Development and Standardization of an Osteoradionecrosis Classification System in Head and Neck Cancer: Implementation of a Risk-Based Model.

PURPOSE: Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN. METHODS: Consecutive patients with head and neck cancer (HNC) treated with curative-intent intensity-modulated radiation therapy (IMRT) (≥45 Gy) from 2011 to 2017 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared with 15 existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection). RESULTS: ORN was identified in 219 of 2,732 (8%) consecutive patients with HNC. Factors associated with high risk of ORN were oral cavity or oropharyngeal primaries, received IMRT dose ≥60 Gy, current/ex-smokers, and/or stage III to IV periodontal condition. The ORN rate for high-risk versus low-risk patients was 12.7% versus 3.1% (P < .001) with an AUC of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, ClinRad, was proposed on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems. CONCLUSION: We identified risk factors for ORN and proposed a novel ORN classification system on the basis of vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN and may facilitate clinical care and clinical trials.

[Predictive factors for mandibular osteoradionecrosis after irradiation of head and neck cancers]. / Facteurs prédictifs de l'ostéoradionécrose mandibulaire après irradiation des cancers des voies aérodigestives supérieures.

The identification of the different risk factors for mandibular osteoradionecrosis (ORN) must be done before and after the management of patients with head and neck cancer. Various clinical criteria for this severe radiation-induced complication are related to the patient (intrinsic radiosensitivity, malnutrition associated with thin weight loss, active smoking intoxication, microcapillary involvement, precarious oral status, hyposalivation) and/or related to the disease (oral cavity, large tumor size, tumor mandibular invasion). Therapeutic risk factors are also associated with a higher risk of ORN (primary tumor surgery, concomitant radio-chemotherapy, post-irradiation dental avulsion, preventive non-observance with the absence of stomatological follow-up and daily installation of gutters fluoride and, non-observance curative healing treatments). Finally, various dosimetric studies have specified the parameters in order to target the dose values distributed in the mandible, which increases the risk of ORN. An mean mandibular dose greater than 48-54Gy and high percentages of mandibular volume receiving 40 to 60Gy appear to be discriminating in the risk of developing an ORN.

Retrospective analysis of osteoradionecrosis of the mandible: proposing a novel clinical classification and staging system.

Osteoradionecrosis of the jaw is a common radiation-induced complication that may be observed in oral cancer patients. Several classifications and staging systems have been proposed for osteoradionecrosis of the mandible based on clinical symptoms, radiological findings, and/or the response to diverse treatments. However, none has been universally accepted because of their individual deficiencies. The aim of this study was to introduce a new clinical classification that can be applied to the treatment of osteoradionecrosis in an easier and more acceptable way, through a retrospective analysis of patients with osteoradionecrosis of the mandible. A review was conducted of 99 patients diagnosed with osteoradionecrosis of the mandible in the study institution between 2000 and 2013. A novel classification was established on the basis of bone necrosis and soft tissue defects. A new staging system with four different stages (stage 0, stage I, stage II, and stage III) is proposed. We believe that this new classification and staging system is easier and more acceptable for clinical evaluation than previous ones.

Osteoradionecrosis of the mandible: A ten year single-center retrospective study.

BACKGROUND: Numerous factors have been associated with the development of osteoradionecrosis (ORN) of the jaws. The purpose of this study was to investigate the factors that are linked to the severity of mandibular ORN. METHODS: A retrospective study was conducted which included all ORN cases treated in the Department of Oral and Maxillofacial Surgery in Munich (LMU) between 2003 and 2012. The cases were categorized according to the necrosis stage and several variables were evaluated in order to identify possible correlation between them and the severity of the necrosis. RESULTS: A total of 115 patients with 153 osteonecrosis lesions were included in the study. Twenty-three cases were of stage I, 31 were of stage II and 99 were of stage III. The initial tumors were predominantly located in the floor of the mouth, the tongue or the pharynx. Diabetes mellitus (OR: 4.955, 95% Cl: 1.965-12.495), active smoking (OR: 13.542, 95% Cl: 2.085-87.947), excessive alcohol consumption (OR: 5.428, 95% Cl: 1.622-18.171) and dental treatment and/or local pathological conditions (OR: 0.237, 95% Cl: 0.086-0.655) were significant predictors for stage III necrosis. CONCLUSIONS: The aforementioned factors are predictive of ORN severity and can guide its prophylaxis and management.

Treatment outcomes of temporal bone osteoradionecrosis.

