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Introduction: This retrospective study aimed to investigate if pretreatment platelet (PLT) levels can predict the risk of osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) who received concurrent chemoradiotherapy (CCRT)., Material &methods: ORNJ instances were identified from LA-NPC patients' pre- and post-CCRT oral exam records. All pretreatment PLT values were acquired on the first day of CCRT. Receiver operating characteristic curve analysis was used to determine the optimal PLT cutoff that divides patients into two subgroups with distinctive ORNJ rates. The primary outcome measure was the association between pretreatment PLT values and ORNJ incidence rates., Results: The incidence of ORNJ was 8.8 % among the 240 LA-NPC patients analyzed. The ideal pre-CCRT PLT cutoff which divided the patients into two significantly different ORNJ rate groups was 285,000 cells/µL (PLT ≤ 285,000 cells/µL (N = 175) vs. PLT > 285,000 cells/µL (N = 65)). A comparison of the two PLT groups revealed that the incidence of ORNJ was substantially higher in patients with PLT > 285,000 cells/L than in those with PLT≤285,000 cells/L (26.2% vs. 2.3 %; P < 0.001). The presence of pre-CCRT ≥3 tooth extractions, any post-CCRT tooth extractions, mean mandibular dose ≥ 34.1 Gy, mandibular V57.5 Gy ≥ 34.7 %, and post-CCRT tooth extractions > 9 months after CCRT completion were also associated with significantly increased ORNJ rates. A multivariate Cox regression analysis demonstrated that each characteristic had an independent significance on ORNJ rates after CCRT., Conclusion: An affordable and easily accessible novel biomarker, PLT> 285,000 cells/L, may predict substantially higher ORNJ rates after definitive CCRT in individuals with LA-NPC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: Fibular free flap necrosis (FFFN) is the most common complication in patients with osteoradionecrosis (ORN) after mandibular reconstruction surgery. However, there are no effective forecasting tools at present. This research is aimed to establish and verify a nomogram model to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients., Methods: A total of 193 ORN patients with mandibular reconstruction using fibular free flap (150 cases in the model group and 43 cases in the validation group) were enrolled in this study. In the model group, the variables were optimized by lasso regression. Then the prediction model was established by binary logistic regression analysis, and the nomogram was drawn. The bootstrap self-sampling method was used for internal verification. Moreover, 43 cases in the validation group were used for external validation., Results: The results of lasso regression and binary logistic regression analysis showed that the radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and American society of anesthesiologists (ASA) III were the independent risk factors for FFFN after mandibular reconstruction surgery in ORNJ patients (P<0.05). Based on the above-mentioned risk factors, the nomogram model was established. The AUC values of the model group and the validation group were 0.936 and 0.964, respectively. The curve analysis showed that when the probability thresholds of the model group and the validation group were 5.699%∼98.229% and 0.413%∼99.721%, respectively. So the patient's clinical net profit rate was the highest., Conclusion: A nomogram combining the factors of radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and ASA III provided a comparatively effective way to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients, which has distinct applied clinical value., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Osteoradionecrosis (ORN) is a late secondary iatrogenic complication of external radiotherapy for cancers of the upper aero-digestive tract. Despite the systematization of intensity-modulated radiotherapy and its potential for preserving salivary secretion and limiting the dose delivered to the supporting bone, ORN remains a feared and frequent complication. The objective of this literature review was to provide an overview of the management of ORN and to determine the key points that would make it possible to improve patient care. The diagnosis of ORN requires to eliminate tumor recurrence then is based on clinical arguments and imaging by CT or Cone Beam evolving in a chronic mode (more than 3-6 months). The harmonization of its classifications aims to offer comprehensive and multidisciplinary care as early as possible. Primary prevention is based on pre-therapeutic oral and dental preparation, then associated with fluoroprophylaxis if salivary recovery is insufficient and requires supervision of invasive dental care and prosthetic rehabilitation. Semi-automatic contouring tools make it possible to identify doses delivered to dental sectors and guide dental care with personalized dosimetric mapping. Conservative medical treatment is offered at an early stage where innovative medical treatments, highlighted by early studies, could be of interest in the future. In the event of advanced ORN, a non-conservative treatment is then proposed and frequently consists of interruptive mandibulectomy associated with reconstruction by bony free flap, the conditions of implantation remaining to be defined with the support of prospective clinical trials., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: In the absence of previous research, we sought to assess the H-Index's predictive significance for radiation-induced trismus (RIT) and osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT)., Patients and Methods: The research comprised 295 LA-NPC patients who had C-CRT and pre- and post-C-CRT oral exams between June 2010 and December 2021. The H-Index was calculated using neutrophils, monocytes, lymphocytes, hemoglobin, and albumin measurements obtained on the first day of C-CRT. Patients were divided into three and two H-index groups, respectively, based on previously established cutoff values (1.5 and 3.5) and the cutoff value determined by our receiver operating characteristic (ROC) curve analysis. The primary objective was the presence of any significant connections between pretreatment H-Index groups and post-C-CRT RIT and ORNJ rates., Results: RIT and ORNJ was diagnosed in 46 (15.6%) and 13 (7.8%) patients, respectively. The original H-Index grouping could only categorize RIT and ORNJ risks at a cutoff value of 3.5, with no significant differences in RIT and ORNJ rates between groups with H-Index 1.5 and 1.5 to 3.5 (P < 0.05 for each). The ideal H-Index cutoff for both RIT and ORNJ rates was found to be 5.5 in ROC curve analysis, which divided the entire research population into two groups: H-Index ≤ 5.5 (N = 195) and H-Index > 5.5 (N = 110). Intergroup comparisons revealed that patients in the H-Index > 5.5 group had significantly higher rates of either RIT (31.8% vs. 5.9%; P < 0.001) or ORNJ (17.3% vs. 2.2%; P < 0.001) than their H-Index ≤ 5.5 counterparts. The results of the multivariate analysis showed that H-Index > 5.5 was independently linked to significantly higher RIT (P < 0.001) and ORNJ (P < 0.001) rates., Conclusion: Pre-C-CRT H-Index > 5.5 is associated with significantly increased RIT and ORNJ rates in LA-NPC patients receiving definitive C-CRT., (© 2023. The Author(s).)

