Cytoprotective Effect of Gallic Acid against Injuries Promoted by Therapeutic Ionizing Radiation in Preosteoblast Cells.

Gallic acid (GA) is a powerful antioxidant extracted from plants of the Brazilian Cerrado. Oxidative stress plays an important role in the occurrence of radiation-induced osteonecrosis in patients treated for head and neck cancer. There is a need to develop research aimed at developing complementary therapies to prevent or reverse bone damage. The aim of the present study was to investigate the effect of GA in preosteoblasts exposed to therapeutic ionizing radiation. MC3T3-E1 preosteoblast cells were treated with 10 µM GA and exposed to 6 Gy ionizing radiation. We performed in vitro assays of cell proliferation, oxidative stress analysis by detection of reactive oxygen species, and alkaline phosphatase assay. GA at lower concentrations was able to significantly increase proliferation and inhibit radiation-induced generation of reactive oxygen species in osteoblast precursor cells, despite ionizing radiation-induced injury. Furthermore, GA significantly increased alkaline phosphatase at a dose of 6 Gy. The findings suggested that GA could attenuate ionizing radiation-induced injuries in osteoblast precursor cells. Moreover, in vivo studies are needed to better investigate the role of GA in osteonecrosis, especially in cancer patients undergoing radiotherapy or taking antiresorptive drugs.

Is the use of Pentoxifylline and Tocopherol effective in the treatment of Osteoradionecrosis of the jaws or for the treatment of medicationosteonecrosis of the jaw? An overview.

PURPOSE: The aim of the present study was to determine the methodological quality of systematic reviews that evaluated the effectiveness of pentoxifylline and tocopherol (PENTO) in the treatment of osteoradionecrosis of the jaw (ORNJ) and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Searches were performed in Databases including PubMed, Scopus, LILACS, DARE, Cochrane Library, and SIGLE through OpenGrey until March 2024, were evaluated by two independent reviewers to answer the following question: Is the use of PENTO protocol effective in the treatment of ORNJ or for the treatment of MRONJ? RESULTS: A total of 256 articles were initially identified; however, following the use of appropriate inclusion and exclusion criteria, five systematic reviews were identified for detailed analysis. The final study sample comprised 588 patients: 397 patients with ORN and 197 patients with MRONJ who were treated with PENTO. The total recovery of individuals who used the PENTO protocol was 62,2 % for ORN and 100 % for MRONJ, with a follow-up period of 1 month to 10 years. The methodological quality of the studies was assessed using the AMSTAR 2 tool, in which four were of low quality and 1 moderate quality. CONCLUSION: The treatment of ORN and MRONJ with pentoxifylline and tocopherol has shown good results in the studies presented, with a partial or total reduction in bone exposure. However, the low quality of the relevant reports highlights the need for primary and secondary studies with better methodological rigor to reduce bias and provide reassurance for this treatment option.

Osteoradionecrosis in a Torus Mandibularis Treated by Antimicrobial Photodynamic Therapy: A Case Report.

Background: Osteoradionecrosis (ORN) of the jaws is a late complication after radiotherapy to head and neck cancer. Objective: To describe a rare case of ORN of the torus mandibularis that was successfully managed exclusively with antimicrobial photodynamic therapy (aPDT). Case report: A 72-year-old man presented an exposed necrotic bone observed in the torus mandibularis, extending to the lingual alveolar ridge with no edema nor suppuration. The treatment provided a noninvasive treatment leading to spontaneous sequestrectomy of the torus in 2 weeks with complete mucosal repair in 5 weeks and absence of lesion signs and/or symptoms even after 6 months of follow-up. Conclusions: The aPDT indicated to be a satisfactory treatment for ORN affecting torus mandibularis, a region with surgical limitations, avoiding surgery.

Extranodal natural killer/T cell lymphoma nasal type simulating osteoradionecrosis with metachronic B lymphoma in the pelvis: Case report.

