Risk Of Osteoradionecrosis Research Articles

Consequences of hyposalivation in relation to cancer treatment and early management of radiation-induced caries: case reports

Given the prevalence of head and neck carcinoma and the salivary changes induced by the oral side effects of radiotherapy, such patients are at higher risk/susceptibility of developing dental caries. Radiation-caries is often under-treated in patients undergoing cervicofacial radiotherapy, yet these lesions can increase the risk of osteoradionecrosis due to necessary subsequent dental extractions. Moreover, xerostomia is accompanied by difficulties with speech, chewing and swallowing. The prevention and/or early management of radiation-induced carious lesions is essential in preventing oral complications and improving patients' quality of life. Based on a French case series, this paper proposes a protocol for the dental management of radiation-induced carious lesions.

Fractal Analysis of Mandible in Panoramic Radiographs of Patients Received Radiotherapy for Nasopharyngeal Carcinoma

Purpose: This study aimed to assess the impact of radiotherapy on the internal structure complexity of mandibular cortical and trabecular bone and to determine the duration required for a return to healthy values post-radiotherapy.Materials and Methods: Panoramic radiographs from patients undergoing radiotherapy for nasopharyngeal carcinoma were analyzed before and after treatment. Four groups were formed based on post-radiotherapy radiography timing (0-6 months, 6-12 months, 12-24 months, and 24-36 months), comprising a total of 59 cases and 118 radiographs. Fractal analysis was conducted on four bilateral regions (ROI) in both trabecular and cortical bone on each radiograph. Additionally, measurements of inferior alveolar canal width and mandibular cortical width were performed. Mean and maximum radiation dose values to the mandible were measured, and their correlation with changes in fractal dimension, inferior alveolar canal width, and mandibular cortical width values was assessed.Results: Fractal dimension values in regions over trabecular bone showed a statistically significant decrease in all groups, although no significant difference was observed among the four groups. In ROI-4 from cortical bone, a significant fractal dimension decrease was noted in all groups except the 0-6 month group. The magnitude of fractal dimension decrease was higher in the 12-24 and 24-36 month groups compared to the 0-6 month group. inferior alveolar canal width and mandibular cortical width values significantly decreased post-radiotherapy in all groups, with a consistent decrease across the groups.Conclusions: Radiotherapy induces a reduction in the internal complexity of trabecular and cortical bone structures in the mandible. Osteoradionecrosis risk persists even three years post-radiotherapy, suggesting a cautious approach to interventional procedures on the bone.

Predicting osteoradionecrosis risk in patients with locoregionally advanced nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: The value of the CARWL index.

Osteoradionecrosis (ORN) is a severe complication that can arise in patients with nasopharyngeal carcinoma due to the aggressive nature of chemoradiotherapy treatment. The purpose of our study was to assess the utility of the recently introduced CARWL index, which integrates the C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in predicting the risk of ORN in patients with locoregionally advanced nasopharyngeal cancer (LA-NPC) undergoing concurrent chemoradiotherapy (CCRT). We conducted a retrospective cohort analysis on 304 patients with LA-NPC treated with CCRT. Patients were categorized into CARWL index groups based on CAR (cut-off: 3.0) and SWL (weight loss > 5% over the past six months): CARWL-0 (CAR < 3.0, SWL ≤ 5%), CARWL-1 (CAR < 3.0 with SWL > 5% or CAR ≥ 3.0 with SWL ≤ 5%), and CARWL-2 (CAR ≥ 3.0 and SWL > 5%). The primary endpoint was the incidence of ORN in each CARWL index group. At a median follow-up of 67.2 months, 28 patients (9.2%) developed ORN. The incidence of ORN was 2.1%, 9.4%, and 16.3% in the CARWL-0, CARWL-1, and CARWL-2 groups, respectively (P < 0.001). Multivariate analysis identified smoking status (HR: 2.58, P = 0.034), N-stage (HR: 1.96, P = 0.008), T-stage (HR: 1.84, P = 0.017), pre-CCRT tooth extraction status (HR: 5.81, P < 0.001), post-CCRT tooth extraction status (HR: 6.82, P < 0.001), mandibular V55.8 Gy (HR: 6.12, P < 0.001), and CARWL score (HR: 5.67, P = 0.002) as significant predictors of ORN. The CARWL index is a reliable predictive tool for evaluating the risk of ORN in LA-NPC patients undergoing CCRT. If further validated, its use in clinical settings could aid in the early identification of high-risk patients and enable the implementation of personalized preventive strategies.

