Comparison of deep-learning multimodality data fusion strategies in mandibular osteoradionecrosis NTCP modelling using clinical variables and radiation dose distribution volumes.

Objective.Normal tissue complication probability (NTCP) modelling is rapidly embracing deep learning (DL) methods, acknowledging the importance of spatial dose information. Finding effective ways to combine information from radiation dose distribution maps (dosiomics) and clinical data involves technical challenges and requires domain knowledge. We propose different multi-modality data fusion strategies to facilitate future DL-based NTCP studies.Approach.Early, joint and late DL multi-modality fusion strategies were compared using clinical and mandibular radiation dose distribution volumes. These were contrasted with single-modality models: a random forest trained on non-image data (clinical, demographic and dose-volume metrics) and a 3D DenseNet-40 trained on image data (mandibular dose distribution maps). The study involved a matched cohort of 92 osteoradionecrosis cases and 92 controls from a single institution.Main results.The late fusion model exhibited superior discrimination and calibration performance, while the join fusion achieved a more balanced distribution of the predicted probabilities. Discrimination performance did not significantly differ between strategies. Late fusion, though less technically complex, lacks crucial inter-modality interactions for NTCP modelling. In contrast, joint fusion, despite its complexity, resulted in a single network training process which included intra- and inter-modality interactions in its model parameter optimisation.Significance.This study is a pioneering effort in comparing different strategies for including image data into DL-based NTCP models in combination with lower dimensional data such as clinical variables. The discrimination performance of such multi-modality NTCP models and the choice of fusion strategy will depend on the distribution and quality of both types of data. Multiple data fusion strategies should be compared and reported in multi-modality NTCP modelling using DL.

Potential of combined red and near-infrared photobiomodulation to mitigate pro-osteoclastic and inflammatory gene expression in human mandibular osteogenic cells.

Appropriate regeneration of jawbone after dental or surgical procedures relies on the recruitment of osteoprogenitor cells able to differentiate into matrix-producing osteoblasts. In this context, photobiomodulation (PBM) has emerged as promising therapy to improve tissue regeneration and to facilitate wound healing processes. The aim of this study was to determine the effect of PBM on human osteoprogenitor cells isolated from mandibular trabecular bone.Bone marrow stromal cell cultures were established from 4 donors and induced toward osteogenic differentiation for 14 days in a standard osteogenic assay. Cells were irradiated with a combined red/near-infrared (NIR) laser following different schedules and expression of osteogenic, matrix-related, osteoclastogenic and inflammatory genes was analyzed by quantitative PCR.Gene expression analysis revealed no overall effects of PBM on osteogenic differentiation. However, a statistically significant reduction was observed in the transcripts of COL1A1 and MMP13, two important genes involved in the bone matrix homeostasis. Most important, PBM significantly downregulated the expression of RANKL, IL6 and IL1B, three genes that are involved in both osteoclastogenesis and inflammation.In conclusion, PBM with a red/NIR laser did not modulate the osteogenic phenotype of mandibular osteoprogenitors but markedly reduced their expression of matrix-related genes and their pro-osteoclastogenic and pro-inflammatory profile.

Prevalence of free flap failure in mandibular osteoradionecrosis reconstruction: a systematic review and meta-analysis.

Our study aimed to estimate the prevalence of total free flap failure following free flap reconstruction for mandibular osteoradionecrosis (mORN) and assess the impact of potential moderators on this outcome. A comprehensive systematic literature search was independently conducted by two reviewers using the Medline, Scopus, Web of Science and Cochrane Library databases. Quality assessment of the selected studies was performed, and prevalence estimates with 95% confidence intervals (CI) were calculated. Outlier and influential analyses were conducted, and meta-regression analyses was employed to investigate the effects of continuous variables on the estimated prevalence. Ultimately, forty-six eligible studies (involving 1292 participants and 1344 free flaps) were included in our meta-analysis. The findings of our study revealed a prevalence of 3.1% (95% CI 1.3-5.4%) for total free flap failure after reconstruction for mORN. No study was identified as critically influential, and meta-regression analysis did not pinpoint any potential sources of heterogeneity. These findings provide valuable insights for researchers and serve as a foundation for future investigations into the management of mandibular osteoradionecrosis and the prevention of free flap failure in this context.

