Radiation Therapy and Mandibular Osteoradionecrosis: State of the Art.

PURPOSE OF REVIEW: This article aims to provide an update on literature data related to mandibular osteoradionecrosis (MORN) secondary to the irradiation of the head and neck region. RECENT FINDINGS: Radiotherapy (RT) plays a crucial role in the contemporary management of head and neck cancer (HNC) patients and, despite intensity-modulated technique (IMRT), mandibular osteoradionecrosis (MORN) remains a significant RT-related complication. Based on its clinical manifestation, MORN can negatively affect patients' quality of life. Preventive interventions should be prioritized. This manuscript is expected to represent an opportunity to guide a clear proposal for clinical measures in the individual MORN situations.

Quality of Life after Free Fibula Flap Reconstruction of Segmental Mandibular Defects.

BACKGROUND: Free fibula flap (FFF) is considered gold standard in the reconstruction of mandibular defects. Despite the frequent use, patients' quality of life (QoL) after reconstruction has been sparsely investigated. This study aims to evaluate QoL and outcomes in patients who have undergone FFF reconstruction of segmental mandibular defects. METHODS: A retrospective cohort study of consecutive patients (n = 73) operated at a single center during the years 2000 to 2014 was performed. Charts were reviewed and all living patients (n = 41) were invited to fill out three quality of life questionnaires (QLQ): SF-36, EORTC QLQ-C30, and QLQ-H&N35. Factors associated with poor outcome were derived from regression models and the results of the QLQs were compared with Swedish reference populations. Subgroup analysis was performed for two groups depending on reconstructive indication: cancer and osteoradionecrosis (ORN). RESULTS: The response rate of the QLQs was 93%. General QoL did not differ from reference populations, but the study group had significantly larger proportions of poor functioning patients in three domains in EORTC QLQ-C30: global health status, role functioning, and social functioning. Patients also reported a high incidence of poor functioning/high symptom burden in EORTC QLQ-H&N35, with a significantly higher frequency in the ORN group compared with the cancer group for the domains "swallowing" and "social eating." The overall flap success rate was 92% and complication rate was 48%. Previous surgery had a significant association with reoperation due to bleeding, and longer duration of surgery was significantly associated with local infection. CONCLUSION: When evaluated with validated QLQs, most patients experienced persistent functional loss in one or several domains, but still perceived a general QoL that is close to that of reference populations. Patients having ORN as the indication for surgery, as compared with cancer, reported a higher frequency of poor functioning patients in disease-specific QoL domains.

Radionecrosis of the frontal lobe as a consequence of malignant ethmoid tumor management: incidence, diagnosis, risk factors, prevention and management.

Malignant ethmoid tumors are treated by surgery followed by radiotherapy. This study aimed to evaluate the incidence, risk factors and outcome of radionecrosis of frontal lobe and determine preventive measures. Retrospective study of ethmoid malignancies treated from 2000 to 2011. All patients underwent surgery with/without anterior skull base resection using endoscopic or external approaches followed by irradiation (mean dose 64 Gy). Median follow-up was 50 months. Eight of 50 patients (16 %) presented with fronto-basal radionecrosis, connected to duraplasty, with a latent interval of 18.5 months. Although asymptomatic in six, radionecrosis triggered seizures and required surgery in two cases. Survival was not impacted. Risk factors included dyslipidemia, occurrence of epilepsy and dural resection. Radionecrosis may result from the combination of anterior skull base resection and radiotherapy for the treatment of ethmoid malignancies. Preventive measures rely on improving the duraplasty and optimization of the Gy-dose delivery.

Low-intensity ultrasound accelerates mandibular implant bone integration in dogs with mandibular osteoradionecrosis.

