Management Of Osteoradionecrosis Research Articles

Conservative Approach of a Severe Case of Osteoradionecrosis of the Mandible- Case Report

Osteoradionecrosis (ORN) of the jaw is a severe, complex, and multifactorial complication of radiotherapy (RT) for head and neck cancers. Most cases of ORN develop during the first 3 years with a peak between 6 months and 2 years after completion of RT however the patient is considered at risk of developing this condition many years later. The management of ORN is usually based on conventional medical care by focusing on comorbidity factors, However, in some refractory ORN cases, the condition requires extensive surgical resection. Based on the “the radiation-induced fibro-atrophic theory” introduced by Delanian, a new conservative approach of ORN seems to be promising by combining antioxidant agents: pentoxifylline and Tocopherol (PtxE) in the treatment of severe cases of ORN. The aim of this paper was to report the case of a severe case of ORN of the mandible stabilized by a conservative approach combining antibiotics, antiseptic agent as well as antioxidant therapy (PtxE), and to discuss the efficacy of this approach.

Does hyperbaric oxygen therapy play a role in the management of osteoradionecrosis? A survey of Dutch oral and maxillofacial surgeons

For decades, hyperbaric oxygen (HBO) has often been part of the treatment of osteoradionecrosis (ORN), despite controversy in the literature about its efficacy. An online survey was conducted to investigate the use of HBO in the treatment of ORN by Dutch oral and maxillofacial surgeons and to assess their perception of its efficacy. Of the 53 Dutch oral and maxillofacial surgery units contacted, 49 (92%) replied. Thirty-five were not head and neck cancer (HNC) units or preferred partner (PP-HNC) units recognized by the Dutch Head and Neck Association. All HNC and PP-HNC units (group 1) treated ORN patients, compared to only 12 (34%) of the non-HNC units (group 2). The average number of ORN patients seen and treated was higher in group 1. The units in group 1 more often referred patients for HBO therapy (HBOT) than those in group 2 (93% vs 84%). The efficacy of HBOT in curing ORN, rated on a scale of 1 to 5 points, was 3.7 in group 1 and 3.2 in group 2. This survey shows a trend towards centralization of ORN care to more experienced units. These units tend to use HBOT in curing ORN.

Role of Hyperbaric Medicine for Osteoradionecrosis and Post Irradiation Wounds: an Institutional Experience.

To study the effectiveness of hyperbaric medicine in osteoradionecrosis and irradiation induced wounds. To evolve a protocol for management with combined surgical modality for irradiation induced injury. This study was carried out in the Plastic Surgery Department, from November 2011 to December 2018. A total of 30 patients with post irradiation patients subjected to hyperbaric oxygen therapy during the management were enrolled in the study. The results regarding the changes in wound and complications were noted. Out of 30 patients, 20 patients were with radiation injury involving the oral cavity, one patient with left lower limb, one with breast, 3 with radiation injury of cheek, 3 of mandible, one with radiation cystitis and one involving the tooth socket. One patient experienced reversible myopia as a complication of hyperbaric therapy. No other complications were noted. Hyperbaric therapy is a useful adjunct for surgery in management of osteoradionecrosis and post irradiation wound and proves therapeutic in some post irradiated wound where we cannot offer surgical correction.

Research Frontiers in Oral Toxicities of Cancer Therapies: Osteoradionecrosis of the Jaws.

The deleterious effects of head and neck radiation on bone, with osteoradionecrosis (ORN) as the major disabling side effect of head and neck cancer treatment, are difficult to prevent and hard to treat. This review focuses on the current state of the science regarding the pathobiology, clinical impact, and management of ORN. With regard to the pathobiology underlying ORN, it is not yet confirmed whether the current radiation schedules by 3-dimensional conformal radiotherapy and intensity modified radiotherapy result in an unchanged, decreased, or increased risk of developing ORN when compared with conventional radiation treatment, the main risk factor being the total radiation dose delivered on any clinically significant surface of the mandible. With regard to the prevention of ORN, a thorough, early pre-irradiation dental assessment is still considered the first step to reduce the hazard of developing ORN post-radiotherapy, and hyperbaric oxygen (HBO) treatment reduces the risk of developing ORN in case of dental surgery in an irradiated field. With regard to the treatment of ORN, the focus is bidirectional: elimination of the necrotic bone and improving the vascularity of the normal tissues that were included in the radiation portal. The cure rate of limited ORN by conservative therapy is approximately 50%, and the cure rate of surgical approaches when conservative therapy has failed is approximately 40%. Whether it is effective to support conservative or surgical treatment with HBO as an adjuvant is not set. HBO treatment is shown to increase the vascularity of hard and soft tissues and has been reported to be beneficial in selected cases. However, in randomized clinical trials comparing the preventive effect of HBO on developing ORN with, eg, antibiotic coverage in patients needing dental surgery, the preventive effect of HBO was not shown to surpass that of a more conservative approach. More recently, pharmacologic management was introduced in the treatment of ORN with success, but its efficacy has to be confirmed in randomized clinical trials. The major problem of performing well-designed randomized clinical trials in ORN is having access to large numbers of patients with well-defined, comparable cases of ORN. Because many institutions will not have large numbers of such ORN cases, national and international scientific societies must be approached to join multicenter trials. Fortunately, the interest of funding organizations and the number researchers with an interest in healthy aging is growing. Research aimed at prevention and reduction of the morbidity of cancer treatment fits well within these programs.