Osteoradionecrosis (ORN) of the femoral head is an important issue for orthopedists and radiologists in clinical practice. With the rapid development of technological advances in radiation therapy and the improvement in cancer survival rates, the incidence of ORN is rising, and there is an unmet need for basic and clinical research. The pathogenesis of ORN is complex, and includes vascular injury, mesenchymal stem cell injury, bone loss, reactive oxygen species, radiation-induced fibrosis, and cell senescence. The diagnosis of ORN is challenging and requires multiple considerations, including exposure to ionizing radiation, clinical manifestations, and findings on physical examination and imaging. Differential diagnosis is essential, as clinical symptoms of ORN of the femoral head can resemble many other hip conditions. Hyperbaric oxygen therapy, total hip arthroplasty, and Girdlestone resection arthroplasty are effective treatments, each with their own advantages and disadvantages. The literature on ORN of the femoral head is incomplete and there is no criterion standard or clear consensus on management. Clinicians should gain a better and more comprehensive understanding on this disease to facilitate its early and better prevention, diagnosis, and treatment. This article aims to review the pathogenesis, diagnosis, and management of osteoradionecrosis of the femoral head.

Objective: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively., Study Design: Retrospective analysis of prospective cohort., Setting: Tertiary care Veterans Health Administration (VHA) medical center., Methods: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively analyzed this patient cohort and extracted clinical and pathologic data for 164 patients with SCC of the oral cavity, oropharynx, larynx, and hypopharynx who received definitive or adjuvant EBRT (2016-2020)., Results: Most patients were dentate and 80 % underwent dental extractions prior to EBRT of which 16 (16 %) had complications. The rate of ORN was 3.7 % for oral cavity SCC patients and 8.1 % for oropharyngeal SCC patients. Median time to ORN development was 156 days and the earliest case was detected at 127 days post EBRT completion. All ORN patients were dentate and underwent extraction prior to EBRT start., Conclusion: ORN development can occur early following EBRT in a Veteran population with significant comorbid conditions but overall rates are in line with the general population. Prospective tracking of HNSCC patients throughout the post-treatment surveillance period is critical to early detection of this devastating EBRT complication., Competing Interests: Declaration of competing interest Contents do not represent the views of the US Department of Veterans Affairs or the US Government. The authors report no conflicts of interest for the existing work., (Published by Elsevier Inc.)

Introduction: Radiotherapy (RT) combined with chemotherapy and surgery is the indicated treatment for head and neck cancers. Even with the advent of modern technological advances in RT and improved oral hygiene awareness, osteoradionecrosis (ORN) still remains as one of the most debilitating side effects of RT., Methodology: This is a retrospective review assessing 72 patients aged over 18 years of age reporting in the Dental Department, for treatment of ORN from April 2010 to July 2019. Each patient was clinically examined and treated according to standard protocol. The stage of ORN was noted at the diagnosis and at follow-up. The demographic data, the tumor characteristics, and the treatment of patients were evaluated using descriptive statistics., Results: At the time of diagnosis, 84.7% of the study population was found to have Epstein Type II chronic persistent nonprogressive lesions and 11.1% of the cohort had Type III active progressive lesions. Statistically significant correlation (P = 0.00) was found for ORN grade at diagnosis and at follow-up. ORN being a chronic pathology, stabilization of the disease was observed in 72.3% of cases. The resolution of the necrotic lesion and down staging of the disease was seen only in 2.8% of patients., Conclusion: ORN is mainly a chronic long standing pathology which is difficult to treat completely. Stabilization of symptoms and preventing further spread of the necrotic lesion should be the ultimate aim of the treatment to improve the quality of life of the patients., Competing Interests: None