BACKGROUND: To investigate whether low-intensity ultrasound accelerates healing in bone tissues close to dental implants with osteoradionecrosis (ORN) of the mandible and is suitable for development as a therapy in patients with dental implants receiving radiotherapy. MATERIALS AND METHODS: Dog models of radiative bone injury surrounding dental implants in both sides of mandible were established by four treatment methods of radiotherapy, each 15Gy. After radiative treatment, antibiotics were administered and the left injury was treated with ultrasound and the right with debridement. Measures for evaluation included spiral computed tomography (SCT), Micro-CT, microvessel density, and pull-out experiment, and data were collected and analyzed. RESULTS: After 4months of radiotherapy, both sides of mandible displayed preclinic symptom of radiative osteonecrosis. Microvessel density of the side treated by ultrasound was 6.2152±0.6508 and that of the debridement side was 3.8490±0.8954 (P<0.05). Micro-CT results showed that bone volume fraction of trabecula, thickness of trabecula, trabecula spacing, ratio of bone surface area to bone volume, and trabecula number of the ultrasound-treated mandible were 0.3605±0.0337, 0.0287±0.0045, 0.0369±0.0073, 71.6124±14.1649, and 7.2915±1.4937, whereas those of the debridement side were 0.1779±0.0178, 0.0151±0.0021, 0.6623±0.1125, 33.2686±5.949, and 5.0689±0.5028, respectively; statistical significance was observed (P<0.05). Pull-out experiment suggested that pull-out strength of the ultrasound-treated side was 0.5793±0.1066 whereas that of the debridement side was 0.2980±0.0243, representing a statistical significance (P<0.05). CONCLUSIONS: Low-intensity ultrasound can accelerate the healing of bone tissues surrounding dental implants in osteoradionecrosis of the mandible animals.

Osteocutaneous free tissue transplantation for mandibular osteoradionecrosis.

OBJECTIVE: To describe the success rate, complications, and functional outcomes of patients who are treated with osteocutaneous free tissue transplantation for grade 4 mandibular osteoradionecrosis (ORN). DESIGN: Retrospective case series. SETTING: Tertiary care academic medical center. PATIENTS: Twelve patients (8 males, 4 females; mean age, 57.6 years) with grade 4 mandibular ORN. Three patients (25%) had a history of primary radiotherapy, two (17%) had previous concurrent chemoradiation, and seven (58%) had undergone postoperative adjuvant radiotherapy. Ten patients (83%) had previous major ablative surgery to treat the primary tumor and five (50%) had been reconstructed with a free tissue transplant prior to the onset of ORN. INTERVENTIONS: All patients underwent reconstruction with an osteocutaneous free tissue transplant for grade 4 mandibular ORN between 1999 and 2006. MAIN OUTCOME MEASURES: Successful treatment of mandibular ORN; major, minor, and late complications; gastrostomy tube (G-tube) dependence; speech and swallowing scores. RESULTS: Grade 4 mandibular ORN was successfully treated in eight (73%) evaluable patients. One patient (8%) died of a second primary tumor before the 12-month assessment. Eight patients (67%) had a major complication, three (25%) had a minor complication, and nine (75%) had a late complication. Three of the five G-tube- dependent patients prior to mandibular reconstruction were able to discontinue the use of their G-tube. Seven of the eight successfully treated patients maintained their nutrition by mouth. Median "range of liquids" score was 6/6 (range, 4 to 6). Median "range of solids" score was 4/6 (range, 3 to 6). Median "understandability of speech" score was 4/5 (range, 2 to 5). CONCLUSIONS: Grade 4 mandibular ORN was treated successfully with an osteocutaneous free tissue transfer in eight evaluable patients (73%). In successfully treated patients, median speech/swallowing scores were highly functional, but the remaining radiated soft tissue resulted in higher local wound complications and a modified diet.

Clinico-therapeutic management of osteoradionecrosis: a literature review and update.

