Skip to main content

Osteoradionecrosis in cancer patients: the evidence base for treatment-dependent frequency, current management strategies, and future studies

Supportive Care in Cancer volume 18, pages 1089–1098 (2010)Cite this article

Abstract

Purpose

The purpose of this study is to review the evidence base from 1990 to 2008 to (1) clarify the impact of cancer therapies on prevalence of osteoradionecrosis (ORN) in head and neck cancer patients, and to (2) evaluate management strategies and their consequences on quality of life and cost of care.

Methods

Articles were selected for the time period beginning after 1989, excluding the 1990 NCI monograph articles from the 1989 NIH-sponsored Oral Complications in Cancer Therapy Symposium that was published in 1990. The search included both Medline/PubMed and Embase and was limited to humans. The search was limited to publications in the English language. No abstracts were utilized in the current review. Each article was evaluated by two reviewers. A weighted prevalence was calculated for the prevalence of ORN while incorporating predetermined quality measures. The level of evidence, recommendation grade, and guideline (if possible) were provided for published preventive and management strategies for ORN.

Results

A total of 43 articles between 1990 and 2008 were reviewed. The weighted prevalence for ORN included conventional radiotherapy (RT) = 7.4%, intensity modulated RT (IMRT) = 5.1%, chemoradiotherapy (CRT) = 6.8%, and brachytherapy = 5.3%. Hyperbaric oxygen may contribute a role in management of ORN. However, no clear guideline recommendations could be established for the prevention or treatment of ORN based on the literature reviewed.

Conclusions

New cancer treatment modalities such as IMRT and concomitant CRT have had minimal effect on prevalence of ORN. No studies to date have systematically addressed impact of ORN on either quality of life or cost of care.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2

References

  1. Katsura K, Sasai K, Sato K, Saito M, Hoshina H, Hayashi T (2008) Relationship between oral health status and development of osteoradionecrosis of the mandible: a retrospective longitudinal study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:731–738

    Article  PubMed  Google Scholar 

  2. Reuther T, Schuster T, Mende U, Kubler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients—a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 32:289–295

    CAS  Article  PubMed  Google Scholar 

  3. National Institutes of Health (1990) Consensus development conference on oral complications of cancer therapies: diagnosis, prevention, and treatment. Bethesda, Maryland, April 17–19, 1989. NCI Monogr 9:1–184

    Google Scholar 

  4. National Institutes of Health (2009) Oral complications of emerging cancer therapies. Bethesda, MD USA, April 14-15, 2009 (Primary funding provided by National Institutes of Health, Bethesda, MD, USA)

  5. Brennan MT, Elting LS, Spijkervet FK (2010) Systematic reviews of oral complications from cancer therapies, Oral Care Study Group, MASCC/ISOO: methodology and quality of the literature. Supp Care Cancer. doi:10.1007/s00520-010-0856-3

  6. Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100(9 Suppl):1995–2025

    Article  PubMed  Google Scholar 

  7. Berard A, Bravo G (1998) Combining studies using effect sizes and quality scores: application to bone loss in postmenopausal women. J Clin Epidemiol 51:801–807

    CAS  Article  PubMed  Google Scholar 

  8. Efron B (1993) An introduction to the bootstrap. Chapman and Hall, New York City

    Google Scholar 

  9. Miura M, Takeda M, Sasaki T, Inoue T, Nakayama T, Fukuda H, Hoshi A, Hoshina M, Shibuya H (1998) Factors affecting mandibular complications in low dose rate brachytherapy for oral tongue carcinoma with special reference to spacer. Int J Radiat Oncol Biol Phys 41:763–770

    CAS  PubMed  Google Scholar 

  10. Marx RE, Johnson RP, Kline SN (1985) Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc 111:49–54

    CAS  PubMed  Google Scholar 

  11. Vudiniabola S, Pirone C, Williamson J, Goss AN (1999) Hyperbaric oxygen in the prevention of osteoradionecrosis of the jaws. Aust Dent J 44:243–247

