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Originally published as JCO Early Release 10.1200/JCO.2004.09.959 on November 1 2004 © 2004 American Society of Clinical Oncology.
Mandibular OsteoradionecrosisUniversity of Florida College of Medicine, Gainesville, FL The presentation of osteoradionecrosis (ORN) after radiotherapy (RT) for head and neck cancer varies from small, asymptomatic bone exposures that may remain stable for months to years or heal with conservative management, to severe necroses necessitating surgical intervention and reconstruction. The risk of developing ORN depends on a number of factors, including primary site, T stage, proximity of the tumor to bone, dentition, type of treatment (external beam RT, brachytherapy, surgery, and chemotherapy), and RT dose. Other factors that probably influence the likelihood of developing ORN include the nutritional status of the patient and continued tobacco or alcohol abuse. The mandible is the most common site of ORN, probably because it is often necessary to deliver a high RT dose to tumors near the mandible and possibly also because the blood supply may be less abundant than that of the maxilla. The incidence of severe ORN, defined as necessitating either surgical intervention, hyperbaric oxygen (HBO) treatments, or both1 in a series of 1,495 patients treated with definitive RT for head and neck squamous cell carcinomas at the University of Florida (Gainesville, FL) is depicted in Table 1. Minimum follow-up was 2 years; all but two patients (0.13%) had follow-up until death or within 1 year of data analysis. Twenty-seven patients (2%) experienced severe ORN, which occurred most often in those patients treated for oral cavity cancers. Although patients treated with definitive RT for oral cavity malignancies are more likely to experience minor or moderate bone complications compared with those treated with surgery and adjuvant RT, the likelihood of severe ORN is probably similar after either treatment strategy.2,3 Patients in whom the RT portals include only the angle or ramus of the mandible, such as those with laryngeal or hypopharyngeal cancers, have a very low likelihood of experiencing severe ORN. Edentulous patients probably have a lower risk of developing ORN than dentulous patients. Patients with poor dentition whose teeth will be in the high-dose fields should undergo extractions before RT and should be allowed to heal for 2 to 3 weeks before initiating treatment. Whether it is advisable to extract healthy teeth that will receive high-dose RT is controversial. The use of ill-fitting dentures after RT increases the risk of ORN and should be avoided.
Patients who develop small, asymptomatic bone exposures are initially managed conservatively with pentoxifylline and vitamin E. Conservative debridement may be necessary to remove spicules of devitalized bone, particularly if the adjacent tongue is abraded. Patients who have ORN that progresses are traditionally treated with HBO alone or combined with debridement. Segmental mandibulectomy and reconstruction are necessary in patients with severe ORN who do not improve with conservative treatment. Theoretically, HBO increases blood oxygen levels and enhances healing of bone necrosis. However, as pointed out by Annane et al,11 the efficacy of HBO is based almost exclusively on uncontrolled studies. The major disadvantages of HBO are that it is time consuming and expensive. In this issue of the Journal of Clinical Oncology, Annane et al11 report on a prospective randomized trial comparing HBO to placebo in the treatment of patients with ORN. Surprisingly, those treated with HBO not only failed to benefit from the treatment, they actually had a more unfavorable outcome than the patients treated with placebo. Although it is not surprising that those treated with HBO did not benefit from the treatment, particularly given the small sample size, it is difficult to explain why they did not do as well. The treatment of ORN is unsatisfactory. Although it has been tempting to employ HBO because it should theoretically work, the data supporting its use are solely from uncontrolled trials. The prospective randomized trial reported by Annane et al,11 albeit underpowered, suggests that it is ineffective. Although it is unfortunate that the trial was terminated prematurely with only 68 patients entered, it seems unlikely that HBO would have proven beneficial even if the study had been completed with a total planned accrual of 222 patients. Thus, at the present time, the efficacy of HBO in the treatment of ORN is unclear and further investigation is warranted. As pointed out by Annane et al, it is possible that a subset of patients, such as those with more severe ORN, may benefit from HBO. Author’s Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest.
REFERENCES 1. Taylor JM, Mendenhall WM, Lavey RS: Dose, time, and fraction size issues for late effects in head and neck cancers. Int J Radiat Oncol Biol Phys 22:3-11, 1992[Medline] 2. Rodgers LW Jr, Stringer SP, Mendenhall WM, et al: Management of squamous cell carcinoma of the floor of the mouth. Head Neck 15:16-19, 1993[Medline] 3. Fein DA, Mendenhall WM, Parsons JT, et al: Carcinoma of the oral tongue: A comparison of results and complications of treatment with radiotherapy and/or surgery. Head Neck 16:358-365, 1994[Medline] 4. Mendenhall WM, Parsons JT, Mancuso AA, et al: Radiotherapy for squamous cell carcinoma of the supraglottic larynx: An alternative to surgery. Head Neck 18:24-35, 1996[CrossRef][Medline]
5. Mendenhall WM, Stringer SP, Amdur RJ, et al: Is radiation therapy a preferred alternative to surgery for squamous cell carcinoma of the base of tongue? J Clin Oncol 18:35-42, 2000 6. Erkal HS, Serin M, Amdur RJ, et al: Squamous cell carcinomas of the soft palate treated with radiation therapy alone or followed by planned neck dissection. Int J Radiat Oncol Biol Phys 50:359-366, 2001[CrossRef][Medline] 7. Fein DA, Mendenhall WM, Parsons JT, et al: Pharyngeal wall carcinoma treated with radiotherapy: Impact of treatment technique and fractionation. Int J Radiat Oncol Biol Phys 26:751-757, 1993[Medline] 8. Amdur RJ, Mendenhall WM, Stringer SP, et al: Organ preservation with radiotherapy for T1–T2 carcinoma of the pyriform sinus. Head Neck 23:353-362, 2001[CrossRef][Medline]
9. Mendenhall WM, Parsons JT, Mancuso AA, et al: Definitive radiotherapy for T3 squamous cell carcinoma of the glottic larynx. J Clin Oncol 15:2394-2402, 1997 10. Hinerman RW, Mendenhall WM, Amdur RJ, et al: Carcinoma of the supraglottic larynx: Treatment results with radiotherapy alone or with planned neck dissection. Head Neck 24:456-467, 2002[CrossRef][Medline]
11. Annane D, Depondt J, Aubert P, et al: Hyperbaric oxygen therapy for radionecrosis of the jaw: A randomized, placebo-controlled, double-blind trial. J Clin Oncol 22:4893-4900, 2004
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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