Surgical management of osteoradionecrosis using three-dimensional isodose curve visualization: a multi center retrospective study

Surgical management of osteoradionecrosis using three-dimensional isodose curve visualization: a multi center retrospective study

Is there a role for pentoxifylline and tocopherol in the management of advanced osteoradionecrosis of the jaws with pathological fractures? Case reports and review of the literature

Osteoradionecrosis (ORN) is an infrequent but serious complication of radiotherapy, especially in the head and neck region. It is a slowly progressive condition, with management in the early stages focused on symptom control, and surgery usually reserved for advanced ORN. However, established ORN is difficult to treat. The role of hyperbaric oxygen therapy has recently been contested. The use of pentoxifylline in the management of ORN was first described by Delanian in 2004, but its benefits have not been replicated in other studies. In cases of advanced ORN with pathological fractures, many centres still advocate surgical resection and reconstruction. However, in this group of patients who often have multiple medical comorbidities, many of whom have previously undergone significant surgery, a resective plan is not always ideal. This paper presents two successful cases of bony union after the use of pentoxifylline and tocopherol to manage grade III ORN of the mandible. Both patients had pathological fractures and orocutaneous fistulas and were deemed unsuitable for surgery. The possible reasons for the success of pentoxifylline and tocopherol are discussed, and a review of the current literature evidence of similar cases is presented. Pentoxifylline and tocopherol should be considered for the management of advanced ORN where surgical management is not appropriate.

Current trends in the medical management of osteoradionecrosis using triple therapy

Recent guidelines from the National Institute for Health and Care Excellence (NICE) have suggested that the medical management of osteoradionecrosis (ORN) of the jaws should be used in clinical trials only, and some drugs and therapeutics committees have withdrawn funds for such prescriptions. With increased scrutiny on the use of these agents, the aims of this study were to ascertain current trends in the presentation and management of ORN, with particular focus on which agents are being used.

Exploration of an Early Imaging Biomarker of Osteoradionecrosis in Oropharyngeal Cancer Patients: Case-Control Study of the Temporal Changes of Mandibular Radiomics Features

We aim to characterize the kinetics of radiomics features of various mandibular subvolumes after IMRT and identify subvolumes at high risk for developing osteoradionecrosis (ORN). We included oropharyngeal cancer patients treated by IMRT with subsequent radiographically proven ≥G2 ORN. Mandibular subvolumes showing ORN as well as a neighboring radiographically intact mandibular subvolume receiving the same dose (Control) were manually segmented. For each patient, pre-IMRT, 2-, and 6-month post-IMRT scans were co-registered. ORN and Control ROIs were propagated to all time points. A total of 145 radiomics features were extracted from each ROI using automated software. A histogram approach and Spearman correlation test were used to exclude features according to extreme degrees of variability and high level of correlation, respectively. This resulted in 50 features from the following categories: shape, gray-level co-occurrence matrix (GLCM) 3D, GLCM 2.5D, neighbor intensity difference (NID) 3D, NID 2.5D, and intensity histogram. We computed the underlying temporal trajectory signatures using Functional Principal Component Analysis. Random Forest classification was used to build a predictive model. Seventeen patients, with the majority having base of tongue primary. Ten patients had G2, 7 G3 ORN, which were ipsilateral to the tumor subsite of origin in 82.4% of cases. Median time to ORN diagnosis was 15.4 months. The ORN ROI mean dose was 63 Gy (±6.5). The corresponding AUCs and 95% confidence intervals (C.I.) for the prediction of ORN, according to the 5 models, are illustrated in the Table. A combination of baseline features and temporal trajectories proved to be the best classifier. Conversely, delta changes at intermediate time points (model 2 and 3) held were the least predictive of ORN incidence. This suggests that the functional approach yields a superior predictive power in the correlation of radiomics features to normal tissue toxicity over time.Tabled 1Abstract 207Predictive ModelAUC95% Low C.I.- High C.I.1Baseline features only0.740.58-0.922Baseline/2-month post-IMRT Delta0.590.38-0.803Baseline/6-month post-IMRT Delta0.670.47-0.864All time points temporal trajectories0.720.54-0.935Combination of baseline features and temporal trajectories0.840.71-0.98 Open table in a new tab Temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of mandibular injury. Radiomics may convey additional clinical information from routine imaging studies in radiation oncology towards antecedently preemptive management of ORN.

