Advertisement

Translational Research for Rehabilitation of Swallowing in Head and Neck Cancer Patients

  • Uttam K. Sinha
Chapter

Abstract

Patients with head and neck cancer (HNC) suffer from difficulty in swallowing termed dysphagia due to the disease process itself and surgical and nonsurgical treatment of cancer [1]. Dysphagia has a most detrimental influence on quality of life (QOL) [2, 3]. Also, an estimated 65–88% of patients with dysphagia have several episodes of silent aspiration. This is a potentially fatal complication [4, 5]. A large number of predictive factors of swallowing function have been identified in multiple studies. They can be treatment-related factors (concurrent chemoradiation therapy (CRT), accelerated radiotherapy (RT), bilateral neck treatment [6], non-conformal RT [7], RT treatment field length [8, 9] and volume [10]), patient-related factors (baseline dysphagia, odynophagia, acute mucositis, xerostomia [11]), or tumor-related factors (advanced T-stage [6, 7], clinical stage IV [11], and tumor site [oropharynx] [6]. In the interest of survival improvement, modifications of the conventional RT have included concurrent chemotherapy (CT) and altered fractionated RT, particularly accelerated regimens [12, 13]. These strategies increase the tumoricidal effects of RT [14]. Nevertheless, the radiation-sensitizing effects of CT have been shown to result in increased acute problems like mucositis and late complications like fibrosis and stenosis [15]. These problems of C/RT have recently been acknowledged as one of the main hurdles to winning the fight against HNC [16].

Notes

Acknowledgments

The current work was supported by the National Institute on Deafness and Other Communication Disorders (NIDCD), Watt Family Endowed Chair, and Whittier Foundation. The author would like to thank Brenda Villegas, MS, CCC-SLP; Melody Ouyoung, MS, CCC-SLP; Yihe Zu, MD, PhD; Rizwan Masood, PhD; Srikanth Narayanan, PhD; and Gerald Loeb, MD, for their contribution in dysphagia research.