Prognostic Factors of Mandibular Osteoradionecrosis Including Accurate Colocalization of Avulsions and Dosimetric Dental Mapping Software, a Case-control Study.

PURPOSE: Osteoradionecrosis (ORN) of the mandible remains a significant complication in the intensity modulated radiation therapy (IMRT) era. Dental dose cannot be predicted from heterogeneous IMRT dose distributions; mandibular dose metrics cannot guide dentist avulsion decisions in high-risk ORN situations. Using a mapping tool to report dental root dose, avulsions, and ORN sites, we re-examined ORN risk factors in a case-control study. METHODS AND MATERIALS: From 2008 to 2019, 897 consecutive patients with oral cavity/oropharynx or unknown primary cancer undergoing IMRT were analyzed to identify ORN cases. These were matched (1 ORN/2 controls) retrospectively for tumor location, surgery, and tobacco consumption in a monocentric case-control study. Univariate and multivariate analyses integrated ORN factors and accurate dental dose data (grouped into 4 mandibular sectors). Generalizability was investigated in a simulated population database. RESULTS: A total of 171 patients were included. The median follow-up was 5.2 and 4.5 years in the ORN and control groups, respectively. The median time to ORN was 12 months. In univariate analysis, post-IMRT avulsions at the ORN site (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.5-8.9; P = .005), tumor laterality (HR, 4.4; 95% CI, = 1.4-14, P = .01), mean mandibular dose (HR, 1.1; 95% CI, = 1.01-1.1; P = .018) and mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) correlated with higher ORN risk. In multivariate analysis, mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) and post-IMRT avulsions at the ORN site (HR, 4.6; 95% CI, = 1.5-14.7; P = .009) were associated with ORN. For each increase in gray in dental dose, the ORN risk increased by 12%. Simulations confirmed study observations. CONCLUSIONS: Dental dose and avulsions are associated with ORN, with a 12% increase in risk with each additional gray. Accurate dose information can help dentists in their decisions after IMRT.

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.

PURPOSE: Given 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. METHODS AND MATERIALS: The analysis was conducted on retrospective data of 1259 patients with head and neck cancer treated at The University of Texas MD Anderson Cancer Center between 2005 and 2015. During a minimum 12-month posttherapy 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 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. RESULTS: The K-means clustering method identified 6 clusters among the DVHs. Based on the first 5 clusters, the dose-volume space was partitioned by the soft-margin support vector machine 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 preradiation dental extraction status (a statistically significant, nondose related risk factor for ORN) was reported as the corresponding risk index. CONCLUSIONS: This study presents an unsupervised-learning analysis of a large-scale data set to evaluate the risk of mandibular ORN among patients with head and neck cancer. The results provide a visual risk-assessment tool for ORN (based on the whole DVH and preradiation dental extraction status) as well as a range of constraints for dose optimization under different risk levels.

Irradiation Induced Biochemical Changes in Human Mandibular Bone: A Raman Spectroscopic Study.

Understanding the biochemical changes in irradiated human mandible after radiotherapy of cancer patients is critical for oral rehabilitation. The underlying mechanism for radiation-associated changes in the bone at the molecular level could lead to implant failure and osteoradionecrosis. The study aimed to assess the chemical composition and bone quality in irradiated human mandibular bone using Raman spectroscopy. A total of 33 bone biopsies from 16 control and 17 irradiated patients were included to quantify different biochemical parameters from the Raman spectra. The differences in bone mineral and matrix band intensities between control and irradiated groups were analyzed using unpaired Student's t-test with statistical significance at p < 0.05. Findings suggest that the intensity of the phosphate band is significantly decreased and the carbonate band is significantly increased in the irradiated group. Further, the mineral crystallinity and carbonate to phosphate ratio are increased. The mineral to matrix ratio is decreased in the irradiated group. Principal component analysis (PCA) based on the local radiation dose and biopsy time interval of irradiated samples did not show any specific classification between irradiation sub-groups. Irradiation disrupted the interaction and bonding between the organic matrix and hydroxyapatite minerals affecting the bone biochemical properties. However, the normal clinical appearance of irradiated bone would have been accompanied by underlying biochemical and microscopical changes which might result in radiation-induced delayed complications.