Extranodal Natural Killer/T Cell Lymphoma Nasal Type (EN-NK/T-CL-NT) is a non-Hodgkin extranodal lymphoma of unfavorable prognosis due to its aggressive nature. This neoplasm mainly affects the paranasal sinuses, nasopharynx, oropharynx, oral cavity, palate, and rarely intestinal, gastric and skin regions. 50-year-old female with a history of lymphoma in nasal and pelvic region. At four years of tumors-free, has facial asymmetry, accompanied by sub-palpebral, nasal and lip edema. Intraoral examination revealed a large ulceration suggestive of osteoradionecrosis. Gum biopsy shows Extranodal NK/T Cell Lymphoma Nasal Type (EN-NK/T-CL-NT). In this case we highlight the characteristics of EN-NK/T-CL-NT with a presentation of osteoradionecrosis-like. Unfortunately, the nature of this tumor led to the patient's death. Clinical follow-up of patients with cancer is imperative to mend and/or decrease treatment complications, as well as to identify second primary tumors or the spread of the underlying disease.

The impact of radiation caries on morbidity and mortality outcomes of head and neck squamous cell carcinoma patients.

AIMS: Radiation caries (RC) is a highly prevalent and chronic complication of head and neck radiotherapy (HNRT) and presents a challenge for clinicians and patients. The present study aimed to assess the impact of RC on the morbidity and mortality outcomes of head and neck squamous cell carcinoma (HNSCC) patients. METHODS AND RESULTS: Patients were divided into three groups: (1) RC (n = 20), (2) control (n = 20), and (3) edentulous (n = 20). Information regarding the number of appointments, dental procedures, osteoradionecrosis (ORN), prescriptions, and hospital admissions were collected. Mortality outcomes were assessed through disease-free survival (DFS) and overall survival (OS) rates. RC patients required more dental appointments (p < .001), restorations (p < .001), extractions (p = .001), and antibiotic and analgesic prescriptions (p < .001). Kaplan-Meier subgroup analyses showed a significantly increased risk of ORN in RC compared to edentulous patients (p = .015). RC patients presented lower DFS rates (43.2 months) than the control and edentulous groups (55.4 and 56.1 months, respectively). CONCLUSIONS: RC impacts morbidity outcomes among cancer survivors due to increased demand for medication prescriptions, multiple specialized dental appointments, invasive surgical treatments, increased risk of ORN, and increased need for hospital admissions.

Treatment of osteoradionecrosis of the jaw with injectable platelet-rich fibrin (i-PRF): case series / Tratamento de osteorradionecrose dos maxilares com fibrina rica em plaquetas injetável (i-PRF): série de casos

Objective: This study evaluated the use of autogenous blood concentrate (injectable platelet-rich fibrin) [i-PRF] for promoting soft tissue healing in osteoradionecrosis (ORN) lesions in patients who underwent head and neck radiotherapy. Material and Methods: This study included five ORN lesions in four patients who were treated with i-PRF (applied weekly for 4 weeks to the lesions). Soft tissue features were evaluated through clinical analysis at baseline and at 7, 15, 30, 60, and 90 days after the first session of i-PRF. Extension of the bone lesions was evaluated radiographically. Patient-centered related outcomes were evaluated using quality-of-life questionnaires at baseline and 90 days after the first treatment session. Quality of life data were analyzed using descriptive and frequency statistics and the Wilcoxon test. Results: Of the 5 treated lesions, 1 was completely closed and 3 remained open. The open lesions showed increased necrotic tissue exposure. No changes were observed in the radiographic appearance of the lesions. There was also no impact on the patient's quality of life. Conclusion: The results suggest that the majority of ORN lesions remained stable after the application of i-PRF, with a slight improvement in the quality of the mucosa around the lesions. Furthermore, it was observed that i-PRF did not compromise the quality of life of patients during treatment.(AU)

Objetivo: Este estudo avaliou o uso de concentrado de sangue autógeno (fibrina rica em plaquetas injetável) [i-PRF] para promover a cicatrização de tecidos moles em lesões de osteorradionecrose (ORN) em pacientes submetidos a radioterapia de cabeça e pescoço. Material e Métodos: Este estudo incluiu cinco lesões de ORN em quatro pacientes tratados com i-PRF (aplicado semanalmente por 4 semanas nas lesões). As características do tecido mole foram avaliadas por meio de análises clínicas no início e aos 7, 15, 30, 60 e 90 dias após a primeira sessão de i-PRF. A extensão das lesões ósseas foi avaliada radiograficamente. Os resultados centrados no paciente foram avaliados usando questionários de qualidade de vida no início e 90 dias após a primeira sessão de tratamento. Os dados de qualidade de vida foram analisados usando estatísticas descritivas e de frequência, além do teste de Wilcoxon. Resultados: Das 5 lesões tratadas, 1 foi completamente fechada e 3 permaneceram abertas. As lesões abertas mostraram aumento na exposição de tecido necrótico. Não foram observadas mudanças na aparência radiográfica das lesões. Também não houve impacto na qualidade de vida do paciente. Conclusão: Os resultados sugerem que a maioria das lesões de ORN permaneceu estável após a aplicação de i-PRF, com uma discreta melhora na qualidade da mucosa ao redor das lesões. Além disso, observou-se que a i-PRF não comprometeu a qualidade de vida dos pacientes durante o tratamento.(AU)

