Skip to main content

Advertisement

SpringerLink
Log in

Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer

  • Review Paper
  • Published:
Dysphagia Aims and scope Submit manuscript

Abstract

Oncologic treatments, such as curative radiotherapy and chemoradiation, for head and neck cancer can cause long-term swallowing impairments (dysphagia) that negatively impact quality of life. Radiation-induced dysphagia comprised a broad spectrum of structural, mechanical, and neurologic deficits. An understanding of the biomolecular effects of radiation on the time course of wound healing and underlying morphological tissue responses that precede radiation damage will improve options available for dysphagia treatment. The goal of this review is to discuss the pathophysiology of radiation-induced injury and elucidate areas that need further exploration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Society AC. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015.

    Google Scholar 

  2. Kuo P, Chen MM, Decker RH, Yarbrough WG, Judson BL. Hypopharyngeal cancer incidence, treatment, and survival: temporal trends in the United States. Laryngoscope. 2014;124(9):2064–9.

    Article  PubMed  Google Scholar 

  3. Batth SS, Caudell JJ, Chen AM. Practical considerations in reducing swallowing dysfunction following concurrent chemoradiotherapy with intensity-modulated radiotherapy for head and neck cancer. Head Neck. 2014;36(2):291–8. doi:10.1002/hed.23246.

    Article  PubMed  Google Scholar 

  4. Fenwick JD, Pardo-Montero J, Nahum AE, Malik ZI. Impact of schedule duration on head and neck radiotherapy: accelerated tumor repopulation versus compensatory mucosal proliferation. Int J Radiat Oncol Biol Phys. 2012;82(2):1021–30. doi:10.1016/j.ijrobp.2010.12.048.

    Article  PubMed  Google Scholar 

  5. Peters LJ, Ang KK, Thames HD Jr. Accelerated fractionation in the radiation treatment of head and neck cancer. A critical comparison of different strategies. Acta Oncol. 1988;27(2):185–94.

    Article  CAS  PubMed  Google Scholar 

  6. Eisbruch A, Schwartz M, Rasch C, Vineberg K, Damen E, Van As CJ, Marsh R, Pameijer FA, Balm AJ. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys. 2004;60(5):1425–39. doi:10.1016/j.ijrobp.2004.05.050.

    Article  PubMed  Google Scholar 

  7. Roe JW, Carding PN, Dwivedi RC, Kazi RA, Rhys-Evans PH, Harrington KJ, Nutting CM. Swallowing outcomes following intensity modulated radiation therapy (IMRT) for head & neck cancer—a systematic review. Oral Oncol. 2010;46(10):727–33. doi:10.1016/j.oraloncology.2010.07.012.

    Article  PubMed  Google Scholar 

  8. Ekberg O, Nylander G. Pharyngeal dysfunction after treatment for pharyngeal cancer with surgery and radiotherapy. Gastrointest Radiol. 1983;8(2):97–104.

    Article  CAS  PubMed  Google Scholar 

  9. Starmer HM. Dysphagia in head and neck cancer: prevention and treatment. Curr Opin Otolaryngol Head Neck Surg. 2014;22(3):195–200. doi:10.1097/MOO.0000000000000044.

    Article  PubMed  Google Scholar 

  10. Barcellos-Hoff MH, Park C, Wright EG. Radiation and the microenvironment—tumorigenesis and therapy. Nat Rev Cancer. 2005;5(11):867–75. doi:10.1038/nrc1735.

    Article  CAS  PubMed  Google Scholar 

  11. Bentzen SM. Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer. 2006;6(9):702–13. doi:10.1038/nrc1950.

    Article  CAS  PubMed  Google Scholar 

  12. Hopewell JW. Persistent and late occurring lesions in irradiated feet of rats: their clinical relevance. Br J Radiol. 1982;55(656):574–8. doi:10.1259/0007-1285-55-656-574.

    Article  CAS  PubMed  Google Scholar 

  13. Hopewell JW, Foster JL, Young CM, Wiernik G. Late radiation damage to pig skin. Radiology. 1979;130(3):783–8. doi:10.1148/130.3.783.

