Erkan Topkan¹*, Efsun Somay², Busra Yilmaz³, Berrin Pehlivan⁴, Ugur Selek⁵

¹Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey
²Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Baskent University, Ankara, Turkey
³Department of Oral and Maxillofacial Radiology, School of Dental Medicine, Bahcesehir University, Istanbul, Turkey
⁴Department of Radiation Oncology, Bahcesehir University, Istanbul, Turkey
¹⁵Department of Radiation Oncology, School of Medicine, Koc University, Istanbul, Turkey

*Corresponding Author: Erkan Topkan, Department of Radiation Oncology, Faculty of Medicine, Baskent University, Adana, Turkey.

Received: July 11, 2023; Published: July 29, 2023

Abstract

Radiotherapy is an essential component of curative treatment for head and neck cancer, either as a neoadjuvant or adjuvant treatment to surgery or as a definitive treatment with or without chemotherapy, depending on the stage of the disease and general health. However, aggressive RT or chemoradiotherapy can result in radiation-induced severe late toxicities, including the severely debilitating osteoradionecrosis of the jaws (ORNJ), which may affect a relatively small but significant proportion of this patient population. ORNJ is characterized by necrosis of bone tissue and failure to heal for at least three months. In the majority of cases, ORNJ progresses gradually, worsening and becoming more painful, which results in infection and pathological fracture. In the absence of a proven curative treatment other than aggressive surgeries, the prevalence of ORNJ could theoretically be decreased by implementing a well-organized multidisciplinary oral care program and reducing the ORNJ-related risk factors. These risk factors include the patient, the tumor, pre-radiotherapy mandibular surgery, tooth extractions, implant placement, radiation modality, and radiation dosimetry-related factors. Therefore, the present paper provides a literature review and update on the established and frequently disputed risk factors underlying ORNJ and their radiobiological bases.