Riesgo de osteorradionecrosis de los maxilares según el tipo de radioterapia / Risk of Osteoradionecrosis of the Jaws according to Type of Radiotherapy

Introducción: El cáncer de cabeza y cuello es el séptimo más común a nivel mundial. Las opciones terapéuticas para su manejo incluyen la radioterapia, la cual debe procurar un equilibrio entre la eliminación del tumor y la preservación del tejido sano porque su aplicación implica el riesgo de desarrollar una osteorradionecrosis de los maxilares. Objetivo: Valorar si el riesgo de que se produzca osteorradionecrosis de los maxilares varía en función del tipo de radioterapia. Métodos: Diseño documental, retrospectivo basado en los principios de las revisiones sistemáticas exploratorias según lo establece la lista de chequeo PRISMA Extension for Scoping Reviews (PRISMA-ScR). Se realizaron búsquedas en inglés y español en PubMed, LILACS, ScienceDirect, Tripdatabase y Epistemonikos. Resultados: En total se incluyeron 12 estudios publicados entre 2016 y 2022 con diversos diseños de investigación; el estudio de cohorte retrospectivo fue el que tuvo mayor representación. Se analizaron distintas opciones de radioterapia y sus protocolos, entre ellos, la radioterapia de intensidad modulada, la terapia de protones de intensidad modulada, la radioterapia corporal estereotáctica y la radioterapia tridimensional. La literatura refiere que los protocolos que implican dosis totales más bajas representan un menor riesgo de osteorradionecrosis. Conclusiones: El riesgo de osteorradionecrosis de los maxilares debe atribuirse, en mayor medida, a la dosis total de radiación recibida por el paciente y a la dosis por fracción que al tipo de radioterapia(AU)

Introduction: Head and neck cancer is the seventh most common cancer worldwide. Therapeutic options for its management include radiotherapy, which should seek a balance between tumor elimination and preservation of healthy tissue because its application implies the risk of developing osteoradionecrosis of the jaws. Objective: To assess whether the risk of developing osteoradionecrosis of the jaws varies according to the type of radiotherapy. Methods : Documentary, retrospective design based on the principles of exploratory systematic reviews as established by the PRISMA Extension for Scoping Reviews (PRISMA-ScR) checklist. PubMed, LILACS, ScienceDirect, Tripdatabase and Epistemonikos were searched in English and Spanish. Results: In total, 12 studies published between 2016 and 2022 with various research designs were included; the retrospective cohort study had the highest representation. Different radiotherapy options and their protocols were analyzed, including intensity-modulated radiotherapy, intensity-modulated proton therapy, stereotactic body radiotherapy, and three-dimensional radiotherapy. The literature refers that protocols involving lower total doses represent a lower risk of osteoradionecrosis. Conclusions: The risk of osteoradionecrosis of the jaws should be attributed, to a greater extent, to the total radiation dose received by the patient and the dose per fraction than to the type of radiotherapy(AU)

Use of Phototherapy and Er-YAG Laser in the Management of Mandible Osteoradionecrosis: A Case Report.

Introduction: Osteoradionecrosis (ORN) is a secondary complication from radiotherapy, which is difficult to manage and significantly reduces the life quality of the affected patients. Case Report: A 59-year-old female patient, diagnosed with infiltration by squamous cell carcinoma in the left cervical region, underwent adjuvant cervical-facial radiotherapy with a total dose of 66.6 Gy of radiation. Eight years after the diagnosis, the patient underwent multiple extractions and, subsequently, the installation of osseointegrated implants, evolving to extensive intraoral bone exposure associated with oral cutaneous fistula. The patient was initially exposed to photobiomodulation therapy (PBMT), with a low-power laser at wavelengths of 660 nm and 808 nm, and thereafter to antimicrobial photodynamic therapy (aPDT). After an improvement in the clinical condition and resolution of the oral cutaneous fistula, a surgical procedure with the Er: YAG laser was performed to remove the remaining necrotic bone. Once the ORN condition was completely treated, the patient's oral rehabilitation was implemented by the installation of an upper mucous-supported total prosthesis and a lower implant-supported prosthesis. Conclusion: The patient is in a clinical follow-up and has no signs of bone necrosis recurrence, suggesting that low and high-power laser treatment can be an effective therapeutic alternative to resolve this condition.