    Article  CAS  PubMed  Google Scholar 

  14. Withers HR, Thames HD Jr, Flow BL, Mason KA, Hussey DH. The relationship of acute to late skin injury in 2 and 5 fraction/week gamma-ray therapy. Int J Radiat Oncol Biol Phys. 1978;4(7–8):595–601.

    Article  CAS  PubMed  Google Scholar 

  15. Castadot P, Geets X, Lee JA, Gregoire V. Adaptive functional image-guided IMRT in pharyngo-laryngeal squamous cell carcinoma: is the gain in dose distribution worth the effort? Radiother Oncol. 2011;101(3):343–50. doi:10.1016/j.radonc.2011.06.011.

    Article  PubMed  Google Scholar 

  16. Dorr W, Hendry JH. Consequential late effects in normal tissues. Radiother Oncol. 2001;61(3):223–31.

    Article  CAS  PubMed  Google Scholar 

  17. Denham JW, Hauer-Jensen M. The radiotherapeutic injury—a complex ‘wound’. Radiother Oncol. 2002;63(2):129–45.

    Article  PubMed  Google Scholar 

  18. Dörr W. Modulation of repopulation processes in oral mucosa: experimental results. Int J Radiat Biol. 2003;79(7):531–7. doi:10.1080/09553002310001600925.

    Article  PubMed  Google Scholar 

  19. Dörr W, Hamilton CS, Boyd T, Reed B, Denham JW. Radiation-induced changes in cellularity and proliferation in human oral mucosa. Int J Radiat Oncol Biol Phys. 2002;52(4):911–7. doi:10.1016/S0360-3016(01)02721-3.

    Article  PubMed  Google Scholar 

  20. Kam WW, Banati RB. Effects of ionizing radiation on mitochondria. Free Radic Biol Med. 2013;65:607–19. doi:10.1016/j.freeradbiomed.2013.07.024.

    Article  CAS  PubMed  Google Scholar 

  21. Yamamori T, Yasui H, Yamazumi M, Wada Y, Nakamura Y, Nakamura H, Inanami O. Ionizing radiation induces mitochondrial reactive oxygen species production accompanied by upregulation of mitochondrial electron transport chain function and mitochondrial content under control of the cell cycle checkpoint. Free Radic Biol Med. 2012;53(2):260–70. doi:10.1016/j.freeradbiomed.2012.04.033.

    Article  CAS  PubMed  Google Scholar 

  22. Logemann JA, Pauloski BR, Rademaker AW, Lazarus CL, Gaziano J, Stachowiak L, Newman L, MacCracken E, Santa D, Mittal B. Swallowing disorders in the first year after radiation and chemoradiation. Head Neck. 2008;30(2):148–58. doi:10.1002/hed.20672.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Logemann JA, Rademaker AW, Pauloski BR, Lazarus CL, Mittal BB, Brockstein B, MacCracken E, Haraf DJ, Vokes EE, Newman LA, Liu D. Site of disease and treatment protocol as correlates of swallowing function in patients with head and neck cancer treated with chemoradiation. Head Neck. 2006;28(1):64–73. doi:10.1002/hed.20299.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Pauloski BR, Rademaker AW, Logemann JA, Lundy D, Bernstein M, McBreen C, Santa D, Campanelli A, Kelchner L, Klaben B, Discekici-Harris M. Relation of mucous membrane alterations to oral intake during the first year after treatment for head and neck cancer. Head Neck. 2011;33(6):774–9. doi:10.1002/hed.21542.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wygoda A, Rutkowski T, Hutnik M, Składowski K, Goleń M, Pilecki B. Acute mucosal reactions in patients with head and neck cancer. Three patterns of mucositis observed during radiotherapy. Strahlenther Onkol. 2013;189(7):547–51. doi:10.1007/s00066-013-0311-8.

    Article  CAS  PubMed  Google Scholar 

  26. Rademaker AW, Vonesh EF, Logemann JA, Pauloski BR, Liu D, Lazarus CL, Newman LA, May AH, MacCracken E, Gaziano J, Stachowiak L. Eating ability in head and neck cancer patients after treatment with chemoradiation: a 12-month follow-up study accounting for dropout. Head Neck. 2003;25(12):1034–41. doi:10.1002/hed.10317.