Purpose: It is unclear whether certain bacteria initiate the development of inflammatory jaw conditions, or whether these diseases create a milieu for dysbiosis and secondary colonization of indigenous flora. At present, there are no comparative studies on the types of bacteria that colonize different inflammatory jaw conditions. Accordingly, this study aims to identify and compare the types of bacteria isolated in osteomyelitis, osteoradionecrosis, and MRONJ., Methods: This is a retrospective cohort study of patients diagnosed with inflammatory jaw conditions. The predictor variables were classification of bacteria as oral flora, categorized herein as resident bacteria, non-resident bacteria, or opportunistic organisms. The outcome variables were a diagnosis of osteomyelitis, osteoradionecrosis, and MRONJ. Covariates were age, sex, penicillin allergy, a diagnosis of diabetes and a history of smoking. Data analysis was performed using ANOVA and chi-squared tests., Results: A total of 105 patients with inflammatory jaw conditions were enrolled. The final sample size was 69 subjects of which 16 were diagnosed with osteomyelitis, 20 with osteoradionecrosis, and 33 with MRONJ. There was no difference in the frequency that resident bacteria were isolated. Non-resident bacteria, which included Staphylococcus and Enterococcus among others, were isolated more frequently at 75% in osteomyelitis compared to 60% in osteoradionecrosis and 48% in MRONJ cases. There is weak evidence of significant difference when comparing osteomyelitis and MRONJ cases (P = .08). Opportunistic organisms, which included Mycobacterium and Candida, were isolated more frequently in osteoradionecrosis at 30% compared to 12.5% in osteomyelitis and 12.12% in MRONJ cases. There is weak evidence of significant difference when comparing osteoradionecrosis and MRONJ cases (P = .1)., Conclusion: Non-resident bacteria including Staphylococcus and Enterococcus may be more frequently isolated in patients with osteomyelitis, while opportunistic organisms like Mycobacterium and Candida may be more frequently found in patients diagnosed with osteoradionecrosis., (Copyright © 2022 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Advanced mandibular osteoradionecrosis requires a segmental mandibulectomy with reconstruction using a free fibular flap. The conservation of labiomental sensation by lateralization of the inferior alveolar nerve is unusual during a segmental mandibulectomy. A protocol for the evaluation of labiomental sensation has been created for the clinical follow-up of operated patients. The patients included were patients with mandibular osteoradionecrosis who underwent a segmental mandibulectomy with reconstruction by free fibular flap and whose pre-operative labiomental sensation was preserved. All patients were followed-up by the same examiner and operated on by the same surgeon. The neuro-sensitive examination analyses the different forms of sensation at 1 week and at 12 months postoperatively. Between May 2017 and May 2018, 3 consecutive patients were assessed. The results of the labiomental sensitive evaluation using our evaluation protocol attest to the preservation of labiomental sensation. The operating time was increased by an average of 35 min per surgical procedure. The conservation and re-routing of the inferior alveolar nerve in segmental mandibulectomy with fibula free flap reconstruction in patients with osteoradionecrosis allows for the preservation of labiomental sensation, which improves the quality of life of patients. Our protocol can be used in all surgical procedure that affect sensibility., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives/hypothesis: To report the largest single-institution review of temporal bone osteoradionecrosis (TBORN), and characterize the disease's natural history, prognostic factors, management, and outcomes., Study Design: Retrospective chart review., Methods: Retrospective review was conducted to identify patients with TBORN. Pertinent data were extracted. Descriptive statistics were used to summarize patient, tumor, and treatment characteristics. Multivariable analyses were conducted to explore associations between these characteristics and time to TBORN diagnosis and risk of developing diffuse disease., Results: TBORN was identified in 145 temporal bones from 128 patients. Mean age at diagnosis was 62 years, and mean time to diagnosis after radiotherapy was 10 years. Age greater than 50 years was associated with earlier diagnosis. According to the Ramsden criteria, 76% of TBs had localized and 24% had diffuse disease at initial diagnosis; 37% had diffuse disease at last follow-up. On multivariable analysis, diabetes, three-dimensional conformal radiotherapy (3D-CRT), and periauricular skin malignancy were significant risk factors for developing diffuse disease. Localized disease was successfully managed with conservative measures, whereas surgery was often necessary for diffuse disease. When TBORN spread outside the mastoid or infratemporal fossa, conservative measures were always unsuccessful., Conclusions: TBORN occurs earlier in older patients. While diffuse disease is less common than localized disease, it occurs more frequently in patients with diabetes, history of 3D-CRT, and periauricular skin malignancies. Conservative management is appropriate for localized disease, while surgery is often necessary for diffuse disease. The prognostic factors identified helped propose a TBORN staging system and treatment guidelines which may improve patient risk stratification and disease management., Level of Evidence: 4 Laryngoscope, 131:2578-2585, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Tooth extraction post radiotherapy is one of the most important risk factors of osteoradionecrosis of the jawbones. The objective of this study was to determine the predictors of osteoradionecrosis (ORN) which were associated with a dental extraction post radiotherapy., Methods: A retrospective analysis of medical records and dental panoramic tomogram (DPT) of patients with a history of head and neck radiotherapy who underwent dental extraction between August 2005 to October 2019 was conducted., Results: Seventy-three patients fulfilled the inclusion criteria. 16 (21.9%) had ORN post dental extraction and 389 teeth were extracted. 33 sockets (8.5%) developed ORN. Univariate analyses showed significant associations with ORN for the following factors: tooth type, tooth pathology, surgical procedure, primary closure, target volume, total dose, timing of extraction post radiotherapy, bony changes at extraction site and visibility of lower and upper cortical line of mandibular canal. Using multivariate analysis, the odds of developing an ORN from a surgical procedure was 6.50 (CI 1.37-30.91, p = 0.02). Dental extraction of more than 5 years after radiotherapy and invisible upper cortical line of mandibular canal on the DPT have the odds of 0.06 (CI 0.01-0.25, p < 0.001) and 9.47 (CI 1.61-55.88, p = 0.01), respectively., Conclusion: Extraction more than 5 years after radiotherapy, surgical removal procedure and invisible upper cortical line of mandibular canal on the DPT were the predictors of ORN., (© 2021. The Author(s).)