Is immediate dental implant in fibula free flap beneficial for implant survival and osteoradionecrosis in jaw reconstruction?

ObjectivesThis study aimed to compare the risk of osteoradionecrosis and implant survival in oral cancer patients undergoing immediate dental implants during jaw reconstruction, termed “Jaw in a Day” (JIAD), with those receiving no implants or delayed implants (non-JIAD). Patients & methodsClinicopathologic data were collected from prospectively enrolled JIAD patients (n = 10, 29 implants) and retrospectively from non-JIAD patients (n = 117, 86 implants). Survival analyses were performed to assess implant survival and osteoradionecrosis-free survival. ResultsOsteoradionecrosis occurred in 0 % of JIAD cases compared to 19.3 % in non-JIAD cases without implants and 71.4 % in non-JIAD cases with delayed implants (p = 0.008). Osteoradionecrosis-free survival was significantly better in the JIAD group than the non-JIAD group (p = 0.0059). Implants in the JIAD group all survived regardless of radiation therapy (29/29, 100 %) and 95.1 % (58/61) of implants survived in delayed implants in non-irradiated fibula without radiotherapy. Meanwhile, only 11 of 25 implants placed in irradiated fibula flaps survived, even when the implants were placed after a median time interval of 624 days after radiotherapy, and none of them were earlier than 360 days. The survival analysis revealed a significant difference (p < 0.0001). ConclusionJIAD appears to offer superior outcomes in terms of implant survival and osteoradionecrosis prevention compared to delayed implant placement. Placing implants in irradiated fibula, even after years, significantly poses high risk of implant failure and osteoradionecrosis. JIAD represents a promising approach for optimal rehabilitation, particularly in oral cancer patients requiring postoperative radiotherapy. Proper positioning and orientation of implants and flaps are crucial for implant survival.

The rehabilitation of a combined mid-facial defect using a magnetretained intra- and extra-oral prosthesis: a case report

There are several treatment options available to restore function and appearance in patients with combined mid-facial defects. Owing to the size of the defect and the associated size and weight of the prostheses, adequate retention can be challenging to achieve. Retention of a facial prosthesis can be improved using several techniques, such as medical grade adhesives, attachments, or osseo-integrated implants. For patients with a history of radiotherapy, surgical rehabilitation may be less favourable than non-surgical approaches owing to the risk of osteoradionecrosis and a reduced blood supply in the surgical fields. This clinical case report highlights the conservative rehabilitation of a combined mid-facial defect using a magnet-retained intra-oral and extra-oral prosthesis. CPD/Clinical Relevance: A thorough medical and clinical assessment will highlight factors that will influence the treatment planning process when managing a combined mid-facial defect.

Pre-chemoradiotherapy high platelet counts predict jaw osteoradionecrosis in locally advanced nasopharyngeal carcinoma patients

IntroductionThis 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 &MethodsORNJ 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. ResultsThe 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. ConclusionAn 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.

Cluster-Based Toxicity Estimation of Osteoradionecrosis Via Unsupervised Machine Learning: Moving Beyond Single Dose-Parameter Normal Tissue Complication Probability by Using Whole Dose-Volume Histograms for Cohort Risk Stratification

PurposeGiven the limitations of extant models for normal tissue complication probability estimation for osteoradionecrosis (ORN) of the mandible, the purpose of this study was to enrich statistical inference by exploiting structural properties of data and provide a clinically reliable model for ORN risk evaluation through an unsupervised-learning analysis that incorporates the whole radiation dose distribution on the mandible. Materials and MethodsThe analysis was conducted on retrospective data of 1,259 head and neck cancer (HNC) patients treated at XXX between 2005 and 2015. During a minimum 12-month post-therapy follow-up period, 173 patients in this cohort (13.7%) developed ORN (grades I to IV). The (structural) clusters of mandibular dose-volume histograms (DVHs) for these patients were identified using the K-means clustering method. A soft-margin support vector machine (SVM) was used to determine the cluster borders and partition the dose-volume space. The risk of ORN for each dose-volume region was calculated based on incidence rates and other clinical risk factors. ResultsThe K-means clustering method identified six clusters among the DVHs. Based on the first five clusters, the dose-volume space was partitioned by the soft-margin SVM into distinct regions with different risk indices. The sixth cluster entirely overlapped with the others; the region of this cluster was determined by its envelopes. For each region, the ORN incidence rate per pre-radiation dental extraction status (a statistically significant, non-dose related risk factor for ORN) was reported as the corresponding risk index. ConclusionThis study presents an unsupervised-learning analysis of a large-scale data set to evaluate the risk of mandibular ORN among HNC patients. The results provide a visual risk-assessment tool for ORN (based on the whole DVH and pre-radiation dental extraction status) as well as a range of constraints for dose optimization under different risk levels.