Keywords: Head and Neck Cancer; Toxicity; Osteoradionecrosis; Risk Factors

References

1. Mireștean CC., et al. “New horizons in modulating the radio-sensitivity of head and neck cancer - 100 years after Warburg' effect discovery”. Frontiers in Oncology 12 (2022): 908695.
2. Lacas B., et al. “Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group”. Radiotherapy and Oncology 156 (2021): 281-293.
3. Sroussi HY., et al. “Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis”. Cancer Medicine 6 (2017): 2918-2931.
4. Strojan P., et al. “Treatment of late sequelae after radiotherapy for head and neck cancer”. Cancer Treatment Reviews 59 (2017): 79-92.
5. Chronopoulos A., et al. “Osteoradionecrosis of the jaws: definition, epidemiology, staging and clinical and radiological findings. A concise review”. International Dental Journal 68 (2018): 22-30.
6. Frankart AJ., et al. “Osteoradionecrosis: Exposing theevidence not the bone”. International Journal of Radiation Oncology - Biology - Physics5 (2021): 1206-1218.
7. Singh A., et al. “Osteoradionecrosis of the jaw following proton radiation therapy for patients with head and neck cancer”. JAMA Otolaryngology-Head and Neck Surgery (2022).
8. Notani K., et al. “Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy”. Head Neck3 (2003): 181-186.
9. Jacobson AS., et al.” Quality of life after manage-ment of advanced osteoradionecrosis of the mandible”. International Journal of Oral and Maxillofacial Surgery9 (2013): 1121-1128.
10. Rogers SN., et al. “Longitudinal evaluation of health-related quality of life after osteoradionecrosis of the mandible”. British Journal of Oral and Maxillofacial Surgery9 (2015): 854-857.
11. Jin T., et al. “Preoperative status and treatment of osteoradionecrosis of the jaw: a retrospective study of 252 cases”. British Journal of Oral and Maxillofacial Surgery10 (2020): e276-282.
12. Chieng CY., et al. “Health related quality of life and patient concerns in patients with osteoradionecrosis”. British Journal of Oral and Maxillofacial Surgery9 (2021): 1061-1066.
13. Danielsson D., et al. “Quality of life after microvascular mandibular reconstruction for osteoradionecrosis-A prospective study”. Head Neck7 (2019): 2225-2230.
14. de Graeff A., et al. “A prospective study on quality of life of laryngeal cancer patients treated with radiotherapy”. Head Neck4 (1999): 291-296.
15. List MA., et al. “Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination”. Journal of Clinical Oncology 3 (1999): 1020-1028.
16. Aoyama K., et al. “Jaw thrust maneuver for endotracheal intubation using a fiberoptic stylet”. Anesthesia and Analgesia6 (2000): 1457-1458.
17. Dhanda J., et al. “Current concepts in osteoradionecrosis after head and neck radiotherapy”. Clinical oncology (Royal College of Radiologists)7 (2016): 459-466.
18. Yilmaz B., et al. “Challenges in the radiological diagnosis of osteoradionecrosis of the jaw in head and neck cancer patients”. In: Sergi CM, editor. Advancements in Cancer Research. Brisbane (AU): Exon Publications; Online first (2022): 1-22.
19. Brooker RC., et al. “Genetic variants associated with mandibular osteoradionecrosis following radiotherapy for head and neck malignancy”. Radiotherapy and Oncology 165 (2021): 87-93.
20. Danielsson D., et al. “Influence of genetic background and oxidative stress response on risk of mandibular osteoradionecrosis after radiotherapy of head and neck cancer”. Head Neck3 (2016): 387-393.
21. Owosho AA., et al. “The prevalence and risk factors associated with osteoradionecrosis of the jaw in oral and oropharyngeal cancer patients treated with intensity-modulated radiation therapy (IMRT): The Memorial Sloan Kettering Cancer Center experience”. Oral Oncology 64 (2017): 44-51.
22. Kluth EV., et al. “A study of factors contributing to the development of osteoradionecrosis of the jaws”. Journal of Prosthetic Dentistry59 (1988): 194-201.
23. Acharya S., et al. “Risk assessment for osteoradionecrosis of the jaws in patients with head and neck cancer”. Medicine and Pharmacy 2 (2020): 195-199.
24. Topkan E., et al. “Comment on: Osteoradionecrosis after postoperative radiotherapy for oral cavity cancer: A retrospective cohort study”. Oral Oncology 134 (2022): 106098.
25. Messner B., et al. “Apoptosis and necrosis: two different outcomes of cigarette smoke condensate-induced endothelial cell death”. Cell Death and Disease11 (2012): e424.
