HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

PURPOSE: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible. METHODS AND MATERIALS: HOPON was a randomized, controlled, phase 3 trial. Participants who required dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy were recruited. Eligible patients were randomly assigned 1:1 to receive or not receive HBO. All patients received chlorhexidine mouthwash and antibiotics. For patients in the HBO arm, oxygen was administered in 30 daily dives at 100% oxygen to a pressure of 2.4 atmospheres absolute for 80 to 90 minutes. The primary outcome measure was the diagnosis of ORN 6 months after surgery, as determined by a blinded central review of clinical photographs and radiographs. The secondary endpoints included grade of ORN, ORN at other time points, acute symptoms, pain, and quality of life. RESULTS: A total of 144 patients were randomized, and data from 100 patients were analyzed for the primary endpoint. The incidence of ORN at 6 months was 6.4% and 5.7% for the HBO and control groups, respectively (odds ratio, 1.13; 95% confidence interval, 0.14-8.92; P = 1). Patients in the hyperbaric arm had fewer acute symptoms but no significant differences in late pain or quality of life. Dropout was higher in the HBO arm, but the baseline characteristics of the groups that completed the trial were comparable between the 2 arms. CONCLUSIONS: The low incidence of ORN makes recommending HBO for dental extractions or implant placement in the irradiated mandible unnecessary. These findings are in contrast with a recently published Cochrane review and previous trials reporting rates of ORN (non-HBO) of 14% to 30% and challenge a long-established standard of care.

Osteoradionecrosis of the mandible: a case series at a single institution.

BACKGROUND: Osteoradionecrosis (ORN) defines exposed irradiated bone, which fails to heal over a period of 3-6 months without evidence of residual or recurrent tumor. In the previous decades, a staging and treatment protocol suggested by Marx, has dominated the approach to ORN. However, recently this paradigm is shifting. The purpose of this study was to evaluate our institutional experience in managing ORN through a retrospective review of case series from a large urban academic cancer centre. METHODS: A retrospective chart review was conducted to include all ORN cases from 2003 to 2009 diagnosed at the Department of Otolaryngology - Head and Neck Surgery and the Department of Dentistry. The staging of ORN was assessed as affected by tumor site, tumor stage, radiotherapy modality and dose, chemotherapy, dental work, and time to diagnosis. The effectiveness of hyperbaric oxygen therapy (HBO) and surgery in the management of ORN was evaluated. RESULTS: Fourteen cases of ORN were documented (incidence 0.84%). Primary subsites included tonsils, tongue, retromolar trigone, parotid gland, soft palate and buccal mucosa. There were 5 (35.7%) stage 1, 3 (21.4%) stage 2, and 6 (42.9%) stage 3 cases. ORN severity was not significantly associated with gender, smoking, alcohol use, tumor site, T stage, N stage, AJCC stage, or treatment modality (radiation alone, surgery with adjuvant radiation or adjuvant chemoradiation). Patients treated with intensity-modulated radiotherapy developed less severe ORN compared to those treated with conventional radiotherapy (p < 0.015). ORN stage did not correlate with radiation dose. In one patient only dental procedures were performed following radiation and could be implicated as the cause of ORN. HBO therapy failed to prevent ORN progression. Surgical treatment was required for most stage 2 (partial resections and free tissue transfers) and stage 3 patients (mandibulectomies and free tissue transfers, including two flaps in one patient). At an average follow up of 26 months, all patients were cancer-free, and there was no evidence of ORN in 84% of patients. CONCLUSIONS: In early ORN, we advocate a conservative approach with local care, while reserving radical resections with robust reconstruction with vascularized free tissue for advanced stages.

Hyperbaric oxygen and dental extractions in irradiated patients: short- and long-term outcomes.

PURPOSE: Mandibular osteoradionecrosis (ORN) can occur in patients post-radiation therapy. This study assessed the incidence of ORN in the setting of adjunctive hyperbaric oxygen therapy (HBO2) and sought to identify risk factors that may predispose to its development. METHODS: A retrospective chart review was completed on patients with a history of radiation therapy to the head and neck who underwent HBO2 prior to and immediately following dental extractions between January 1, 1995, and December 31, 2005, in the hyperbaric medicine unit. RESULTS: The incidence of ORN in 40 patients immediately following completion of HBO was 0%. Available follow-up longer than six months after completion of HBO2 on 19 of these patients showed an incidence of ORN increased to 15.8%. None of the considered risk factors for development of ORN reach statistical significance. CONCLUSION: The incidence of ORN at the completion of HBO2 was less than previously reported incidences between 1.5%-4.2%. However, long-term follow-up indicated a much higher incidence of 15.8%. The difference in incidence of ORN immediately upon completion of HBO2 approximately two weeks after dental extractions compared to that at least six months later identifies a need for more long-term follow-up of these patients following their dental extractions.