    CAS  Article  PubMed  Google Scholar 

  12. Sulaiman F, Huryn JM, Zlotolow IM (2003) Dental extractions in the irradiated head and neck patient: a retrospective analysis of Memorial Sloan-Kettering Cancer Center protocols, criteria, and end results. J Oral Maxillofac Surg 61:1123–1131

    Article  PubMed  Google Scholar 

  13. Adkinson C, Anderson T, Chavez J, Collier R, MacLeod S, Nicholson C, Odland R, Vellis P (2005) Hyperbaric oxygen therapy: a meeting place for medicine and dentistry. Minn Med 88:42–45

    PubMed  Google Scholar 

  14. Marx RE, Johnson RP (1988) Problem wounds in oral and maxillofacial surgery: the role of hyperbaric oxygenation. In: Davis JC, Hunt TK (eds) Problem wounds-the role of oxygen. Elsevier, New York, pp 65–128

    Google Scholar 

  15. Notani K, Yamazaki Y, Kitada H, Sakakibara N, Fukuda H, Omori K, Nakamura M (2003) Management of mandibular osteoradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy. Head Neck 25:181–186

    Article  PubMed  Google Scholar 

  16. Jisander S, Grenthe B, Salemark L (1999) Treatment of mandibular osteoradionecrosis by cancellous bone grafting. J Oral Maxillofac Surg 57:936–942, discussion 942-943

    CAS  Article  PubMed  Google Scholar 

  17. David LA, Sandor GK, Evans AW, Brown DH (2001) Hyperbaric oxygen therapy and mandibular osteoradionecrosis: a retrospective study and analysis of treatment outcomes. J Can Dent Assoc 67:384

    CAS  PubMed  Google Scholar 

  18. Maier A, Gaggl A, Klemen H, Santler G, Anegg U, Fell B, Karcher H, Smolle-Juttner FM, Friehs GB (2000) Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygenation. Br J Oral Maxillofac Surg 38:173–176

    CAS  Article  PubMed  Google Scholar 

  19. Annane D, Depondt J, Aubert P, Villart M, Gehanno P, Gajdos P, Chevret S (2004) Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. J Clin Oncol 22:4893–4900

    Article  PubMed  Google Scholar 

  20. Aitasalo K, Niinikoski J, Grenman R, Virolainen E (1998) A modified protocol for early treatment of osteomyelitis and osteoradionecrosis of the mandible. Head Neck 20:411–417

    CAS  Article  PubMed  Google Scholar 

  21. Delanian S, Depondt J, Lefaix JL (2005) Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck 27:114–123

    Article  PubMed  Google Scholar 

  22. Militsakh ON, Wallace DI, Kriet JD, Tsue TT, Girod DA (2005) The role of the osteocutaneous radial forearm free flap in the treatment of mandibular osteoradionecrosis. Otolaryngol Head Neck Surg 133:80–83

    Article  PubMed  Google Scholar 

  23. Claus F, Duthoy W, Boterberg T, De Gersem W, Huys J, Vermeersch H, De Neve W (2002) Intensity modulated radiation therapy for oropharyngeal and oral cavity tumors: clinical use and experience. Oral Oncol 38:597–604

    Article  PubMed  Google Scholar 

  24. van den Broek GB, Balm AJ, van den Brekel MW, Hauptmann M, Schornagel JH, Rasch CR (2006) Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer. Radiother Oncol 81:143–150

    Article  PubMed  Google Scholar 

  25. Studer G, Studer SP, Zwahlen RA, Huguenin P, Gratz KW, Lutolf UM, Glanzmann C (2006) Osteoradionecrosis of the mandible: minimized risk profile following intensity-modulated radiation therapy (IMRT). Strahlenther Onkol 182:283–288

    Article  PubMed  Google Scholar 

  26. Mendenhall WM, Morris CG, Amdur RJ, Hinerman RW, Malyapa RS, Werning JW, Lansford CD, Villaret DB (2006) Definitive radiotherapy for tonsillar squamous cell carcinoma. Am J Clin Oncol 29:290–297

