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.

Viability of Free Bone Graft in Combination With Free Tissue Transfer and Post-Operative RT in Orbital Floor Reconstruction.

Orbital floor reconstruction post cancer ablation is challenging especially when associated with extensive soft tissue defects. Due consideration is to be given to the possible toxicities of adjuvant radiotherapy as well. Free bone-soft tissue flaps are ideally suited in such situations. However, a single flap may fall inadequate for large defects. Using two free flaps in combination increases operating time and donor site morbidities. Non-vascularized bone grafts combined with large soft tissue flaps harbor the risk of bone resorption and osteo-radio necrosis. Alloplastic implants can lead to exposure and infection. We conducted a study researching the outcome of non-vascularized cortico-cancellous iliac bone graft (NVCIBG) used in orbital floor reconstruction along with free anterolateral thigh (FALT) flap in subjects undergoing extensive surgical ablation and adjuvant radiotherapy. Ten consecutive subjects who underwent maxillo-mandibular resection with or without skin were included in the study. The parameters assessed were diplopia, ectropion, bone viability, and osteointegration. Subjects were assessed in the immediate post-operative period, 1 month after surgery, and after 1 year of radiotherapy. The size of iliac bone harvested ranged from 3 to 5.5 cm (mean 4.8 cm). Forty percent subjects complained of binocular diplopia in the initial post-operative period which subsided subsequently. Thirty percent subjects developed ectropion all of whom required external skin reconstruction. None developed osteoradionecrosis. NVCIBG along with FALT flap is an excellent reconstructive option for orbital floor defects. It can withstand the toxicities of adjuvant radiotherapy and avoids the need for double free flap reconstruction. 4 Laryngoscope, 2024.

Development of a Preclinical Double Model of MandibularIrradiated Bone and Osteoradionecrosis in NewZealand Rabbits.

Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches. Nine New Zealand white rabbits were irradiated using a single beam positioned to the left of the mandible and directed perpendicular to the left mandible. A 10 × 10 mm2 region of interest (ROI) located below the first molar tooth on the left side was identified and irradiated with 7 Gy each fraction, once every 2 days, for five fractions. Dose distributions demonstrated that the corresponding ROI on the contralateral (right) mandibular side received approximately 5 Gy each fraction, thus bilateral irradiation of the mandible was achieved. ROIs were categorized as ROIH on the left side receiving the high dose and ROIL on the right side receiving the low dose. Rabbits were followed up clinically and imaged monthly. After 4 months, the irradiated bone was excised, and histological examination of ROIs was performed. Radiological signs suggestive for ORN were detected in the entire population (100%) 16 weeks after irradiation on ROIH, which consisted of cortical erosion and loss of trabeculae. ROIL did not show any radiological evidence of bone damage. Histologically, both sides showed comparable signs of injury, with marked reduction in osteocyte count and increase in empty lacunae count. A preclinical double model was successfully developed. The side receiving the higher dose showed radiological and histological signs of bone damage, resulting in an ORN model. Whereas the contralateral side, receiving the lower dose, presented with histological damage only and a normal radiological appearance. This work describes the creation of a double model, an ORN and irradiated bone model, for further study using this animal species.

Patient-Reported Quality of Life for Osteoradionecrosis Reconstruction in the Head and Neck: A Longitudinal Framework and Risk Factors.

Osteoradionecrosis (ORN) is an aggressive sequela of head and neck cancer, treatment of which focuses on functional restoration and quality-of-life (QoL). This study aims to identify risks for poor QoL in ORN reconstruction and build a chronologic, longitudinal framework for QoL. A prospective database of reconstructions performed by the senior author was reviewed from 2015-2023. QoL metrics (University of Washington [UWQoL]v4) were prospectively administered prior to surgery, one year post-operatively, and each yearly follow-up. 56 ORN patients were included (average 58.2years, mean 6,412Gy radiation). Reconstruction commonly was achieved with the fibula(55.4%) and anterolateral-thigh flaps(37.5%). The total complication rate was 23.2%, median 10.7mo post-operatively.Both "health-related QoL in comparison with prior to cancer diagnosis" (62.5 vs 43.5;p=0.030) and "Overall QoL during the past 7-days" (50.5 vs 41.7;p=0.029) were higher post-ORN reconstruction than before. Physical-QoL was higher pre-cancer reconstruction (79.0) than prior to ORN reconstruction (50.6;p<0.001) and following reconstruction (52.5;p=0.001). Social-emotional function was higher following ORN reconstruction compared to pre-reconstruction (68.7 vs 59.6;p=0.010).On multi-variate analysis, both post-operative social-emotional and physical function were impacted by betelnut use (p=0.038;p=0.025). Poor improvement in QoL from pre to post-ORN reconstruction were affected by maxilla involvement (p=0.048), fistula (p=0.004), and hardware issues (p=0.001). Our longitudinal experience trended decline in QoL at ORN diagnosis with gradual improvement following reconstruction, with eventual social-emotional, pain, anxiety, chewing, and global-QoL significantly improved following surgery. Betelnut was a risk factor for poor post-operative QoL. Maxillary involvement, post-op fistula and hardware issues were risks for non-improvement in QoL.

