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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.

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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.

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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.

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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.

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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.

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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.

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.

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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)

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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.

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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.

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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.

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