Empirical modeling of the percent depth dose for megavoltage photon beams.

INTRODUCTION: This study presents an empirical method to model the high-energy photon beam percent depth dose (PDD) curve by using the home-generated buildup function and tail function (buildup-tail function) in radiation therapy. The modeling parameters n and µ of buildup-tail function can be used to characterize the Collimator Scatter Factor (Sc) either in a square field or in the different individual upper jaw and lower jaw setting separately for individual monitor unit check. METHODS AND MATERIALS: The PDD curves for four high-energy photon beams were modeled by the buildup and tail function in this study. The buildup function was a quadratic function in the form of [Formula: see text] with the main parameter of d (depth in water) and n, while the tail function was in the form of e-µd and was composed by an exponential function with the main parameter of d and µ. The PDD was the product of buildup and tail function, PDD = [Formula: see text]. The PDD of four-photon energies was characterized by the buildup-tail function by adjusting the parameters n and µ. The Sc of 6 MV and 10 MV can then be expressed simply by the modeling parameters n and µ. RESULTS: The main parameters n increases in buildup-tail function when photon energy increased. The physical meaning of the parameter n expresses the beam hardening of photon energy in PDD. The fitting results of parameters n in the buildup function are 0.17, 0.208, 0.495, 1.2 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The parameter µ can be treated as attenuation coefficient in tail function and decreases when photon energy increased. The fitting results of parameters µ in the tail function are 0.065, 0.0515, 0.0458, 0.0422 of four-photon energies, 4 MV, 6 MV, 10 MV, 18 MV, respectively. The values of n and µ obtained from the fitted buildup-tail function were applied into an analytical formula of Sc = nE(S)0.63µE to get the collimator to scatter factor Sc for 6 and 10 MV photon beam, while nE, µE, S denotes n, µ at photon energy E of field size S, respectively. The calculated Sc were compared with the measured data and showed agreement at different field sizes to within ±1.5%. CONCLUSIONS: We proposed a model incorporating a two-parameter formula which can improve the fitting accuracy to be better than 1.5% maximum error for describing the PDD in different photon energies used in clinical setting. This model can be used to parameterize the Sc factors for some clinical requirements. The modeling parameters n and µ can be used to predict the Sc in either square field or individual jaws opening asymmetrically for treatment monitor unit double-check in dose calculation. The technique developed in this study can also be used for systematic or random errors in the QA program, thus improves the clinical dose computation accuracy for patient treatment.

Refining the mandibular osteoradionecrosis rat model by in vivo longitudinal µCT analysis.

Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients. Today, our lack of knowledge about the physiopathology restricts the development of new treatments. In this study, we refined the ORN rat model and quantitatively studied the progression of the disease. We tested the impact of radiation doses from 20 to 40 Gy, delivered with incident 4MV X-ray beams on the left mandible of the inbred Lewis Rat. We used micro-computed tomography (µCT) to obtain in vivo images for longitudinal bone imaging and ex vivo images after animal perfusion with barium sulphate contrast agent for vessel imaging. We compared quantification methods by analyzing 3D images and 2D measurements to determine the most appropriate and precise method according to the degree of damage. We defined 25 Gy as the minimum irradiation dose combined with the median molar extraction necessary to develop non-regenerative bone necrosis. µCT image analyses were correlated with clinical and histological analyses. This refined model and accurate methods for bone and vessel quantification will improve our knowledge of the progression of ORN pathology and allow us to test the efficacy of new regenerative medicine procedures.

[Impact of neck dissection in N2-3 oropharyngeal squamous cell carcinomas treated with definitive chemoradiotherapy: An observational real-life study]. / Impact du curage ganglionnaire cervical dans la prise en charge par chimioradiothérapie exclusive des cancers de l'oropharynx de stade N2-3 : étude observationnelle en vie réelle.