In the management of head and neck cancer, radiotherapy is usually a coadjuvant to surgery, or is applied on a palliative basis. The most important complication of such radiotherapy is osteoradionecrosis, which manifests as an area of exposed necrotic bone in the maxillae or mandible that fails to heal during at least three months. In most cases osteoradionecrosis gradually progresses, becoming more extensive and painful, and its late manifestations comprise infection and pathological fracture. The present study provides a literature review and update on the risk factors underlying osteoradionecrosis, its clinical and diagnostic particulars, prevention, and most widely accepted treatment options, as well as new possibilities relating to clinical management of the disorder. Lastly, a new early management protocol is proposed based on the current consensus criteria relating to maxillary osteonecrosis secondary to treatment with bisphosphonates, together with the adoption of new therapies supported by increased levels of evidence.

A preliminary investigation into the effects of X-ray radiation on superficial cranial vascularization.

Radiation therapy (RT) is an established treatment modality for malignant neoplasms. RT induces tissue damage that may lead to osteoradionecrosis in more severe cases. Suitable animal models to study RT-induced changes in membranous craniofacial bone are currently not available. The aim of this study was therefore to quantify RT-induced changes in cranial microcirculation using a newly developed calvaria chamber model and to relate these changes to RT-induced histological damage. New Zealand white rabbits received a total radiation dose of 18.75 Gy through the calvaria chamber, and the number of vessels, the vessel length density (VLD), and angiogenic sprouting were quantified on a weekly basis during a 12-week period. At the end of 12 weeks, the RT-treated (n = 5) or control (n = 5) calvarias were biopsied for histopathological analysis. RT resulted in a steep reduction in the number of vessels and the VLD during the first 3 weeks, particularly in larger-diameter vessels, followed by a flat stabilization/remodeling phase in the subsequent 9 weeks that never restored to baseline values. Histomorphometric analysis revealed a high degree of osteocytic depletion, prominent hypocellularity in the lacunae and intraosseous vasculature, enlarged and nonconcentric Haversian systems, and a severely disorganized bone matrix in the RT-treated calvarias. Despite the prevalence of some angiogenic potential, the RT-induced effects in the early phase persisted in the intermediate to late phase, which may have contributed to the poor recovery of the RT-treated bone.

HDR brachytherapy irradiation of the jaw - as a new experimental model of radiogenic bone damage.

INTRODUCTION: Hitherto, no suitable experimental model exists to test new treatments for radiogenic bone damage, such as new step from knowledge about bone growth factors or angiogenesis factors. The goal of this investigation was to establish such a standardised experimental model. MATERIAL AND METHODS: Twenty-four rats were used in this study. In 12 rats a plastic tube was implanted along the right half of the mandible and treated with a single dose of 20 Gy at a high-dose-rate (HDR) using an afterloading machine, the remainder served as control (n=12). One hundred days after irradiation both sides of the mandible were examined using paraffin embedding and non-decalcified histology. RESULTS: All HDR irradiated rats developed localised alopecia within 2 weeks of radiotherapy. In the irradiated group, a clear growth reduction of the ipsilateral incisor was observed. Paraffin histology revealed minimal damage of the bone structure with slightly increased signs of regeneration. The bone apposition rate was significantly reduced on the irradiated right side, compared with the left side (p=0.028). The average diameter of the mandibular condyles on the irradiated right sides was significantly reduced when compared with the left sides (p=0.023). CONCLUSIONS: It is possible to induce radiogenic damage of the mandible by using HDR brachytherapy with a single dose of 20 Gy comparable to 45 x 2 Gy of conventional irradiation. This new model is easy and predictable and appears to be suitable for the testing of new treatment modalities. It is advantageous for the testing of bone growth and angiogenesis factors that the contralateral side exhibits completely normal bone apposition characteristics enabling a split-mouth design for future experiments.

BMP-2 and bFGF in an irradiated bone model.