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., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Osteoradionecrosis of the jaw (ORNJ) is one of the most devastating complications caused by radiation therapy in head and neck region, which is among the greatest challenges within stomatology. Treatment methods have been enriched because of expanded understanding of the pathogenic mechanism of ORNJ. Meanwhile, the diagnosis and treatment of ORNJ have been uniformed and improved gradually in China, making progress on several aspects from the establishment of classification and hierarchy system and publication of the consensus on ORNJ treatment. In the present comment, the author reviewed the history and current situation of diagnosis and treatment of ORNJ and prospected the hot topics of basic, translational and clinical research.

Objectives: Mandible osteoradionecrosis (ORN) is one of the most severe toxicities in patients with head and neck cancer (HNC) undergoing radiotherapy (RT). The existing literature focuses on the correlation of mandible ORN and clinical and dosimetric factors. This study proposes the use of machine learning (ML) methods as prediction models for mandible ORN incidence., Methods: A total of 96 patients (ORN incidence ratio of 1:1) treated between 2011 and 2015 were selected from the local HNC toxicity database. Demographic, clinical and dosimetric data (based on the mandible dose-volume histogram) were considered as model variables. Prediction accuracy (measured using a stratified fivefold nested cross-validation), sensitivity, specificity, precision and negative predictive value were used to evaluate the prediction performance of a multivariate logistic regression (LR) model, a support vector machine (SVM) model, a random forest (RF) model, an adaptive boosting (AdaBoost) model and an artificial neural network (ANN) model. The different models were compared based on their prediction accuracy and using the McNemar's hypothesis test., Results: The ANN model (77% accuracy), closely followed by the SVM (76%), AdaBoost (75%) and LR (75%) models, showed the highest overall prediction accuracy. The RF model (71%) showed the lowest prediction accuracy. However, based on the McNemar's test applied to all model pair combinations, no statistically significant difference between the models was found., Conclusion: Based on our results, we encourage the use of ML-based prediction models for ORN incidence as has already been done for other HNC toxicity end points., Advances in Knowledge: This research opens a new path towards personalised RT for HNC using ML to predict mandible ORN incidence.

Osteoradionecrosis is a relatively rare but potentially morbid and costly complication of radiation therapy for head and neck cancer. Multidisciplinary diagnosis and treatment are essential. Despite evidence guiding individual aspects of care for osteoradionecrosis, there is a lack of broad consensus on the overall diagnosis and management of this condition. This study comprehensively reviews the literature, with a focus on the past 10 years, to guide evaluation and treatment., (Published by Elsevier Inc.)