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

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

Machine learning for the prediction of toxicities from head and neck cancer treatment: A systematic review with meta-analysis.

INTRODUCTION: The aim of the present systematic review (SR) is to summarize Machine Learning (ML) models currently used to predict head and neck cancer (HNC) treatment-related toxicities, and to understand the impact of image biomarkers (IBMs) in prediction models (PMs). The present SR was conducted following the guidelines of the PRISMA 2022 and registered in PROSPERO database (CRD42020219304). METHODS: The acronym PICOS was used to develop the focused review question (Can PMs accurately predict HNC treatment toxicities?) and the eligibility criteria. The inclusion criteria enrolled Prediction Model Studies (PMSs) with patient cohorts that were treated for HNC and developed toxicities. Electronic database search encompassed PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, LILACS, and Gray Literature (Google Scholar and ProQuest). Risk of Bias (RoB) was assessed through PROBAST and the results were synthesized based on the data format (with and without IBMs) to allow comparison. RESULTS: A total of 28 studies and 4,713 patients were included. Xerostomia was the most frequently investigated toxicity (17; 60.71 %). Sixteen (57.14 %) studies reported using radiomics features in combination with clinical or dosimetrics/dosiomics for modelling. High RoB was identified in 23 studies. Meta-analysis (MA) showed an area under the receiver operating characteristics curve (AUROC) of 0.82 for models with IBMs and 0.81 for models without IBMs (p value < 0.001), demonstrating no difference among IBM- and non-IBM-based models. DISCUSSION: The development of a PM based on sample-specific features represents patient selection bias and may affect a model's performance. Heterogeneity of the studies as well as non-standardized metrics prevent proper comparison of studies, and the absence of an independent/external test does not allow the evaluation of the model's generalization ability. CONCLUSION: IBM-featured PMs are not superior to PMs based on non-IBM predictors. The evidence was appraised as of low certainty.

A incidência de osteorradionecrose em pacientes com câncer de cavidade oral tratados por radioterapia de intensidade modulada (IMRT): uma revisão sistemática e meta-análise / The incidence of osteoradionecrosis in oral cavity cancer patients treated with intensity-modulated radiotherapy (IMRT): a systematic review and meta-analysis

Os valores de incidência de osteorradionecrose dos maxilares reportados ao longo das últimas décadas variaram. Nos estudos que reportam baixos valores de incidência de osteorradionecrose através do uso de técnicas de radioterapia, que começaram a entregar altas dose de radiação ao volume tumoral alvo poupando tecidos circunjacentes sadios, os cânceres de cavidade oral frequentemente estão atrelados a maior parte dos casos, tornando a realidade dos resultados de incidência contraditórios, uma vez que a presença de coortes mistas, com cânceres em diferentes localizações de cabeça e pescoço, dão poucos ou nenhum dado específico para os pacientes com câncer de cavidade oral. Com o objetivo de avaliar a incidência de osteorradionecrose em pacientes com câncer de cavidade oral tratados com a radioterapia de intensidade modulada e os fatores de risco que influenciam no desenvolvimento e subsequentemente, a incidência culmulativa de osteorradionecrose, foi realizada uma revisão sistemática com meta-análise da literatura registrada na plataforma preferenciais para revisão sistemática e metanálise sob o registro de protocoloco CRD42021295524. Inicialmente foram elaboradas estratégias de buscas para seis bases de dados, que resultaram em 884 artigos, posteriormente transportados para o aplicativo online Rayyan® para a primeira seleção. Após a exclusão de 200 duplicatas, 689 registros foram avaliados por título e resumo, sendo eleitos para análise completa do texto, 87. Por fim, 11 estudos foram incluídos para a síntese qualitativa e desses, 6 foram incluídos também para a síntese quantitativa. Em 1.434 pacientes com câncer de cavidade oral tratados por radioterapia de intensidade modulada, 150 desenvolveram osteorradionecrose. A incidências brutas individuais dos estudos variaram de 0 a 20,7%, com tempo médio entre o fim da radioterapia e o diagnóstico de osteorradionecrose de 31,7±9,7 meses em um acompanhamento médio de 46,2±13,1 meses. Os fatores mais correlacionados ao desenvolvimento da osteorradionecrose foram cirurgia préradioterapia (12%), tumores localizados em assoalho bucal ou língua (4%), carcinoma de células escamosas (42%) e mandíbula (80%). A meta-análise dos 6 estudos revelou a incidência acumulada de 8% (I2 = 0%, t2 = 0, p = 0,84). Oito dos 11 artigos incluídos tiveram o risco de viés avaliados como moderado e três como baixo. Podemos concluir que a radioterapia de intensidade modulada foi efetiva na preservação dos ossos da mandíbula e maxila que resultou em um baixo índice de incidência de osteorradionecrose em um sítio de alto risco como a cavidade oral. (AU)