INTRODUCTION: Basic fibroblast growth factor (bFGF) is considered to enhance angiogenesis and to support bone formation in the presence of vital bone cells. Bone morphogenetic protein-2 (rhBMP-2) is known to induce bone formation. The aim of this study was to analyze the effect of bFGF and rhBMP-2 in the irradiated mandible. MATERIAL AND METHODS: The right mandibles of 24 rats were irradiated with a single dose of 20 Gy at a high-dose-rate (HDR) after loading machine (bio effective equivalent dose to ca. 45 x 2 Gy). After 12 weeks 100 microg rhBMP-2 (n=6 animals, group 1), 100 microg bFGF (n=6 animals, group 2) and 100 microg rhBMP-2 plus 100 microg bFGF (n=6 animals, group 3) were injected along the right mandible (left mandible: no irradiation, no growth factor). Another 6 animals (group 4) remained untreated after the irradiation. After another 7 weeks the specimens were examined by non-decalcified histology. RESULTS: Bone apposition of the experimental versus control sides was not statistically significantly different when one of the growth factors was applied alone (rhBMP-2: p=0.917; bFGF: p=0.345). Average bone apposition was significantly decreased on the experimental sides of group 3 (rhBMP-2+bFGF: p=0.046) and group 4 (p=0.008). Average bone densities were unaffected in all settings (for all p>0.1). CONCLUSIONS: The application of bFGF and the application of rhBMP-2 alone did result in predictable bone generation in the irradiated mandible with the bone apposition being equal to that of the non-irradiated side. The application of both growth factors together or none at all after irradiation results in significantly reduced bone apposition.

Hyperbaric Oxygen Therapy as an Adjunct for Treating an Individual with Poorly Healing Bilateral Mandibular Fractures Suspect of Developing Towards Osteomyelitis: A Case Report and Clinical Experience.

PURPOSE: To present a case that benefited from utilizing hyperbaric oxygen therapy in conjunction with antibiotics for a non-healing mandibular fracture that was highly suspicious of osteomyelitis. Also, to discuss research set forth by Undersea and Hyperbaric Medical Society that supports the use hyperbaric oxygen in such cases. CASE: A 25-year-old male status post fist to face resulting in bilateral mandibular fracture. He underwent two surgeries in an attempt to plate the fracture with the assistance of a bone graft. After failure of the bone graft and significant soft tissue wound breakdown, the surgeon was concerned for osteomyelitis and began therapy with intravenous antibiotics and hyperbaric oxygen therapy. CONCLUSION: The patient completed 30 hyperbaric oxygen treatments and 30 d of intravenous antibiotics. Clinically, the patient responded well and showed healed intraoral wounds and an objective decrease in erythrocyte sedimentation rate over the course of treatment. Unfortunately, on serial imaging the patient showed to have fibrous non-bony union of left fracture site. Even though the patient will need a final definitive plate for his fracture, it will be performed from an extraoral approach with no evidence of underlying infection.

Oral Cavity Reconstruction Outcomes Using a Porcine Urinary Bladder Matrix: A Retrospective Case Series.

OBJECTIVE: The purpose of this study is to assess healing outcomes in full-thickness mucosal wounds following the use of a porcine urinary bladder matrix to augment mixed oral cavity repairs. MATERIALS AND METHODS: A retrospective chart analysis was conducted over a 58-month timespan. Participants included individuals with osteoradionecrosis. Descriptive measures obtained in the postoperative setting were used to examine wound healing outcomes. RESULTS: Thirty-nine encounters with 35 patients met inclusion criteria for assessment. The mean defect size repaired was 14 cm2. Successful healing occurred in 64% of cases. Scarring was observed in 10 cases, and 3 cases demonstrated transient functional deficits. Reapplication of the xenograft was required in 4 cases. Only 1 acute event of hemorrhage and 1 infection were observed in the postoperative period. CONCLUSIONS: Use of porcine urinary bladder matrix grafts for oral cavity reconstruction was well tolerated in a diverse number of wound scenarios with a relatively low risk of postoperative complication. The use of porcine urinary bladder matrix was not observed to provide any noteworthy advantages for the healing of recalcitrant osteoradionecrosis wounds.