    Article  PubMed  Google Scholar 

  27. Silver HJ, Dietrich MS, Murphy BA. 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. 2007;29(10):893–900. doi:10.1002/hed.20607.

    Article  PubMed  Google Scholar 

  28. Denham JW, Peters LJ, Johansen J, Poulsen M, Lamb DS, Hindley A, O’Brien PC, Na Spry, Penniment M, Krawitz H, Williamson S, Bear J, Tripcony L. Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer? Radiother Oncol. 1999;52(2):157–64. doi:10.1016/S0167-8140(99)00107-3.

    Article  CAS  PubMed  Google Scholar 

  29. Jung H, Beck-Bornholdt HP, Svoboda V, Alberti W, Herrmann T. Quantification of late complications after radiation therapy. Radiother Oncol. 2001;61(3):233–46.

    Article  CAS  PubMed  Google Scholar 

  30. Lin YS, Jen YM, Lin JC. Radiation-related cranial nerve palsy in patients with nasopharyngeal carcinoma. Cancer. 2002;95(2):404–9. doi:10.1002/cncr.10668.

    Article  PubMed  Google Scholar 

  31. Remy J, Wegrowski J, Crechet F, Martin M, Daburon F. Long-term overproduction of collagen in radiation-induced fibrosis. Radiat Res. 1991;125(1):14–9.

    Article  CAS  PubMed  Google Scholar 

  32. Martin M, Lefaix JL, Pinton P, Crechet F, Daburon F. Temporal modulation of TGF-beta 1 and beta-actin gene expression in pig skin and muscular fibrosis after ionizing radiation. Radiat Res. 1993;134(1):63–70.

    Article  CAS  PubMed  Google Scholar 

  33. Wegrowski J, Lefaix JL, Lafuma C. Accumulation of glycosaminoglycans in radiation-induced muscular fibrosis. Int J Radiat Biol. 1992;61(5):685–93.

    Article  CAS  PubMed  Google Scholar 

  34. Robbins ME, Zhao W. Chronic oxidative stress and radiation-induced late normal tissue injury: a review. Int J Radiat Biol. 2004;80(4):251–9. doi:10.1080/09553000410001692726.

    Article  CAS  PubMed  Google Scholar 

  35. Rudolph R, Arganese T, Woodward M. The ultrastructure and etiology of chronic radiotherapy damage in human skin. Ann Plast Surg. 1982;9(4):282–92.

    Article  CAS  PubMed  Google Scholar 

  36. Martin M, Remy J, Daburon F. Abnormal proliferation and aging of cultured fibroblasts from pigs with subcutaneous fibrosis induced by gamma irradiation. J Invest Dermatol. 1989;93(4):497–500.

    Article  CAS  PubMed  Google Scholar 

  37. El Nabout R, Martin M, Remy J, Kern P, Robert L, Lafuma C. Collagen synthesis and deposition in cultured fibroblasts from subcutaneous radiation-induced fibrosis. Modification as a function of cell aging. Matrix (Stuttgart, Germany). 1989; 9 (5):411–420.

  38. Rodningen OK, Overgaard J, Alsner J, Hastie T, Borresen-Dale AL. Microarray analysis of the transcriptional response to single or multiple doses of ionizing radiation in human subcutaneous fibroblasts. Radiother Oncol. 2005;77(3):231–40. doi:10.1016/j.radonc.2005.09.020.

    Article  PubMed  Google Scholar 

  39. Rodningen OK, Borresen-Dale AL, Alsner J, Hastie T, Overgaard J. Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis. Radiother Oncol. 2008;86(3):314–20. doi:10.1016/j.radonc.2007.09.013.

    Article  CAS  PubMed  Google Scholar 

  40. van der Laan HP, Bijl HP, Steenbakkers RJ, van der Schaaf A, Chouvalova O, Vemer-van den Hoek JG, Gawryszuk A, van der Laan BF, Oosting SF, Roodenburg JL, Wopken K, Langendijk JA. Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia. Radiother Oncol. 2015;. doi:10.1016/j.radonc.2015.01.019.

