Timing of development of osteoradionecrosis post head and neck radiotherapy: does a safe time interval exist for dental extraction?

INTRODUCTION: Risk factors for developing osteoradionecrosis (ORN) are well known, but less is known about factors influencing the interval between radiotherapy and the onset of ORN. Also, it is unknown whether there is any specific period post-radiotherapy with a reduced probability of ORN when irradiated teeth require extraction. PURPOSE: The primary aim of this study was to identify factors influencing the interval in developing ORN in the following subgroups of patients: (1) patients who spontaneously developed ORN, (2) surgical-intervention-related ORN with a particular focus on patients after mandibulectomy. The secondary aim was to attempt to identify a possible time for safer dental intervention after primary treatment. MATERIALS AND METHODS: The authors retrospectively analysed 1608 head and neck cancer (HNC) patients treated in a single centre. Time intervals were measured from the end of radiotherapy to the development of ORN and further analysed in the subgroups listed above. RESULTS: In all, 141 patients (8.8%) developed intra-oral ORN. Median time from radiotherapy to ORN development in the whole cohort was 9 months. Median interval for spontaneous ORN was 8 months, 6.5 months for intervention-related ORN, and 15 months for patients post-mandibulectomy. In patients who required dental extraction preradiotherapy, median interval of ORN onset was 5 months. CONCLUSION: In our study, a slightly higher proportion of patients with intervention developed ORN earlier in comparison with spontaneous ORN. The period from 12-18 months after radiotherapy was identified as having the highest probability of developing ORN in patients after mandibulectomy. A time for safer dental intervention after primary treatment was not identified.

Bridging the gap - Establishing a dental-oncology service in a cancer centre.

Dental disease remains the most common non-communicable disease worldwide. It predisposes patients to significant morbidities following bone modifying agents or radiation therapy to the head and neck. Preventative dental regimes effectively reduce the risk of both medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) in these patients. Co-ordination of routine dental care as a component of mainstream oncology treatment optimises long term outcomes for oncology patients. This case series offers insights into patient, institutional and social difficulties that challenge the dental-oncology interface. These obstacles and subsequent resolutions experienced whilst establishing a dental-oncology service in a cancer centre highlight the importance of effective multidisciplinary lead care for oncology patients. It reinforces the need for structured, supported dental pathways for these oncology patients.

Risk factors of post-irradiation carotid blowout syndrome in patients with nasopharyngeal carcinoma.

PURPOSE: Carotid blowout syndrome (CBS) is a severe complication of radiotherapy in patients with nasopharyngeal carcinoma (NPC). This study is aimed at analyzing risk factors of post-irradiation CBS in patients with NPC. METHODS: We retrospectively analyzed 660 patients with NPC between 2006 and 2019. The patients were divided into those with and without CBS, and their characteristics and outcomes were evaluated. Independent predictors of CBS were determined by multivariate logistic regression analysis. RESULTS: We identified 17 NPC patients with CBS in our study. In multivariate logistic regression analysis, lower body mass index (BMI) (P = 0.018), tumor encasement (P = 0.039), local recurrence (P = 0.006), and skull base osteoradionecrosis (P < 0.001) were independent predictors of CBS, and a predictive equation model was established. Log-rank test revealed that patients with low BMI, tumor encasement of carotid vessels, local recurrence, and skull base osteoradionecrosis all exhibited shorter CBS-free time (all P < 0.001). CONCLUSION: We demonstrated that low BMI, tumor encasement, local recurrence, and skull base osteoradionecrosis were independent predictors for CBS in NPC patients. Physicians can use these factors for the early detection and prevention of CBS.

Efficacy of adjunctive modalities during tooth extraction for the prevention of osteoradionecrosis: A systematic review and meta-analysis.

BACKGROUND: Jaw osteoradionecrosis (ORN) is a complication in patients with previous head and neck radiotherapy. Its incidence increases with dental extractions. Hence, this review aimed to evaluate the efficacy of adjunctive treatment modalities undertaken at the time of extraction in previous head and neck radiotherapy patients in preventing ORN. METHODS: A systematic review was conducted, where studies with data on ORN incidence after extraction with or without adjunctive interventions were included. Meta-analyses were conducted to estimate the pooled prevalence of ORN per intervention and the pooled odds ratio for incidence of ORN between interventions. RESULTS: In total, 1520 patients in 29 studies were included. Interventions identified were hyperbaric oxygen (HBO), pentoxifylline-tocopherol (PENTO), antibiotics (ABX), platelet-rich fibrin and photobiomodulation. The pooled prevalence of ORN for HBO (4.6%), PENTO (3.4%) and ABX (3.8%) was significantly lower than the Control (17.6%). For studies with direct comparisons between groups, HBO had lower but not significant odds of developing ORN than the Control (OR 0.27) and ABX (OR 0.57). CONCLUSIONS: HBO, PENTO and ABX may reduce the incidence of ORN compared to no intervention. Given that all three have similar incidences of ORN, ABX may be the most cost-effective and accessible adjunctive modality.