26. Kisseleva T and Brenner DA. “Mechanisms of fibrogenesis”. Experimental Biology and Medicine2 (2008): 109-122.
27. Frazier K., et al. “Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor”. Journal of Investigative Dermatology3 (1996): 404-411.
28. Takeuchi H., et al. “Nicotine-induced CCN2: from smoking to periodontal fibrosis”. Journal of Dental Research 1 (2010): 34-39.v
29. Möring MM., et al. “Osteoradionecrosis after postoperative radiotherapy for oral cavity cancer: A retrospective cohort study”. Oral Oncology 133 (2022): 106056.
30. Reuther T., et al. “Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients--a report of a thirty year retrospective review”. International Journal of Oral and Maxillofacial Surgery3 (2003): 289-295.
31. Goldwaser BR., et al. “Risk factor assessment for the development of osteoradionecrosis”. Journal of Oral and Maxillofacial Surgery11 (2007): 2311-2316.
32. Huang Q., et al. “Nutritional status in patients of mandibular osteoradionecrosis: A single-institution experience”. Oral Diseases2 (2022): 513-520.
33. Nadella KR., et al. “A. Osteoradionecrosis of the jaws: Clinico-therapeutic management: A literature review and update”. Journal of Oral and Maxillofacial Surgery4 (2015): 891-901.
34. Chrcanovic BR., et al. “Osteoradionecrosis of the jaws--a current overview--Part 2: dental management and therapeutic options for treatment”. Oral and Maxillofacial Surgery2 (2010): 81-95.
35. Kuhnt T., et al. “Potential risk factors for jaw osteoradionecrosis after radiotherapy for head and neck cancer”. Radiation Oncology 11 (2016): 101.
36. Monnier Y., et al. “Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors”. Otolaryngology-Head and Neck Surgery5 (2011): 726-732.
37. Yilmaz B., et al. “Letter to the Editor: To extract or not extract teeth prior to head and neck radiotherapy? Supportive Care in Cancer1 (2022): 90.
38. Singh A., et al. “Osteoradionecrosis of the jaw: A mini review”. Front Oral Health 3 (2022): 980786.
39. Caparrotti F., et al. “Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy”. Cancer 19 (2017): 3691-3700.
40. Chen YC., et al. “Outcomes of re-irradiation for oral cavity squamous cell carcinoma”. Biomedical Journal6 (2022): 940-947.
41. Kubota H., et al. “Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma”. Radiation Oncology 1 (2021): 1.
42. Sathasivam HP., et al. “Predictive factors for osteoradionecrosis of the jaws: A retrospective study”. Head Neck1 (2018): 46-54.
43. Tucker JR., et al. “Osteoradionecrosis in patients with salivary gland malignancies”. Oral Oncology 57 (2016): 1-5.
44. Chen JA., et al. “Osteoradionecrosis of mandible bone in patients with oral cancer--associated factors and treatment outcomes”. Head Neck 5 (2016): 762-768.
45. Wang TH., et al. “Risk factors for and the role of dental extractions in osteoradionecrosis of the jaws: A national-based cohort study: Osteoradionecrosis of the jaws and dental extractions”. Head Neck 39 (2017): 1313-1321.
46. Chopra S., et al. “Factors predictive of severity of osteoradionecrosis of the mandible”. Head Neck11 (2011): 1600-1605.v
47. Chang DT., et al. “Do pre-irradiation dental extractions reduce the risk of osteoradionecrosis of the mandible?”. Head Neck6 (2007): 528-536.
48. Beaumont S., et al. “Timing of dental extractions in patients undergoing radiotherapy and the incidence of osteoradionecrosis: a systematic review and meta-analysis”. British Journal of Oral and Maxillofacial Surgery5 (2021): 511-523.
49. Urquhart O., et al. “Effect of preradiation dental intervention on incidence of osteoradionecrosis in patients with head and neck cancer: A systematic review and meta-analysis”. Journal of the American Dental Association. 153.10 (2022): 931-942.e32.
50. Balermpas P., et al. “Dental extraction, intensity-modulated radiotherapy of head and neck cancer, and osteoradionecrosis: A systematic review and meta-analysis”. Strahlentherapie und Onkologie3 (2022): 219-228.
51. Srinivas B., et al. “Wound healing and bone regeneration in postextraction sockets with and without platelet-rich fibrin”. Annals of Maxillofacial Surgery1 (2018): 28-34.
52. Hoffmann L., et al. “Dental management before radiotherapy of the head and neck region: 4-year single-center experience”. Clinical and Experimental Dental Research6 (2022): 1478-1486.
