Management Of Osteoradionecrosis Research Articles

Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study

Introduction Although relatively uncommon, osteoradionecrosis (ORN) remains a serious complication following radiotherapy. Various therapeutic approaches, including hyperbaric oxygen therapy (HBOT), are utilized in managing ORN. This study aims to evaluate the role of HBOT in ORN management and to identify predictive factors influencing the evolution of head and neck ORN after HBOT. Methods This retrospective study includes 46 patients who received HBOT for head and neck ORN between 2017 and 2020. The patients were divided into two groups: Group 1 (n=36) included those with regression or stabilization of ORN, while Group 2 (n=10) comprised patients with worsening lesions. We performed a statistical study in order to identify factors influencing ORN progression under treatment. Results ORN affected the mandible in 93.5% of patients, the maxilla in 2 cases, and the skull base in 4 cases. All patients received HBOT, with an average of 44.65 sessions. Pre-operative HBOT was administered in 17% of cases, and post-operative HBOT was given in 42% of cases. After at least 20 sessions, ORN regressed in 33% of cases, stabilized in 45%, and worsened in 22%. Analysis of factors influencing ORN progression on the univariate study revealed significant associations with high blood pressure (p=0.046), larger tumor size (p=0.004), advanced tumor stages (p=0.048), mean radiation dose (p=0.002), delays between dental care and radiotherapy (p=0.045), and the location of ORN within the mandible (p=0.049). Additionally, the number of HBOT sessions significantly affected ORN evolution, with more sessions correlating with better outcomes (p=0.001). In the multivariate analysis, variables such as the average interval between dental care and radiotherapy (p=0.043) as well as the number of HBOT sessions (p=0.040) emerged as significant influencers of ORN evolution. Conclusion Our study provides valuable insights into the management of ORN by identifying key predictors that influence the post-therapeutic evolution of head and neck ORN after HBOT.

Prevention of osteoradionecrosis in patients with head and neck cancer treated with radiation therapy.

Osteoradionecrosis is a long-term, serious side effect of head and neck radiation therapy and is associated with significant morbidity and quality of life issues. This paper sought to determine consensus on the prevention and management of osteoradionecrosis by an international panel of multidisciplinary professionals expert in the management of patients with head and neck cancer using a Delphi methodology. Unique to this work is our direct inclusion of the views of patients and carers in our findings. This study reached consensus on the importance of pre and post oral health assessment and education for patients with head and neck cancer. This was also noted by the patients and carers who took part in the study. This work highlights the need for a standardized oral health assessment tool and multidisciplinary care of patients to prevent and manage osteoradionecrosis.

Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline.

To provide evidence-based recommendations for prevention and management of osteoradionecrosis (ORN) of the jaw secondary to head and neck radiation therapy in patients with cancer. The International Society of Oral Oncology-Multinational Association for Supportive Care in Cancer (ISOO-MASCC) and ASCO convened a multidisciplinary Expert Panel to evaluate the evidence and formulate recommendations. PubMed, EMBASE, and Cochrane Library databases were searched for randomized controlled trials and observational studies, published between January 1, 2009, and December 1, 2023. The guideline also incorporated systematic reviews conducted by ISOO-MASCC, which included studies published from January 1, 1990, through December 31, 2008. A total of 1,539 publications were initially identified. There were 487 duplicate publications, resulting in 1,052 studies screened by abstract, 104 screened by full text, and 80 included for systematic review evaluation. Due to limitations of available evidence, the guideline relied on informal consensus for some recommendations. Recommendations that were deemed evidence-based with strong evidence by the Expert Panel were those pertaining to best practices in prevention of ORN and surgical management. No recommendation was possible for the utilization of leukocyte- and platelet-rich fibrin or photobiomodulation for prevention of ORN. The use of hyperbaric oxygen in prevention and management of ORN remains largely unjustified, with limited evidence to support its practice.Additional information is available at www.asco.org/head-neck-cancer-guidelines.

Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline Clinical Insights.