Predictive factors for osteoradionecrosis of the jaws: A retrospective study.

BACKGROUND: Osteoradionecrosis of the jaw (ORNJ) is a well-recognized complication of radiotherapy. The purpose of this study was to assess predictive factors for the development of ORNJ. METHODS: A retrospective study of 325 patients with head and neck squamous cell carcinoma (HNSCC) treated at one institution between January 1, 1999, and December 31, 2008, was conducted. Outcome measure was the presence/absence of ORNJ. Time to event was recorded and Cox proportional hazard regression analysis was used to determine statistically significant predictive factors. RESULTS: Fifty-nine patients had ORNJ. Statistical analysis using Cox regression analysis identified several statistically significant variables: dentoalveolar surgery; peri-resective surgery of the jaw; continued tobacco usage after radiotherapy, diabetes mellitus type 2 (DM2); and total radiation dose. CONCLUSION: Patients at greater risk of developing ORNJ can be identified and measures can be instituted to reduce its incidence and expedite management when it does occur.

Osteoradionecrosis: a review of pathophysiology, prevention and pharmacologic management using pentoxifylline, α-tocopherol, and clodronate.

A significant complication of radiotherapy to the head and neck for cancer treatment is osteoradionecrosis (ORN) of the jaws. The management of ORN can be complex and often requires a multimodality approach. Nonsurgical treatments with or without adjunct measures and surgical interventions have all been employed on the basis of staging of the disease process. New theories on the pathophysiology of ORN have led to the identification of novel treatment modalities, including pharmacologic management using pentoxifylline, tocopherol, and clodronate (together referred to as "Pentoclo"). In this review article, we discuss the definition and staging of ORN, its etiology and pathophysiology, and traditional treatment options and present the available information on pentoxifylline, tocopherol, and clodronate and their use in combined therapy for ORN. Limited studies to date have demonstrated the effective pharmacologic use of Pentoclo in treating ORN and radiation-induced injury at other body sites. Further research is necessary to elucidate any potential role for the use of Pentoclo in the management of this debilitating disease process.

The histological and histomorphometric changes in the mandible after radiotherapy: An animal model.

PURPOSE: Approximately 5% of irradiated head and neck cancer patients develop osteoradionecrosis of the mandible. The current non-surgical treatment options for osteoradionecrosis have limited effects and are based on a small number of studies. Therefore, we aimed to enhance the understanding of the pathophysiology of osteoradionecrosis by investigating changes induced by external irradiation in mini-pigs. METHODS: Sixteen Göttingen mini-pigs were divided into four groups for the application in two fractions with total equivalent radiation dosages of 25, 50, 70 Gray, and one group served as control. Thirteen weeks after irradiation, the left lateral teeth the mandible were removed and implants were placed. The pigs were sacrificed twenty-six weeks after irradiation, and the bone samples were stained with Masson's trichrome. RESULTS: The amount of fibrosis, resorption lacunae, necrosis, and the woven/lamellar bone ratios were increased after higher radiation dosages. The diameter of the lumen of the inferior alveolar artery was reduced depending on the irradiation dosages. The rate of bone remodeling decreased after irradiation. CONCLUSION: Both surgery and increasing irradiation dosages cause architectural bone changes and damage the vascularization. This might result in a chronic hypoxic state of the mandibular bone. In general, the bone formation rate was markedly decreased after radiotherapy.

Symptom burden and dysphagia associated with osteoradionecrosis in long-term oropharynx cancer survivors: A cohort analysis.

