://doi.org/10.6004/jnccn.2017.0101
Alexander S, Minton O, Andrews P, Stone P (2009) A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome. Eur J Cancer 45:384–392. https://doi.org/10.1016/j.ejca.2008.09.010
Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35. https://doi.org/10.1056/nejmoa0912217
Bell DG (1993) The influence of air temperature on the EMG/force relationship of the quadriceps. Eur J Appl Physiol Occup Physiol 67:256–260. https://doi.org/10.1007/BF00864225
Van Belle S, Paridaens R, Evers G et al (2005) Comparison of proposed diagnostic criteria with FACT-F and VAS for cancer-related fatigue: proposal for use as a screening tool. Support Care Cancer 13:246–254. https://doi.org/10.1007/s00520-004-0734-y
Bigland-Ritchie B, Furbush F, Woods JJ (1986) Fatigue of intermittent submaximal voluntary contractions: central and peripheral factors. J Appl Physiol 61:421–429. https://doi.org/10.1152/jappl.1986.61.2.421
Bohannon RW, Magasi SR, Bubela DJ et al (2012) Grip and Knee extension muscle strength reflect a common construct among adults. Muscle Nerve 46:555–558. https://doi.org/10.1002/mus.23350
Borg G (1985) An introduction to Borg’s RPE-scale. Mouv Publ, Paris
Borg G (1998) Borg’s perceived exertion and pain scales. Human Kinetics, Leeds
Bressan V, Stevanin S, Bianchi M et al (2016) The effects of swallowing disorders, dysgeusia, oral mucositis and xerostomia on nutritional status, oral intake and weight loss in head and neck cancer patients: a systematic review. Cancer Treat Rev 45:105–119. https://doi.org/10.1016/j.ctrv.2016.03.006
Cai B, Allexandre D, Rajagopalan V et al (2014) Evidence of significant central fatigue in patients with cancer-related fatigue during repetitive elbow flexions till perceived exhaustion. PLoS ONE. https://doi.org/10.1371/journal.pone.0115370
Chaturvedi AK, Engels EA, Pfeiffer RM et al (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29:4294–4301. https://doi.org/10.1200/JCO.2011.36.4596
Cohen J (1988) Statistical power analysis for the behavioral sciences. Erlbaum, Hillsdale
Couch ME, Lai V, Cannon T et al (2007) Cancer cachexia syndrome in head and neck cancer patients: Part I. Diagnosis, impact on quality of life and survival, and treatment. Head Neck 29:401–411. https://doi.org/10.1002/hed.20447
Couch ME, Dittus K, Toth MJ et al (2015) Cancer cachexia update in head and neck cancer: definitions and diagnostic features. Head Neck 37:594–604. https://doi.org/10.1002/hed.23599
Cramer JD, Burtness B, Le QT, Ferris RL (2019) The changing therapeutic landscape of head and neck cancer. Nat Rev Clin Oncol. https://doi.org/10.1038/s41571-019-0227-z
Der-Torossian H, Asher SA, Winnike JH et al (2013) Cancer cachexia’s metabolic signature in a murine model confirms a distinct entity. Metabolomics 9:730–739. https://doi.org/10.1007/s11306-012-0485-6
Doyle-Baker D, Temesi J, Medysky ME et al (2018) An innovative ergometer to measure neuromuscular fatigue immediately after cycling. Med Sci Sports Exerc 50:375–387. https://doi.org/10.1249/MSS.0000000000001427
Elting LS, Keefe DM, Sonis ST et al (2008) Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer 113:2704–2713. https://doi.org/10.1002/cncr.23898
Evans WJ, Morley JE, Argilés J et al (2008) Cachexia: a new definition. Clin Nutr 27:793–799. https://doi.org/10.1016/j.clnu.2008.06.013
Fearon K, Strasser F, Anker SD et al (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12:489–495. https://doi.org/10.1016/S1470-2045(10)70218-7
Ferris MJ, Zhong J, Switchenko JM et al (2017) Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy. Radiother Oncol. https://doi.org/10.1016/j.radonc.2017.08.008
Franz F, Erdfelder E, Lang A-G, Buchner A (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical science. Behav Res Methods 39:175–191. https://doi.org/10.3758/BF03193146
Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C (2015) Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol 33:3235–3242. https://doi.org/10.1200/JCO.2015.61.6995