Personalizing dental screening and prevention protocols in dentulous patients with oropharyngeal cancer undergoing radiotherapy: A retrospective cohort study

ObjectivesPatients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased risk of osteoradionecrosis. We evaluated the risk factors for post-RT tooth extraction to personalise dental screening and prevention protocols prior to RT. Materials and methodsThis retrospective cohort study included dentulous patients diagnosed with oropharyngeal cancer who had undergone radiation therapy at doses 60–70 Gy and achieved a disease-free survival of ≥ 1 year (N = 174). Risk factors were assessed using Cox regression models. ResultsThe cumulative incidence of post-RT tooth extraction was 30.7 % at 5 years. Main indications for extraction (n = 62) were radiation caries (n = 20) and periodontal disease (n = 27). Risk factors associated (p < 0.05) with radiation caries-related extractions included active smoking, alcohol abuse, poor oral hygiene, parotid gland irradiation, and mandibular irradiation. A high-dose volume in the mandible was associated with periodontal disease events. ConclusionPost-RT extractions due to radiation caries were influenced by lifestyle factors and RT dose in the mandible and parotid glands. Periodontal disease-related extractions were primarily associated with the mandibular dose. During dental screening these post-RT risk factors should be taken into account to prevent osteoradionecrosis.

Predictive potential of pan-immune-inflammation value / hemoglobin index as biomarker for osteoradionecrosis risk in locally advanced nasopharyngeal carcinomas

ObjectiveWe aimed to investigate whether the Pan-Immune-Inflammation-Value/Hemoglobin (PIV/Hb) index could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal cancer (LA-NPC). Materials and methodsThis retrospective analysis included LA-NPC patients who underwent CCRT and pre-CCRT oral exams at our institution's Departments of Radiation Oncology and Dentistry between January 2010 and December 2022. The relationship between ORN rates and PIV-Hb levels was explored using receiver operating characteristic curve analysis. The primary objective was to establish a correlation between pre-CCRT PIV-Hb levels and ORN rates, while the secondary objective was to identify other risk factors for ORN. ResultsOf 249 eligible patients, 21 (8.4 %) were diagnosed with ORN. The optimal pre-CCRT PIV/Hb cutoff was 73.8, which divided patients into two subgroups with distinctive ORN risk estimates: Group 1: PIV/Hb < 73.8 (N = 206), and Group 2: PIV/Hb ≥ 73.8 (N = 43). The results of the comparative analysis indicated that the cohort with PIV/Hb ≥ 73.8 exhibited substantially higher rates of ORN than the PIV/Hb < 73.8 cohort (44.2 % vs. 1.0 %; P < 0.001). The multivariate logistic regression analysis indicated that the pretreatment PIV/Hb ≥ 73.8 was independently associated with higher ORN rates (P < 0.001). ConclusionThe results of our current investigation indicate that higher levels of pretreatment PIV/Hb were associated with a significant independent increase in ORN rates in LA-NPC patients who received CCRT.

Risk factor analysis and development of predictive models for osteoradionecrosis in patients with nasopharyngeal carcinoma after concurrent chemoradiotherapy.

Nasopharyngeal carcinoma (NPC) is a malignant tumor that targets the nasopharyngeal mucosal epithelium. Concurrent chemoradiotherapy (CCRT) is a pivotal treatment modality for NPC, yet it poses a risk for osteoradionecrosis (ORN), a complication that can impede further treatment. This study sought to explore the risk factors for ORN in NPC patients post-CCRT and to construct predictive models. We performed a retrospective analysis of clinical data from 417 NPC patients treated with CCRT at the Affiliated Hospital of Jiangnan University, with 204 patients from Longyan First Hospital as a validation cohort for the models. Our findings indicated that a high radiation dose, tooth extraction after radiotherapy, inadequate oral hygiene, smoking, anemia, and advanced T staging were associated with an elevated risk of ORN in NPC patients following CCRT. We formulated risk prediction models for ORN utilizing a nomogram, gradient boosting machine (GBM), and random forest (RF) algorithms. The area under the curve (AUC) was 0.813 (95% CI: 0.724-0.902) for the nomogram model in the validation cohort, 0.821 (95% CI: 0.732-0.910) for the GBM, and 0.735 (95% CI: 0.614-0.855) for the RF. Delong's test indicated no statistically significant differences in the AUC values among the three models. The nomogram has strong performance across both the training and validation cohorts, featuring a straightforward structure that is both intuitive and comprehensible. Taking into account the model's discriminative power, generalizability, and clinical practicability, the nomogram was proven to be highly applicable in the current study.