    Google Scholar 

  41. Hutcheson KA, Lewin JS, Barringer DA, Lisec A, Gunn GB, Moore MW, Holsinger FC. Late dysphagia after radiotherapy-based treatment of head and neck cancer. Cancer. 2012;118(23):5793–9. doi:10.1002/cncr.27631.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Hutcheson KA. Late radiation-associated dysphagia (RAD) in head and neck cancer survivors. Perspect Swal Swal Dis (Dysph). 2013;22:61–72. doi:10.1044/sasd22.2.61.

    Article  Google Scholar 

  43. Eisele DW, Koch DG, Tarazi AE, Jones B. Case report: aspiration from delayed radiation fibrosis of the neck. Dysphagia. 1991;6(2):120–2.

    Article  CAS  PubMed  Google Scholar 

  44. Jensen K, Lambertsen K, Grau C. Late swallowing dysfunction and dysphagia after radiotherapy for pharynx cancer: frequency, intensity and correlation with dose and volume parameters. Radiother Oncol. 2007;85(1):74–82. doi:10.1016/j.radonc.2007.06.004.

    Article  PubMed  Google Scholar 

  45. Nguyen NP, Moltz CC, Frank C, Vos P, Smith HJ, Karlsson U, Dutta S, Midyett FA, Barloon J, Sallah S. Dysphagia following chemoradiation for locally advanced head and neck cancer. Ann Oncol: Off J Eur Soc Med Oncol/ESMO. 2004;15(3):383–8.

    Article  CAS  Google Scholar 

  46. Wall LR, Ward EC, Cartmill B, Hill AJ. Physiological changes to the swallowing mechanism following (chemo)radiotherapy for head and neck cancer: a systematic review. Dysphagia. 2013;28(4):481–93. doi:10.1007/s00455-013-9491-8.

    Article  PubMed  Google Scholar 

  47. Levendag PC, Teguh DN, Voet P, van der Est H, Noever I, de Kruijf WJ, Kolkman-Deurloo IK, Prevost JB, Poll J, Schmitz PI, Heijmen BJ. Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship. Radiother Oncol. 2007;85(1):64–73. doi:10.1016/j.radonc.2007.07.009.

    Article  PubMed  Google Scholar 

  48. Caudell JJ, Schaner PE, Desmond RA, Meredith RF, Spencer SA, Bonner JA. Dosimetric factors associated with long-term dysphagia after definitive radiotherapy for squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2010;76(2):403–9. doi:10.1016/j.ijrobp.2009.02.017.

    Article  PubMed  Google Scholar 

  49. Caglar HB, Tishler RB, Othus M, Burke E, Li Y, Goguen L, Wirth LJ, Haddad RI, Norris CM, Court LE, Aninno DJ, Posner MR, Allen AM. Dose to larynx predicts for swallowing complications after intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2008;72(4):1110–8. doi:10.1016/j.ijrobp.2008.02.048.

    Article  PubMed  Google Scholar 

  50. Starmer HM, Quon H, Kumar R, Alcorn S, Murano E, Jones B, Humbert I. The effect of radiation dose on swallowing: evaluation of aspiration and kinematics. Dysphagia. 2015;30(4):430–7. doi:10.1007/s00455-015-9618-1.

    Article  PubMed  Google Scholar 

  51. Schwartz DL, Hutcheson K, Barringer D, Tucker SL, Kies M, Holsinger FC, Ang KK, Morrison WH, Rosenthal DI, Garden AS, Dong L, Lewin JS. Candidate dosimetric predictors of long-term swallowing dysfunction after oropharyngeal intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2010;78(5):1356–65. doi:10.1016/j.ijrobp.2009.10.002.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Kumar R, Madanikia S, Starmer H, Yang W, Murano E, Alcorn S, McNutt T, Le Y, Quon H. Radiation dose to the floor of mouth muscles predicts swallowing complications following chemoradiation in oropharyngeal squamous cell carcinoma. Oral Oncol. 2014;50(1):65–70. doi:10.1016/j.oraloncology.2013.10.002.