References

  1. 1.
    Moayer R, Sinha U. Dysphagia in head and neck cancer: a review. OJST. 2013;3:486–91.CrossRefGoogle Scholar
  2. 2.
    Hassan SJ, Weymuller EA Jr. Assessment of quality of life in head and neck cancer patients. Head Neck. 1993;15:485–96.CrossRefGoogle Scholar
  3. 3.
    Ojo B, Genden EM, Teng MS, Milbury K. A systematic review of head and neck cancer quality of life assessment instruments. Oral Oncol. 2012;48:923–37.CrossRefGoogle Scholar
  4. 4.
    O’Connell DA, Rieger J, Harris JR, et al. Swallowing function in patients with base of tongue cancers treated with primary surgery and reconstructed with a modified radial forearm free flap. Arch Otolaryngol Head Neck Surg. 2008;134:857–64.CrossRefGoogle Scholar
  5. 5.
    Garcia-Peris P, Paron L, Velasco C, et al. Long-term prevalence of oropharyngeal dysphagia in head and neck cancer patients: impact on quality of life. Clin Nutr. 2007;26:710–7.CrossRefGoogle Scholar
  6. 6.
    Langendijk JA, Doornaert P, Rietveld DH, et al. A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol. 2009;90:189–95.CrossRefGoogle Scholar
  7. 7.
    Frowen J, Cotton S, Corry J, Perry A. Impact of demographics, tumor characteristics, and treatment factors on swallowing after (chemo)radiotherapy for head and neck cancer. Head Neck. 2010;32:513–28.PubMedGoogle Scholar
  8. 8.
    Poulsen MG, Riddle B, Keller J, Porceddu SV, Tripcony L. Predictors of acute grade 4 swallowing toxicity in patients with stages III and IV squamous carcinoma of the head and neck treated with radiotherapy alone. Radiother Oncol. 2008;87:253–9.CrossRefGoogle Scholar
  9. 9.
    Patterson JM, McColl E, Carding PN, Hildreth AJ, Kelly C, Wilson JA. Swallowing in the first year after chemoradiotherapy for head and neck cancer: clinician and patient re- ported outcomes. Head Neck. 2014;36:352–8.CrossRefGoogle Scholar
  10. 10.
    van der Laan HP, Bijl HP, Steenbakkers RJ, et al. Acute symptoms during the course of head and neck radiotherapy or chemoradiation are strong predictors of late dysphagia. Radiother Oncol. 2015;115:56–62.CrossRefGoogle Scholar
  11. 11.
    Akst LM, Chan J, Elson P, Saxton J, Strome M, Adelstein D. Functional outcomes following chemoradiotherapy for head and neck cancer. Otolaryngol Head Neck Surg. 2004;131:950–7.CrossRefGoogle Scholar
  12. 12.
    Fu KK, Pajak TF, Trotti A, et al. A radiation oncology group phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2000;48:7–16.CrossRefGoogle Scholar
  13. 13.
    Pignon JP, Bourhis J, Domenge C. Chemotherapy added to locoregional treatment for head and neck squamous cell carcinoma: three meta-analyses of updated individual data. Lancet. 2000;355:949–55.CrossRefGoogle Scholar
  14. 14.
    Lawrence TS, Blackstock AW, McGinn C. The mechanism of action of radiosensitization of conventional chemotherapeutic agents. Semin Radiat Oncol. 2003;13:13–21.CrossRefGoogle Scholar
  15. 15.
    Nguyen NP, Sallah S. Combined chemotherapy and radiation in the treatment of locally advanced head and neck cancers. In Vivo. 2000;14:35–9.PubMedGoogle Scholar
  16. 16.
    Kulbersh BD, Rosenthal EL, McGrew BM, et al. Pretreatment, preoperative swallowing exercises may improve dysphagia quality of life. Laryngoscope. 2006;116:883–6.CrossRefGoogle Scholar
  17. 17.
    Allal AS, Nicoucar K, Mach N, Dulquerov P. Quality of life in patients with oropharynx carcinomas: assessment after accelerated radiotherapy with or without chemotherapy versus radical surgery and postoperative radiotherapy. Head Neck. 2003;25:833–9.CrossRefGoogle Scholar
  18. 18.
    Hurtuk AM, Marcinow A, Agrawal A, Old M, Teknos TN, Ozer E. Quality-of-life outcomes in transoral robotic surgery. Otolaryngol Head Neck Surg. 2012;146:68–73.CrossRefGoogle Scholar
  19. 19.
    Kokot N, Mazhar K, O'Dell K, Huang N, Lin A, Sinha UK. Transoral robotic resection of oropharyngeal synovial sarcoma in a pediatric patient. Int J Pediatr Otorhinolaryngol. 2013;77:1042–4.CrossRefGoogle Scholar
  20. 20.
    Barnhart MK, Ward EC, Cartmill B, et al. Pretreatment factors associated with functional oral intake and feeding tube use at 1 and 6 months post-radiotherapy (+/− chemotherapy) for head and neck cancer. Eur Arch Otorhinolaryngol. 2017;274:507–16.CrossRefGoogle Scholar