Background: Osteoradionecrosis (ORN) of the jaw is currently defined by the development of osteonecrosis in head/neck irradiated patients, regardless of lesion exposure. To diagnose medication-related osteonecrosis of the jaw (MRONJ), a history of any radiation therapy to the jaw region must be ruled out. The aim of this study was to assess the accuracy of current osteonecrosis criteria, while introducing new modifications for improved diagnosis and treatment., Methods: One hundred and forty-one necrotic lesions were analyzed from patients exposed to bone-modifying agents (BMAs) and/or received head and neck regional radiation therapy, where the maximal dose of radiation exposure to the jaw osteonecrosis site was calculated. Modified diagnostic criteria were used to reassess all cases and a comparison of outcomes was performed using Pearson's Chi-Square/Fisher's exact test., Results: Only in patients with primary head and neck carcinomas did the maximal mean radiation dose in the necrotic jaw site reach ranges associated with ORN formation (>40 Gy), with individual cases showing exposures as low as 0-2 Gy. Based on the modified diagnostic criteria almost 2/3 of the necrotic cases diagnosed as ORN should be diagnosed as MRONJ., Conclusions: ORN diagnosis should only be considered in cases of radiation exposure >40 Gy to prevent misdiagnosis and suboptimal treatment. A modified criterion for MRONJ diagnosis is recommended where radiation exposure <40 Gy in the necrotic site is included. In cases with exposure >40 Gy and BMA administration, an additional modification to diagnostic criteria of 'medication- and radiation-related osteonecrosis of the jaw', should be used., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Osteoradionecrosis of the jaws (ORNJ) is a late complication of head and neck irradiation estimated at around 3% of irradiated patients. The PENTO protocol (Pentoxyfilline and Tocopherol), with the eventual adjunction of Clodronate (PENTOCLO), showed interesting results even in advanced ORNJ. The current literature does not describe the long-term outcomes and particularly after the completion of the protocol. The PENTO or PENTOCLO protocol should be prescribed as a life-long treatment or the outcome should be monitored at least as long as the duration of the protocol after its end., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Bony free flaps are used to reconstruct head and neck cancer defects. The most commonly used flaps are the free fibula flap and the deep circumflex iliac artery (DCIA) flap. Radiotherapy may be given post-operatively to prevent cancer recurrence. This radiotherapy can, however, destroy the bone; a complication termed osteoradionecrosis (ORN). Although there have been studies comparing free fibula and DCIA flaps in terms of success rates and complications, few have assessed the incidence of ORN in both groups., Methods: A retrospective cohort study was conducted involving patients from Royal Melbourne Hospital and St Vincent's Hospital Melbourne who had either a free fibula or DCIA flap for head and neck cancer reconstruction in the past 10 years. Data collected included demographic, operative, and postoperative data. Analysis was performed using Statistical Package for Social Sciences and Microsoft Excel, utilising t-tests, chi-square tests and logistic regression analyses., Results: A total of 154 patients were identified. Of these patients, 127 had free fibula flaps and 27 had free DCIA flaps. Twelve patients had ORN post-op, 10 had free fibula flaps, and 2 had free DCIA flaps. No statistically significant difference was found between the ORN rates in free fibula flaps and free DCIA flaps., Conclusion: Rates of ORN incidence should not be a major consideration in preoperative planning of free flaps for mandibular reconstruction as both fibula and DCIA free flaps are comparable., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

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., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: Despite recent advances in radiotherapy, osteoradionecrosis (ORN) remains a common and difficult complication of radiation therapy in head and neck cancer patients. Available treatment options are complementary to its complex pathophysiology and the currently available theories of ORN development. The efficacy of hyperbaric oxygen therapy has recently been questioned, and therapies targeting the fibroatrophic process have become a focus of ORN treatment. The objective of this review is to evaluate the literature regarding ORN of the mandible, with a focus on available treatment options., Recent Findings: The recently proposed fibroatrophic theory has challenged the traditional hypovascular-hypoxic-hypocellular theory as the mechanism of ORN. Medical management targeting this fibroatrophic process offers promising results, but has yet to be confirmed with robust clinical trials. The routine use of hyperbaric oxygen therapy is not substantiated in the literature, but may be justified for select patients. Systemic steroids may also have a role, though data are limited., Summary: The fibroatrophic process has gained acceptance as a main mechanism of ORN. No gold standard treatment or consensus guidelines exist, though a combination of therapeutic strategies should be considered, taking into account the severity of disease and individual patient characteristics.

Purpose: The appearance of osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) is similar, but clinically important differences between ORN and MRONJ exist. The aim of this study was to compare the clinical data between ORN and MRONJ and to reveal the critical differences between these diseases., Methods: We retrospectively reviewed the epidemiological data, clinical findings, and treatment in 27 ORN and 61 MRONJ patients. Radiographic signs before the initiation of treatment were also assessed., Results: The median age (P = 0.0474) and the ratio of female to male patients (P < 0.0001) were significantly higher in MRONJ patients. There were significantly more MRONJ patients who reported a history of pain when compared with ORN patients (P = 0.0263). As an aetiological factor, tooth extraction was significantly more relevant to MRONJ than ORN (P = 0.0352). When assessing the radiographic signs on computed tomographic images, periosteal reaction was found only in MRONJ patients (P = 0.0158). Minimal debridement was performed significantly more frequently for MRONJ (P = 0.0093), and by contrast, surgical resection was performed more frequently for ORN (P = 0.0002)., Conclusions: Understanding the clinical and underlying pathological differences between ORN and MRONJ probably contributes to the selection of appropriate treatment for each patient.