PURPOSE: The purpose of this study was to assess the efficacy in terms of neck failure of an initial neck dissection before definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinomas, as well as the dosimetric impact and the acute and delayed morbidity of this approach. MATERIALS AND METHODS: All patients consecutively treated between 2009 and 2018 with definitive chemoradiotherapy using intensity-modulated conformal radiotherapy (IMRT) for a histologically proven N2-3 oropharyngeal squamous cell carcinomas were retrospectively included. The therapeutic approach consisted of induction chemotherapy, followed by cisplatine-based chemoradiotherapy preceded or not by neck dissection. Neck dissection was discussed on a case-by-case basis in a dedicated multidisciplinary tumour board for patients with a dissociated response to induction chemotherapy, defined as a better response on the primary than on the node. Chemoradiotherapy without neck dissection was systematically performed in case of a major lymph node response to induction chemotherapy (decrease in size of 90% or more). Intensity-modulated radiotherapy using a simultaneous-integrated boost delivered 70Gy in 35 fractions on macroscopic tumour volumes, 63Gy on intermediate-risk levels or extra-nodal extension and 54Gy on prophylactic lymph node areas. RESULTS: Two groups were constituted: 47 patients without an initial neck dissection (62.7%), and 28 patients with a neck dissection prior to definitive chemoradiotherapy (37.3%). Initial patient characteristics were not statistically different between the two groups. The median follow-up was 60.1months (range: 3.2-119months). Incidence of neck failure was higher in patients without neck dissection (P=0.015). The neck failure rate at 5years was 19.8% (95% confidence interval: 7.4-30.6%; P=0.015) without neck dissection versus 0% following neck dissection. All lymph node failures occurred in the planned target volume at 70Gy. Upfront neck dissection suggested a decrease in the mean dose received by the homolateral parotid gland (P=0.01), mandible (P=0.02), and thyroid gland (P=0.02). Acute toxicity of chemoradiotherapy after neck dissection suggested a reduction in grade≥3 adverse events (P=0.04), early discontinuation of concomitant chemotherapy (P=0.009) and feeding tube-dependence (P=0.008) in univariate analysis. During follow-up, there was no difference between the two groups in terms of xerostomia, dysgeusia, dysphagia or gastrostomy dependence in univariate analysis. CONCLUSION: Neck dissection prior to definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinoma was associated with high neck control without additional mid and long-term morbidity.

Comparison of machine learning methods for prediction of osteoradionecrosis incidence in patients with head and neck cancer.

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

Intraoperative Stromal Vascular Fraction Therapy Improves Histomorphometric and Vascular Outcomes in Irradiated Mandibular Fracture Repair.

BACKGROUND: Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction. METHODS: Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with stromal vascular fraction treatment. Irradiated groups received a fractioned dose of 35 Gy before mandibular osteotomy. Stromal vascular fraction was harvested from the inguinal fat of isogenic donors, centrifuged, and placed intraoperatively into the osteotomy site. All mandibles were evaluated for bony union and vascularity using micro-computed tomography before histologic analysis. RESULTS: Union rates were significantly improved in the irradiated fracture with stromal vascular fraction treatment group (82 percent) compared to the irradiated fracture group (25 percent) and were not statistically different from the fracture group (100 percent). Stromal vascular fraction therapy significantly improved all metrics of bone vascularization compared to the irradiated fracture group and was not statistically different from fracture. Osteocyte proliferation and mature bone formation were significantly reduced in the irradiated fracture group. Bone cellularity and maturity were restored to nonirradiated levels in the irradiated fracture with stromal vascular fraction treatment group despite preoperative irradiation. CONCLUSIONS: Vascular and cellular depletion represent principal obstacles in the reconstruction of irradiated bone. This study demonstrates the efficacy of stromal vascular fraction therapy in remediating these damaging effects and provides a promising foundation for future studies aimed at developing noncultured, cell-based therapies for clinical implementation.

Mandibular metastases in neuroblastoma: Outcomes and dental sequelae.