Oral Surgery and Osteoradionecrosis in Patients Undergoing Head and Neck Radiation Therapy: An Update of the Current Literature.

Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient's quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol ("PENTO protocol"), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making.

Adjuvant Reirradiation With Proton Therapy in Head and Neck Squamous Cell Carcinoma

BackgroundFor patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant re-irradiation (re-RT). Given an absence of clear consensus on the role of adjuvant re-RT, we sought to assess histopathologic risk factors of HNSCC patients and their resulting outcomes after adjuvant re-RT with proton therapy. Methods and MaterialsWe conducted a retrospective analysis of HNSCC patients who underwent salvage surgery at our institution followed by adjuvant re-RT with proton therapy over 1.5 years. All included patients received prior radiotherapy. The Kaplan-Meier method was used to evaluate locoregional recurrence-free survival (RFS) and overall survival (OS). ResultsThe cohort included 22 patients, with disease subsites including oropharynx, oral cavity, hypopharynx, larynx, and nasopharynx. Depending on adverse pathologic features, adjuvant re-RT to 66Gy (32% of cohort) or 60Gy (68%), with (59%) or without (41%) concurrent systemic therapy was administered. The majority (86%) completed re-RT with no reported treatment delay; 3 patients experienced grade >=3 acute Common Terminology Criteria for Adverse Events (CTCAE) toxicity and no patient required enteral feeding tube placement during re-RT. Median follow-up was 21.0 months (IQR 11.7-25.2 months). Five patients had biopsy-proven disease recurrences a median of 5.9 months (IQR 3.8-9.7 months) after re-RT. Locoregional RFS was 95.2%, 70.2%, 64.8% at 6, 12, and 24 months, respectively. OS was 100%, 79.2%, and 79.2% at 6, 12, and 24 months, respectively. Four patients had osteoradionecrosis on imaging a median of 13.2 months (IQR 8.7-17.4 months) after re-RT, with two requiring surgical intervention. ConclusionsAdjuvant re-RT for HNSCC patients was well-tolerated and offered reasonable local control in this high risk cohort, but appears to be associated with a risk of osteoradionecrosis. Further study and longer follow-up could help define optimal patient management in this patient population.

Dental Extractions Before Radiation Therapy and the Risk of Osteoradionecrosis in Patients With Head and Neck Cancer

Patients with head and neck cancer undergo extraction of teeth with poor prognoses to minimize post-radiation therapy (RT) extractions, which are known to cause osteoradionecrosis (ORN). However, many patients are required to start RT before the extraction sites are completely healed. The role of pre-RT extractions in the development of ORN has been disputed in literature. To determine whether the timing of pre-RT dental extractions is associated with ORN development in patients with head and neck cancer. This retrospective cohort study was conducted at a single institution (Princess Margaret Cancer Centre, Toronto, Canada) between January 1, 2011, and January 1, 2018, and included 879 patients with head and neck cancer who underwent pre-RT dental extractions before curative RT of 45 Gy or greater. Patient demographic information and clinical characteristics (eg, primary cancer site, nodal involvement, chemotherapy, smoking status, dental pathology) were considered. Data analyses were performed from July to December 2022. Timing (number of days) from dental extractions to RT start date and pre-RT extractions categorized as healed, minor bone spicules (MBS), or ORN. The study population consisted of 879 patients with a median (range) age of 62 (20-96) years, with 685 men (78%) and 194 women (22%). Of these, 847 (96.3%) healed from pre-RT dental extractions, 16 (1.8%) developed MBS, and 16 (1.8%) developed ORN. The median (range) time in number of days from pre-RT extraction(s) to start of RT was 9 (0-98) days in the healed cohort, 6 (3-23) days in the MBS cohort, and 6 (0-12) days in the ORN cohort. There was a large difference in the timing of pre-RT extractions between the healed and the MBS cohorts (mean 11.9 vs 7.4 days to radiation; difference 4.4; 95% CI, 1.5-7.3), and the healed and the ORN cohorts (mean 11.9 vs 7.1 days; difference 4.8 days; 95% CI, 2.6-7.1). The findings of this retrospective cohort study suggest that there was an important association between the timing of pre-RT dental extractions and ORN when extractions occurred within 7 days of the RT start date. Despite this, ORN after pre-RT extractions is relatively rare. These findings indicate that patients with head and neck cancer who are to undergo RT should not delay treatment for extractions when it might compromise oncologic control.