OBJECTIVE: The purpose is to examine the relationship between mandibular osteoradionecrosis (ORN) and chronic dysphagia in long-term oropharynx cancer (OPC) survivors, and to determine the perceived symptom burden associated with ORN. MATERIALS AND METHODS: Medical records of 349 OPC patients treated with bilateral IMRT and systemic therapy were reviewed. ORN was graded using a published 4-point classification schema. Patients were considered to have chronic dysphagia if they had aspiration pneumonia, stricture or aspiration detected by fluoroscopy or endoscopy, and/or feeding tube dependence in long-term follow-up ⩾1year following radiotherapy. MD Anderson Symptom Inventory - Head and Neck Module (MDASI-HN) scores were analyzed in a nested cross-sectional survey sample of 118 patients. RESULTS: 34 (9.7%, 95% CI: 6.8-13.3%) patients developed ORN and 45 (12.9%, 95% CI: 9.6-16.9%) patients developed chronic dysphagia. Prevalence of chronic dysphagia was significantly higher in ORN cases (12/34, 35%) compared to those who did not develop ORN (33/315, 11%, p<0.001). ORN grade was also significantly associated with prevalence of dysphagia (p<0.001); the majority of patients with grade 4 ORN requiring major surgery (6 patients, 75%) were found to have chronic dysphagia. Summary MDASI-HN symptom scores did not significantly differ by ORN grade. Significantly higher symptom burden was reported, however, among ORN cases compared to those without ORN for MDASI-HN swallowing (p=0.033), problems with teeth and/or gums (p=0.016) and change in activity (p=0.015) item scores. CONCLUSIONS: ORN is associated with excess burden of chronic dysphagia and higher symptom severity related to swallowing, dentition and activity limitations.

Ameliorative effect of black grape juice on systemic alterations and mandibular osteoradionecrosis induced by whole brain irradiation in rats.

PURPOSE: Whole brain irradiation (WBI) causes a variety of secondary side-effects including anorexia and bone necrosis. We evaluated the radiomodifying effect of black grape juice (BGJ) on WBI alterations in rats measuring food and water intake, body weight, hemogram, and morphological and histological mandibular parameters. MATERIALS AND METHODS: Forty male rats (200-250 g) were exposed to eight sessions of cranial X-ray irradiation. The total dose absorbed was 32 Gy delivered over 2 weeks. Four groups were defined: (i) NG: non-irradiated, glucose and fructose solution-supplemented (GFS); (ii) NJ: non-irradiated, BGJ-supplemented; (iii) RG: irradiated, GFS-supplemented; and (iv) RJ: irradiated, BGJ-supplemented. Rats received daily BGJ or GFS dosing by gavage starting 4 days before, continuing during, and ending 4 days after WBI. RESULTS: RJ rats ingested more food and water and showed less body weight loss than RG rats during the irradiation period. Forty days after WBI, irradiated animals started losing weight again compared with controls as a consequence of masticatory hypofunction by mandibular osteoradionecrosis (ORN). Osteoclastic activity and inflammation were apparent in RG rat mandibles. BGJ was able to attenuate the severity of ORN as well as to improve white and red blood cell counts. CONCLUSIONS: Fractionated whole brain irradiation induces mandibular changes that interfere with normal feeding. BGJ can be used to mitigate systemic side-effects of brain irradiation and ORN.

Axial four-dimensional computed tomographic images to analyze crosswise differences in protrusive condylar movement in patients who underwent mandibulectomy and free flap reconstruction.

OBJECTIVE: Few studies evaluate condylar movement following mandibular reconstruction. The main objective of this study was to show that axial four-dimensional computed tomography (4DCT) could visualize bilateral protrusive condylar movement directly. We used axial 4DCT images to assess condylar protrusion in patients who underwent mandibular reconstruction. METHODS: We enrolled seven healthy volunteers (median age 30 years, range 27-38 years) and seven patients (median age 65 years, range 52-80 years), who underwent mandibulectomy (segmental in five, hemi in one, marginal in one) and free flap reconstruction (using the fibula in six and the radial forearm in one). Six study subjects were instructed to masticate a cookie during the 4DCT scan (the seventh made chewing motions). The distance between the most anterior and posterior positions of the bilateral condyles on 4DCT (axial view) images was then measured and compared between controls and patients using the Mann-Whitney U-test. RESULTS: The crosswise difference in the distances of condylar protrusion was significantly greater in patients than in the controls. CONCLUSION: Axial 4DCT images can visualize a bilateral condylar protrusive path. Axial 4DCT images for patients who have undergone mandibulectomy and reconstruction may be useful for evaluation of functional movement of condyles.