BACKGROUND: Although metastatic involvement of bony sites including cranial bones is common in neuroblastoma (NB), mandibular metastases (MM) are uncommon, and specific outcomes have not been reported upon in the modern therapeutic era. METHODS: In this retrospective study, medical records on patients with MM from NB were reviewed. Statistical analysis was performed using the Kaplan-Meier method. RESULTS: Of 29 patients, nine (31%) had MM at diagnosis, whereas in 20 (69%) MM were first detected at NB relapse at a median time of 26 (6-89) months from diagnosis. Median maximal diameter of lesions was 3 (range 0.8-4.9) cm. MM were unilateral in 83% of patients, with ascending ramus (55%) and mandibular body (38%) being the two most common sites. All patients received systemic chemotherapy, and 26 (93%) patients received radiotherapy to MM. At a median follow-up of 37.3 (24.2-219.5) months, eight of nine patients with MM at diagnosis did not experience mandibular progressive disease. Eighteen of 20 patients with MM at relapse received therapeutic radiotherapy; objective responses were noted in 78%. Seventy-two percent (5/18) had not experienced relapse within the radiation field at a median of 12 (2-276) months postradiotherapy. Dental findings at follow-up after completion of NB therapy included hypodontia, hypocalcification of enamel, and trismus. Median 3-year overall survival in patients with relapsed MM was 51 ± 12% months from relapse. CONCLUSION: MM when detected at diagnosis is associated with a prognosis similar to that for other skeletal metastases of NB. Radiotherapy is effective for control of MM detected both at diagnosis and relapse. Significant dental abnormalities posttherapy warrant regular dental evaluations and appropriate intervention.

Osteoradionecrosis: Exposing the Evidence Not the Bone.

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

Comparing two radiotherapy techniques of whole central nervous system tumors, considering tumor and critical organs' dose provided by treatment planning system and direct measurement.

AIMS: In central nervous system (CNS) tumors, surgery combined with radiotherapy may cure many tumors. The basic technique in conventional radiotherapy is craniospinal radiotherapy; in this technique, spinal cord can be treated with electron or photon beams. This study was aimed to compare two radiotherapy techniques in craniospinal radiotherapy, (a) treatment of spine with a single photon beam and (b) with a combination of photon and electron beams. MATERIALS AND METHODS: The two techniques were planned. In the first technique, both brain and spine were irradiated with 6 MV photon beams. In the second technique, brain was irradiated with 6 MV photon and spine with 18 MeV electron beams. To compensate the dose deficiency in lumbar area, an anterior field of 15 MV photon beam was also applied in the second technique. The dose to target volume and organ at risks (OARs) were measured by thermoluminescent dosimeter and compared with the corresponding values calculated by Isogray treatment planning system. RESULTS: OARs including heart, mandible, thyroid, and lungs received lower dose from technique 2 compared with technique 1; kidneys were exceptions which received higher dose in the technique 2. CONCLUSIONS: The dose to thyroid, mandible, heart, and lungs were lower in technique 2, while kidneys received higher dose in technique 2. This was caused by using the anterior 15 MV photon beam. Based on these results, for children, instead of photon beam for treatment of spinal cord, it is wiser to use electron beam.

Aumento da hiperdensidade da cortical óssea línguo-basal após radioterapia em região de cabeça e pescoço: relato de caso / Hyperdensity of the lingual-basal bone cortex incresead after radiotherapy in the head and neck region: case report

Objetivo: relatar um caso de aumento da hiperdensidade da cortical óssea línguo-basal pós-radioterapia em região de cabeça e pescoço por meio de avaliação imaginológica. Relato de caso: paciente do sexo feminino, 80 anos, procurou tratamento odontológico com a finalidade de reabilitação oral com implantes dentários. Na anamnese, relatou histórico de carcinoma espinocelular em regiões distintas da cavidade oral. No exame clínico, notou-se que a paciente era edêntula total e foi solicitado um exame de tomografia computadorizada de feixe cônico. Foi observado, na região anterior inferior, aumento da hiperdensidade da cortical óssea línguo-basal, com osso compacto mais espesso, achado incomum na literatura após radioterapia. Considerações finais: os efeitos da radioterapia em mandíbula estão relatados na literatura. No caso clínico em questão, detectou-se uma alteração pouco notada em pacientes submetidos à radioterapia, fazendo surgir novos questionamentos, sendo eles sobre o diagnóstico dessa modificação na estrutura óssea e suas repercussões. (AU)

Objective: to report a case of increased hyperdensity of the lingual-basal bone cortex after radiotherapy in the head and neck region by means of imaging evaluation. Case report: female patient, 80 years old, sought dental treatment for the purpose of oral rehabilitation with dental implants. In the anamnesis, she reported a history of squamous cell carcinoma in different regions of the oral cavity. Upon clinical examination, it was noted that the patient was total edentulous and a cone beam computed tomography examination was requested. An increase in the hyperdensity of the lingual-basal bone cortex was observed in the lower anterior region, with thicker compact bone, an unusual finding in the literature after radiotherapy. Final considerations: the effects of radiotherapy on the mandible are reported in the literature. In the clinical case in question, a little-noticed change was detected in patients undergoing radiotherapy, leading to new questions, concerning the diagnosis of this change in bone structure and its repercussions.(AU)

Dosimetric impact of switching from AAA to Acuros dose-to-water and dose-to-medium for RapidArc plans of nasopharyngeal carcinomas.