OBJECTIVE: To investigate the clinical relevance of the classification systems used for temporal bone osteoradionecrosis (ORN) and to define a treatment protocol for temporal bone ORN. STUDY DESIGN: Retrospective case series. SETTING: Amsterdam, department of otorhinolaryngology and head and neck surgery. SUBJECTS AND METHODS: Classification of temporal bone ORN was performed through use of clinical data and radiologic imaging. Outcomes of conservative and surgical treatment were investigated and compared for different grades of ORN. RESULTS: Of the 49 ears included in this study, 35 were primarily treated conservatively. At start of conservative treatment, 23 were classified as a localized and 8 as a diffuse form of ORN; 4 could not be classified. There was a significant difference in clinical outcome between the localized and diffuse forms of ORN (χ(2) = 5.862, P = .015), and mastoid air cell destruction on preoperative computed tomography scan was found to be a significant predictor for a negative outcome of conservative treatment (χ(2) = 4.34, P = .037). Fourteen ears with diffuse ORN were primarily treated surgically, and 11 were secondarily treated surgically following a period of conservative treatment. Twenty-two patients were treated with subtotal petrosectomy, of which 20 were cured. Three patients were treated with canal wall down mastoidectomy, and 2 had recurrence of disease. CONCLUSION: Ramsden's classification system is clinically relevant in predicting conservative treatment outcomes. Mastoid air cell destruction on computed tomography differentiates between the localized and diffuse forms of ORN. Given our results and experience with treating temporal bone ORN, we propose a treatment protocol.

Osteoradionecrosis--a review of current concepts in defining the extent of the disease and a new classification proposal.

Osteoradionecrosis (ORN) is potentially a debilitating and serious consequence of radiotherapy to the head and neck. Although it is often defined as an area of exposed bone that does not heal, it can also exist without breaching the mucosa or the skin. Currently, 3 classifications of ORN are in use, but they depend on the use of hyperbaric oxygen or are too complicated to be used as a simple aide-mémoire, and include features that do not necessarily influence its clinical management. We propose a new classification to cover these shortcomings and to take into account the increasingly widespread use of antifibrotic medical treatment. We classified a series of 85 patients with varying severities of ORN into 4 groups. An analysis of the outcomes of the series showed that the classification staged the severity of the condition simply and that the stage was relevant to both treatment and outcome. The new classification was therefore verified by the series presented.

Changing trends and the role of medical management on the outcome of patients treated for osteoradionecrosis of the mandible: experience from a regional head and neck unit.

This study is a retrospective review of treatment outcomes of osteoradionecrosis (ORN) of the mandible with specific reference to the evolving role of medical management with pentoxifylline, tocopherol, and doxycycline. We reviewed the presentation and management of 71 patients treated for ORN of the mandible at the regional head and neck unit during a 15-year period to January 2011, and categorised them into three grades using the Notani classification: grade I (n=28), grade II (n=16), and grade III (n=27). Twelve patients with grade I ORN, 3 with grade II, and 10 with grade III, were prescribed medical treatment. Of these, three with grade I, and two with grade II ORN were cured, and progression of the disease had halted and there was satisfactory control of symptoms in eight with grade I and four with grade III disease. Patients who failed to respond to conservative treatment were further analysed for the need for free flap reconstruction. Medical management was introduced as a standard treatment in January 2006. Of the 39 patients diagnosed before this, 20 (51%) required resection and free flap reconstruction compared with only 8/32 (25%) after it had been introduced.

Proposal for a new staging system for osteoradionecrosis of the mandible.

A new staging system for osteoradionecrosis of the mandible has been retrospectively applied to a group of 31 patients. In this system clinicoradiographic signs and symptoms are incorporated in a simplified manner. For imaging purposes the use of plain radiographs such as periapical films and panoramic radiographs is recommended, mainly because of their readily availability. The presented staging system seems well reproducible, facilitating the comparison of study groups dealing with the various issues of osteoradionecrosis of the mandible. It is yet to be evaluated whether the presently proposed staging system is useful for management purposes.

Feasibility and toxicity of concurrent chemoradiation for elderly patients with head and neck cancer.