It is largely known that some oral diseases can be diagnosed based upon their clinical manifestation combined with the patient's medical history and generally not depending on examination. This is the case of some bone diseases such as osteoradionecrosis of the jaw (ORNJ), osteomyelitis of the jaw (OMJ), and medication-related osteonecrosis of the jaw (MRONJ). The present study aimed to analyze the histopathological features of these specific bone diseases in order to evaluate similarities and differences. Forty-four bone specimens resected from each bone disease (22 cases of ORNJ, 6 cases of OMJ, and 16 cases of MRONJ) were analyzed by two experienced oral pathologists without prior knowledge of the diagnosis, considering bone tissue condition, inflammation, vascularization, and the presence of microorganisms. In addition, the examiners formulated a diagnostic hypothesis for each specimen. Many histopathological similarities were found among the diseases, especially considering the presence of necrotic bone, inflammation, and microorganisms. Statistically significant differences were detected in empty bone lacunae, which was decreased in ORN (p = 0.042), and considering neutrophil count, which was low in the MRONJ group (p ≤ 0.001). The Kappa coefficient was calculated and agreement was detected based on the histopathological parameters, but not for diagnostic suggestion (p=0.23). In conclusion, histopathological aspects of ORNJ, OMJ, and MRONJ do not permit a conclusive diagnosis, emphasizing the necessity of a detailed clinical report.

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life-long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Microsurgical reconstructive techniques have revolutionized the treatment of large head and neck defects. These defects were once forever life altering because of the considerable morbidity to both the form and function of the patient. As time has progressed, microsurgical technique has improved dramatically and has become institutionalized in our training programs. Free flap outcomes in head and neck reconstruction have improved dramatically, and optimization of these outcomes is now key. One overlooked area has been neurosensory reconstruction. In our practice we have focused on this detail, which has proved to be quite important to the patient. This case report details one such case in which a mandibular resection was performed to treat osteoradionecrosis. We, as the reconstructive team, elected to perform a double-barrel fibular free flap procedure with simultaneous inferior alveolar nerve reconstruction using a 70-cm processed nerve allograft. Normal neurosensory function returned in this patient. As the state of the art advances with continued successful osseous and soft tissue reconstruction in the head and neck, we propose concomitant neurosensory functional reconstruction always be considered., (Published by Elsevier Inc.)

Orbital osteoradionecrosis is a rare complication of orbital radiotherapy. It can occur in children, associated with orbital radiotherapy treatment, mimicking recurrence of malignancy and infection. In children, it is most likely to be associated with orbital malignancies treated with higher doses of radiotherapy, such as recurrent orbital rhabdomyosarcoma.

Background: Preradiotherapy dental extractions often form a part of the management plan for patients treated with radiotherapy for head and neck cancers in order to prevent complications, such as osteoradionecrosis. There is contention about whether these extractions should be performed and the timing of such extractions. The purpose of this study was to determine if pre-RT extractions were associated with the development of osteoradionecrosis of the jaws., Methods: Retrospective data on patients treated with RT for oropharyngeal cancer were pooled with a cross-sectional survey., Results: Pre-radiotherapy dental extractions were associated with a statistically significant increase in the risk of developing ORN., Conclusion: Pre-radiotherapy dental extractions do not protect against the development of osteoradionecrosis. © 2016 Wiley Periodicals, Inc. Head Neck 39: 128-132, 2017., (© 2016 Wiley Periodicals, Inc.)

A cancer patient delays needed dental care before radiation treatment and develops a painful, incurable disease., (Project HOPE—The People-to-People Health Foundation, Inc.)

Purpose: Osteoradionecrosis is a complication of head and neck radiotherapy, with a difficult resolution and no well-established treatment. The disease progression can cause important loss on patient's quality of life after cancer treatment. The options for treatment are limited and include clinical monitoring, prescription, or surgical procedures. As an alternative for bone necrosis treatment, a combination of drugs, pentoxifylline and tocopherol, can be used. Studies have shown that this combination significantly reduces chronic radiotherapy damage. The article reports successful treatment with this prescription protocol., Methods: We report three cases of patients referred to the Service of Oral and Maxillofacial Surgery at Erasto Gaertner Hospital, in Curitiba, Brazil. They were submitted to radiotherapy for the treatment of malignant head and neck tumors and later developed osteoradionecrosis. They were treated with the combination pentoxifylline and tocopherol., Results: All patients achieved complete remission in less than 1 year, with complete healing of bone exposure and without clinical symptoms., Conclusions: This results show that this combination of drugs is beneficial in cases of bone necrosis induced by radiation, avoiding more aggressive treatments and reducing morbidity.

