Therapy-Induced Changes in Head and Neck

  • Michael M. Lell
Part of the Medical Radiology book series (MEDRAD)


Radiation with or without concomitant chemotherapy of the head and neck region is associated with acute and chronic toxicity and adverse effects on organ function. Therapy-induced dysphagia is a complex multifactorial disorder, constituting one of the most common and prominent problems affecting quality of life of the patients. Classical fluoroscopy is still the method of choice to search for morphologic (fistula, stricture, resection defect) and functional (impaired sensory or motor function of the pharyngoesophageal tube and larynx, xerostomia) deficits. Bone injury is another severe, although relatively rare, condition induced by radiation and specific drugs, especially bisphosphonates. While fatty replacement of the bone marrow within the radiation field is a deterministic effect without clinical significance for the patient, radiation-induced inflammation, fibrosis, disorganization of extracellular matrix, and tissue remodeling may lead to devitalized bone with mucosal ulceration, pathologic fracture, and fistula formation. Similar effects have been associated with osteoclast-inhibiting therapies, including bisphosphonates and denosumab.


Apparent Diffusion Coefficient Lower Esophageal Sphincter Pharyngeal Transit Time Free Flap Reconstruction Suprahyoid Muscle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Apparent diffusion coefficient


American Society for Bone and Mineral Research




Cone beam computed tomography


Contrast material




Dysphagia-aspiration-related structures


Diffusion-weighted imaging


Fiber-optic endoscopic evaluation of swallowing


Modified barium swallow


Nasopharyngeal cancer


Osteonecrosis of the jaw


Oropharyngeal swallow efficiency


Oral residue




Oral transit time


Pharyngeal constrictors


Pharyngeal residue


Pharyngeal transit time




Radiation Therapy Oncology Group


Radiation therapy


  1. Asao C, Korogi Y, Kitajima M et al (2005) Diffusion-weighted imaging of radiation-induced brain injury for differentiation from tumor recurrence. AJNR Am J Neuroradiol 26:1455–1460PubMedGoogle Scholar
  2. Avril L, Lombardi T, Ailianou A et al (2014) Radiolucent lesions of the mandible: a pattern-based approach to diagnosis. Insights Imaging 5:85–101PubMedCentralCrossRefPubMedGoogle Scholar
  3. Bazan JG, Luxton G, Kozak MM et al (2013) Impact of chemotherapy on normal tissue complication probability models of acute hematologic toxicity in patients receiving pelvic intensity modulated radiation therapy. Int J Radiat Oncol Biol Phys 87:983–991CrossRefPubMedGoogle Scholar
  4. Blanco AI, Chao KS, El Naqa I et al (2005) Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys 62:1055–1069CrossRefPubMedGoogle Scholar
  5. Borggreven PA, Verdonck-de Leeuw I, Rinkel RN et al (2007) Swallowing after major surgery of the oral cavity or oropharynx: a prospective and longitudinal assessment of patients treated by microvascular soft tissue reconstruction. Head Neck 29:638–647CrossRefPubMedGoogle Scholar
  6. Bronstein AD, Nyberg DA, Schwartz AN et al (1987) Increased salivary gland density on contrast-enhanced CT after head and neck radiation. AJR Am J Roentgenol 149:1259–1263CrossRefPubMedGoogle Scholar
  7. Brunello A, Saia G, Bedogni A et al (2009) Worsening of osteonecrosis of the jaw during treatment with sunitinib in a patient with metastatic renal cell carcinoma. Bone 44:173–175CrossRefPubMedGoogle Scholar
  8. Caglar HB, Tishler RB, Othus M et al (2008) Dose to larynx predicts for swallowing complications after intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 72:1110–1118CrossRefPubMedGoogle Scholar
  9. Carmona R, Pritz J, Bydder M et al (2014) Fat composition changes in bone marrow during chemotherapy and radiation therapy. Int J Radiat Oncol Biol Phys 90:155–163PubMedCentralCrossRefPubMedGoogle Scholar
  10. Cheung M, Chan AS, Law SC et al (2000) Cognitive function of patients with nasopharyngeal carcinoma with and without temporal lobe radionecrosis. Arch Neurol 57:1347–1352PubMedGoogle Scholar