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

This study compares the outcomes of osteocutaneous radial forearm free flap (OC-RFFF) and fibula free flap (FFF) reconstruction of mandibular osteoradionecrosis (ORN). 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. 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). 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.

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.

Are prophylactic antibiotics effective in preventing osteoradionecrosis after high-risk dental extractions?

A systematic review and meta-analysis. To assess and compare the effectiveness of different adjunctive treatments during tooth extraction in post-radiotherapy head and neck patients for preventing osteoradionecrosis (ORN). Two independent reviewers conducted an electronic search through PubMed, Embase, Cochrane Libraries, Scopus and Web of Science databases using relevant search terms. Additionally, references of relevant articles were manually searched for eligible studies. Included were full-length articles (randomized controlled trials (RCTs), clinical trials, or observational studies) published in English, reporting on ORN occurrence after dental extraction, with or without adjunctive interventions, in patients who had previous radiotherapy. Data extraction was similarly performed by two independent researchers. For quality assessment, bias in observational studies was evaluated using the ROBINS-I tool, while the RoB 2 tool was used for RCTs. One-arm meta-analyses estimated pooled ORN prevalence rates for different adjunctive treatments based on patient-level outcomes. For studies with direct comparisons between two modalities, pooled odds ratios for ORN were calculated using pairwise meta-analyses. This systematic review followed PRISMA guidelines and was registered in the PROSPERO database. A total of 29 studies with 1520 patients were included, comprising 4 RCTs, 4 prospective studies, and 21 retrospective observational studies. Five adjunctive treatment modalities around the time of dental extractions were identified: hyperbaric oxygen (HBO), pentoxifylline-tocopherol (PENTO), antibiotics (ABX), platelet-rich fibrin and photobiomodulation. Of the 25 observational studies included, 11 had a serious risk of bias, while all RCTs but 1 had low risk of bias. Egger's test showed no publication bias for the HBO and ABX groups (p > 0.05). Antibiotics were used in 17 studies, with significant variations in preoperative and postoperative protocols. Most studies utilized penicillin or clindamycin. The pooled prevalence of ORN was significantly lower in the HBO (4.6%), PENTO (3.4%), and ABX (3.8%) groups compared to the Control (17.6%), as indicated by the non-overlapping 95% CIs between the Control and any of the intervention groups. In studies with direct comparisons, HBO exhibited lower odds of developing ORN than the Control (odds ratio [OR] = 0.27) and ABX (OR = 0.57), although these differences were not statistically significant. HBO, PENTO, and ABX show similar reduction in ORN rates compared to no intervention. Given its cost-effectiveness and accessibility, ABX may be the most practical prophylactic modality at present.

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.

Computed tomography radiomics-based cross-sectional detection of mandibular osteoradionecrosis in head and neck cancer survivors.