Pentoxifylline and tocopherol in the management of cancer patients with medication-related osteonecrosis of the jaw: an observational retrospective study of initial case series

Very few studies have evaluated the efficacy of pentoxifylline and tocopherol (PENT-E) in the management of medication-related osteonecrosis of the jaw (MRONJ), although some studies have shown the therapeutic and prophylactic benefit of PENT-E in the management of osteoradionecrosis. We report the outcomes of MRONJ managed with PENT-E in patients with metastatic bone disease or multiple myeloma. Seven patients diagnosed with established cases of refractory MRONJ caused by antiresorptive medications for the management of metastatic bone tumors or multiple myeloma were administered PENT-E for a mean period of 16.8months (range 3-48months). At the latest follow-up visit, all patients demonstrated relief of symptoms. There was radiographic evidence of new bone fill of prior radiolucent defect in all patients. Two patients had resolution of exposed bone, two patients had partial resolution, one patient had no change in exposed bone, and one patient with three sites of exposed bone before starting PENT-E had resolution in one site, partial resolution in another site, and no change in the third site. PENT-E was well tolerated in all patients. Our case series demonstrated that PENT-E was well tolerated and may be an effective adjunct in the management of MRONJ.

Osteoradionecrosis in patients with salivary gland malignancies

The present study was undertaken to evaluate osteoradionecrosis (ORN) in patients with salivary gland malignancies (SGM) after treatment with radiation therapy. The medical records of 172 patients treated with radiation therapy for SGM during a 12-year period (August 2001 to November 2013) were reviewed. Incidence, time to event, staging and management of ORN were analyzed. Of the 172 patients, 7 patients (4%) developed ORN (median latency: 19months, range: 4-72months). Of those 7 patients, 4 required major surgery, 1 required hyperbaric oxygen therapy (HBO), one required minor debridement, and one required conservative management. Total prescribed radiation dose varied from 50Gy (1 case) to 70Gy (1 case) among those patients who developed ORN, and radiotherapy was delivered postoperatively after osseous resection in 4 of 7 cases. Three of the 7 cases of ORN occurred after traumatic injury to the bone. Of the 7 patients who developed ORN, 3 had SGM of the major glands, 3 had other sites of the oral cavity, and 1 had a sinonasal location. While the rate of ORN after radiotherapy for SGM was somewhat lower (4%) than previously published data on patients with squamous cell carcinomas of the head and neck treated with radiation therapy (8-14%), ORN necessitating major surgery remains a clinically significant, possible late effect of radiotherapy in SGM survivors. Location of SGM is very important, with cases that developed ORN disproportionally having primary disease arising in the oral cavity.

Use of pentoxifylline and tocopherol in the management of osteoradionecrosis

Osteoradionecrosis (ORN) is a complication of radiotherapy, and is difficult to manage once established. However, its pathogenesis has been reinvestigated, and it is now thought to be potentially amenable to treatment with pentoxifylline and tocopherol (vitamin E). We made a retrospective analysis of 62 patients with established ORN who were treated in this way. When only pentoxifylline and vitamin E was used ORN resolved in 14/25 (56%) but paradoxically, when it was combined with antibiotics, only 6/22 resolved (27%). The next stage would ideally be to incorporate the treatment in a randomised clinical trial against both standard antibiotic treatment and hyperbaric oxygen.