OBJECTIVES: Although concurrent chemoradiation is increasingly used for patients with locally advanced head and neck cancer, many elderly patients receive radiation alone due to toxicity concerns. We evaluate acute and late toxicity among patients age ≥ 65 who received concurrent chemoradiation for head and neck cancer. DESIGN: Retrospective review. SETTING: Tertiary care center. PARTICIPANTS: Between 6/2003 and 8/2011, 40 consecutive patients age ≥ 65 underwent combined chemoradiation for head and neck cancer. Ten patients were treated in the postoperative setting and 30 underwent definitive chemoradiation. Twenty-eight patients received concurrent platinum-based chemotherapy and 12 received concurrent weekly paclitaxel. Treatment plans were designed to provide a dose of 66-72 Gy at 2-2.12 Gy/fraction to >95% of the gross tumor volume in the definitive setting or for positive margins and 60-66 Gy at 2 Gy/fraction post-operatively. Median follow-up was 23.2 months (range: 0-94.4 months). MAIN OUTCOMES MEASURES: Acute skin and mucosal toxicity, unplanned treatment interruptions, and chronic treatment related toxicity including gastrostomy tube dependence as graded by the CTCAE v3.0. RESULTS: Eight patients (20%) required a radiation treatment break of ≥ 3 days. Thirteen (33%) required unplanned hospitalization during or immediately following treatment. No grade 4+ skin or mucosal toxicity was noted. Five patients remained PEG tube dependent at >1 year. One patient developed non-healing mandibular osteoradionecrosis >3 years following chemoradiation. The 2-year Kaplan-Meier estimate of overall survival was 55%. CONCLUSION: Higher-than-expected rates of in-patient hospitalization with significant acute toxicity were noted in this cohort with a correspondingly high rate of radiation treatment breaks. Late toxicity rates were similar to those observed in historical controls with younger patients. Careful patient selection criteria should be employed for elderly patients considering concurrent chemoradiation for head and neck cancer.

[Clinical classification of osteoradionecrosis of temporal bone and the treatment of massive osteonecrosis].

OBJECTIVE: To explore the effective treatment regimen for osteoradionecrosis of temporal bone. METHOD: Twenty-seven patients with massive osteoradionecrosis in temporal bone were included and retrospectively analyzed, in which, 15 cases received surgery and the other 12 cases adopted non-surgical treatment. RESULT: In the surgery group, three cases died one year postoperatively and died of massive hemorrhage due to internal carotid blowout. One case died four years after surgery without clear cause of death, and two cases were lost to follow up. Out of the nine survivors, the follow up period ranged from four months to eight years (one was followed up eight years, one was followed up over four years, four were followed up two-three years, one was followed up over one year, one was followed up nine months, and one was followed up four months, respectively). Patients classified as the type III received best outcome, and patients of type V and IV without invasion of the internal carotid artery received good surgical effects, while patients classified as the type IV with internal carotid artery invasion presented low survival rate. Two cases in the non-surgical group died of internal carotid rupture, and the other ten cases presented with repeated infection and expansion of the osteoradionecrosis lesion. CONCLUSION: The new classification criteria is helpful in diagnosis of location of lesions,and can serve as a guide for clinical therapy. Massive osteoradionecrosis in temporal bone responded unfavorably to conservative treatment, compared to that, surgery can effectively control the expansion of the lesion and markedly improve patient quality of life. Long-term follow up is necessary because of the slow development of osteoradionecrosis after surgery.

Pentoxifylline and tocopherol in the management of patients with osteoradionecrosis, the Portsmouth experience.

Osteoradionecrosis of the jaw remains the most problematic consequence of radiotherapy for the management of head and neck cancer. Treatment is often complex and multimodal. New theories on its pathophysiology have allowed the development of potential treatment modalities, including the use of pentoxifylline and tocopherol. In this retrospective case series we examined the outcomes of patients with ORN prescribed pentoxifylline and tocopherol.

Free flap reconstruction of osteoradionecrosis of the mandible: a 10-year review and defect classification.

BACKGROUND: The purpose of this study was to evaluate outcomes of free flap reconstruction for advanced osteoradionecrosis (ORN) defects and develop an algorithm to guide surgical planning. METHODS: All cases involving free flap reconstruction for ORN of the mandible between 1998 and 2008 were reviewed. A defect classification scheme was developed. Flap selection and outcomes were analyzed and evaluated by defect type. RESULTS: Seventy-five free flaps and 13 pedicle flaps were performed in 63 patients. Total flap loss was 5%. Overall surgical complication was 32%. Complication rates were higher with bone flaps than with soft tissue flaps (p = .018). A full oral diet was tolerated in 57% of patients, whereas 26% required partial tube feeding, and 16% were tube-feeding dependent. CONCLUSION: Free flap reconstruction of advanced ORN defects can be safely performed in a variety of flap configurations with good outcomes. The classification scheme may assist in flap selection.

Hyperbaric oxygen in the management of late radiation injury to the head and neck. Part I: treatment.