  21. 21.
    Peng G, Masood K, Gantz O, Sinha UK. Neuromuscular electrical stimulation improves radiation-induced fibrosis through Tgf-B1/MyoD homeostasis in head and neck cancer. J Surg Oncol. 2016;114:27–31.CrossRefGoogle Scholar
  22. 22.
    Ten Dijke P, Goumans MJ, Itoh F, et al. Regulation of cell proliferation by Smad proteins. J Cell Physiol. 2002;191:1–16.CrossRefGoogle Scholar
  23. 23.
    Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J. 2004;18:816–27.CrossRefGoogle Scholar
  24. 24.
    Xu P, Liu J, Derynck R. Post-translational regulation of TGF-b receptor and Smad signaling. FEBS Lett. 2012;586:1871–84.CrossRefGoogle Scholar
  25. 25.
    Hill CST. New insights into TGF-beta-Smad signalling. Trends Biochem Sci. 2004;29:265–73.CrossRefGoogle Scholar
  26. 26.
    Massague J. TGF-b signaling in development and disease. FEBS Lett. 2012;586:1833.CrossRefGoogle Scholar
  27. 27.
    Martin JF, Li L, Olson EN. Repression of myogenin function by TGF-beta 1 is targeted at the basic helix-loop-helix motif and is independent of E2A products. J Biol Chem. 1992;267:10956–60.PubMedGoogle Scholar
  28. 28.
    Lyons G, Muhlebach S, Moser A, et al. Developmental regulation of creatine kinase gene expression by myogenic factors in embryonic mouse and chick skeletal muscle. Development. 1991;113:1017–29.PubMedGoogle Scholar
  29. 29.
    Liu D, Black BL, Derynck R. TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev. 2001;15:2950–66.CrossRefGoogle Scholar
  30. 30.
    Liu D, Kang JS, Derynck R. TGF-beta-activated Smad3 represses MEF2-dependent transcription in myogenic differentiation. EMBO J. 2004;23:1557–66.CrossRefGoogle Scholar
  31. 31.
    Kale VP, Vaidya AA. Molecular mechanisms behind the dose-dependent differential activation of MAPK pathways induced by transforming growth factor-beta1 in hematopoietic cells. Stem Cells Dev. 2004;13:536–47.CrossRefGoogle Scholar
  32. 32.
    Brennan TJ, Edmondson DG, Li L, et al. Transforming growth factor beta represses the actions of myogenin through a mechanism independent of DNA binding. Proc Natl Acad Sci U S A. 1991;88:3822–6.CrossRefGoogle Scholar
  33. 33.
    Eisbruch A, Cyder T, Bradford CR, et al. Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2002;53:23–8.CrossRefGoogle Scholar
  34. 34.
    Murray T, Madasu R, Martin A, Robbins KT. Acute and chronic changes in swallowing and quality of life following intra-arterial chemoradiation for organ preservation in patients with advanced head and neck cancer. Head Neck. 1998;20:31–7.CrossRefGoogle Scholar
  35. 35.
    Krisciunas GP, Castellano K, McCulloch TM, et al. Impact of compliance on dysphagia rehabilitation in head and neck cancer patients: results from a multi-center clinical trial. Dysphagia. 2017;32:327–36.CrossRefGoogle Scholar
  36. 36.
    Loeb GE, Richmond FJ, Baker LL. The BION devices: injectable interfaces with peripheral nerves and muscles. Neurosurg Focus. 2006;20:E2.CrossRefGoogle Scholar
  37. 37.
    Loeb GE, Zamin CJ, Schulman JH, Troyk PR. Injectable microstimulator for functional electrical stimulation. Med Biol Eng Comput. 1991;29:NS13–9.CrossRefGoogle Scholar
  38. 38.
    Cameron T, Loeb GE, Peck RA, et al. Micromodular implants to provide electrical stimulation of paralyzed muscles and limbs. IEEE Trans Biomed Eng. 1997;44:781–90.CrossRefGoogle Scholar
  39. 39.
    Loeb GE, Peck RA, Moore WH, Hood K. BION system for distributed neural prosthetic interfaces. Med Eng Phys. 2001;23:9–18.CrossRefGoogle Scholar
  40. 40.
    Dupont Salter AC, Richmond FJ, Loeb GE. Prevention of muscle disuse atrophy by low-frequency electrical stimulation in rats. IEEE Trans Neural Syst Rehabil Eng. 2003;11:218–26.CrossRefGoogle Scholar
  41. 41.
    Weber DJ, Stein RB, Chan KM, Loeb GE, Richmond FJ, et al. Functional electrical stimulation using microstimulators to correct foot drop: a case study. Can J Physiol Pharmacol. 2004;82:784–92.CrossRefGoogle Scholar
  42. 42.
    Brummer SB, Robblee LS, Hambrecht FT. Criteria for selecting electrodes for electrical stimulation: theoretical and practical considerations. Ann N Y Acad Sci. 1983;405:159–71.CrossRefGoogle Scholar