Goodall S, Romer LM, Ross EZ (2009) Voluntary activation of human knee extensors measured using transcranial magnetic stimulation. Exp Physiol 94:995–1004. https://doi.org/10.1113/expphysiol.2009.047902
Grisold W, Grisold A, Löscher WN (2016) Neuromuscular complications in cancer. J Neurol Sci 367:184–202. https://doi.org/10.1016/j.jns.2016.06.002
Hermens HJ, Freriks B, Disselhorst-Klug C, Rau G (2000) Development of recommendations for SEMG sensors and sensor placement procedures. J Electromyogr Kinesiol 10:361–374. https://doi.org/10.1016/S1050-6411(00)00027-4
Iacovelli NA, Galaverni M, Cavallo A et al (2018) Prevention and treatment of radiation-induced acute dermatitis in head and neck cancer patients: a systematic review. Futur Oncol. https://doi.org/10.2217/fon-2017-0359
Jackson AS, Pollock ML (1978) Generalized equations for predicting body density of men. Br J Nutr 40:497. https://doi.org/10.1079/BJN19780152
Jackson AS, Pollock ML, Ward A (1980) Generalized equations for predicting body density of women. Med Sci Sports Exerc 12:175–181. https://doi.org/10.1079/BJN19780152
Jager-Wittenaar H, Dijkstra PU, Vissink A et al (2011) Changes in nutritional status and dietary intake during and after head and neck cancer treatment. Head Neck 33:863–870. https://doi.org/10.1002/hed.21546
Kisiel-Sajewicz K, Siemionow V, Seyidova-Khoshknabi D et al (2013) Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue. PLoS ONE. https://doi.org/10.1371/journal.pone.0083636
Kluger BM, Krupp LB, Enoka RM (2013) Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology 80:409–416. https://doi.org/10.1212/WNL.0b013e31827f07be
Langendijk JA, Doornaert P, Verdonck-de Leeuw IM et al (2008) Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol 26:3770–3776. https://doi.org/10.1200/JCO.2007.14.6647
Larsson L, Degens H, Li M et al (2018) Sarcopenia: aging-related loss of muscle mass and function. Physiol Rev 99:427–511. https://doi.org/10.1152/physrev.00061.2017
Mador MJ, Rodis A, Magalang UJ (1995) Reproducibility of Borg scale measurements of dyspnea during exercise in patients with COPD. Chest 107:1590–1597. https://doi.org/10.1378/chest.107.6.1590
Mercadante S, Aielli F, Adile C et al (2015) Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients. Support Care Cancer 23:3249–3255. https://doi.org/10.1007/s00520-015-2720-y
Merton PA (1954) Voluntary strength and fatigue. J Physiol 123:553–564. https://doi.org/10.1113/jphysiol.1954.sp005070
Millet GY, Bachasson D, Temesi J et al (2012) Potential interests and limits of magnetic and electrical stimulation techniques to assess neuromuscular fatigue. Neuromuscul Disord 22:S181–S186. https://doi.org/10.1016/j.nmd.2012.10.007
Orell-Kotikangas H, Osterlund P, Makitie O et al (2017) Cachexia at diagnosis is associated with poor survival in head and neck cancer patients. Acta Otolaryngol 137:778–785. https://doi.org/10.1080/00016489.2016.1277263
Place N, Yamada T, Bruton JD, Westerblad H (2010) Muscle fatigue: from observations in humans to underlying mechanisms studied in intact single muscle fibres. Eur J Appl Physiol 110:1–15. https://doi.org/10.1007/s00421-010-1480-0
Ringash J, Bezjak A, O’Sullivan B, Redelmeier DA (2004) Interpreting differences in quality of life: the FACT-H&N in laryngeal cancer patients. Qual Life Res 13:725–733. https://doi.org/10.1023/B:QURE.0000021703.47079.46
Ringash J, Lockwood G, O’Sullivan B et al (2008) Hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer: quality of life in a prospective phase I/II trial. Radiother Oncol 87:181–187. https://doi.org/10.1016/j.radonc.2007.12.028
Rogers L, Anton PM, Fogleman A et al (2013) Pilot, randomized trial of resistance exercise during radiation therapy for head and neck cancer. Head Neck 35:1178–1188. https://doi.org/10.1002/hed.23118
Sandmæl JA, Bye A, Solheim TS et al (2017) Feasibility and preliminary effects of resistance training and nutritional supplements during versus after radiotherapy in patients with head and neck cancer: a pilot randomized trial. Cancer 123:4440–4448. https://doi.org/10.1002/cncr.30901