Osteoradionecrosis (ORN) is a serious condition following treatment for head and neck cancer with serious associated morbidity and mortality. While the use of hyperbaric oxygen (HBO) in treating established osteoradionecrosis has been standard practice in many units for years, the evidence base for this remains remarkably weak. The published evidence has been made even more controversial by trial protocols that do not use HBO as it is generally advocated. This review describes the classification, incidence, and treatment of ORN, and explores the available published evidence with particular emphasis on randomised trials of treatment with HBO.

[Mandibular osteoradionecrosis: part I: severity factors]. / Ostéoradionécroses mandibulaires: partie I: facteurs de gravité

INTRODUCTION: The severe evolution for some patient presenting with osteoradionecrosis, even if classified in the same stages as other patients, suggests that there are aggravating factors. MATERIAL AND METHOD: A retrospective study was made between 1992 and 2002 on all patient operated for mandibular osteoradionecrosis. Fifty-nine patients were included and the mandibular defects were reconstructed with a bone or a composite free flap (fibula 21%, iliac crest 49%, scapula 6%, antebrachial 3%), and with a periosteal free flap (13%). RESULTS: The study included severe cases (87% of stage II or III) operated on several times without success. Free flap reconstruction was successful in 90% of the cases. However, complications were present in 60% of cases (24% minor complications, 48% major complications), and were more frequent with a higher stage. The analysis allowed identifying morbidity factors. DISCUSSION: Studying the morbidity allowed identifying severity factors of osteoradionecrosis; spontaneous onset, important irradiation (important dose, bone proximity of the tumor, bilateral damage), vascular damage (symphyseal localization, lack of sequestrum, facial artery ligature, active tobacco addiction), actinomycosis colonization, non-observance of medical treatment. Understanding aggravating factors should allow us to offer more efficient surgery on an early osteoradionecrosis stage, also decreasing the morbidity linked to reconstructive surgery.

Osteoradionecrosis of the mandible: scientific basis for clinical staging.

Osteoradionecrosis of the mandible can be a serious complication of radiotherapy for head and neck cancer. The disorder generally presents in one of several distinct clinical variations. This is probably because of a complex interaction of etiologic factors. A clinical staging system for the disorder is described. Such a system is necessary for the conduct of clinical research, and for the development and assessment of treatment regimens.

A review of the Marx protocols: prevention and management of osteoradionecrosis by combining surgery and hyperbaric oxygen therapy.

The 30/10 protocol is employed in the treatment of established osteoradionecrosis. No surgery should be attempted before the first 30 HBO treatments have provided sufficient angiogenesis to support surgical wounding. After 30 treatments surgical management can be staged according to the extent of improvement achieved after HBO and the size of sequestrum or area of osteolysis. If the ORN extends to the inferior border of the mandible or if it manifests as an orocutaneous fistula or pathological fracture, discontinuity resection of the necrotic bone and soft tissue will be required to resolve the disease. Unless HBO and surgery are combined in the management of ORN, the results are not long lasting or satisfactory. Even though resection of stage three ORN seems unduly aggressive, it has stood the test of time. By using the Marx protocols in the treatment of ORN, more than 95 per cent of patients can be successfully cured of their disease with predictable, functional and aesthetically acceptable outcomes.

[The RTOG score (Radiation Therapy Oncology Group) as a guide to treatment of the irradiated field]. / Der RTOG-Score (Radiation Therapy Oncology Group) als Leitfaden zur Behandlung im vorbestrahlten Gebiet.

The RTOG score, which describes radiation-caused side effects in a reproducible way, was introduced as a guide for the treatment of irradiated patients. By means of a prospective study (27 patients; acute effects) and a retrospective study (81 patients; long-term effects) the score was evaluated. Special importance was placed on the recording of dental and maxillofacial findings as well as on the therapeutic outcome. It was shown that frequency of dental lesions increased with the score of radiation effects while dental treatment decreased inverse to the score of radiation effects. Evaluation of radiation reactions of the lower jaw showed better results concerning preventive treatment and osteoradionecrosis than have been described in the literature.

Osteoradionecrosis: clinical experience and a proposal for classification.

Osteoradionecrosis is a severe complication of radiation therapy for cancer. Prevention of osteoradionecrosis is most important as the condition may be chronic, progressive and lead to pathologic fracture. The clinical experience at the Cancer Control Agency of British Columbia with 26 cases in approximately 1000 patients treated with radical radiation therapy to the head and neck region is presented and discussed. A clinical classification system is proposed to provide a guide for treatment selection, and to allow classification for research purposes.