    Article  PubMed  Google Scholar 

  53. Amdur RJ, Li JG, Liu C, Hinerman RW, Mendenhall WM. Unnecessary laryngeal irradiation in the IMRT era. Head Neck. 2004;26(3):257–63. doi:10.1002/hed.10379.

    Article  PubMed  Google Scholar 

  54. Dornfeld K, Simmons JR, Karnell L, Karnell M, Funk G, Yao M, Wacha J, Zimmerman B, Buatti JM. Radiation doses to structures within and adjacent to the larynx are correlated with long-term diet- and speech-related quality of life. Int J Radiat Oncol Biol Phys. 2007;68(3):750–7. doi:10.1016/j.ijrobp.2007.01.047.

    Article  PubMed  Google Scholar 

  55. Sanguineti G, Adapala P, Endres EJ, Brack C, Fiorino C, Sormani MP, Parker B. Dosimetric predictors of laryngeal edema. Int J Radiat Oncol Biol Phys. 2007;68(3):741–9. doi:10.1016/j.ijrobp.2007.01.010.

    Article  PubMed  Google Scholar 

  56. Szczesniak MM, Maclean J, Zhang T, Graham PH, Cook IJ. Persistent dysphagia after head and neck radiotherapy: a common and under-reported complication with significant effect on non-cancer-related mortality. Clin Oncol (R Coll Radiol). 2014;26(11):697–703. doi:10.1016/j.clon.2014.08.009.

    Article  CAS  Google Scholar 

  57. Coppes RP, Vissink A, Konings AW. Comparison of radiosensitivity of rat parotid and submandibular glands after different radiation schedules. Radiother Oncol. 2002;63(3):321–8.

    Article  PubMed  Google Scholar 

  58. Gillette EL, Mahler PA, Powers BE, Gillette SM, Vujaskovic Z. Late radiation injury to muscle and peripheral nerves. Int J Radiat Oncol Biol Phys. 1995;31(5):1309–18. doi:10.1016/0360-3016(94)00422-h.

    Article  CAS  PubMed  Google Scholar 

  59. Bleier BS, Levine MS, Mick R, Rubesin SE, Sack SZ, McKinney K, Mirza N. Dysphagia after chemoradiation: analysis by modified barium swallow. Ann Otol Rhinol Laryngol. 2007;116(11):837–41.

    Article  PubMed  Google Scholar 

  60. Bergstrom RM, Salmi A. Radiation-induced damage in the ultrastructure of striated muscle. Exp Cell Res. 1962;26:226–8.

    Article  CAS  PubMed  Google Scholar 

  61. Bergstrom RM, Blafield R, Salmi A. The effect of x-irradiation on the electrical and mechanical activity of striated frog muscle. Int J Radiat Biol. 1962;4:351–61.

    CAS  PubMed  Google Scholar 

  62. Khan MY. Radiation-induced changes in skeletal muscle. An electron microscopic study. J Neuropathol Exp Neurol. 1974;33(1):42–57.

    Article  CAS  PubMed  Google Scholar 

  63. Schwenen M, Altman KI, Schroder W. Radiation-induced increase in the release of amino acids by isolated, perfused skeletal muscle. Int J Radiat Biol. 1989;55(2):257–69.

    Article  CAS  PubMed  Google Scholar 

  64. Hardee JP, Puppa MJ, Fix DK, Gao S, Hetzler KL, Bateman TA, Carson JA. The effect of radiation dose on mouse skeletal muscle remodeling. Radiol Oncol. 2014;48(3):247–56. doi:10.2478/raon-2014-0025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Mu L, Sanders I. Neuromuscular compartments and fiber-type regionalization in the human inferior pharyngeal constrictor muscle. Anat Rec. 2001;264(4):367–77.

    Article  CAS  PubMed  Google Scholar 

  66. Lazarus CL, Logemann JA, Pauloski BR, Colangelo LA, Kahrilas PJ, Mittal BB, Pierce M. Swallowing disorders in head and neck cancer patients treated with radiotherapy and adjuvant chemotherapy. Laryngoscope. 1996;106(9 Pt 1):1157–66.