Natural History and Clinical/Dosimetric Determinants of Osteoradionecrosis in a Large Cohort of Head and Neck Cancer Following Curative Radiotherapy: Debunking the Myth of Decreased Rates of Osteoradionecrosis in the Modern Radiotherapy Era

Osteoradionecrosis (ORN) of the mandible is the most devastating toxicity following head and neck cancer (HNC) radiotherapy (RT). The rate of ORN occurrence has been debatable in the modern era of advanced RT. We aim to determine the natural history and time to ORN development in a large cohort of HNC. After IRB approval, we identified HNC patients treated with curative-intent RT between 2005 and 2020 at MD Anderson Cancer Center. Dental oncology notes were reviewed and all dental procedures were recorded. Available dose volume histograms (DVHs) for the segmented mandibular volumes were extracted. Based on our previously published ORN normal tissue complication probability (NTCP) model, any dental procedure pre-RT is a clinical high-risk factor and, therefore, data were coded as (high vs. low clinical risk) accordingly. We also coded the dosimetric risk factors to (high vs. low dosimetric risk) according to our published DVH thresholds (high dosimetric risk if any applies: V45≥40%, V55≥25%, and/or D30 ≥40 Gy). Finally, patients were classified to four groups according to combined clinical and dosimetric risk factors (No, clinical, dosimetric, and both). We used the Kaplan-Meier method to calculate time to ORN development and ORN-free survival. For time to ORN development, any grade ORN occurrence was coded as event and all others were censored. For ORN-free survival, death and ORN were coded as events and all others were censored. Log-rank test was used to compared curves of different risk groups. One thousand eight hundred sixty-six patients were included. Median follow-up was 38 months (range 4-162). ORN was reported in 252 patients (13.5%). The median time to ORN development was 18.5 months (range 4-145). 95 patients (37.7%) developed ORN after 2-years post-RT. The 1-, 3-, and 5-year ORN rates were 4.7%, 12.7%, and 17.8%, respectively. The 1-, 3-, and 5-year ORN-free survival were 94.3%, 85.5%, and 80.3%, respectively. There were statistically significant differences (P < 0.0001) between ORN-free survival in different clinical/dosimetric risk factors. The patients with no, clinical-only, dosimetric-only, and both clinical and dosimetric risk factors were 35%, 19%, 22%, and 24%, respectively. The 5-year ORN-free survival was 94.3%, 89.8%, 76.3%, and 69.6% for patients with no, clinical-only, dosimetric-only, and both clinical and dosimetric risk factors, respectively. The hazard-ratio (HR) of ORN development in clinical-only, dosimetric-only, and both clinical and dosimetric risk groups was 2.1, 5.4, and 7.5 compared to the no risk group (P<0.05 for all). Our findings indicate that ORN remains a remarkable toxicity hazard for HNC survivors. A prolonged surveillance time is required for the majority of HNC survivor since more than one-third of the ORN events occurred after 2-year follow-up. Patients with combined clinical and dosimetric risk factors have a staggering ORN risk profile and are proper candidates for future prophylactic pharmacotherapy clinical studies.

Evaluation of single-fraction high dose FLASH radiotherapy in a cohort of canine oral cancer patients.

FLASH radiotherapy (RT) is a novel method for delivering ionizing radiation, which has been shown in preclinical studies to have a normal tissue sparing effect and to maintain anticancer efficacy as compared to conventional RT. Treatment of head and neck tumors with conventional RT is commonly associated with severe toxicity, hence the normal tissue sparing effect of FLASH RT potentially makes it especially advantageous for treating oral tumors. In this work, the objective was to study the adverse effects of dogs with spontaneous oral tumors treated with FLASH RT. Privately-owned dogs with macroscopic malignant tumors of the oral cavity were treated with a single fraction of ≥30Gy electron FLASH RT and subsequently followed for 12 months. A modified conventional linear accelerator was used to deliver the FLASH RT. Eleven dogs were enrolled in this prospective study. High grade adverse effects were common, especially if bone was included in the treatment field. Four out of six dogs, who had bone in their treatment field and lived at least 5 months after RT, developed osteoradionecrosis at 3-12 months post treatment. The treatment was overall effective with 8/11 complete clinical responses and 3/11 partial responses. This study shows that single-fraction high dose FLASH RT was generally effective in this mixed group of malignant oral tumors, but the risk of osteoradionecrosis is a serious clinical concern. It is possible that the risk of osteonecrosis can be mitigated through fractionation and improved dose conformity, which needs to be addressed before moving forward with clinical trials in human cancer patients.