Sawada NO, De Paula JM, Sonobe HM et al (2012) Depression, fatigue, and health-related quality of life in head and neck cancer patients: a prospective pilot study. Support Care Cancer 20:2705–2711. https://doi.org/10.1007/s00520-012-1390-2
Schindler A, Denaro N, Russi EG et al (2015) Dysphagia in head and neck cancer patients treated with radiotherapy and systemic therapies: literature review and consensus. Crit Rev Oncol Hematol 96:372–384. https://doi.org/10.1016/j.critrevonc.2015.06.005
Scott JM, Martin DS, Ploutz-Snyder R et al (2017) Panoramic ultrasound: a novel and valid tool for monitoring change in muscle mass. J Cachexia Sarcopenia Muscle 8:475–481. https://doi.org/10.1002/jcsm.12172
Shen W, Punyanitya M, Wang Z et al (2004) Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol 97:2333–2338. https://doi.org/10.1152/japplphysiol.00744.2004.-A
Silver HJ, Dietrich MS, Murphy BA (2007) Changes in body mass, energy balance, physical function, and inflammatory state in patients with locally advanced head and neck cancer treated with concurrent chemoradiation after low-dose induction chemotherapy. Head Neck 29:893–900. https://doi.org/10.1002/hed.20607
Strojnik V, Komi PV (1998) Neuromuscular fatigue after maximal stretch-shortening cycle exercise. J Appl Physiol 84:344–350. https://doi.org/10.1152/jappl.1998.84.1.344
Tamm AS, Lagerquist O, Ley AL, Collins DF (2009) Chronotype influences diurnal variations in the excitability of the human motor cortex and the ability to generate torque during a maximum voluntary contraction. J Biol Rhythms 24:211–224. https://doi.org/10.1177/0748730409334135
Taylor JL, De Haan A, Gerrits KHL, De Ruiter CJ (2009) Point:Counterpoint: the interpolated twitch does/does not provide a valid measure of the voluntary activation of muscle. J Appl Physiol 107:354–357. https://doi.org/10.1152/japplphysiol.91220.2008
Twomey R, Aboodarda SJ, Kruger R et al (2017) Neuromuscular fatigue during exercise: methodological considerations, etiology and potential role in chronic fatigue. Neurophysiol Clin 47:95–110. https://doi.org/10.1016/j.neucli.2017.03.002
Uta R, Laurent M, Axel L et al (2018) Immunotherapy in head and neck cancer—scientific rationale, current treatment options and future directions. Swiss Med Wkly. https://doi.org/10.4414/smw.2018.14625
Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45:309–316. https://doi.org/10.1016/j.oraloncology.2008.06.002
Wyss A, Hashibe M, Chuang SC et al (2013) Cigarette, cigar, and pipe smoking and the risk of head and neck cancers: Pooled analysis in the international head and neck cancer epidemiology consortium. Am J Epidemiol 178:679–690. https://doi.org/10.1093/aje/kwt029
Yavuzsen T, Davis MP, Ranganathan VK et al (2009) Cancer-related fatigue: central or peripheral? J Pain Symptom Manag 38:587–596. https://doi.org/10.1016/j.jpainsymman.2008.12.003
Yellen SB, Cella DF, Webster K et al (1997) Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Symptom Manag 13:63–74. https://doi.org/10.1016/S0885-3924(96)00274-6
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RT and GYM conceived and designed the study. CL and RT were responsible for recruitment, data collection, statistical analysis and interpretation of the data. CL drafted the manuscript. RT, GYM, NCR, HL and GF provided critical revisions of the manuscript and contributed important intellectual contents. All authors approved the final manuscript.
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Lavigne, C., Lau, H., Francis, G. et al. Neuromuscular function and fatigability in people diagnosed with head and neck cancer before versus after treatment. Eur J Appl Physiol 120, 1289–1304 (2020). https://doi.org/10.1007/s00421-020-04362-0
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DOI: https://doi.org/10.1007/s00421-020-04362-0