    Article  CAS  PubMed  Google Scholar 

  67. Anderson EJ, Neufer PD. Type II skeletal myofibers possess unique properties that potentiate mitochondrial H(2)O(2) generation. Am J Physiol Cell Physiol. 2006;290(3):C844–51. doi:10.1152/ajpcell.00402.2005.

    Article  CAS  PubMed  Google Scholar 

  68. Holzer P. Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system. Pharmacol Ther. 2011;131(1):142–70. doi:10.1016/j.pharmthera.2011.03.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Viet CT, Corby PM, Akinwande A, Schmidt BL. Review of preclinical studies on treatment of mucositis and associated pain. J Dent Res. 2014;93(9):868–75. doi:10.1177/0022034514540174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Simonyan K, Feng X, Henriquez VM, Ludlow CL. Combined laryngeal inflammation and trauma mediate long-lasting immunoreactivity response in the brainstem sensory nuclei in the rat. Front Integr Neurosci. 2012;6:97. doi:10.3389/fnint.2012.00097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Steele CM, Miller AJ. Sensory input pathways and mechanisms in swallowing: a review. Dysphagia. 2010;25(4):323–33. doi:10.1007/s00455-010-9301-5.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Rong X, Tang Y, Chen M, Lu K, Peng Y. Radiation-induced cranial neuropathy in patients with nasopharyngeal carcinoma. A follow-up study. Strahlenther Onkol. 2012;188(3):282–6. doi:10.1007/s00066-011-0047-2.

    Article  CAS  PubMed  Google Scholar 

  73. Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol. 2004;73(2):119–31. doi:10.1016/j.radonc.2004.08.021.

    Article  PubMed  Google Scholar 

  74. Krisciunas GP, Sokoloff W, Stepas K, Langmore SE. Survey of usual practice: dysphagia therapy in head and neck cancer patients. Dysphagia. 2012;27(4):538–49. doi:10.1007/s00455-012-9404-2.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Kraaijenga SA, van der Molen L, Jacobi I, Hamming-Vrieze O, Hilgers FJ, van den Brekel MW. Prospective clinical study on long-term swallowing function and voice quality in advanced head and neck cancer patients treated with concurrent chemoradiotherapy and preventive swallowing exercises. Eur Arch Otorhinolaryngol. 2015;272(11):3521–31. doi:10.1007/s00405-014-3379-6.

    Article  PubMed  Google Scholar 

  76. Carnaby-Mann G, Crary MA, Schmalfuss I, Amdur R. “Pharyngocise”: randomized controlled trial of preventative exercises to maintain muscle structure and swallowing function during head-and-neck chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2012;83(1):210–9. doi:10.1016/j.ijrobp.2011.06.1954.

    Article  PubMed  Google Scholar 

  77. Kulbersh BD, Rosenthal EL, McGrew BM, Duncan RD, McColloch NL, Carroll WR, Magnuson JS. Pretreatment, preoperative swallowing exercises may improve dysphagia quality of life. Laryngoscope. 2006;116(6):883–6. doi:10.1097/01.mlg.0000217278.96901.fc.

    Article  PubMed  Google Scholar 

  78. Paleri V, Roe JW, Strojan P, Corry J, Gregoire V, Hamoir M, Eisbruch A, Mendenhall WM, Silver CE, Rinaldo A, Takes RP, Ferlito A. Strategies to reduce long-term postchemoradiation dysphagia in patients with head and neck cancer: an evidence-based review. Head Neck. 2014;36(3):431–43. doi:10.1002/hed.23251.

    Article  PubMed  Google Scholar 

  79. Hutcheson KA, Bhayani MK, Beadle BM, Gold KA, Shinn EH, Lai SY, Lewin J. Eat and exercise during radiotherapy or chemoradiotherapy for pharyngeal cancers: use it or lose it. JAMA otolaryngol—Head Neck Surg. 2013;139(11):1127–34. doi:10.1001/jamaoto.2013.4715.