Background/objective: Osteoradionecrosis is a rare, but feared, late complication after radiotherapy of the head and neck region. Its localization to the sternoclavicular joint has rarely been described so far., Materials and Methods: Data are from a retrospective study that included all patients admitted to the authors' clinic with osteoradionecrosis of the sternoclavicular joint during the last 5 years. Therapy and outcome were evaluated and compared to the established literature., Results: Over the past 5 years, 2 patients have been treated for pronounced osteoradionecrosis of the sternoclavicular joint. Both patients had received postoperative radiotherapy for tumors of the neck and chest, and presented with lesions involving the clavicle and the sternum. After eliminating the suspicion of recurrent cancer, both radiologic imaging and histopathologic evaluation confirmed an infection. Aggressive debridement with partial claviculectomy, partial sternectomy, and reconstruction using a pectoralis flap lead to the patients' recovery., Conclusion: Osteoradionecrosis does not only affect bone, but also the surrounding soft tissue. Due to the changes associated with previous radiotherapy, osteoradionecrosis should always be treated with radical debridement of the infected area, followed by flap reconstruction using unaffected tissue. The prognosis for the patient is then good.

Osteonecrosis of the jaw is a major public health concern throughout the world. Use of radiotherapy for head and neck cancer and bone antiresorptives and antiangiogenic agents have increased its incidence. Medication-related osteonecrosis of the jaw is more common relative to other types of osteonecrosis. Osteoradionecrosis occurs despite better treatment planning and shielding to minimize collateral damage to bone. Other related necrotic lesions are secondary to usage of recreational drugs and steroids. This article provides comprehensive information about these different types of bone necrosis; provides the readers with radiographic diagnostic criteria and updates on current theories on pathophysiology of osteonecrosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Endoscopic endonasal techniques have recently become the method of choice in dealing with cerebrospinal fluid leak involving the anterior cranial fossa. However, most surgeons prefer an intracranial approach when leaks involve the middle cranial fossa. This case report illustrates the possibilities of using endoscopic techniques for cerebrospinal fluid leaks involving the middle fossa., Case Report: A 37-year-old male patient presented with multiple areas of cranial defect with cerebrospinal fluid leak due to osteoradionecrosis following radiation for nasopharyngeal carcinoma 4 years earlier. Clinical examination showed involvement of all cranial nerves except the IInd and XIth nerves on the left side. A prior attempt to repair the cerebrospinal fluid leak with craniotomy was not successful., Conclusion: This case demonstrates the successful endoscopic repair of a large cranial defect with cerebrospinal fluid leak.

Background: Radiation therapy plays an essential part in modern treatment regimes of musculoskeletal tumors. Nevertheless damage to the surrounding tissue does occur inevitably. Postradiogenic changes of bone are associated with decreased stability and an increased fracture rate. The orthopedic surgeon therefore faces a challenging situation with altered bone metabolism, changes in perfusion and soft tissue problems., Patients/material and Methods: We present 3 cases of radiation induced fractures during the treatment of soft tissue tumors, all of which received radiation doses of > 58 Gy. All fractures occurred over 1 year after the exposure to radiation in otherwise uneventful follow ups., Results: Postoperative follow up showed fracture healing or in the case of the arthroplasty, osseous integration without further complications., Conclusions: Radiation doses of ≥ 58 Gy are a major risk factor for pathological fractures in long bones. Regardless of their low incidence, fracture rates between 1,2 and 6,4 % prove their importance. Local tumor control has therefore to be weighed against the resulting decrease in bone quality and stability. Treatment options should always take into consideration the increased risk for complications such as infection, pseudarthroses and wound healing disorders. Our results show that substitution of vitamin D and calcium as well as the the use of reamed intramedullary implants benefits the outcome.

Background: Radiation therapy is a commonly used treatment in head and neck oncology, whether used alone or as an adjunct to other treatments. Osteoradionecrosis and radiation-induced malignancy are both rare, late complications of radiation therapy., Methods: This paper describes a case of radiation-induced sarcoma of the mandible initially presenting as osteoradionecrosis. In addition, the literature on the identification and treatment of these entities is reviewed., Results: The patient underwent excision and reconstruction of the presumed osteoradionecrosis. Final pathology demonstrated radiation-induced sarcoma. The patient suffered tumour recurrence at seven months post-operatively., Conclusion: When evaluating a patient with osteoradionecrosis, clinicians should be cognisant of the risk of malignancy. This paper describes the first case of radiation-induced sarcoma presenting as osteoradionecrosis. Primary treatment of radiation-induced sarcoma is wide surgical extirpation, with a very limited role for chemotherapy. Overall survival for this entity is poor.

Osteoradionecrosis (ORN) is one of the most serious complications of oral and nasopharyngeal malignant neoplasms after radiotherapy. The incidence of mandibular ORN is significantly higher than that of maxilla. A radical surgical intervention such as mandibulectomy for advanced ORN is appropriate and effective to relieve pain and control infection. However, recovery of functionality and aesthetics is usually not the primary purpose of the one-stage radical surgery. Some patients often need a 2-stage operation owing to the bone defect, scar contracture, or recurrence. Although free flap has been proven as a reliable way to repair the complex maxillofacial defects, it is still a great challenge for surgeons to reconstruct the secondary complex mandibular ORN defects. Here, we report a case of secondary composite mandibular ORN reconstruction using the preoperative 3-dimensional biomodel planning and flowthrough radial forearm flap for free fibula osteocutaneous flap.