    Article  PubMed  Google Scholar 

  27. Ryu JK, Stern RL, Robinson MG, Bowers MK, Kubo HD, Donald PJ, Rosenthal SA, Fu KK (1995) Mandibular reconstruction using a titanium plate: the impact of radiation therapy on plate preservation. Int J Radiat Oncol Biol Phys 32:627–634

    CAS  PubMed  Google Scholar 

  28. Leborgne F, Leborgne JH, Zubizarreta E, Mezzera J (2002) Cesium-137 needle brachytherapy boosts after external beam irradiation for locally advanced carcinoma of the tongue and floor of the mouth. Brachytherapy 1:126–130

    Article  PubMed  Google Scholar 

  29. Allal AS, Bieri S, Miralbell R, Marchal F, Lehmann W, Kurtz JM (1997) Feasibility and outcome of a progressively accelerated concomitant boost radiotherapy schedule for head and neck carcinomas. Int J Radiat Oncol Biol Phys 38:685–689

    CAS  Article  PubMed  Google Scholar 

  30. Toljanic JA, Ali M, Haraf DJ, Vokes EE, Moran WJ, Graham L (1998) Osteoradionecrosis of the jaws as a risk factor in radiotherapy: a report of an eight-year retrospective review. Oncol Rep 5:345–349

    CAS  PubMed  Google Scholar 

  31. Grabenbauer GG, Rodel C, Brunner T, Schulze-Mosgau S, Strnad V, Muller RG, Iro H, Sauer R (2001) Interstitial brachytherapy with Ir-192 low-dose-rate in the treatment of primary and recurrent cancer of the oral cavity and oropharynx. Review of 318 patients treated between 1985 and 1997. Strahlenther Onkol 177:338–344

    CAS  Article  PubMed  Google Scholar 

  32. Takacsi-Nagy Z, Polgar C, Oberna F, Somogyi A, Major T, Remenar E, Fodor J, Kasler M, Nemeth G (2004) Interstitial high-dose-rate brachytherapy in the treatment of base of tongue carcinoma. Strahlenther Onkol 180:768–775

    Article  PubMed  Google Scholar 

  33. Abitbol A, Abdel-Wahab M, Lewin A, Troner M, Rodrigues MA, Hamilton-Nelson KL, Markoe A (2002) Phase II study of tolerance and efficacy of hyperfractionated radiotherapy and 5-fluorouracil, cisplatin, and paclitaxel (Taxol) in stage III and IV inoperable and/or unresectable head-and-neck squamous cell carcinoma: A-2 protocol. Int J Radiat Oncol Biol Phys 53:942–947

    CAS  PubMed  Google Scholar 

  34. Umeda M, Komatsubara H, Nishimatsu N, Yokoo S, Shibuya Y, Komori T (2000) High-dose rate interstitial brachytherapy for stage I-II tongue cancer. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 90:667–670

    CAS  Article  PubMed  Google Scholar 

  35. Pernot M, Luporsi E, Hoffstetter S, Peiffert D, Aletti P, Marchal C, Kozminski P, Noel A, Bey P (1997) Complications following definitive irradiation for cancers of the oral cavity and the oropharynx (in a series of 1134 patients). Int J Radiat Oncol Biol Phys 37:577–585

    CAS  PubMed  Google Scholar 

  36. De Crevoisier R, Domenge C, Wibault P, Koscielny S, Lusinchi A, Janot F, Bobin S, Luboinski B, Eschwege F, Bourhis J (2001) Full dose reirradiation combined with chemotherapy after salvage surgery in head and neck carcinoma. Cancer 91:2071–2076

    Article  PubMed  Google Scholar 

  37. Carl W, Ikner C (1998) Dental extractions after radiation therapy in the head and neck area and hard tissue replacement (HTR) therapy: a preliminary study. J Prosthet Dent 79:317–322