Does Segmental or Marginal Mandibulectomy with Adjuvant Radiation Confer Greater Risk of Osteoradionecrosis in Oral Squamous Cell Carcinoma Subjects?

Does Segmental or Marginal Mandibulectomy with Adjuvant Radiation Confer Greater Risk of Osteoradionecrosis in Oral Squamous Cell Carcinoma Subjects?

Implication of dental insurance status on patterns of pre-radiation dental extraction and risk of osteoradionecrosis of the jaw in head-and-neck cancer patients

Oral toxicities such as osteoradionecrosis can be minimized by dental screening and prophylactic dental care prior to head and neck (HN) radiation therapy (RT). However, limited information is available about how dental insurance interacts with prophylactic dental care and osteoradionecrosis. To address this gap in knowledge, we conducted a cohort study of 2743 consecutive adult patients treated with curative radiation for HN malignancy who underwent pre-radiation dental assessment and where required, prophylactic dental treatment. Charts were reviewed to determine patient demographics, dental findings, dental treatment and development of osteoradionecrosis following radiation. Three insurance cohorts were identified: private-insured (50.4 %), public-insured (7.3 %), being patients with coverage through government-funded disability and welfare programs, and self-pay (42.4 %).More than half the public-insured patients underwent prophylactic pre-radiation dental extractions, followed by self-pay patients (44 %) and private-insured patients (26.6 %). After a median follow-up time of 4.23 years, 6.5 % of patients developed osteoradionecrosis. The actuarial rate of osteoradionecrosis in the public-insured patients was 14.7 % at 5-years post-RT, compared to 7.5 % in private-insured patients and 6.7 % in self-pay patients. On multivariable analysis, dental insurance status, DMFS160, age at diagnosis, sex, tumor site, nodal involvement, years smoked and gross income were all significant risk factors for tooth removal prior to HN radiation. However, only public-insured status, tumor site and years smoked were significant risk factors for development of osteoradionecrosis. Our findings demonstrate that lack of comprehensive dental coverage (patients who self-pay or who have limited coverage under public-insured programs) associates strongly with having teeth removed prior to HN RT. Nearly 1 in 6 patients covered under public-insurance developed osteoradionecrosis within 5 years of completing their treatment. Well-funded dental insurance programs for HN cancer patients might reduce the number of pre-RT extractions performed in these patients, improving quality of life post-RT.

Dental assessment pre radiotherapy for head and neck cancer

Statement of the problem Head and neck cancer (HNC) and its treatment can dramatically change a patient’s appearance, speech, and oral function. Radiotherapy (RT) as a primary or adjuvant management strategy can result in osteoradionecrosis (ORN), salivary gland hypofunction, and can contribute to dental caries, among other sequelae. Assessment by a dentist prior to RT is important to remove suspect teeth in the field of radiation and commence preventive and restorative care for the long term. This can reduce subsequent ORN risk, reduce oral complaints during RT, and optimise oral health-related quality of life (OHRQoL). Purpose of the study This is a large-scale cohort study investigating dental treatment provided to a group undergoing RT for primary tumours of the head and neck. Materials and methods A retrospective chart review was carried out of all patients who had presented at the pre-RT dental clinic at Dublin Dental University Hospital from 2018 to 2019. Results A total of 490 patients were included. The mean age at presentation was 63 years (SD = 11). Approximately 50% of patients required removal of at least one unit and 12.7% of patients required basic dental restorations prior to commencement of RT. Most patients (93%) were assessed and treated within the requested timeframe. Conclusions Pre-RT assessment of HNC patients is important, as many require dental treatments such as extractions or basic restorations. Early planning for dental review should be considered to allow adequate time for assessment and proper treatment of long-standing dental issues.

The predictive value of pretreatment hemoglobin-to-platelet ratio on osteoradionecrosis incidence rates of locally advanced nasopharyngeal cancer patients managed with concurrent chemoradiotherapy

BackgroundThis retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors.ResultsWe distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months.ConclusionLow pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.

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

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. 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. 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 ≥ 60Gy, age < 55 y/o, mandibulectomy, chronic periodontitis, and chemotherapy were significantly associated with a higher risk of ORN. 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.