The reported incidence values of jaw osteoradionecrosis have varied over the past decades. In studies reporting low incidence rates of osteoradionecrosis through the use of radiotherapy techniques that started delivering high radiation doses to the target tumor volume while sparing surrounding healthy tissues, oral cavity cancers are often associated with the majority of cases. This has led to contradictory incidence results, as the presence of mixed cohorts, with cancers in different head and neck locations, provides limited to no specific data for patients with oral cavity cancer. In order to assess the incidence of osteoradionecrosis in oral cavity cancer patients treated with intensity-modulated radiotherapy and the risk factors influencing its development and subsequent cumulative incidence, a systematic review with meta-analysis of the literature registered in the preferred platform for systematic review and meta-analysis under protocol registration CRD42021295524 was conducted. Initially, search strategies were developed for six databases, resulting in 884 articles, which were subsequently imported into the online Rayyan® application for the initial selection. After excluding 200 duplicates, 689 records were evaluated by title and abstract, with 87 selected for full-text analysis. Finally, 11 studies were included for qualitative synthesis, and of those, 6 were also included for quantitative synthesis. Among 1,434 oral cavity cancer patients treated with intensity-modulated radiotherapy, 150 developed osteoradionecrosis. Individual raw incidence rates in the studies ranged from 0 to 20.7%, with a mean time between the end of radiotherapy and osteoradionecrosis diagnosis of 31.7±9.7 months in an average follow-up of 46.2±13.1 months. The factors most correlated with osteoradionecrosis development were preradiotherapy surgery (12%), tumors located in the floor of the mouth or tongue (4%), squamous cell carcinoma (42%), and mandibular involvement (80%). Meta-analysis of the 6 studies revealed a cumulative incidence of 8% (I2 = 0%, t2 = 0, p = 0.84). Eight of the 11 included articles had their bias risk assessed as moderate, and three as low. In conclusion, intensity-modulated radiotherapy was effective in preserving the jaw and maxilla bones, resulting in a low incidence of osteoradionecrosis in a high-risk site like the oral cavity (AU)

Análise fractal do osso mandibular e a ocorrência de osteorradionecrose: um estudo transversal com grupo controle / Fractal analysis of mandibular bone and occurrence of osteoradionecrosis: a cross-sectional study with control group

A radioterapia (RT) é amplamente utilizada para o tratamento do câncer em região de cabeça e pescoço. A osteorradionecrose (ORN) é uma das mais severas complicações desta modalidade terapêutica. Todos os pacientes tratados com radioterapia são considerados de alta risco para o desenvolvimento da ORN, devido à falta de fatores preditivos dessa comorbidade, a morbidade e a imprevisibilidade da resposta ao tratamento. A análise fractal é utilizada para descrever a complexidade de uma estrutura e avaliar anormalidades e gravidade de distúrbios da arquitetura óssea. Entretanto, poucos estudos utilizaram a análise fractal para avaliar a estrutura óssea de pacientes submetidos à RT em região de cabeça e pescoço. Portanto, o objetivo deste trabalho foi avaliar a dimensão fractal (DF) e lacunaridade do osso mandibular em indivíduos submetidos à RT para tratamento de câncer de cabeça e pescoço, comparando aqueles desenvolveram ORN (grupo caso) com aqueles que não desenvolveram ORN (grupo controle). O estudo foi aprovado pelo Comitê de Ética em Pesquisa da UFMG (CAAE 30560820.9.0000.5149). É um estudo transversal com grupo controle, no qual 34 pacientes foram incluídos e divididos em grupo caso (com ORN, n=17) e grupo controle (sem ORN, n=17). Uma radiografia panorâmica digital, adquirida após o término da RT, foi avaliada para cada paciente. A DF e lacunaridade do osso mandibular foram determinados usando o software ImageJ. Foi realizada análise estatística bivariada, bem como análise da curva ROC. A significância foi estabelecida em p< 0,05. Os valores médios de DF e lacunaridade não foram significativamente diferentes entre os grupos. A área sob a curva para DF foi de 0,576 e para lacunaridade foi de 0,626. O ponto de corte encontrado para DF foi ≤1,1736 e >0,4155 para lacunaridade, os quais classificaram corretamente casos e controles. A maioria dos pacientes com ORN (92.9%) tiveram DF> 1.1736 e todos os controles tiveram DF≤ 1.1736 (p< 0.001). Para a lacunaridade, a maioria dos pacientes com ORN (71.4%) apresentaram valor > 0.4155 e todos os controles tiveram valor ≤ 0.4155 (p< 0.001). Em conclusão, os pontos de corte da DF e lacunaridade do osso mandibular, estabelecidos pela análise de radiografias panorâmicas, puderam classificar corretamente pacientes com ORN e sem ORN.