Risk Factors for Infection Recurrence After Surgical Resection of Advanced Stage Osteonecrosis of the Mandible.

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.

Microstructural changes in the irradiated and osteoradionecrotic bone: a SEM study.

Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing risk of infection and osteoradionecrosis. This study aims to investigate the radiotherapy-induced microstructural changes in the human mandible by scanning electron microscopy (SEM). Mandibular cortical bone biopsies were obtained from control, irradiated, and patients with osteoradionecrosis (ORN). Bone samples were prepared for light microscopy and SEM. The SEM images were analyzed for the number of osteons, number of Haversian canal (HC), diameter of osteon (D.O), the diameter of HC (D.HC), osteonal wall thickness (O.W.Th), number of osteocytes, and number of osteocytic dendrites. The number of osteons, D.O, D.HC, O.W.Th, the number of osteocytes, and osteocytic dendrites were significantly decreased in both irradiated and ORN compared to controls (p < .05). The number of HCs decreased in irradiated and ORN bone compared to the control group. However, this was statistically not significant. The deleterious effect of radiation continues gradually altering the bone quality, structure, cellularity, and vascularity in the long term (>5 years mean radiation biopsy interval). The underlying microscopic damage in bone increases its susceptibility and contributes further to radiation-induced bone changes or even ORN.

An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications. METHODS: A 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary-CUP) was admitted with a right-sided epi-/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction. RESULTS: Due to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient's airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief. CONCLUSIONS: The present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

Hyperbaric oxygen therapy as an adjunct treatment of periodontitis, MRONJ, and ONJ: a systematic literature review.

OBJECTIVE: To review the available prospective literature on hyperbaric oxygen (HBO) therapy for periodontal conditions. MATERIALS AND METHODS: A comprehensive electronic and manual search was performed to identify clinical studies on adult patients who underwent hyperbaric oxygen therapy for periodontal treatments. A systematic literature search was conducted in PubMed, Cochrane, and Dentistry Oral Sciences Source databases. RESULTS: Fourteen articles were included in the final literature review, of which five were RCTs and 11 were prospective clinical studies. Four studies discussed HBO as an adjunct to nonsurgical treatment of periodontitis, eight reported on HBO and osteoradionecrosis, and one examined HBO in bisphosphonate-related necrosis of the jaws. CONCLUSIONS: HBO has shown superior efficacy compared to antibiotics as a prophylactic measure in preventing osteoradionecrosis (ORN) in patients with a history of high mandibular irradiation. Clinicians should consider referring such patients for HBO therapy before and after tooth extractions. However, for the surgical excision of existing ORN lesions, HBO therapy does not yield significant benefits but does not negatively impact outcomes either. Regarding the treatment of periodontitis patients, the variability among studies prevents definitive conclusions. HBO therapy as an adjunct to SRP in periodontitis treatment produces mixed results. CLINICAL RELEVANCE: This study's clinical relevance lies in its exploration of the potential benefits of HBO for periodontal conditions. Also, it provides clinicians with insights into when and how to integrate HBO therapy into their treatment approaches, particularly for patients with a history of irradiation and those undergoing complex dental procedures.

Comparing the Outcomes of Osteocutaneous Radial Forearm and Fibula Free Flaps in the Reconstruction of Mandibular Osteoradionecrosis.

BACKGROUND: This study compares the outcomes of osteocutaneous radial forearm free flap (OC-RFFF) and fibula free flap (FFF) reconstruction of mandibular osteoradionecrosis (ORN). METHODS: Retrospective review of patients undergoing OC-RFFF/FFF reconstruction for mandible ORN between 2005 and 2020 at a tertiary center. Patient characteristics, postoperative complications, and functional outcomes were evaluated using chi-squared and logistic regression analysis. RESULTS: Fifty-six patients were included (OC-RFFF: 38; FFF: 18). Significantly more OC-RFFF patients had lateral mandible defects (94% vs. 61%, p = 0.0014). There were significantly more patients with exposed intraoral bone in the OC-RFFF group (23% vs. 0% p = 0.02), but no significant differences in hardware complications or flap failure. Donor site partial skin graft loss was more common in the FFF group (22% vs. 2.6%, p = 0.016), but no other significant differences in donor site morbidity were seen. Bivariable analysis showed no impact of flap type, tobacco/alcohol use, diabetes, or hypothyroidism on postoperative complications. Sixty percent of OC-RFFF, and 67% of FFF, patients resumed an oral diet after surgery. Oral diet was not impacted by flap type (OR = 0.769, 95% CI = 0.201-2.706, p = 0.688). CONCLUSION: The OC-RFFF is an acceptable option in the reconstruction of ORN involving the lateral mandible, though there is increased risk of bone exposure. These findings can help guide surgeon selection of microvascular free flap donor sites and appropriate patient counseling.