Osteoradionecrosis: Case report

Patients undergoing radiotherapy alone or as part of the treatment of head and neck cancer are likely to develop osteoradionecrosis (ORN). Dental extractions have been inferred as the main triggering factor of ORN, particularly in mandibular molars. The osteoradionecrosis has been reported in up to 20% of irradiated patients undergoing dental extraction and is recognized as the most severe complication of radiotherapy in the mandible, causing great discomfort and loss of quality of life of patients. The risk of ORN development is related to the dose, technique, and volume of irradiated tissue, and other predisposing factors such as: extraction at peri-radiotherapy period, site of extraction, pre-existing periodontal disease, general trauma, poor oral hygiene, nutritional deficiency, alcohol and smoking, and systemic diseases. The cellular injury and hypoxia caused by decreased blood supply reduce the recoverability of soft tissue and bone, predisposing them to necrosis and osteonecrosis, even spontaneous. Clinical management of osteoradionecrosis is complex and depending on the degree of involvement, it may require analgesics and antibiotics in addition to the adoption of surgical procedures, aiming to eliminate pain, control infection, and prevent or reduce the progression of the lesion. This paper aimed to report a case of osteoradionecrosis treated in the multidisciplinary clinic of the Onco Project - ICT/UNESP (São José dos Campos/SP, Brazil). A female patient aged 65 years with osteoradionecrosis and fistula after radiotherapy of squamous cell carcinoma in gingiva was submitted to tooth extraction, antibiotic therapy and local care with good response and flow interruption through the fistula. During the treatment, the carcinoma relapsed and the patient was referred for oncologic treatment.

English

Osteoradionecrosis (ORN) defines exposed irradiated bone, which fails to heal over a period of 3–6 months without evidence of residual or recurrent tumor. It is a long term and serious complication of therapeutic radiotherapy for head and neck cancer. The pathogenesis of ORN has been proposed relating it to a fibroatrophic mechanism including free radical formation, endothelial dysfunction, inflammation, microvascular thrombosis leading to bone and tissue necrosis. Risk factors mainly include radiation related risk factors, surgery, tobacco and alcohol abuse. Removing of diseased teeth after radiotherapy is generally considered the main risk factor in ORN. Prevention of ORN is based on the preventive extractions of decayed or periodontally compromised teeth before radiotherapy. Based on the clinical staging various therapeutic protocols have been suggested. We here report a case of Bilateral mandibular ORN with discussion of clinical features, pathogenesis, preventive measures, and management of ORN.

PENTOCLO for Treatment of Osteoradionecrosis of the Temporal Bone

Objectives: Osteoradionecrosis is a rare but devastating complication of radiation therapy that often requires surgical intervention. The objective of this report is to describe a case of osteoradionecrosis (ORN) of the temporal bone that was managed medically with PENTOCLO (pentoxifylline-tocopherol-clodronate). The use of PENTOCLO in the treatment of ORN of other sites in the head and neck will also be described. Methods: We report the case of a patient treated at our institution and present a review of literature. A 52-year-old woman presented with ORN of the temporal bone 20 years following radiation therapy for an ipsilateral parotid tumor. The patient had chronic infections and otorrhea. Results: She failed conservative treatment including antibiotic-steroid ear drops and aural lavage. As an alternative to hyperbaric oxygen and/or temporal bone resection, treatment with PENTOCLO was pursued and her condition improved dramatically. A literature review of ORN of the temporal bone and the use of PENTOCOLO in the management of ORN of other sites of the head and neck are described. Conclusions: PENTOCLO was effectively used in the management of our patient and may represent a valuable management option for other patients with ORN of the temporal bone. Further research is required to determine the effectiveness of PENTOCLO.

Experience of long-term management for osteoradionecrosis of the maxilla after carbon ion radiotherapy