This study aims to identify radiomic features extracted from contrast-enhanced CT scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in patients with head and neck cancer (HNC) treated with radiotherapy (RT). Contrast-enhanced CT (CECT) images were collected for 150 patients (80% train, 20% test) with confirmed ORN diagnosis at The University of Texas MD Anderson Cancer Center between 2008 and 2018. Using PyRadiomics, radiomic features were extracted from manually segmented ORN regions and the corresponding automated control regions, the later defined as the contralateral healthy mandible region. A subset of pre-selected features was obtained based on correlation analysis (r > 0.95) and used to train a Random Forest (RF) classifier with Recursive Feature Elimination. Model explainability SHapley Additive exPlanations (SHAP) analysis was performed on the 20 most important features identified by the trained RF classifier. From a total of 1316 radiomic features extracted, 810 features were excluded due to high collinearity. From a set of 506 pre-selected radiomic features, the optimal subset resulting on the best discriminative accuracy of the RF classifier consisted of 67 features. The RF classifier was well calibrated (Log Loss 0.296, ECE 0.125) and achieved an accuracy of 88% and a ROC AUC of 0.96. The SHAP analysis revealed that higher values of Wavelet-LLH First-order Mean and Median were associated with ORN of the jaw (ORNJ). Conversely, higher Exponential GLDM Dependence Entropy and lower Square First-order Kurtosis were more characteristic of normal mandibular tissue. This study successfully developed a CECT-based radiomics model for differentiating ORNJ from healthy mandibular tissue in HNC patients after RT. Future work will focus on the detection of subclinical ORNJ regions to guide earlier interventions.

Platelet-Rich Fibrin Treatment Evaluation in Patients with Medication-Related Osteonecrosis of the Jaw and Osteoradionecrosis.

Background. Medication-related osteonecrosis of the jaw (MRONJ) and osteoradionecrosis (ORN) are associated with severe disability and continuous pain, both of which are very difficult to control. This study aims to evaluate the outcome of platelet-rich fibrin (PRF) treatment compared to iodoform gauze packing and the primary suture of oral mucosa in patients with both MRONJ and ORN. Methods. Patients suffering from MRONJ and ORN who were treated in the Oral and Maxillofacial Surgery Clinic of Cluj-Napoca in the last 10 years were selected for this study from the hospital database. Results. PRF treatment proved to be a reliable method to help heal the necrotic bone sites. High-ASA risk patients and immunosuppressed patients are more prone to recurrence and persistent signs and symptoms. Intravenous bisphosphonates produce more intense symptomatology compared to oral administration. The posterior mandible is more difficult to treat compared to other sites. Conclusions. The quality of life of MRONJ and ORN patients may be improved by a protocol that reduces pain and hospitalization.

Free fibula mandible reconstruction for osteoradionecrosis is more challenging than for primary cancer.

Osteoradionecrosis (ORN) of the mandible is an unfortunate potential sequela of radiotherapy for head and neck cancer. In advanced cases of ORN, mandibulectomy, and free fibula flap reconstruction are required. We hypothesized that patients undergoing fibula free flap reconstruction and mandibulectomy for ORN pose unique challenges and experience more complications than patients undergoing fibula free flaps after oncologic mandibulectomy. After IRB approval, we created a database of all free fibula flaps for mandible reconstruction from April 2005 through February 2019. Medical records were retrospectively reviewed for patient and surgical characteristics and postoperative outcomes. Four-hundred seventy-nine patients met the inclusion criteria (168 ORN vs. 311 non-ORN patients). Propensity-matching was performed based on age, BMI, smoking status, preoperative chemotherapy, and virtual surgery planning use, which yielded 159 patients in each group. ORN patients received more double-skin-island fibula flaps than non-OR patients (20.8% vs. 5.7%, p < 0.001). Recipient artery other than the facial artery was utilized more commonly in ORN patients (42.1% vs. 17.0%, p < 0.001). In the unmatched cohort, ORN patients had higher rates of delayed wound healing (26.2% vs. 16.8%, p = 0.01) and surgical site infections (21.4% vs. 13.2%, p = 0.02). Rates of flap loss, return to the operating room, hematoma, operative time, and length of stay were similar between the groups. On logistic regression analysis, osteoradionecrosis was an independent risk factor for delayed wound healing. Based on these data, mandibular reconstruction with fibula flaps for osteoradionecrosis appears more complicated than mandible reconstruction following de novo cancer resection. Surgeons should anticipate employing two skin islands for intraoral and extraoral resurfacing, utilizing unconventional recipient vessels, and managing the delayed wound healing that ensues more commonly than non-ORN patients.

Microvascular reconstruction of midface osteoradionecrosis.

Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population. Retrospective multi-institutional review of FF reconstruction for midface ORN (2005-2022; n = 54). The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02). In this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.

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.