  11. Chrcanovic BR, Reher P, Sousa AA et al (2010) Osteoradionecrosis of the jaws–a current overview–part 1: physiopathology and risk and predisposing factors. Oral Maxillofac Surg 14:3–16CrossRefPubMedGoogle Scholar
  12. Christianen ME, Langendijk JA, Westerlaan HE et al (2011) Delineation of organs at risk involved in swallowing for radiotherapy treatment planning. Radiother Oncol 101:394–402CrossRefPubMedGoogle Scholar
  13. Christodoulou C, Pervena A, Klouvas G et al (2009) Combination of bisphosphonates and antiangiogenic factors induces osteonecrosis of the jaw more frequently than bisphosphonates alone. Oncology (Williston Park) 76:209–211CrossRefGoogle Scholar
  14. Denham JW, Hauer-Jensen M, Peters LJ (2001) Is it time for a new formalism to categorize normal tissue radiation injury? Int J Radiat Oncol Biol Phys 50:1105–1106CrossRefPubMedGoogle Scholar
  15. Eisbruch A, Ten Haken RK, Kim HM et al (1999) Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 45:577–587CrossRefPubMedGoogle Scholar
  16. Eisbruch A, Schwartz M, Rasch C et al (2004) 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 60:1425–1439CrossRefPubMedGoogle Scholar
  17. Feng FY, Kim HM, Lyden TH et al (2007) Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: early dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys 68:1289–1298CrossRefPubMedGoogle Scholar
  18. Gensheimer MF, Liao JJ, Garden AS et al (2014) Submandibular gland-sparing radiation therapy for locally advanced oropharyngeal squamous cell carcinoma: patterns of failure and xerostomia outcomes. Radiat Oncol 9:255PubMedCentralCrossRefPubMedGoogle Scholar
  19. Guarneri V, Miles D, Robert N et al (2010) Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer. Breast Cancer Res Treat 122:181–188CrossRefPubMedGoogle Scholar
  20. Hsiao KY, Yeh SA, Chang CC et al (2010) Cognitive function before and after intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma: a prospective study. Int J Radiat Oncol Biol Phys 77:722–726CrossRefPubMedGoogle Scholar
  21. Karagozoglu KH, Dekker HA, Rietveld D et al (2014) Proposal for a new staging system for osteoradionecrosis of the mandible. Med Oral Patol Oral Cir Bucal 19:e433–e437PubMedCentralCrossRefPubMedGoogle Scholar
  22. Kauczor HU, Dieti B, Brix G et al (1993) Fatty replacement of bone marrow after radiation therapy for Hodgkin disease: quantification with chemical shift imaging. J Magn Reson Imaging 3:575–580CrossRefPubMedGoogle Scholar
  23. Khan AA, Morrison A, Hanley DA et al (2015) Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res 30:3–23CrossRefPubMedGoogle Scholar
  24. Khariwala SS, Vivek PP, Lorenz RR et al (2007) Swallowing outcomes after microvascular head and neck reconstruction: a prospective review of 191 cases. Laryngoscope 117:1359–1363CrossRefPubMedGoogle Scholar
  25. Khosla S, Burr D, Cauley J et al (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22:1479–1491CrossRefPubMedGoogle Scholar
  26. Kumar AJ, Leeds NE, Fuller GN et al (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217:377–384CrossRefPubMedGoogle Scholar
  27. Lear CS, Flanagan JB Jr, Moorrees CF (1965) The frequency of deglutition in man. Arch Oral Biol 10:83–100CrossRefPubMedGoogle Scholar
  28. Lee NY, O’Meara W, Chan K et al (2007) Concurrent chemotherapy and intensity-modulated radiotherapy for locoregionally advanced laryngeal and hypopharyngeal cancers. Int J Radiat Oncol Biol Phys 69:459–468CrossRefPubMedGoogle Scholar
  29. Lell M, Baum U, Greess H et al (2000) Head and neck tumors: imaging recurrent tumor and post-therapeutic changes with CT and MRI. Eur J Radiol 33:239–247CrossRefPubMedGoogle Scholar
  30. Lell MM, Gmelin C, Panknin C et al (2008) Thin-slice MDCT of the neck: impact on cancer staging. AJR Am J Roentgenol 190:785–789CrossRefPubMedGoogle Scholar
  31. Liu RM, Gaston Pravia KA (2010) Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis. Free Radic Biol Med 48:1–15PubMedCentralCrossRefPubMedGoogle Scholar
  32. Lyons A, Ghazali N (2008) Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment. Br J Oral Maxillofac Surg 46:653–660CrossRefPubMedGoogle Scholar