53. Koga DH., et al. “Dental extractions and radiotherapy in head and neck oncology: review of the literature”. Oral Diseases1 (2008): 40-44.
54. Yilmaz B., et al. “Pretreatment systemic immune-inflammation index predict needs for teeth extractions for locally advanced head and neck cancer patients undergoing concurrent chemoradiotherapy”. Therapeutics and Clinical Risk Management 17 (2021): 1113-1121.
55. Girardi FM., et al. “Risk factors for jaw osteoradionecrosis: a case control study”. Brazilian Oral Research 36 (2022): e132.
56. Jereczek-Fossa BA and Orecchia R. “Radiotherapy-induced mandibular bone complications”. Cancer Treatment Reviews 28 (2002): 65-74.
57. Kuo TJ., et al. “Jaw osteoradionecrosis and dental extraction after head and neck radiotherapy: a nationwide population-based retrospective study in Taiwan”. Oral Oncology 56 (2016): 71-77.
58. Nabil S and Samman N. “Incidence and prevention of osteoradionecrosis after dental extraction in irradiated patients: a systematic review”. International Journal of Oral and Maxillofacial Surgery3 (2011): 229-243.
59. Khoo SC., et al. “Predictors of osteoradionecrosis following irradiated tooth extraction”. Radiation Oncology1 (2021): 130.
60. Marx RE and Johnson RP. “Studies in the radiobiology of osteoradionecrosis and their clinical significance”. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 4 (1987): 379-390.
61. Somay E., et al. “Quality of life changes in patients with osteoradionecrosis and their measurement”. Journal of Advances in Medicine and Medical Research 21 (2022): 48-61.
62. Nelson K., et al. “Survival analysis and clinical evaluation of implant-retained prostheses in oral cancer resection patients over a mean follow-up period of 10 years”. Journal of Prosthetic Dentistry 98 (2007): 405-410.
63. Buddula A., et al. “Survival of turned and roughened dental implants in irradiated head and neck cancer patients: a retrospective analysis”. Journal of Prosthetic Dentistry 106 (2011): 290-296.
64. De Angelis F., et al. “Implant survival and success rates in patients with risk factors: results from a longterm retrospective study with a 10 to 18 years follow-up”. European Review for Medical and Pharmacological Sciences3 (2017): 433-437.
65. Vanegas-Acosta JC., et al. “Mathematical model of the coagulation in the bone-dental implant interface”. Computers in Biology and Medicine10 (2010): 791-801.
66. Kudo M., et al. “A histomorphometric study of the tissue reaction around hydroxyapatite implants irradiated after placement”. Journal of Oral and Maxillofacial Surgery3 (2001): 293-300; discussion 301.
67. Toneatti DJ., et al. “Survival of dental implants and occurrence of osteoradionecrosis in irradiated head and neck cancer patients: a systematic review and meta-analysis”. Journal Clinical Oral Investigations10 (2021): 5579-5593.
68. Schiegnitz E., et al. “Dental implants in patients with head and neck cancer-A systematic review and meta-analysis of the influence of radiotherapy on implant survival”. Clinical Oral Implants Research10 (2022): 967-999.
69. Koudougou C., et al. “Postimplantation radiation therapy in head and neck cancer patients: Literature review”. Head Neck4 (2020): 794-802.
70. Phulpin B., et al. “Feasibility of treating irradiated bone with intramedullary delivered autologous mesenchymal stem cells”. Journal of Biotechnology and Biomedicine (2011): 560257.
71. Engleman MA., et al. “Radiation-induced skeletal injury”. Cancer Treatment and Research 128 (2006): 155-169.
72. Lajolo C., et al. “Tooth extraction before radiotherapy is a risk factor for developing osteoradionecrosis of the jaws: A systematic review”. Oral Diseases7 (2021): 1595-1605.
73. Beech N., et al. “Preradiotherapy dental extractions and health-related quality of life”. Oral Surgery, Oral Medicine, Oral Pathology Oral Radiology 122.6 (2016): 672-679.
74. Wahl MJ. “Osteoradionecrosis prevention myths”. International Journal of Radiation Oncology - Biology - Physics3 (2006): 661-669.
75. Beumer J., et al. “Osteoradionecrosis: predisposing factors and outcomesof therapy”. Head Neck Surgery4 (1984): 819-827.
76. Jawad H., et al. “A review of dental treatment of head and neck cancer patientsbefore, during and after radiotherapy: par 2”. British Dental Journal2 (2015): 69-74.
77. Okamoto K., et al. “Osteoimmunology: The conceptual framework unifying the immune and skeletal systems”. Physiological Reviews4 (2017): 1295-1349.