  43. 43.
    Cameron T, Liinamaa TL, Loeb GE, Richmond FJ. Long-term biocompatibility of a miniature stimulator implanted in feline hind limb muscles. IEEE Trans Biomed Eng. 1998;45:1024–35.CrossRefGoogle Scholar
  44. 44.
    Sinha UK, Villegas B, Kuo C, Richmond FJ, Masood R, Nelson NI, Loeb GE. Safety of microstimulator during radiation therapy - a preliminary study on head and neck cancer patients. J Nucl Med Radiat Ther. 2014;5:197.Google Scholar
  45. 45.
    Hughes HL, Bendetto JM. Radiation effects and hardening of MOS technology: devices and circuits. IEEE Trans Nucl Sci. 2003;50:500–21.CrossRefGoogle Scholar
  46. 46.
    Briere TM, Beddar AS, Gillin MT. Evaluation of precalibrated implantable MOSFET radiation dosimeters for megavoltage photon beams. Med Phys. 2005;32:3346–9.CrossRefGoogle Scholar
  47. 47.
    Stoeckli SJ, Huisman TA, Seifert B, Martin-Harris BJ. Interrater reliability of videofluoroscopic swallow evaluation. Dysphagia. 2003;18:53–7.CrossRefGoogle Scholar
  48. 48.
    Hartl DM, Albiter M, Kolb F, Luboinski B, Sigal R. Morphologic parameters of normal swallowing events using single-shot fast spin echo dynamic MRI. Dysphagia. 2003;18:255–62.CrossRefGoogle Scholar
  49. 49.
    Anagnostara A, Stoeckli S, Weber OM, Kollias SS. Evaluation of the anatomical and functional properties of deglutition with various kinetic high-speed MRI sequences. J Magn Reson Imaging. 2001;14:194–9.CrossRefGoogle Scholar
  50. 50.
    Breyer T, Echternach M, Arndt S, et al. Dynamic magnetic resonance imaging of swallowing and laryngeal motion using parallel imaging at 3 T. Magn Reson Imaging. 2009;27:48–54.CrossRefGoogle Scholar
  51. 51.
    Zhang S, Olthoff A, Frahm J. Real-time magnetic resonance imaging of normal swallowing. J Magn Reson Imaging. 2012;35:1372–9.CrossRefGoogle Scholar
  52. 52.
    Panebianco V, Ruoppolo G, Pelle G, et al. Morpho-functional patterns of physiologic oropharyngeal swallowing evaluated with dynamic fast MRI. Eur Arch Otorhinolaryngol. 2010;267:1461–6.CrossRefGoogle Scholar
  53. 53.
    Albiter M, Petrow P, Kolb F, Bretagne E, Luboinski B, Sigal R. Swallowing study with kinetic MRI using a single shot fast spin echo sequence in healthy volunteers and patients treated for head and neck cancer [in French]. J Radiol. 2003;84:311–6.PubMedGoogle Scholar
  54. 54.
    Fauvet F, Charpiot A, Schultz P, et al. Cine-MRI contribution to assess swallowing mechanism and oro-pharyngeal dysphagia [in French]. Rev Laryngol Otol Rhinol. 2008;129:85–90.Google Scholar
  55. 55.
    Hartl DM, Kolb F, Bretagne E, Marandas P, Sigal R. Cine magnetic resonance imaging with single-shot fast spin echo for evaluation of dysphagia and aspiration. Dysphagia. 2006;21:156–62.CrossRefGoogle Scholar
  56. 56.
    Hartl DM, Kolb F, Bretagne E, Bidault F, Sigal R. Cine-MRI swallowing evaluation after tongue reconstruction. Eur J Radiol. 2010;73(1):108–13.CrossRefGoogle Scholar
  57. 57.
    Kitano H, Asada Y, Hayashi K, Inoue H, Kitajima K. The evaluation of dysphagia following radical surgery for oral and pharyngeal carcinomas by cine-magnetic resonance imaging (cine-MRI). Dysphagia. 2002;17:187–91.CrossRefGoogle Scholar
  58. 58.
    Kreeft AM, Rasch CR, Muller SH, Pameijer FA, Hallo E, Balm AJM. Cine MRI of swallowing in patients with advanced oral or oropharyngeal carcinoma: a feasibility study. Eur Arch Otorhinolaryngol. 2012;269:1703–11.CrossRefGoogle Scholar
  59. 59.
    Zu Y, Narayanan SS, Kim YC, et al. Evaluation of swallow function after tongue cancer treatment using real-time magnetic resonance imaging: a pilot study. JAMA Otolaryngol Head Neck Surg. 2013;139:1312–9.CrossRefGoogle Scholar
  60. 60.
    Narayanan S, Nayak K, Lee S, Sethy A, Byrd D. An approach to real-time magnetic resonance imaging for speech production. J Acoust Soc Am. 2004;115:1771–6.CrossRefGoogle Scholar
  61. 61.
    Santos JM, Wright GA, Pauly JM. Flexible real-time magnetic resonance imaging framework. Conf Proc IEEE Eng Med Biol Soc. 2004;2:1048–51.PubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Uttam K. Sinha
    • 1
  1. 1.Department of Head and Neck SurgeryKeck Medical Center, University of Southern CaliforniaLos AngelesUSA

Personalised recommendations