Radiotherapy (RT) is widely used in the treatment of head and neck cancer. Osteoradionecrosis (ORN) is one of the most severe complication of this therapeutic modality. All patients treated with RT are considered at high risk for the development of ORN, due to the lack of predictive factors for ORN, the morbidity, and the unpredictable response to treatment. Fractal analysis is used to describe the complexity of a structure and to assess abnormalities and the severity of bone architecture disorders. However, few studies have used fractal analysis to assess the bone structure of patients undergoing RT in head and neck region. Therefore, the aim of this study was to evaluate the FD and lacunarity of the mandibular bone in individuals who received radiation therapy for HNC, comparing those who had developed ORN to those who had not developed ORN (control group). The study was approved by the Research Ethics Committee of the Universidade Federal de Minas Gerais (certificate number: 30560820.9.0000.5149). This is a cross-sectional study with a control group and thirty-four patients were included and divided into case group (with ORN, n=17) and control group (without ORN, n=17). One digital panoramic radiograph acquired after the end of RT was evaluated for each patient. FD and lacunarity of the mandibular bone were determined using ImageJ software. Bivariate statistics was done, as well as ROC curve analysis. Significance was stablished at p< 0.05. The mean FD and lacunarity values were not significantly different between the groups. The area under the curve for FD and lacunarity were 0.576 and 0.626, respectively. The cut-off point found for FD was ≤1.1736 and >0.4155 for lacunarity, allowing us to correctly classify cases and controls. Most participants in the case group (92.9%) had a FD >1.1736 and all participants in the control group had a FD ≤ 1.1736 (p < 0.001). For lacunarity, most individuals in the case group (71.4%) had a value >0.4155 and all participants in the control group had a value ≤0.4155 (p <0.001). Conclusion: The cut-off values of FD and lacunarity of mandibular bone, assessed on panoramic radiographs, differ between patients with and without ORN.

Effects of systemic Anatolian propolis administration on a rat-irradiated osteoradionecrosis model

Abstract Objective Radiotherapy after head and neck cancer is associated with the risk of osteonecrosis development. This study aims to investigate the effectiveness of systemic propolis application to prevent the disease as it has no definite treatment protocol despite the proposed treatment methods and significantly decreases individuals' quality of life. Methodology In total, 29 male Wistar-Albino rats were divided into control, 35 Gy irradiation (Group 1), 35 Gy irradiation+100 mg/kg/ml propolis administration (Group 2), and 35 Gy irradiation+200 mg/kg/ml propolis administration groups (Group 3). Propolis was first applied on the day after radiotherapy, except for the control group. Right first and second molars were extracted from all rats three weeks following radiotherapy. Samples were collected seven weeks after radiotherapy. Osteoblast and osteoclast counts were calculated by histomorphometric analysis. Immunohistochemical analysis determined bone morphogenic protein-2 (BMP-2) and transforming growth factor beta-3 (TGFβ-3). Results Group comparison found non-significant differences regarding osteoblast (p=0.130) and osteoclast (p=0.063) counts. However, Group 1 showed the lowest mean osteoblast (OBL: 82.63 [±13.10]) and highest mean osteoclast counts (OCL: 12.63 [±5.55]). OBL/OCL ratio showed significant differences between groups (p=0.011). Despite the significant difference between the Control and Groups 1 (p=0.006) and 2 (p=0.029), Group 3 showed a non-significant difference (p=0.091). For BMP-2 and TGFB3, the control group showed significant differences with the other two groups (p<0.001), except for Group 3. Conclusion Anatolian propolis showed beneficial effects in a radiotherapy-mediated osteonecrosis model, highlighting its potential as a promising intervention.