    Article  PubMed  PubMed Central  Google Scholar 

  80. De Lisio M, Kaczor JJ, Phan N, Tarnopolsky MA, Boreham DR, Parise G. Exercise training enhances the skeletal muscle response to radiation-induced oxidative stress. Muscle Nerve. 2011;43(1):58–64. doi:10.1002/mus.21797.

    Article  PubMed  Google Scholar 

  81. Hood DA. Invited Review: contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol. 2001;90(3):1137–57.

    CAS  PubMed  Google Scholar 

  82. Adhihetty PJ, Irrcher I, Joseph AM, Ljubicic V, Hood DA. Plasticity of skeletal muscle mitochondria in response to contractile activity. Exp Physiol. 2003;88(1):99–107.

    Article  CAS  PubMed  Google Scholar 

  83. Scheele C, Nielsen S, Pedersen BK. ROS and myokines promote muscle adaptation to exercise. Trends Endocrinol Metabolism: TEM. 2009;20(3):95–9. doi:10.1016/j.tem.2008.12.002.

    Article  CAS  PubMed  Google Scholar 

  84. Venditti P, Masullo P, Di Meo S. Effect of training on H(2)O(2) release by mitochondria from rat skeletal muscle. Arch Biochem Biophys. 1999;372(2):315–20. doi:10.1006/abbi.1999.1494.

    Article  CAS  PubMed  Google Scholar 

  85. Phillips SM, Glover EI, Rennie MJ. Alterations of protein turnover underlying disuse atrophy in human skeletal muscle. J Appl Physiol. 2009;107(3):645–54. doi:10.1152/japplphysiol.00452.2009.

    Article  CAS  PubMed  Google Scholar 

  86. Glover EI, Phillips SM, Oates BR, Tang JE, Tarnopolsky MA, Selby A, Smith K, Rennie MJ. Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion. J Physiol. 2008;586(Pt 24):6049–61. doi:10.1113/jphysiol.2008.160333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Paddon-Jones D, Sheffield-Moore M, Cree MG, Hewlings SJ, Aarsland A, Wolfe RR, Ferrando AA. Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. J clin Endocrinol Metabolism. 2006;91(12):4836–41. doi:10.1210/jc.2006-0651.

    Article  CAS  Google Scholar 

  88. Langmore SE, McCulloch TM, Krisciunas GP, Lazarus CL, Van Daele DJ, Pauloski BR, Rybin D, Doros G. Efficacy of electrical stimulation and exercise for dysphagia in patients with head and neck cancer: a randomized clinical trial. Head Neck. 2015;. doi:10.1002/hed.24197.

    PubMed  Google Scholar 

  89. Lin PH, Hsiao TY, Chang YC, Ting LL, Chen WS, Chen SC, Wang TG. Effects of functional electrical stimulation on dysphagia caused by radiation therapy in patients with nasopharyngeal carcinoma. Support Care Cancer. 2011;19(1):91–9. doi:10.1007/s00520-009-0792-2.

    Article  PubMed  Google Scholar 

  90. Ryu JS, Kang JY, Park JY, Nam SY, Choi SH, Roh JL, Kim SY, Choi KH. The effect of electrical stimulation therapy on dysphagia following treatment for head and neck cancer. Oral Oncol. 2009;45(8):665–8. doi:10.1016/j.oraloncology.2008.10.005.

    Article  PubMed  Google Scholar 

  91. Humbert IA, Poletto CJ, Saxon KG, Kearney PR, Crujido L, Wright-Harp W, Payne J, Jeffries N, Sonies BC, Ludlow CL. The effect of surface electrical stimulation on hyolaryngeal movement in normal individuals at rest and during swallowing. J Appl Physiol. 2006;101(6):1657–63. doi:10.1152/japplphysiol.00348.2006.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Ludlow CL, Humbert I, Saxon K, Poletto C, Sonies B, Crujido L. Effects of surface electrical stimulation both at rest and during swallowing in chronic pharyngeal dysphagia. Dysphagia. 2007;22(1):1–10. doi:10.1007/s00455-006-9029-4.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Suiter DM, Leder SB, Ruark JL. Effects of neuromuscular electrical stimulation on submental muscle activity. Dysphagia. 2006;21(1):56–60. doi:10.1007/s00455-005-9010-7.