Medial Femoral Condyle Periosteal Free Flap for Bone Coverage Following Debridement of Intermediate-Stage Osteoradionecrosis of the Jaw.

STUDY DESIGN: Case report. Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. The progression of ORN can lead to loss of bone, teeth, soft tissue necrosis, pathologic fracture, and oro-cutaneous fistula. Reconstructive surgery has mostly been reserved for late-stage disease where segmental resections are frequently necessary. Evidence is emerging to support earlier treatment in the form of debridement in combination with soft tissue free flaps for intermediate-stage ORN. The authors present a case of a 76-year-old male with persistent Notani 2 ORN of the mandible, treated with surgical removal of all remaining mandibular teeth, transoral debridement of all necrotic mandibular bone, and bone coverage with a left medial femoral condyle (MFC) periosteal free flap based on the descending genicular artery. Treatment was uneventful both intraoperatively and postoperatively. Since surgery (15 mo) the patient has remained free from clinical and radiologic signs of ORN. The MFP periosteal free flap provided an excellent result with minimal surgical complexity and morbidity in this case. Such treatment at an intermediate stage likely results in a reduction in segmental resections, less donor site morbidity, less operative time, less overall treatment time, and possibly fewer postoperative complications compared with the status quo.

Application of Submandibular Gland Flap in the Repair of Postoperative Defects in Clinical Stage III Osteoradionecrosis of the Jaw.

OBJECTIVE: Investigating the clinical efficacy of submandibular gland flap repair for postoperative defects in clinical stage III osteoradionecrosis of the jaw was the objective of this study. METHODS: The study included 3 patients who declined vascularized fibula flap repair for mandibular defects and 1 patient who was not fit for mandibular reconstruction due to poor systemic condition. The postoperative defects were successfully repaired using a submandibular gland flap, and the clinical outcomes were monitored. RESULTS: After a 6 to 8 month postoperative follow-up, all patients exhibited good wound healing, no signs of infection, no pain, and normal submandibular gland function. CONCLUSION: The study demonstrated that submandibular gland flap repair is an effective and feasible approach for addressing postoperative defects in clinical stage III osteoradionecrosis of the jaw, yielding satisfactory clinical results.

Long-term follow-up of osteoradionecrosis of the mandible.

AIM: Investigating the prevalence of mandibular ORN in a single Swedish Oncology Center. METHODS: A total of 450 patients, treated with radiotherapy for squamous cell carcinoma in the oropharynx between 2004 and 2014 were included. Three different techniques of radiotherapy were studied. ORN diagnosis was set when clinical signs according to Marx were observed, or if radiological signs were staged according to Schwartz and Kagan. RESULTS: Using the staging system, 90 patients (20%) were diagnosed with ORN. The mean age of the ORN patients was 56.6 years, the older the patient the lower the risk of developing ORN (p = .01). The risk of developing ORN for patients receiving Intensity Modulated Radiotherapy was lower compared to patients treated with the other techniques in the multivariable analysis. Brachytherapy significantly increases the risk of ORN. The risk of ORN increased by 8% each year after radiation (p = .04). The mean time to the ORN diagnosis was 3.9 years. In the multivariate analysis, the risk of ORN increased by 13% each year after radiation (p = .0013). CONCLUSION: The mean radiation dose was of greater importance for the risk of ORN than the maximum dose. Elderly people with oropharyngeal cancer were less prone to develop ORN.

Oral microbiota may affect osteoradionecrosis following radiotherapy for head and neck cancer.