A murine model for bone loss from therapeutic and space-relevant sources of radiation.

Cancer patients receiving radiation therapy are exposed to photon (gamma/X-ray), electron, and less commonly proton radiation. Similarly, astronauts on exploratory missions will be exposed to extended periods of lower-dose radiation from multiple sources and of multiple types, including heavy ions. Therapeutic doses of radiation have been shown to have deleterious consequences on bone health, occasionally causing osteoradionecrosis and spontaneous fractures. However, no animal model exists to study the cause of radiation-induced osteoporosis. Additionally, the effect of lower doses of ionizing radiation, including heavy ions, on general bone quality has not been investigated. This study presents data developing a murine model for radiation-induced bone loss. Female C57BL/6 mice were exposed to gamma, proton, carbon, or iron radiation at 2-Gray doses, representing both a clinical treatment fraction and spaceflight exposure for an exploratory mission. Mice were euthanized 110 days after irradiation. The proximal tibiae and femur diaphyses were analyzed using microcomputed tomography. Results demonstrate profound changes in trabecular architecture. Significant losses in trabecular bone volume fraction were observed for all radiation species: gamma, (-29%), proton (-35%), carbon (-39%), and iron (-34%). Trabecular connectivity density, thickness, spacing, and number were also affected. These data have clear implications for clinical radiotherapy in that bone loss in an animal model has been demonstrated at low doses. Additionally, these data suggest that space radiation has the potential to exacerbate the bone loss caused by microgravity, although lower doses and dose rates need to be studied.

Use of osseointegrated implants in the restoration of head and neck defects.

Osseointegrated implants can be applied to facilitate retention, stability, and support for facial and intraoral prostheses used to restore head and neck defects. At the University of California, Los Angeles, Maxillofacial Prosthetics Clinic, retrospective studies have indicated that in nonirradiated maxillectomy patients, implant survival rates are 82.6 percent. In mandibles reconstructed with fibula free flaps, survival rates are 94.6 percent. Similarly, high implant survival rates have been observed for most sites used to support facial prostheses. Cumulative six-year survival rates for auricular sites exceed 95 percent and for floor of nose sites, success rates exceed 87 percent. However, survival rates are low (53 percent) for implants placed in the frontal bone for retention of orbital prostheses and even lower for irradiated bone sites ranging from 63 percent in the maxilla to 27 percent in the orbit.

New perspectives on the conservative management of osteoradionecrosis of the mandible: A literature review.

Over the last decades, several therapeutic options were considered in the treatment of the osteoradionecrosis (ORN) of the mandible, including supportive measures, ultrasound therapy, corticosteroids, hyperbaric oxygen, surgical resection with reconstruction, and, more recently, drugs capable of reversing the fibroatrophic process. Once established, the ORN does not spontaneously disappear and a standard treatment has not yet been defined. The clear clinical effectiveness of hyperbaric oxygen therapy (HBOT) varies according to the literature and there are some economic/logistic issues to be considered; the triplet tocopherol/pentoxifylline/clodronate demands greater evidence from randomized clinical trials and also resilience from the patient, given the long treatment duration and its possible side effects. Controversy around the ideal treatment of the initial stage ORN of the mandible persists. More rigorous randomized prospective trials are essential. The purpose of this article was to review the relevant literature on the physiopathology of ORN of the mandible and discuss the new perspectives of its conservative treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.