Prevention and Management of Osteoradionecrosis in Patients With Head and Neck Cancer Treated With Radiation Therapy: ISOO-MASCC-ASCO Guideline Clinical Insights.

Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.

Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.

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

BackgroundAdvanced 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. PurposeThe 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, sampleThis 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 variableThe primary predictor variable was viability of resection margins on histopathologic analysis (viable or non-viable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. Main outcome variableThe 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. CovariatesNot applicable. AnalysesDescriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of p ≤ 0.05 was considered significant. ResultsThe 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 one and two year survival of 75.8% and 66.2%, respectively. Non-viable resection margins were associated with earlier time to infection recurrence (p ≤ 0.001, Hazard Ratio (HR) = 11.9, 95% Confidence Interval (CI) = 3.84 – 36.7) as was younger age (p = 0.005, HR = 0.921, 95% CI = 0.869 – 0.976) and atypical pathogen growth on culture (p = 0.002, HR = 8.58, 95% CI = 2.24 – 32.8). Conclusions and RelevanceHistopathologic 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.

The management of osteoradionecrosis in palliative head and neck cancer patients

AbstractObjectiveOsteoradionecrosis (ORN) is a well‐recognised complication of radiotherapy in the cured head and neck cancer (HNC) patients. More recently with improved survivorship in the palliative HNC group, there is an increasing population that is also burdened by radiation late effects such as ORN. Currently, there is no proven approach to manage ORN in this cohort of patients. This study reports the management and outcome of a case series of palliative care HNC patients with established ORN.Materials and MethodsThe clinical records of 20 palliative care HNC patients with an established ORN diagnosis were identified and reviewed retrospectively.ResultsAll 20 patients were managed via a conservative approach. Medical management via PENTO (n = 4, 20%) or PENTOCLO (n = 8, 40%) was the most popular approach. All but two patients had ORN that healed (4/20, 20%), or was stabilised (14/20, 70%). The two patients with progressive ORN had a tumour diagnosis adjacent to the necrotic site.ConclusionMedical management via PENTO/CLO provided promising results in this small cohort of palliative patients with ORN. The overall combined healing and stability of ORN status are comparable to those in the literature, though most cases are stabilised as opposed to cured.

Histopathological insight into a healed case of osteoradionecrosis treated with triple therapy medical management

AbstractThere is increasing interest in the management of osteoradionecrosis via pharmacological therapy as an alternative to surgery. Successful outcomes have been presented in the literature based on clinical and radiographic assessment. The current case reports on a clinically healed case of osteoradionecrosis who subsequently underwent resection for the purpose of oro‐dento‐facial rehabilitation providing a rare insight into the histopathological status of resolved case via medical management.

Osteoradionecrosis treatment in head and neck cancer patients: An overview of systematic reviews.

Evaluate the existing evidence of osteoradionecrosis (ORN) treatment in adults with head and neck cancer, the methodological quality and the evidence grade within systematic reviews (SRs). An extensive systematic literature search of SRs that addressed ORN in head and neck cancer patients was conducted with screening of eligible studies, data extraction, methodological (AMSTAR 2) and evidence quality assessment (GRADE) of the SRs by independent and calibrated authors. A total of six SRs were enrolled. Based primarily on studies from the 1990s, there is critically low- or moderate-quality evidence that hyperbaric oxygen therapy (HBO) improves ORN healing. From 2005 onward, evidence has been discovered in relation to treatment with pentoxifylline and tocopherol (PENTO). The SRs indicate that the management of ORN with PENTO appears to be promising. The greatest rates of healing are seen in mild and moderate stages of ORN. However, the quality of evidence regarding PENTO, surgery and other treatments remains critically low. There is no standardized protocol to treat ORN. PENTO appears to be the most promising conservative treatment; however, the current level of evidence regarding PENTO is still critically low. More robust clinical studies are needed to establish the best treatment for ORN.