Clinical dental management of the head and neck irradiated patient: topics of interest for clinicians

To discuss important topics regarding the dental procedures performed in patients before, during and after the radiotherapy treatment. The biological effects of ionizing radiation on bone tissue focusing on clinical care will be described. The invasive and not invasive procedures after radiotherapy treatment in the head and neck region will be addressed using scientific evidences to determine the appropriate moment for tooth extractions, periodontal management, and preventive procedures for osteoradionecrosis. Methods: Thirty-three studies including original studies and reviews were selected in MEDLINE database (PubMed). No year of publication restriction was applied. Language was restricted to the English, and the following Medical Subject Heading terms were used: radiotherapy, osteoradionecrosis, dental management. Studies of osteoradionecrosis involving clinical management of irradiated patients, with an emphasis on updated guidelines and protocols were selected. Results: Care in dental procedures were related about restorative treatment, endodontic treatment, rehabilitation for edentulous regions using prostheses and implants and periodontal procedures before, during and after RTX treatment. Conclusions: The dental procedures should and can be performed before, during but also after radiotherapy. However, the clinical procedures should be less invasive as possible. A maintenance plan that reduces the necessity for major and more invasive treatments after radiotherapy is recommended

Efficacy of photobiomodulation therapy on healing of ionizing irradiated bone: a systematic review of in vivo animal studies.

This systematic review aimed to answer the research focused question: What are the effects of photobiomodulation (PBM) therapy on bone healing after ionizing irradiation in animal models? The EMBASE, LILACS, LIVIVO, PubMed, Scopus, and Web of Science databases, including gray literature, were searched using the following keywords: "Head and Neck Neoplasms"; "Ionizing Radiation"; "Low-Level Light Therapy"; and "Bone regeneration", focusing on the primary studies that assessed the effects of PBM therapy on animal models of irradiated bone. Six studies have met the eligibility criteria and presented an overall regular quality according to the risk of bias assessment tools. All the studies utilized rat animal model and near-infrared laser PBM at low power output setting. Most of the studies showed increased new bone formation, osteocytes, osteoblasts, and vascularization networking, as a result of PBM therapy. However, only one out of the six studies has not shown any differences in bone healing in both lased and non-lased animal groups. Nevertheless, PBM therapy is a potential tool to improve bone healing induced by ionizing radiation. However, due to the scarce number of studies and the great variability of laser parameters and treatment protocols, a clear conclusion cannot be drawn. Hence, extensive preclinical in vivo studies are warranted to ensure these beneficial effects have been addressed prior to translational clinical trials.

Secondary primary tumor mimicking osteoradionecrosis.

Nasopharyngeal carcinoma (NPC) is a malignant tumor rarely found in the head and neck, representing about 1% of all malignancies. The main treatment for NPC is radiation therapy, which is often given in combination with chemotherapy. However, such treatment may lead to long-term complications, including second primary tumors (SPTs) and osteoradionecrosis (ORN). Both complications have similar radiological characteristics, which can lead to erroneous diagnoses. This paper describes a case of a second primary tumor in a patient after 20 years of radiotherapy in the area where a previous extraction was performed, mimicking an osteoradionecrosis process.

The role of hyperbaric oxygen therapy in the treatment of radiation lesions.

INTRODUCTION: Cancer remains one of the leading causes of death worldwide, with 50-60% of patients requiring radiotherapy during the course of treatment. Patients' survival rate has increased significantly, with an inevitable increase in the number of patients experiencing side effects from cancer therapy. One such effect is late radiation injuries in which hyperbaric oxygen therapy appears as complementary treatment. With this work we intend to divulge the results of applying hyperbaric oxygen therapy among patients presenting radiation lesions in our Hyperbaric Medicine Unit. MATERIALS AND METHODS: Retrospective analysis of clinical records of patients with radiation lesions treated at the Hyperbaric Medicine Unit assessed by the scale Late Effects of Normal Tissues-Subjective, Objective, Management, Analytical (LENT-SOMA) before and after treatment, between October 2014 and September 2019 were included. Demographic characteristics, primary tumor site, subjective assessment of the LENT-SOMA scale before and after treatment were collected and a comparative analysis (Students t test) was done. RESULTS: 88 patients included: 33 with radiation cystitis, 20 with radiation proctitis, 13 with osteoradionecrosis of the mandible and 22 with radiation enteritis. In all groups, there was a significant decrease (p < 0.005) in the subjective parameter of the LENT-SOMA scale. DISCUSSION: Late radiation lesions have a major influence on patients' quality of life. In our study hyperbaric oxygen therapy presents as an effective therapy after the failure of conventional treatments. CONCLUSION: Hyperbaric oxygen therapy is an effective complementary therapy in the treatment of refractory radiation lesions.