78. Curi MM., et al. “Histopathologic and histomorphometric analysis of irradiation injury in bone and the surrounding soft tissues of the jaws”. Journal of Oral and Maxillofacial Surgery 74 (2016): 190-199.
79. Delanian S and Lefaix JL. “The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway”. Radiotherapy and Oncology 73 (2004): 119-131.
80. Chandra A., et al. “Potential role of senescence in radiation-induced damage of the aged skeleton”. Bone 120 (2019): 423- 431.
81. Herberg S., et al. “Total body irradiation is permissive for mesenchymal stem cell-mediated new bone formation following local transplantation”. Tissue Engineering (Part A) 20 (2014): 3212-3227.
82. Green DE., et al. “Devastation of adult stem cell pools by irradiation precedes collapse of trabecular bone quality and quantity”. Journal of Bone and Mineral Research27 (2012): 749-759.
83. Preciado S., et al. “Mesenchymal stromal cell irradiation interferes with the adipogenic/osteogenic differentiation balance and improves their hematopoietic-supporting ability”. Biology of Blood and Marrow Transplantation 24 (2018): 443-451.
84. Zou Q., et al. “Bone marrow stem cell dysfunction in radiation-induced abscopal bone loss”. Journal of Orthopaedic Surgery and Research 11 (2016): 3.
85. Marx RE and Johnson RP. “Studies in the radiobiology of osteoradionecrosis and their clinical significance”. Oral Surgery, Oral Medicine, Oral Pathology Oral Radiology 64 (1987): 379-390.
86. Lyons A and Ghazali N. “Osteoradionecrosis of the jaws: current understanding of its pathophysiology and treatment”. British Journal of Oral and Maxillofacial Surgery8 (2008): 653-660.
87. Bras J., et al. “Osteoradionecrosis of the mandible: pathogenesis”. American Journal of Otolaryngology 4 (1990): 244-250.
88. Xu J., et al. “Early-stage pathogenic sequence of jaw osteoradionecrosis in vivo”. Journal of Dental Research7 (2012): 702-708.
89. Dekker H., et al. “The irradiated human mandible: A quantitative study on bone vascularity”. Oral Oncology 87 (2018): 126-130.
90. Somay E., et al. “Initial neutrophil-to-lymphocyte ratio predicts radiation-induced trismus in parotid gland cancer”. Oral Diseases (2022).
91. Nguyen NP., et al. “Effectiveness of intensity-modulated and image-guided radiotherapy to spare the mandible from excessive radiation”. Oral Oncology 48.7 (2012): 653-657.
92. Zhang W., et al. “Intensity-modulated proton therapy and osteoradionecrosis in oropharyngeal cancer”. Radiotherapy and Oncology3 (2017): 401-405.
93. Aarup-Kristensen S., et al. “Osteoradionecrosis of the mandible after radiotherapy for head and neck cancer: risk factors and dose-volume correlations”. Acta Oncologica10 (2019): 1373-1377.
94. MD Anderson and Head and Neck Cancer Symptom Working Group. “Dose-volume correlates of mandibular osteoradionecrosis in oropharynx cancer patients receiving intensity-modulated radiotherapy: Results from a case-matched comparison”. Radiotherapy and Oncology 124.2 (2017): 232-239.
95. De Felice F., et al. “Osteoradionecrosis following treatment for head and neck cancer and the effect of radiotherapy dosimetry: the Guy's and St Thomas' Head and Neck Cancer Unit experience”. Oral Surgery, Oral Medicine, Oral Pathology Oral Radiology1 (2016): 28-34.
96. vanDijk LV., et al. "Normal Tissue Complication Probability (NTCP) prediction model for osteoradionecrosis of the mandible in patients with head and neck cancer after radiation therapy: large-scale observational cohort”. International Journal of Radiation Oncology - Biology - Physics2 (2021): 549-558.
97. Tsai CJ., et al. “Osteoradionecrosis and radiation dose to the mandible in patients with oropharyngealcancer”. International Journal of Radiation Oncology - Biology - Physics2 (2013): 415-420.
98. Caparrotti F., et al. “Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy”. Cancer19 (2017): 3691-3700.
99. Lang K., et al. “Frequency of osteoradionecrosis of the lower jaw after radiotherapy of oral cancer patients correlated with dosimetric parameters and other risk factors”. Head and Face Medicine1 (2022): 7.

Citation

Citation: Erkan Topkan., et al. “Risk Factors for Osteoradionecrosis of the Jaw in the Era of Modern Head and Neck RadiotherapyActa Scientific Dental Sciences 7.8 (2023): 68-81.

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Copyright: © 2023 Erkan Topkan., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.