Incidence and Risk Factors for Extremity Osteoradionecrosis after Limb-Sparing Surgery and Adjuvant Radiotherapy

Osteoradionecrosis (ORN) is a major complication after radiotherapy. Most studies on ORN have focused on patients with mandibular lesions, with few studies including patients with extremity soft tissue sarcoma (STS). We included 198 patients with extremity STS who underwent limb-sparing surgery and adjuvant radiotherapy between 2004 and 2017. The incidence rate of extremity ORN was 3.5% (7/198), with most lesions (6/7) located in the lower extremities. The mean follow-up time was 62 months. Clinical presentations included chronic ulcers, soft tissue necrosis, sinus discharge, bone nonunion, and pathological fractures. Compared with the non-ORN group, the ORN group had a significantly higher total radiation dose (68 Gy vs. 64 Gy, p = 0.048) and greater use of intraoperative periosteal stripping (p = 0.008). Repeat surgeries and subsequent soft tissue reconstruction or limb amputation were performed as treatments. The risk and management of ORN in patients with extremity STS was ignored previously. Because the disease is complex and affects both clinicians and patients, careful surveillance should be undertaken.

Mesenchymal stem cell therapy for treatment of osteoradionecrosis of mandible in head and neck surgery patients - A way forward into the future with promising clinical Outcomes.

Managing osteoradionecrosis is an integral part of complication management in head and neck cancer patients. While essentially an infection, the management of this complication has a considerable task for head and neck surgeons. While various measures have been discussed for the management, stem cells injection therapy is a potential management option. Mesenchymal stem cell therapy provides the local tissue with growth factors and proliferative cells that can aid a radiated tissue in the healing process. The article intends to review the bedrock of the pathology, ranging from pathophysiological and the epidemiological concerns to sparking a potential discussion on the use of mesenchymal stem cell therapy in osteoradionecrosis of mandible in head and neck cancer surgery and thus the ensuing future of the regenerative medicine. Moreover, the article has considered the management option in a developing nation thus explaining the procedural as well as the financial pitfalls and has highlighted the potential loop holes to be addressed in the management of osteoradionecrosis with stem cell therapy.

144. Efficacy of pentoxifylline-tocopherol-clodronate in the management of mandibular osteoradionecrosis: A multicentre retrospective case series

Osteoradionecrosis (ORN) is a long-term and debilitating complication related to radiotherapy-based treatment for head and neck cancer (HNC). With no universal consensus on an optimal treatment regime, ORN management remains challenging. Treatment for advanced or refractory ORN has historically been limited to surgical resection and reconstruction. The fibroatrophic hypothesis for the aetiopathogenesis of ORN led to administration of pentoxifylline, tocopherol and clodronate (PENTOCLO) in the management of ORN.

IS ANTIMICROBIAL PHOTODYNAMIC THERAPY EFFECTIVE AS AN ADJUNCT MANAGEMENT FOR OSTEORADIONECROSIS? - A CASES SERIES

Management of osteoradionecrosis (ORN) has not yet reached a consensus, so it remains complex and difficult to manage, with a poor prognosis. The objective was to report the treatment of ORN based on a protocol including antimicrobial photodynamic therapy (aPDT), irrigation with 0.12% chlorhexidine, surgical debridement, and application of 0.2% chlorhexidine gel. Fifteen patients were enrolled in this case series comprising 100% men; 66.6% were submitted to conformational radiotherapy, 86.6% underwent chemotherapy as part of the treatment, 86.6% were smokers, and 73.3% were alcohol addicts. The diagnosis was made both in clinical and imaging exams. Of the 15 cases, 73.3% had mucosal healing without pathological fracture, 13.3% had no wound healing and/or pathological fracture, and 6.6% had pathological mandible fracture without area healing. It was concluded that aPDT management associated with 2% chlorhexidine gel and 0.12% chlorhexidine solution plus surgical debridement was effective in 86.6% of ORN cases reaching no pathologic fracture and/or mucosal healing.

Advances and Controversies in the Management of Osteoradionecrosis After Head and Neck Cancer Treatment: A Narrative Review.