  33. Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117CrossRefPubMedGoogle Scholar
  34. McConnel FM, Pauloski BR, Logemann JA et al (1998) Functional results of primary closure vs flaps in oropharyngeal reconstruction: a prospective study of speech and swallowing. Arch Otolaryngol Head Neck Surg 124:625–630CrossRefPubMedGoogle Scholar
  35. Mittal RK (2011) Motor function of the pharynx, esophagus, and its sphincters. Morgan & Claypool Life Sciences, San RafaelGoogle Scholar
  36. Mu L, Sanders I (2010) Human tongue neuroanatomy: nerve supply and motor endplates. Clin Anat 23:777–791PubMedCentralCrossRefPubMedGoogle Scholar
  37. Murdoch-Kinch CA, Kim HM, Vineberg KA et al (2008) Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 72:373–382PubMedCentralCrossRefPubMedGoogle Scholar
  38. Nabil S, Samman N (2011) Incidence and prevention of osteoradionecrosis after dental extraction in irradiated patients: a systematic review. Int J Oral Maxillofac Surg 40:229–243CrossRefPubMedGoogle Scholar
  39. Nguyen NP, Moltz CC, Frank C et al (2004) Dysphagia following chemoradiation for locally advanced head and neck cancer. Ann Oncol 15:383–388CrossRefPubMedGoogle Scholar
  40. Nomayr A, Lell M, Sweeney R et al (2001) MRI appearance of radiation-induced changes of normal cervical tissues. Eur Radiol 11:1807–1817CrossRefPubMedGoogle Scholar
  41. Nutting CM, Morden JP, Harrington KJ et al (2011) Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 12:127–136PubMedCentralCrossRefPubMedGoogle Scholar
  42. Okunieff P, Chen Y, Maguire DJ et al (2008) Molecular markers of radiation-related normal tissue toxicity. Cancer Metastasis Rev 27:363–374PubMedCentralCrossRefPubMedGoogle Scholar
  43. Pauloski BR, Rademaker AW, Logemann JA et al (2004) Surgical variables affecting swallowing in patients treated for oral/oropharyngeal cancer. Head Neck 26:625–636CrossRefPubMedGoogle Scholar
  44. Popovtzer A, Cao Y, Feng FY et al (2009) Anatomical changes in the pharyngeal constrictors after chemo-irradiation of head and neck cancer and their dose-effect relationships: MRI-based study. Radiother Oncol 93:510–515PubMedCentralCrossRefPubMedGoogle Scholar
  45. Prisman E, Miles BA, Genden EM (2013) Prevention and management of treatment-induced pharyngo-oesophageal stricture. Lancet Oncol 14:e380–e386CrossRefPubMedGoogle Scholar
  46. Rademaker AW, Pauloski BR, Logemann JA et al (1994) Oropharyngeal swallow efficiency as a representative measure of swallowing function. J Speech Hear Res 37:314–325CrossRefPubMedGoogle Scholar
  47. Russi EG, Corvo R, Merlotti A et al (2012) Swallowing dysfunction in head and neck cancer patients treated by radiotherapy: review and recommendations of the supportive task group of the Italian Association of Radiation Oncology. Cancer Treat Rev 38:1033–1049CrossRefPubMedGoogle Scholar
  48. Sciubba JJ, Goldenberg D (2006) Oral complications of radiotherapy. Lancet Oncol 7:175–183CrossRefPubMedGoogle Scholar
  49. Sivolella S, Lumachi F, Stellini E et al (2013) Denosumab and anti-angiogenetic drug-related osteonecrosis of the jaw: an uncommon but potentially severe disease. Anticancer Res 33:1793–1797PubMedGoogle Scholar
  50. Sonis ST (2011) Oral mucositis. Anticancer Drugs 22:607–612CrossRefPubMedGoogle Scholar
  51. Stockmann P, Hinkmann FM, Lell MM et al (2010) Panoramic radiograph, computed tomography or magnetic resonance imaging. Which imaging technique should be preferred in bisphosphonate-associated osteonecrosis of the jaw? A prospective clinical study. Clin Oral Investig 14:311–317CrossRefPubMedGoogle Scholar
  52. Valk PE, Dillon WP (1991) Radiation injury of the brain. AJNR Am J Neuroradiol 12:45–62PubMedGoogle Scholar
  53. Wahl MJ (2006) Osteoradionecrosis prevention myths. Int J Radiat Oncol Biol Phys 64:661–669CrossRefPubMedGoogle Scholar
  54. Zuydam AC, Rogers SN, Brown JS et al (2000) Swallowing rehabilitation after oro-pharyngeal resection for squamous cell carcinoma. Br J Oral Maxillofac Surg 38:513–518CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of RadiologyUniversity ErlangenErlangenGermany

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