The dental implant survival rate in 18 patients with post-operation revolutionary jaw reconstruction using free fibular flap, dental implants, and overdentures

Background/purposeThis retrospective study assessed the risks and complications associated with dental implants after jaw surgery and radiotherapy for large defects, highlighting challenges for reconstructive surgeons and prosthetic dentists. Materials and methodsFrom 2002 to 2008, National Taiwan University's Department of Maxillofacial Surgery used preoperative stereolithographic models and microvascular flaps for mandibular reconstruction in 18 patients with defects from ameloblastoma or advanced gingival cancer. They received free fibular flap grafts, followed by 46 osseointegrated dental implants. Patient outcomes, monitored for up to 60 months, were assessed through clinical and radiographic evaluations of implant success. ResultsThe overall survival rate of dental implants following tumor surgery and radiotherapy was 84.8%. Seven implants failed due to peri-implantitis (3), tumor recurrence (2), and osteoradionecrosis (ORN) (2). The ameloblastoma group did not contribute to implant failure, with 4 implant failures in the stage III gingival cancer group, and 3 implant failures in the stage IV gingival cancer group. ConclusionFollowing segmental mandibulectomy for mandible lesions, free fibular bone graft reconstruction restored mandible continuity, while subsequent dental implantation and overdenture fabrication restored occlusion and aesthetics for patients. Besides considering treatment strategies for ameloblastoma groups, similar approaches can be extended to oral cancer patients undergoing post-operative reconstruction. However, additional considerations (peri-implant soft tissue condition, tumor recurrence, ORN, etc.) are necessary for oral cancer patients predisposed to dental implant failure post-surgery.

Design and evaluation of a deep learning-based automatic segmentation of maxillary and mandibular substructures using a 3D U-Net

BackgroundCurrent segmentation approaches for radiation treatment planning in head and neck cancer patients (HNCP) typically consider the entire mandible as an organ at risk, whereas segmentation of the maxilla remains uncommon. Accurate risk assessment for osteoradionecrosis (ORN) or implant-based dental rehabilitation after radiation therapy may require a nuanced analysis of dose distribution in specific mandibular and maxillary segments. Manual segmentation is time-consuming and inconsistent, and there is no definition of jaw subsections. Materials and methodsThe mandible and maxilla were divided into 12 substructures. The model was developed from 82 computed tomography (CT) scans of HNCP and adopts an encoder-decoder three-dimensional (3D) U-Net structure. The efficiency and accuracy of the automated method were compared against manual segmentation on an additional set of 20 independent CT scans. The evaluation metrics used were the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and surface DSC (sDSC). ResultsAutomated segmentations were performed in a median of 86 s, compared to manual segmentations, which took a median of 53.5 min. The median DSC per substructure ranged from 0.81 to 0.91, and the median HD95 ranged from 1.61 to 4.22. The number of artifacts did not affect these scores. The maxillary substructures showed lower metrics than the mandibular substructures. ConclusionsThe jaw substructure segmentation demonstrated high accuracy, time efficiency, and promising results in CT scans with and without metal artifacts. This novel model could provide further investigation into dose relationships with ORN or dental implant failure in normal tissue complication prediction models.

Risk factors associated with the development of osteoradionecrosis (ORN) in Head and Neck cancer patients in Ireland: A 10-year retrospective review

Background and PurposesTo assess osteoradionecrosis (ORN) incidence in a population of Irish Head and Neck cancer (HNC) patients, and assess precipitating factors that may contribute to ORN development to aid prevention. Materials and MethodsReview of 1050 HNC patients attending the Dental Oncology Clinic, CUDSH between 2010 and 2021 identified 47 cases of ORN. Medical, dental and radiotherapy records of these forty-seven patients were retrospectively reviewed. Patient-, tumour-, and treatment-related variables were investigated in association with osteoradionecrosis development. Analysis conducted using SPSS, Pearson’s Chi-square test (p < 0.05), and ordinal regression model. ResultsORN incidence was 4.4 %. Median time from radiotherapy (RT) to ORN development was 9.5 months (range 1–98.5 months). ORN development within the mandibular surgical site was significant (p <.001), presenting at a higher Notani grade (p =.002), in mid-mandibular body region (p =.028), at radiation doses ≥ 60 Gy (p =.035), due to induced causes (p =.029), and without resolution (p =.019). ConclusionThis is the first retrospective study of ORN in HNC patients in Ireland over 10-year period. ORN incidence was extremely low (4.4%). As patients reported high smoking/alcohol use and poor dental attendance pre-diagnosis, this suggests intensive dental intervention pre/post-diagnosis contributed to low ORN rates. Mandibular surgery pre-RT increased risk of developing ORN at the surgical site. Therefore, we recommend future treatment planning should contour the surgical site, designating it an organ at risk (OAR), assigning a dose constraint, where oncologically possible, with emphasis on reducing the hot-spot to this region; findings reinforce importance of life-long expert dental care to reduce ORN incidence.