PURPOSE: This work aims to evaluate the dosimetric consequences of replacing the Anisotropic Analytical Algorithm (AAA) by Acuros XB (AXB), dose-to-water (Dw) or dose-to-medium (Dm), for RapidArc plans of nasopharyngeal carcinomas (NPC). MATERIALS AND METHODS: Seventeen NPC plans created with AAA (v15.6) were recalculated with AXB (v15.6) Dw and Dm. The dose-volume parameters to the planning target volumes (PTV) and relevant organs at risk (OAR) were compared. The high dose PTV was divided into bone, air and tissue components and the comparison was performed for each of them. RESULTS: AXB Dw revealed no significant differences in the PTVs compared to AAA. Lower values were observed to spinal cord, brainstem, oral cavity and parotids (0.5% to 2.3%), and higher values to cochleas (up to 5.4%) and mandible (up to 6.7%). AXB Dm predicted lower values than AAA for all PTVs and OARs (2.0% to 6.1%). For the bone PTV subvolume, AXB Dw and Dm predicted respectively higher (2.4%) and lower (2.2% to 3.4%) values. No significant differences were noted in air. AXB predicted lower values than AAA in soft tissues (0.4% to 1.6%). The largest difference was found to the mandible V60Gy parameter, with median differences of 6.7% for AXB Dw and -6.0% for AXB Dm. CONCLUSION: Significant dose differences are expected when switching from AAA to AXB in NPC cases. The dose prescriptions and the tolerance limits for some OARs, especially those of high density, may need to be adjusted depending on the selected dose calculation algorithm and reporting mode.

Assessment of irradiated socket healing in the rabbit's mandible: Experimental study.

As bone healing is altered after external radiation therapy, its evaluation is mandatory and lacks in clinical practice. The aim of the pilot study was to validate micro computed tomography (microCT) as a simple and reliable technique for assessing irradiated bone healing in the rabbit's mandible and compare with histologic findings. Nineteen rabbits (female New Zealand white) were used. The radiation protocol consisted of 5 sessions delivering 8.5 Gy each. MicroCT was performed at D0, D7, D14, D28 and D42 for the control group and D0, D28 and D42 for the irradiated group. A modified Perry's score was determined on histologic samples, and comparison between microCT and histological findings was performed. The main differences between irradiated and non-irradiated rabbits were observed at Day 28 and 42. There was a strong correlation between imaging and histologic findings. Radiation decreases bone quality and bone mineral density. As the correlation was strong between microCT and histologic findings, micro imaging could be considered as a simple and reliable technique to assess bone healing after radiation therapy and allows an easy comparison between samples, without invasive procedures. Great attention should be kept on the parameters and on the region of interest. The development of in-vivo microCT enlarges the perspectives of microCT use in experimental studies, avoiding invasive procedures, and preserving animal lives and well-being, and furthermore lead to clinical applications.

Development of a Rat Model of Mandibular Irradiation Sequelae for Preclinical Studies of Bone Repair.