BACKGROUND: Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer (HNC). However, its etiology and pathogenesis have not been completely elucidated. Recent studies suggest the involvement of the oral microbiota in the development of ORN. The aim of this study was to assess the correlation between oral microbiota and the extent of bone resorption in ORN patients. MATERIALS AND METHODS: Thirty patients who received high-dose radiotherapy for HNC were enrolled. Tissue specimens were collected from the unaffected and affected sides. The diversity, species differences and marker species of the oral microbial community were determined by 16 S rRNA sequencing and bioinformatics analysis. RESULTS: The ORN group had greater microbial abundance and species diversity. The relative abundance of f_Prevotellaceaeand, f_Fusobacteriaceae, f_Porphyromonadaceae, f_Actinomycetaceae, f_Staphylococcaceae, g_Prevotella, g_Staphylococcus, s_Endodontalis and s_Intermedia were particular;y increased in ORN, suggesting a potential association between the oral microbiota and ORN. Furthermore, g_Prevotella, g_Streptococcus, s_parvula and s_mucilaginosa were identified as potential diagnostic and prognostic biomarkers of ORN. Association network analysis also suggested an overall imbalance in species diversity and ecological diversity in the oral microbiota of ORN patients. In addition, pathway analysis indicated that the dominant microbiota in ORN may disrupt bone regeneration by regulating specific metabolic pathways that increase osteoclastic activity. CONCLUSION: Radiation-induced ORN is associated with significant changes in the oral microbiota, and the latter may play a potential role in the etiopathology of post-radiation ORN. The exact mechanisms through which the oral microbiota influence osteogenesis and osteoclastogenesis remain to be elucidated.

Immune microenvironment: novel perspectives on bone regeneration disorder in osteoradionecrosis of the jaws.

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components.

Valero's host index is useful in predicting radiation-induced trismus and osteoradionecrosis of the jaw risks in locally advanced nasopharyngeal carcinoma patients.

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.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

Review of the Pathogenesis, Diagnosis, and Management of Osteoradionecrosis of the Femoral Head.

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.

Pentoxifylline and tocopherol (vitamin E) with/without clodronate for the management of osteoradionecrosis: A scoping review.

BACKGROUND: Treatment of osteoradionecrosis (ORN) is not a straightforward task, and it is unpredictable. However, a combination of pentoxifylline; an antioxidant drug, and tocopherol (vitamin E) works as a potent antifibrotic agent and have shown recently both significant and impressive results. AIMS: This scoping review aims to investigate the most prescribed regimen of pentoxifylline and tocopherol with/without clodronate for the management of ORN. METHODS: Ovid MEDLINE and EMBASE databases were used to retrieve eligible studies using planned search keywords. PROSPERO and Cohcarne library were also searched for ongoing or published systematic reviews, respectively. Included articles were grouped thematically according to the type of studies and accordingly they were summarized. RESULTS: A total of 27 articles met the inclusion criteria and included in the data analyses. All the included articles were published between 1997 and 2020. Of these 27 included studies, two were randomized control trials, two were systematic reviews, six were retrospective studies, five were observational studies, seven were narrative reviews, four were case reports, and lastly one was an in-vitro study. CONCLUSIONS: Treatment by PENTO (800 mg of pentoxifylline + 1000 IU of tocopherol) once daily for an early established ORN or PENTOCLO (PENTO regimen + 1600 mg of clodronate) once daily for the refractory/severe cases of ORN appears to be the most prescribed regimen used for the treatment of ORN using these drugs. These drugs appear safe, effective and inexpensive for the treatment of ORN.

Early detection of mandible osteoradionecrosis risk in a high comorbidity veteran population.

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.

Association between tooth extraction during radiotherapy and the risk of osteoradionecrosis in patients with head and neck cancers.

PURPOSE: It is commonly recommended that tooth extraction should be performed prior to radiotherapy (RT) in patients with head neck cancer to prevent osteoradionecrosis (ORN). However, doctors still occasionally encounter patients who require tooth extraction during RT. This study aimed to determine the risk of ORN in patients who undergo tooth extraction during RT. METHODS: Data were collected from Taiwan's National Health Insurance Research Database. We retrospectively enrolled 24,412 patients with head and neck cancer treated with radiotherapy between 2011 and 2017. The associations between ORN and demographic characteristics, timing of tooth extraction, and treatments were examined using univariate and multivariable Cox proportional hazards regression models. RESULTS: A total of 24,412 head and neck cancer patients were enrolled; 133 patients underwent tooth extraction during RT and 24,279 patients did not undergo tooth extraction during RT. Tooth extraction during RT was not associated with a significantly higher risk of ORN (hazard ratio [HR] = 1.303, P = 0.4862). Tumor site, RT dose ≥ 60 Gy, age < 55 y/o, mandibulectomy, chronic periodontitis, and chemotherapy were significantly associated with a higher risk of ORN. CONCLUSION: The risk of ORN in head and neck cancer is not significantly different between patients who undergo tooth extraction during RT and patients who do not undergo tooth extraction during RT.