To extract or not extract teeth prior to head and neck radiotherapy? A systematic review and meta-analysis.

PURPOSE: Teeth with poor prognosis are generally recommended to be extracted prior to head and neck radiotherapy (RT) to reduce the risk of developing osteoradionecrosis (ORN), although controversies have been reported. The present systematic review aimed to determine whether tooth extraction prior to head and neck RT may be associated with a reduced risk of developing ORN compared to dental extraction during or after RT. METHODS: The review protocol was registered in PROSPERO (CRD42021241631). The review was reported according to the PRISMA checklist and involved a comprehensive search of PubMed, Scopus, Embase, Cochrane Library, LILACS, and Web of Science, in addition to the gray literature. The selection of studies was performed in two phases by two reviewers independently. The risk of bias of individual studies was analyzed using the Joanna Briggs Institute checklist for cross-sectional studies, and the certainty of evidence was assessed using the GRADE tool. RESULTS: Twenty-eight observational studies were included in the qualitative synthesis, which showed substantial heterogeneity regarding the association between the timing of tooth extraction and ORN development. Twenty-seven of 28 studies were pooled in a meta-analysis that demonstrated a significant association between an increased risk of ORN and post-RT tooth extraction (odds ratio: 1.98; 95% CI: 1.17-3.35; p = 0.01). CONCLUSION: It was confirmed with moderate certainty that dental extractions should be performed prior to the start of head and neck RT to reduce the risk of ORN.

Autologous platelet concentrates in extraction sockets for the prevention of osteoradionecrosis: a systematic review of controlled clinical trials.

This systematic review aimed to assess whether the use of autologous platelet concentrates immediately after tooth extraction would prevent ORN in patients treated with radiotherapy (RT) for head and neck cancer (HNC). MEDLINE, Embase, Ovid, Scopus, Web of Science, CENTRAL Cochrane, and OpenGrey databases were searched (up to, and including, June 2021) by two independent reviewers to identify studies, followed by further manual search. As inclusion and exclusion criteria for the studies, only controlled clinical trials (randomized or not) were considered. The risk of bias of each included study was assessed using the Cochrane Risk of Bias Tool. Of the 129 potentially eligible studies, only 2 were included, both randomized controlled clinical trials; however, one used platelet-rich plasma and another leukocyte- and platelet-rich fibrin. Overall, both autologous platelet concentrates had no effect on the outcome assessed. The use of autologous platelet concentrates seems not to be beneficial for ORN prevention following tooth extractions in HNC patients treated with RT; however, according to the available evidence, a reliable statement cannot be made.

Risk factors for jaw osteoradionecrosis: a case control study

Abstract There are divergences among studies regarding features associated to increased risk of osteoradionecrosis (ORN). Our objective was to identify factors that predispose to the development of ORN of the jaw. This was a retrospective, hospital-based, case-control study involving patients with head and neck cancer who had been treated with ≥ 60 Gy external radiotherapy (RT) to the jaw. A total of 19 cases of ORN and 43 controls were included. The patients' demographic data, tumor type, staging, treatment and outcome information, and pre-treatment oral status were collected. Univariate analysis showed that the oral cavity/oropharynx sites were associated with 9.77-fold increased risk of ORN development compared to other sites (p = 0.005). Being an active smoker was associated with 3.95-fold increased risk of ORN development (p = 0.01). A tendency towards increased risk of ORN was observed particularly when tooth extraction occurred after RT (odds ratio (OR): 3.04; p = 0.08). Multivariable analysis showed that tumor site was the only significant risk factor (OR: 21.03, p = 0.01). The oral and oropharyngeal primary site is an important risk factor for ORN. Dental extraction, which did not occur in 28% of the sample, was not an essential event for ORN development.