Repairing mandibular bone defects after radiotherapy of the upper aerodigestive tract is clinically challenging. Although bone tissue engineering has recently generated a number of innovative treatment approaches for osteoradionecrosis (ORN), these modalities must be evaluated preclinically in a relevant, reproducible, animal model. The objective of this study was to evaluate a novel rat model of mandibular irradiation sequelae, with a focus on the adverse effects of radiotherapy on bone structure, intraosseous vascularization, and bone regeneration. Rats were irradiated with a single 80 Gy dose to the jaws. Three weeks after irradiation, mandibular bone defects of different sizes (0, 1, 3, or 5 mm) were produced in each hemimandible. Five weeks after the surgical procedure, the animals were euthanized. Explanted mandibular samples were qualitatively and quantitatively assessed for bone formation, bone structure, and intraosseous vascular volume by using micro-computed tomography, scanning electron microscopy, and histology. Twenty irradiated hemimandibles and 20 nonirradiated hemimandibles were included in the study. The bone and vessel volumes were significantly lower in the irradiated group. The extent of bone remodeling was inversely related to the defect size. In the irradiated group, scanning electron microscopy revealed a large number of polycyclic gaps consistent with periosteocytic lysis (described as being pathognomonic for ORN). This feature was correlated with elevated osteoclastic activity in a histological assessment. In the irradiated areas, the critical-sized defect was 3 mm. Hence, our rat model of mandibular irradiation sequelae showed hypovascularization and osteopenia. Impact statement Repairing mandibular bone defects after radiotherapy of the upper aerodigestive tract is clinically challenging. Novel tissue engineering approaches for healing irradiated bone must first be assessed in animal models. The current rat model of mandibular irradiation sequelae is based on tooth extraction after radiotherapy. However, the mucosal sequelae of radiotherapy often prevent the retention of tissue-engineered biomaterials within the bone defect. We used a submandibular approach to create a new rat model of mandibular irradiation sequelae, which enables the stable retention of biomaterials within the bone defect and should thus facilitate the assessment of bone regeneration.

Radiation Therapy and Mandibular Osteoradionecrosis: State of the Art.

PURPOSE OF REVIEW: This article aims to provide an update on literature data related to mandibular osteoradionecrosis (MORN) secondary to the irradiation of the head and neck region. RECENT FINDINGS: Radiotherapy (RT) plays a crucial role in the contemporary management of head and neck cancer (HNC) patients and, despite intensity-modulated technique (IMRT), mandibular osteoradionecrosis (MORN) remains a significant RT-related complication. Based on its clinical manifestation, MORN can negatively affect patients' quality of life. Preventive interventions should be prioritized. This manuscript is expected to represent an opportunity to guide a clear proposal for clinical measures in the individual MORN situations.

Effect of α2­macroglobulin in the early stage of jaw osteoradionecrosis.

Advanced osteoradionecrosis (ORN) is one of the most serious complications in patients with head and neck cancer, resulting in poor prognosis. Numerous studies have therefore focused on the pathogenesis and interventions of ORN early stage. The present study aimed to investigate whether α2­macroglobulin (α2M) could prevent early­stage jaw osteoradionecrosis caused by radiotherapy (RT). Following local injection of α2M, a single dose of 30 Gy was delivered to rats for pathological exploration. For 28 days, the irradiated mandible and soft tissues were examined for potential changes. Furthermore, primary human bone marrow mesenchymal stem cells pretreated with α2M followed by 8 Gy irradiation (IR) were also used. Tartrate­resistant acid phosphatase assay, terminal uridine deoxynucleotidyl nick end labeling assay and immunohistochemical staining were performed on irradiated mandibular bone, tongue or buccal mucosa tissues from rats. Cell proliferation was assessed by evaluating the cell morphology by microscopy and by using the cell counting kit­8. Fluorescence staining, flow cytometry and western blotting were conducted to detect the reactive oxygen species level, cell apoptosis and protein expression of superoxide dismutase 2 (SOD2), heme oxygenase­1 (HO­1) and phosphorylated Akt following irradiation. The results demonstrated that α2M attenuated physical inflammation, osteoclasts number and fat vacuole accumulation in mandibular bone marrow and bone marrow cell apoptosis following IR in vivo. Furthermore, α2M pretreatment suppressed the expression of 8­hydroxy­2'­deoxyguanosine in mandibular bone and tongue paraffin embedded sections, which is a marker of oxidative damage, and increased SOD2 expression in mucosa and tongue paraffin embedded sections. The present study demonstrated the efficient regulation of antioxidative enzymes, including SOD2 and heme oxygenase­1, and reduction in oxidative damage by α2M. In addition, in vitro results confirmed that α2M may protect cells from apoptosis and suppress reactive oxygen species accumulation. Overall, the present study demonstrated that α2M treatment may exert some radioprotective effects in early­stage ORN via antioxidant mechanisms, and may therefore be considered as a potential alternative molecule in clinical prophylactic treatments.