    CAS  Article  PubMed  Google Scholar 

  38. Hehr T, Classen J, Welz S, Ganswindt U, Scheithauer H, Koitschev A, Bamberg M, Budach W (2006) Hyperfractionated, accelerated chemoradiation with concurrent mitomycin-C and cisplatin in locally advanced head and neck cancer, a phase I/II study. Radiother Oncol 80:33–38

    CAS  Article  PubMed  Google Scholar 

  39. Withers HR, Peters LJ, Taylor JM, Owen JB, Morrison WH, Schultheiss TE, Keane T, O’Sullivan B, van Dyk J, Gupta N et al (1995) Late normal tissue sequelae from radiation therapy for carcinoma of the tonsil: patterns of fractionation study of radiobiology. Int J Radiat Oncol Biol Phys 33:563–568

    CAS  PubMed  Google Scholar 

  40. Le Scodan R, Pommier P, Ardiet JM, Montbarbon X, Malet C, Favrel V, Zrounba P, Poupart M, Ceruse P, Ferlay C, Clippe S (2005) Exclusive brachytherapy for T1 and T2 squamous cell carcinomas of the velotonsillar area: results in 44 patients. Int J Radiat Oncol Biol Phys 63:441–448

    PubMed  Google Scholar 

  41. Skladowski K, Maciejewski B, Golen M, Tarnawski R, Slosarek K, Suwinski R, Sygula M, Wygoda A (2006) Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: long-term results of phase III clinical trial. Int J Radiat Oncol Biol Phys 66:706–713

    PubMed  Google Scholar 

  42. Huguenin P, Glanzmann C, Taussky D, Lutolf UM, Schmid S, Moe K (1998) Hyperfractionated radiotherapy and simultaneous cisplatin for stage-III and -IV carcinomas of the head and neck. Long-term results including functional outcome. Strahlenther Onkol 174:397–402

    CAS  Article  PubMed  Google Scholar 

  43. Olver IN, Hughes PG, Smith JG, Narayan K, Bishop JF (1996) Concurrent radiotherapy and continuous ambulatory infusion 5-fluorouracil in advanced head and neck cancer. Eur J Cancer 32A:249–254

    CAS  Article  PubMed  Google Scholar 

  44. Arias F, Dominguez MA, Illarramendi JJ, Martinez E, Tejedor M, Dominguez S, Duenas M, Villafranca E, Elcarte F, Miqueliz S et al (1995) Split hyperfractionated accelerated radiation therapy and concomitant cisplatin for locally advanced head and neck carcinomas: a preliminary report. Int J Radiat Oncol Biol Phys 33:675–682

    CAS  PubMed  Google Scholar 

  45. Fujita M, Hirokawa Y, Kashiwado K, Akagi Y, Kashimoto K, Kiriu H, Ohtani K, Wada T (1996) An analysis of mandibular bone complications in radiotherapy for T1 and T2 carcinoma of the oral tongue. Int J Radiat Oncol Biol Phys 34:333–339

    CAS  PubMed  Google Scholar 

  46. Langendijk JA, Kasperts N, Leemans CR, Doornaert P, Slotman BJ (2006) A phase II study of primary reirradiation in squamous cell carcinoma of head and neck. Radiother Oncol 78:306–312

    Article  PubMed  Google Scholar 

  47. Eisen MD, Weinstein GS, Chalian A, Machtay M, Kent K, Coia LR, Weber RS (2000) Morbidity after midline mandibulotomy and radiation therapy. Am J Otolaryngol 21:312–317

    CAS  Article  PubMed  Google Scholar 

  48. Tong AC, Leung AC, Cheng JC, Sham J (1999) Incidence of complicated healing and osteoradionecrosis following tooth extraction in patients receiving radiotherapy for treatment of nasopharyngeal carcinoma. Aust Dent J 44:187–194

    CAS  Article  PubMed  Google Scholar 

  49. Gibbs IC, Le QT, Shah RD, Terris DJ, Fee WE, Goffinet DR (2003) Long-term outcomes after external beam irradiation and brachytherapy boost for base-of-tongue cancers. Int J Radiat Oncol Biol Phys 57:489–494