Background: Hyperbaric oxygen (HBO) is used as an adjunctive therapy for a variety of indications. However, there is a lack of high-quality research evaluating HBO treatment outcomes for different indications available in the current literature., Methods: We retrospectively reviewed all patients who underwent HBO therapy at a single hyperbaric center from January 2010 to December 2013 using predetermined criteria to analyze successful, improved, or failed treatment outcomes for the following indications: chronic refractory osteomyelitis, diabetic foot ulcer, failed flap or skin graft, osteoradionecrosis, soft tissue radiation necrosis, and multiple coexisting indications., Results: Among the included 181 patients treated with adjunctive HBO at our center, 81.8% had either successful or improved treatment outcomes. A successful or improved outcome was observed in 82.6% of patients treated for chronic refractory osteomyelitis (n = 23), 74.1% for diabetic foot ulcer (n = 27), 75.7% for failed flap or skin graft (n = 33), 95.7% for osteoradionecrosis (n = 23), 88.1% for soft tissue radiation necrosis (n = 42), and 72.4% for multiple coexisting indications (n = 29). Among 4 patients treated for other indications, 100% of the cases were either successful or improved., Conclusions: This study has provided a comprehensive outcome survey of using HBO for the previously mentioned indications at our center. It supplements the literature with more evidence to support the consideration of HBO in different indications., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Head and neck malignancies constitute a major cause of morbidity and mortality all over the world. Radiotherapy plays a pivotal role in the management of these tumours; however, it has associated complications, with mandibular osteoradionecrosis (ORN) being one of the gravest orofacial complications. Early diagnosis, extent evaluation, and detection of complications of ORN are imperative for instituting an appropriate management protocol. ORN can closely mimic tumour recurrence, the differentiation of which has obvious clinical implications. The purpose of the present review is to acquaint the radiologist with the imaging features of mandibular ORN and the ways to differentiate ORN from tumour recurrence., (Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Osteoradionecrosis of the hyoid bone is a rare complication of therapeutic irradiation performed for head and neck cancer. In this article, we present a 52-year-old male patient who admitted with severe odynophagia following chemo-radiotherapy administration for tonsil carcinoma. Fluorine-18-fluorodeoxy-glucose positron emission tomography-computed tomography revealed a metabolic activity in hyoid bone. The pathological findings were consistent with fungal infection and hyoid bone necrosis. Hyoid osteoradionecrosis should be kept in mind in patients with intractable dysphagia following irradiation for head and neck tumors.

Objective: To study MRI and positron emission tomography (PET)/CT imaging of osteoradionecrosis (ORN) of the subaxial cervical spine, a serious long-term complication of radiation therapy (RT) for head and neck cancers that can lead to pain, vertebral instability, myelopathy and cord compression., Methods: This is a single-institution retrospective review of patients diagnosed and treated for ORN of the subaxial cervical spine following surgery and radiation for head and neck cancer., Results: We report PET/CT imaging and MRI for four patients, each with extensive treatment for recurrent head and neck cancer. Osteomyelitis (OM) and discitis are the end-stage manifestations of ORN of the subaxial spine., Conclusion: ORN of the subaxial spine has variable imaging appearance and needs to be differentiated from recurrent or metastatic disease. Surgical violation of the posterior pharyngeal wall on top of the compromised vasculature in patients treated heavily with RT may pre-dispose the subaxial cervical vertebrae to ORN, with possible resultant OM and discitis. MRI and PET/CT imaging are complimentary in this setting. PET/CT images may be misinterpreted in view of the history of head and neck cancer. MRI should be utilized for definitive diagnosis of OM and discitis in view of its imaging specificity., Advances in Knowledge: We identify the end-stage manifestation of ORN in the sub-axial spine on PET/CT and MRI to facilitate its correct diagnosis.

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.

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.

Purpose: This retrospective analysis was performed to evaluate osteolytic bone lesions of breast cancer in the thoracic and lumbar spine after radiotherapy (RT) in terms of stability using a validated scoring system., Methods: The stability of 157 osteolytic metastases, treated from January 2000 to January 2012, in 115 patients with breast cancer was evaluated retrospectively using the Taneichi score. Predictive factors for stability were analyzed and survival rates were calculated., Results: Eighty-five (54%) lesions were classified as unstable prior to RT. After 3 and 6 months, 109 (70%) and 124 (79%) lesions, respectively, were classified as stable. Thirty fractures were detected prior to RT, and after RT seven cases (4.5%) with pathologic fractures were found within 6 months. None of the examined predictive factors showed significant correlation with stability 6 months after RT. After a median follow-up of 16.7 months, Kaplan-Meier estimates revealed an overall survival of 83% after 5 years., Conclusion: The majority of patients showed an improved or unchanged stability of the involved vertebral bodies after 6 months. The patients showed only minor cancer-related morbidity during follow-up and reached comparably high survival rates.