Purpose: The aim of this study was to evaluate the incident of maxillary osteoradionecrosis (ORN) in patients who underwent carbon ion radiotherapy (CIRT) for head and neck cancer. We report the experience of long-term management for ORN especially required surgical intervention for grade 3 morbidity.Materials and methods: From April 1997 to April 2006, 239 patients with the head and neck cancers were treated with CIRT with a dose of 57.6 GyE per 16 fractions. Patients whose alveolar process and palatine process of maxilla had been irradiated more than 10% of the prescribed dose were selected. We exclude the cases of after operation therapy and after radiation therapy. For this study, we employed the criteria for adverse events presented in Common Terminology Criteria for Adverse Events (CTCAE) v4.0 released by the U.S. National Cancer Institute.Results: Sixty-seven patients were enrolled in this study (Table 1). Of the 67 patients, 33 patients (49.3%) developed ORN. Sixteen patients (23.9%) received no treatment, 13 patients (19.4%) with exposed sequestrum received conservative therapy. All of grade 2 patients could control clinical symptoms treated with analgesics and oral care. Four patients (6.0%) with severe symptoms were undergone sequestrectomy (Table 2). After sequestrectomy, all of four patients showed no signs of sequestrum re-exposure or symptom exacerbation during the average follow-up period of 36.7 months. In addition, masticatory function was maintained using dento-maxillary prosthesis in all cases.Table 1.Patient and tumor characteristicsPatientn (%)Tumor siten (%)Total67 (100)Nasal17 (25.4)Age (years), median (range)56 (16–80)Maxillary sinus13 (19.4)GenderParotid gland10 (14.9) Male38 (56.7)Ethmoid sinus8 (11.9) Female29 (43.3)Palate8 (11.9)PathologyTongue4 (5.7)ACC28 (42)Epipharynx4 (5.9)MMM27 (40)Others3 (4.5)Others12 (18)ACC, adenoidcystic carcinoma; MMM, mucosal malignant melanoma. Table 2.Results of ORN gradingn (%)TherapeuticsAll cases67 (100)—No adverse event34 (50.7)—Grade 116 (23.9)No treatmentGrade 213 (19.4)Conservative therapyGrade 34 (6.0)SequestrectomyConclusions: Although 33 patients developed ORN, only 4 patients needed the surgical treatment. However, we could control the clinical symptoms and improved the QOL for the four patients after surgical intervention.

OP210: Changing trends and the role of medical management on the outcome patients treated for osteoradionecrosis of the mandible: Experience from a regional maxillofacial unit

Retrospective review of treatment outcomes of osteoradionecrosis (ORN) of the mandible with specific reference to the evolving role of Medical Management (MM) with Pentoxifylline and Tocopherol. Patients treated in a period stretching over 15 years to January 2011 were reviewed by categorizing them into three Notani grades. Data was extracted on demographics, treatment and outcomes. All had received one of the following primary treatment: minimal debridement, HBOT or MM. Patients who failed conservative management were further analyzed based on the need for free flap (FF) reconstruction by dividing them into two groups, before and after January 2006 to reflect the change in practice in our unit in favour of MM. Kaplan–Meier estimates of survival were obtained for all patients and also for time-periods before and since 2006, with comparison of survival curves using the log-rank test. Comparison between time periods for treatment mode, Notani grade and outcome of initial management used chi-squared test, and for FF used Fishers exact test. Seventy-one patients were included (grade I = 28, II = 16, III = 27). There was an overwhelming shift in the initial conservative management of ORN in favour of MM from January 2006. Before 2006, 31% (12) were treated with DBR, 64% (25) HBOT, and 5% (2) MM. Since 2006, 19% (6) DBR, 9% (3) HBOT and 72% (23) MM; p < 0.001. MM was prescribed to 12 grade I, 3 grade II and 10 grade III patients. Overall 3 (25%) grade I and 2 (66%) grade II patients were cured. Reassuringly, 8 (67%) grade I and 4 (40%) grade III patients ORN had stable disease. Among patients who failed conservative management, FF was required for 51% (20/39) and 25% (8/32) before and after January 2006 respectively, p = 0.03. This study supports the change in protocol in the unit away from HBOT in favour of MM.

The use of buccal fat pad flap in the treatment of osteoradionecrosis

The use of buccal fat pad in the management of osteoradionecrosis has not been described previously. A series of 10 consecutive cases of osteoradionecrosis treated with a combination of sequestrectomy and buccal fat pad is presented. The data were obtained by reviewing operative and medical records. The combination of sequestrectomy and buccal fat pad flap was successful in 86% of cases of stage II osteoradionecrosis and in 0% of cases of stage III. The overall success rate was 60%. Based on the result of this series, this treatment regime appeared to be beneficial in stage II osteoradionecrosis.

Paradigm shifts in the management of osteoradionecrosis of the mandible

Paradigm shifts in the management of osteoradionecrosis of the mandible

Clinical advance in the use of hyperbaric oxygen therapy in the prevention and management of osteoradionecrosis

头颈部恶性肿瘤放射治疗的不良反应如黏膜炎、放射性龋、口干综合征、味觉丧失、软组织纤维化、放射性骨坏死( osteoradionecrosis,ORN)等越来越受到医务工作者的重视,其中又以ORN最为严重,该病常因曾接受放射治疗颌骨区的感染或创伤因素诱发,也可无明显诱发因素;病程缓慢持久、发病初期常呈持续针刺样疼痛,病情进展可致皮肤黏膜破溃、骨面外露,若继发感染可长期溢脓、经久不愈,甚至病理性骨折,给患者带来极大痛苦,严重影响生活质量。

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

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. 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. 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. 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.