Osteoradionecrosis incidence in pre-radiation teeth extractions: A prospective study.

To evaluate osteoradionecrosis (ORN) incidence in a cohort of patients undergoing tooth extraction (TE) before radiotherapy (RT) for head and neck cancers. The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (ID-2132) and registered at clinicaltrials.gov (ID: NCT04009161). TE was performed in case of signs of pericoronitis, periapical lesions, restorative impossibility, severe periodontitis. ORN was defined as exposed bone at an unhealed post-extraction socket in the absence of oncological recurrence. The RT plans were reviewed, and each post-extractive socket was contoured to calculate the received radiation dose. In total, 156 patients with 610 TE were enrolled. The mean follow-up was 567 days. ORN was diagnosed in four patients (2.6% of patients and 0.7% of TE). Need for osteotomy and radiation dose at the extraction site were associated with ORN (OR for osteotomy: 21.9, 95% CI: 2.17-222.2, p = 0.009; OR for RT dose: 1.1, 95% CI: 1-1.15, p = 0.05). TE appears to be a significant risk factor for ORN, particularly when osteotomy is required, and post-extraction sockets receive a high RT dosage. This study proposes a decision-making algorithm for TE and outlines a straightforward surgical protocol.

Incidence and Factors Associated With the Development of Calvarial Osteoradionecrosis in Patients Treated for Cutaneous Malignancies

Study Design Retrospective cohort study. Objective Calvarial osteoradionecrosis (ORN) is a rare but devastating complication of radiotherapy. The aim of this study was to describe the cumulative incidence of Calvarial ORN in patients in patients treated for cutaneous malignancy of the scalp. Methods Data was compiled from patient records of a large tertiary hospital Plastic Surgery department and radiotherapy records of an affiliated cancer Center. We included all patients that were treated for cutaneous malignancies of the scalp that received radiotherapy. Patient demographics, cancer stage, treatment modalities, intraoperative details, and patient outcome data were recorded. Patients with incomplete radiotherapy data were excluded. Results We analyzed 105 radiotherapy treatments to the scalp administered to 84 patients and recorded 7 cases of calvarial ORN resulting in a gross incidence of 6.67% per radiotherapy treatment. The parietal bone was the most frequently targeted site of radiotherapy and accordingly the most common site of ORN (85.7%). Median time from radiotherapy dose to the development of ORN was 846 days. Higher number of radiotherapy fractionation ( P = .038), cumulative radiotherapy dose ( P = .035), prolonged radiotherapy duration ( P = .022) and skin grafting ( P = .003) were associated with the development of ORN. Conclusions Our findings suggest radiotherapy variables, such as prolonged radiotherapy duration, increased cumulative dose and higher radiotherapy fractions were strongly associated with the development of ORN. In addition, skin grafting following surgical resection was associated with the development of ORN. Further studies with larger sample sizes are required to further explore this relationship.

Dental caries and demineralization in head and neck cancer patients undergoing radiotherapy

The number of head and neck cancer (HNC) patients is steadily increasing, and the use of radiotherapy for treatment in this patient group has been associated with side effects such as mucositis, trismus, xerostomia, dental caries, periodontal disease, and osteoradionecrosis (ORN). Radiation caries (RC) can be atypical, and their treatment can be challenging. Preventing and treating RC become crucial as post-radiotherapy tooth extraction can pave the way for ORN. The aim of this review is to evaluate the restorative dental treatment for HNC patients before, during, and after radiotherapy. This includes examining the impact of radiotherapy on tooth decay and demineralization, and providing solutions to address these effects.

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.