Paradigm shifts in the management of osteoradionecrosis of the mandible.

Osteoradionecrosis (ORN) of the mandible is a significant complication of radiation therapy for head and neck cancer. In this condition, bone within the radiation field becomes devitalized and exposed through the overlying skin or mucosa, persisting as a non-healing wound for three months or more. In 1926, Ewing first recognized the bone changes associated with radiation therapy and described them as "radiation osteitis". In 1983, Marx proposed the first staging system for ORN that also served as a treatment protocol. This protocol advocated that patients whose disease progressed following conservative therapy (hyperbaric oxygen (HBO), local wound care, debridement) were advanced to a radical resection with a staged reconstruction utilizing a non-vascularized bone graft. Since the introduction of Marx's protocol, there have been advances in surgical techniques (i.e. microvascular surgery), as well as in imaging techniques, which have significantly impacted on the diagnosis and management of ORN. High resolution CT scans and orthopantamograms have become a key component in evaluating and staging ORN, prior to formulating a treatment plan. Patients can now be stratified based on imaging and clinical findings, and treatment can be determined based on the stage of disease, rather than determining the stage of disease based on a patient's response to a standardized treatment protocol. Reconstructions are now routinely performed immediately after resection of the diseased tissue rather than in a staged fashion. Furthermore, the transfer of well-vascularized hard and soft tissue using microvascular surgery have brought the utility of HBO treatment in advanced ORN into question.

[Teeth and irradiation in head and neck cancer]. / Dent et irradiation: denture et conséquences sur la denture de la radiothérapie des cancers de la tête et du cou.

Pre-irradiation dental care depends on teeth health, fields and dose of irradiation, compliance to fluorides, cessation of tobacco and psychosocial cofactors. Dental care aims at preventing complications and preserving the quality of life (eating, speech and aesthetics). Approximately 11% of patients do not require any pre-irradiation dental care. Dental complications vary from slight colorations of the teeth to major complication such as osteoradionecrosis. Osteoradionecrosis rates vary from 1 to 9%, and may be decreased by using a 21-day delay between extractions and irradiation, provided that it does not postpone cancer treatment, with a dose-dependent risk (<6% if <40 Gy; 14% between 40 et 60 Gy; > or =20% if >60 Gy). Osteoradionecrosis occurs spontaneously (35%), mostly involves the mandibula (85%).

[Osteoradionecrosis. A review of the literature]. / L'ostéoradionécrose. Une revue de la littérature.

Osteoradionecrosis is a severe complication of radiotherapy characterized by the following sequence: radiation, trauma, bone exposure. The radiation reduces the vascularization potential of the tissues which leads to a hypoxic state that jeopardizes cellular activity and collagen formation. The diagnosis of osteoradionecrosis relies on the clinical examination of chronically exposed bone. Although this type of lesion is not limited to the jaws, the ratio between mandible and maxilla is 24:1. The severity of the lesion is a function of the radiation dosage. The main etiological factors of osteoradionecrosis are related to dental and periodontal pathology as well as to tooth extraction performed after, during or shortly before radiotherapy. Edentulous patients are less exposed to osteoradionecrosis than dentulous patients. Local treatment and antibiotic therapy are initially performed in mild cases. Surgical measures with hemiresection or block resection are indicated depending on the severity of the lesion. Some authors regard hyperbaric oxygen treatment as an efficient therapeutic and preventive technique. Prevention is of major concern. It requires a careful evaluation of soft and hard tissues of the oral cavity as well as the organization of an intensive prophylaxis program. Patient compliance is a prerequisite. This article is a literature review on osteoradionecrosis with its symptoms, incidence, pathogenesis, treatment and prevention.

Osteoradionecrosis of the jaw bones at the University of Kentucky Medical Center.

There is disagreement over the management of teeth in irradiated head and neck cancer patients. Some oral surgeons support preirradiation extraction; others favor maintaining teeth. Before 1974, The University of Kentucky Department of Radiation Medicine found osteoradionecrosis (ORN) of the jaw in 10.9% of 220 irradiated cancer patients. After a program of oral care was instituted, the incidence declined to 2.7%. Of 109 patients who received radiotherapy between 1976 and 1985, only three (2.7%) developed ORN of the mandible. There was also a reduction in patients treated with interstitial therapy during this time. A review of the most recent experiences shows that, with present management methods at the University of Kentucky, ORN is not a significant problem. Of 30 patients treated in 1986, only one had ORN, and this was of the maxilla. Post-irradiation extractions were not identified as a significant risk for necrosis. Hyperbaric oxygen is used as a treatment for persistent ORN.