    Article  PubMed  Google Scholar 

  94. Ludlow CL. Electrical neuromuscular stimulation in dysphagia: current status. Curr Opin Otolaryngol Head Neck Surg. 2010;18(3):159–64. doi:10.1097/MOO.0b013e3283395dec.

    Article  PubMed  Google Scholar 

  95. Humbert IA, Michou E, MacRae PR, Crujido L. Electrical stimulation and swallowing: how much do we know? Semin Speech Lang. 2012;33(3):203–16. doi:10.1055/s-0032-1320040.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Bhatt AD, Goodwin N, Cash E, Bhatt G, Silverman CL, Spanos WJ, Bumpous JM, Potts K, Redman R, Allison WA, Dunlap NE. Impact of transcutaneous neuromuscular electrical stimulation on dysphagia in patients with head and neck cancer treated with definitive chemoradiation. Head Neck. 2015;37(7):1051–6. doi:10.1002/hed.23708.

    Article  PubMed  Google Scholar 

  97. Bauer W. Electrical treatment of severe head and neck cancer pain. Arch Otolaryngol. 1983;109(6):382–3.

    Article  CAS  PubMed  Google Scholar 

  98. Boswell NS, Bauer W. Noninvasive electrical stimulation for the treatment of radiotherapy side-effects. Presented at the international conference on head and neck cancer, Baltimore: July 1984 and Triologic Society of Otolaryngology, New Orleans: January 1985; 2 (3).

  99. Lee J, Rakel B, Dailey D, Vance C, Broderick A, Sleeuwenhoek B, Perkhounkova Y, Sluka K, Anderson C. transcutaneous electrical nerve stimulation (TENS) reduces head and neck cancer pain: a randomized and placebo-controlled double blind pilot study. J Pain; 15 (4): S69. doi:10.1016/j.jpain.2014.01.286.

  100. Lee J, Rakel B, Dailey D, Vance C, Broderick A, Sluka K, Anderson C. The effectiveness of TENS for head and neck cancer pain and function: a randomized and placebo-controlled double blind pilot study. J Pain; 13 (4): S63. doi:10.1016/j.jpain.2012.01.265.

  101. Fenner M, Park J, Schulz N, Amann K, Grabenbauer GG, Fahrig A, Karg J, Wiltfang J, Neukam FW, Nkenke E. Validation of histologic changes induced by external irradiation in mandibular bone. An experimental animal model. J Cranio-maxillo-fac Surg. 2010;38(1):47–53. doi:10.1016/j.jcms.2009.07.011.

    Article  Google Scholar 

  102. Sonstevold T, Johannessen AC, Stuhr L. A rat model of radiation injury in the mandibular area. Radiat Oncol. 2015;10:129. doi:10.1186/s13014-015-0432-6.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Russell JA, Connor NP. Effects of age and radiation treatment on function of extrinsic tongue muscles. Radiat Oncol. 2014;9:254. doi:10.1186/s13014-014-0254-y.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

NIH HL111215; Kentucky Spinal Cord and Head Injury Trust and the Commonwealth of Kentucky Challenge for Excellence.

Author information

Authors and Affiliations

  1. Department of Neurological Surgery, Kentucky Spinal Cord Injury Research Center, University of Louisville, 511 South Floyd St MDR 616, Louisville, KY, 40202, USA

    Suzanne N. King & Teresa Pitts

  2. Department of Radiation Oncology, University of Louisville, Louisville, USA

    Neal E. Dunlap

  3. Department of Otolaryngology—Head and Neck Surgery and Communicative Disorders, University of Louisville, Louisville, USA

    Paul A. Tennant

Authors
  1. Suzanne N. King
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neal E. Dunlap
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul A. Tennant
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teresa Pitts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teresa Pitts.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

King, S.N., Dunlap, N.E., Tennant, P.A. et al. Pathophysiology of Radiation-Induced Dysphagia in Head and Neck Cancer. Dysphagia 31, 339–351 (2016). https://doi.org/10.1007/s00455-016-9710-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00455-016-9710-1

Keywords

Search

Navigation