    Article  PubMed  Google Scholar 

  50. Maguire PD, Meyerson MB, Neal CR, Hamann MS, Bost AL, Anagnost JW, Ungaro PC, Pollock HD, McMurray JE, Wilson EP, Kotwall CA (2004) Toxic cure: hyperfractionated radiotherapy with concurrent cisplatin and fluorouracil for stage III and IVA head-and-neck cancer in the community. Int J Radiat Oncol Biol Phys 58:698–704

    CAS  PubMed  Google Scholar 

  51. Oh HK, Chambers MS, Garden AS, Wong PF, Martin JW (2004) Risk of osteoradionecrosis after extraction of impacted third molars in irradiated head and neck cancer patients. J Oral Maxillofac Surg 62:139–144

    Article  PubMed  Google Scholar 

  52. Medina JA, Rueda A, de Pasos AS, Contreras J, Cobo M, Moreno P, Benavides M, Villanueva A, Alba E (2006) A phase II study of concomitant boost radiation plus concurrent weekly cisplatin for locally advanced unresectable head and neck carcinomas. Radiother Oncol 79:34–38

    CAS  Article  PubMed  Google Scholar 

  53. Wadsley JC, Patel M, Tomlins CD, Gildersleve JQ (2003) Iridium-192 implantation for T1 and T2a carcinoma of the tongue and floor of mouth: retrospective study of the results of treatment at the Royal Berkshire Hospital. Br J Radiol 76:414–417

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgement

The authors thank Ms. Tainika Williams, Department of Oral Medicine, Carolinas Medical Center, North Carolina, USA, for her excellent administrative assistance.

Conflicts of interest

The authors declared that they have no potential conflicts of interests.

Author information

Authors and Affiliations

  1. Department of Oral Health and Diagnostic Sciences, School of Dental Medicine, University of Connecticut Health Center, Farmington, CT, USA

    Douglas E. Peterson

  2. Program in Head & Neck Cancer and Oral Oncology, Neag Comprehensive Cancer Center, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030-1605, USA

    Douglas E. Peterson

  3. Department of Radiotherapy and Radiation Oncology and OncoRay, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany

    Wolfgang Doerr

  4. Radiobiology Laboratory, Department of Radiation Oncology, Oral Care Program, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany

    Wolfgang Doerr

  5. Program of Oral Oncology/Dentistry, British Columbia Cancer Agency, Vancouver, BC, Canada

    Allan Hovan

  6. Department of Oral Medicine, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Andres Pinto

  7. Oral Medicine Center, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 240 S. 40th St, Suite 214, Philadelphia, PA, 19104, USA

    Andres Pinto

  8. Dental Oncology, Sudbury Regional Hospital Regional Cancer Program, Sudbury, ON, Canada

    Debbie Saunders

  9. Section of Health Services Research, Department of Biostatistics and Applied Mathematics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 447, Houston, TX, 77030-4009, USA

    Linda S. Elting

  10. Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700, RG, Groningen, The Netherlands

    Fred K. L. Spijkervet

  11. Department of Oral Medicine, Carolinas Medical Center, P.O. Box 32861, Charlotte, NC, 28232, USA

    Michael T. Brennan

Authors
  1. Douglas E. Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Doerr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Allan Hovan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andres Pinto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Debbie Saunders
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Linda S. Elting
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fred K. L. Spijkervet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael T. Brennan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Douglas E. Peterson.

Additional information

All authors are members of the Oral Care Study Group of the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Peterson, D.E., Doerr, W., Hovan, A. et al. Osteoradionecrosis in cancer patients: the evidence base for treatment-dependent frequency, current management strategies, and future studies. Support Care Cancer 18, 1089–1098 (2010). https://doi.org/10.1007/s00520-010-0898-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-010-0898-6

Keywords

  • Osteoradionecrosis
  • Head and neck radiation
  • Cancer