Osteoradionecrosis (ORN) is a painful and debilitating serious late complication following treatment for head and neck cancer (HNC) often requiring surgical resection of the jaw and complex multidisciplinary management. An important aggravating factor for mandibular ORN is surgical trauma, commonly dental extractions or implant placement following head and neck radiotherapy. The evidence on the treatment protocols ranges from conservative management to more radical surgical strategies including the use of hyperbaric oxygen therapy. The available evidence on the preventive approaches for ORN includes prophylactic dental care prior to radiotherapy, the use of hyperbaric oxygen (HBO) treatment and prophylactic antibiotics for post-radiotherapy extractions. However, the efficacy of hyperbaric oxygen therapy has been questioned recently signifying poor understanding of the pathophysiology of the condition and therapies targeting the fibroatrophic process have become a focus of ORN treatment. Implementing recent IMRT radiation techniques has also shown evidence to reduce the incidence of ORN. This review provides an insight into the variations in definition and classification of the ORN, the controversies in its pathophysiology and the advances in the prevention and management.

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

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. This scoping review aims to investigate the most prescribed regimen of pentoxifylline and tocopherol with/without clodronate for the management of ORN. 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. 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. Treatment by PENTO (800mg of pentoxifylline+1000IU of tocopherol) once daily for an early established ORN or PENTOCLO (PENTO regimen+1600mg 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.

Patients' experience and perceived concerns regarding obtaining and taking prescriptions for head and neck osteoradionecrosis

The main components of the medical management of osteoradionecrosis (ORN) are combinations of clodronate, pentoxifylline, tocopherol, sometimes with antibiotics or chlorhexidine rinses. Anecdotally in the Cheshire and Merseyside network, patients report having difficulties getting and taking their prescription, hence the aim was to survey patient experience of obtaining prescriptions, administration of the medications, and side effects. Patients prescribed tocopherol and pentoxifylline from the pharmacy department’s record database from the period of January 2019 to June 2020 were invited to take part in a semi-structured telephone survey. Sixteen patients out of a total 33 (48%) responded. 11 patients (69%) reported some issue collecting their repeat prescriptions, commonly low stock of medicines in community or unwillingness of GPs to prescribe. One patient permanently stopped treatment owing to difficulties obtaining medication, whilst for three there were temporary gaps in treatment. Difficulty in administration of the medications was reported in 7 patients (44%) patients, most commonly in those with pre-existing dysphagia. Issues related to difficulties in swallowing the large pentoxifylline tablet or with the vitamin E capsules. Patients crushed the medications, but this was associated with gastrointestinal side-effects in one patient who had to stop treatment. One patient stopped chlorhexidine mouthwash due to oral soreness. In conclusion, medical management of ORN is well tolerated by patients. There is difficulty for patients getting prescriptions in primary care. Few patients need to stop taking the medication due to difficulty in administration or side-effects. More patient information would be useful for all concerned.

Computed Tomography Radiomics Kinetics as Early Imaging Correlates of Osteoradionecrosis in Oropharyngeal Cancer Patients.

Osteoradionecrosis (ORN) is a major side-effect of radiation therapy in oropharyngeal cancer (OPC) patients. In this study, we demonstrate that early prediction of ORN is possible by analyzing the temporal evolution of mandibular subvolumes receiving radiation. For our analysis, we use computed tomography (CT) scans from 21 OPC patients treated with Intensity Modulated Radiation Therapy (IMRT) with subsequent radiographically-proven ≥ grade II ORN, at three different time points: pre-IMRT, 2-months, and 6-months post-IMRT. For each patient, radiomic features were extracted from a mandibular subvolume that developed ORN and a control subvolume that received the same dose but did not develop ORN. We used a Multivariate Functional Principal Component Analysis (MFPCA) approach to characterize the temporal trajectories of these features. The proposed MFPCA model performs the best at classifying ORN vs. Control subvolumes with an area under curve (AUC) = 0.74 [95% confidence interval (C.I.): 0.61–0.90], significantly outperforming existing approaches such as a pre-IMRT features model or a delta model based on changes at intermediate time points, i.e., at 2- and 6-month follow-up. This suggests that temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of RT-induced mandibular injury, and consequently aid in earlier management of ORN.

Management of Osteoradionecrosis of the Anterior Thoracic Wall Using Omental Flaps: a Prospective Case Series and Literature Review

Rib-sternal osteoradionecrosis is a rare but serious complication of chest radiotherapy. No consensus-based method of managing deep sternal wounds that develop after radiotherapy is available. Usually patients require long-term antibiotics. The surgical placement of a muscle, an omental flap, or a prosthesis is described. We report, in pictures, four successful omental flap placements. Between March 2015 and July 2018, four women with deep sternal wound injuries that developed after radiation therapy to treat breast cancer underwent rib-sternal reconstruction with omental flap placement. The first signs of infected radionecrosis developed 28.5 years after radiotherapy. Despite prolonged antibiotic treatment, surgery was necessary. The mean age at surgery was 76 years (range: 62–86 years). All necrotic tissue was excised and debridement was performed before the placement of a pedicled omental flap dissected along the transverse colon and raised through a subcutaneous tunnel. No skin graft or osteosynthesis was required. After surgery, lubricated bandages were applied daily, and antibiotics were prescribed for a few weeks. Complete healing was obtained after surgery without clinical complication. Our experience suggests that a pedicled omental flap is an affordable, simple, and very useful option for reconstructing deep rib-sternal wounds caused by radiation.

Autologous Platelet-Rich Fibrin (PRF) as an Adjunct in the Management of Osteoradionecrosis and Medication-Related Osteonecrosis of Jaws. Case Series in A Single Centre

Osteoradionecrosis (ORN) of the jaws and medication-related osteonecrosis of the jaws (MRONJ) are uncommon but serious diseases affecting the oral and maxillofacial region with clinically similar appearance but distinct pathophysiology. Management of ORN and MRONJ is inherently challenging and the treatment outcomes are unpredictable. The use of autologous platelet concentrates (APCs) to promote hard and soft tissue healing is well described in the literature, and the efficacy of leucocyte and platelet-rich fibrin (L-PRF) has been well documented in a number of clinical studies. The aim of this study was to present our treatment strategy and the outcomes of incorporating L-PRF as a surgical adjunct in management of ORN and MRONJ in our centre. Methods: eight cases of ORN and MRONJ were treated with a combination of sequestrectomy and L-PRF as a surgical adjunct. Results: the overall success was 87.5%. Using L-PRF as an adjunct, we were able to predictably manage ORN and MRONJ without causing significant morbidity. Conclusion: our experience shows that L-PRF may be used as a valuable and cost-effective adjunct to surgical management of ORN and MRONJ. However, due to a limited number of patients, and a short period of review, the true effectiveness of the method is yet to be demonstrated in a longer follow-up study including a greater number of patients, besides the inclusion of a control group.

The use of pentoxifylline, tocopherol and clodronate in the management of osteoradionecrosis of the jaws

AimsMedical management of osteoradionecrosis (ORN) via pentoxifylline, tocopherol (PENTO) and clodronate (PENTOCLO) has shown both promise and early positive outcomes. We aimed to determine clinical outcomes for patients with established ORN managed solely via PENTO or PENTOCLO. MethodsThe study retrospectively reviewed and collected data from the medical records of 169 patients diagnosed with ORN and treated via medical management. Patients that received any additional interventions such as surgery or hyperbaric oxygen were not included. ResultsMedical management led to healed ORN in 54.4% (n = 92/169) of patients after an average of 12.9 months. Outcome comparison between PENTO and PENTOCLO identified the former regime to be significantly superior (p = 0.0001). There is an inverse relationship with increasing ORN severity and healing with medical management (p < 0.0001) with oropharyngeal cancer (p = 0.0347) patients responding favourably via this approach. Infection had a critical role in the final outcome with those healing requiring 1.3 antibiotic prescriptions, while those that had disease progression requiring 4.3 prescriptions. ConclusionMedical management is a viable treatment option for ORN. It appears to be most effective in Notani I and non-infected ORN. When healing was not achieved the regime was able to stabilise the condition.