Treatment and survival outcomes of oral squamous cell carcinoma patients submitted to photobiomodulation for the prevention of oral mucositis

Orientador: Alan Roger dos Santos SilvaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: Objetivo: Descrever os padrões de resposta ao tratamento e sobrevida em pacientes com carcinoma espinocelular (CEC) de cavidade oral submetidos à fotobiomodulação (FBM) profilática para mucosite oral (MO). Material e métodos: Estudo clínico longitudinal retrospectivo realizado entre os anos de 2009 e 2014, baseado em pacientes diagnosticados com CEC de cavidade oral (C02; C03; C04; C05; C06) que concluíram protocolos curativos de radioterapia (RT) adjuvante à cirurgia ou quimiorradioterapia (QRT), bem como protocolos profiláticos de FBM para MO (InGaAlP; 660 nm, 40 mW, densidade de energia 10 J/cm2; 10 s/ponto; spot size 4mm2). Os prontuários digitais dos pacientes incluídos no estudo foram avaliados para coleta e análise de dados clínicos referentes ao grau de MO (Common Terminology Criteria for Adverse Events, National Cancer Institute, Version 4.0, 2010). Adicionalmente, foram coletadas informações relacionadas aos padrões clínicos de resposta tumoral ao tratamento oncológico e sobrevida. Resultados: Cento e cinquenta e dois pacientes com doença avançada ao diagnóstico foram incluídos no estudo, 88 (57,9%) foram submetidos à cirurgia, 152 (100%) à radioterapia e 100 (65.8%) à quimioterapia. Após um período médio de 40,84 (±11,71) meses de acompanhamento pós-tratamento, as taxas de sobrevida global e sobrevida livre de doenças foram de 46,7% e 51,8%, respectivamente. Quarenta e cinco pacientes (29.6%) desenvolveram recorrência locorregional, 10 (6,57%) pacientes desenvolveram metástase à distância e 19 (12,5%) pacientes desenvolveram segundos tumores primários. Conclusão: Os resultados de resposta ao tratamento multimodal e de sobrevida descritos no presente estudo foram similares aos encontrados em estudos clínicos previamente publicados na literatura pertinente a pacientes com CEC de boca em estágios avançados. Em suma, protocolos contemporâneos de FMB profiláticos para a MO não parecem gerar impacto negativo na sobrevida de pacientes com CEC de bocaAbstract: Aim: To describe the patterns of treatment response and overall survival in patients with oral squamous cell carcinoma (OSCC) which were submitted to prophylactic photobiomodulation (PBM) for oral mucositis (OM). Material and Methods: This was a retrospective longitudinal clinical study carried out in the period between the years 2009 and 2014, based on patients diagnosed with OSCC (C02; C03; C05; C06) that have concluded curative protocols of radiotherapy (RT) adjuvant to surgery or chemoradiotherapy (CRT), as well as prophylactic protocols of PBM for OM (InGaAlP; 660nm, 40Mw, density of energy 10J/cm2; 10 s/spot; spot size 4mm2). Digital medical records of the patients included in the study were assessed for data collection and analysis of clinical data referent to the OM grade (Common Terminology Criteria for Adverse Events, National Cancer Institute, Version 4.0, 2010). Additionally, data related to clinical patterns of tumor response to oncological treatment and overall survival were collected. Results: One hundred and fifty-two patients with advanced disease at the diagnosis were included in the study, 88 (57.9%) were submitted to surgery, 152 (100%) to RT and 100 (65.8%) to chemotherapy (QT). After a mean time of 40.84 (±11,71) months of post-treatment follow-up the overall survival and disease-free survival rates were 46.7% and 51.8%, respectively. Forty-five patients (29.6%) developed locoregional recurrence, 10 (6.57%) patients developed distant metastasis and 19 (12.5%) patients developed second primary tumors. Conclusion: The results of the response to multimodality treatment and of overall survival described in the present study were similar to the results found in clinical trials previously published in the literature regarding patients with OSCC in advanced stages. In conclusion, contemporary protocols of prophylactic PBM for OM do not seem to cause a negative impact on the overall survival of patients with OSCCDoutoradoEstomatologiaDoutora em Estomatopatologi

Insights into immune responses in oral cancer through proteomic analysis of saliva and salivary extracellular vesicles

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOThe development and progression of oral cavity squamous cell carcinoma (OSCC) involves complex cellular mechanisms that contribute to the low five-year survival rate of approximately 20% among diagnosed patients. However, the biological processes essential to tumor progression are not completely understood. Therefore, detecting alterations in the salivary proteome may assist in elucidating the cellular mechanisms modulated in OSCC and improve the clinical prognosis of the disease. The proteome of whole saliva and salivary extracellular vesicles (EVs) from patients with OSCC and healthy individuals were analyzed by LC-MS/MS and label-free protein quantification. Proteome data analysis was performed using statistical, machine learning and feature selection methods with additional functional annotation. Biological processes related to immune responses, peptidase inhibitor activity, iron coordination and protease binding were overrepresented in the group of differentially expressed proteins. Proteins related to the inflammatory system, transport of metals and cellular growth and proliferation were identified in the proteome of salivary EVs. The proteomics data were robust and could classify OSCC with 90% accuracy. The saliva proteome analysis revealed that immune processes are related to the presence of OSCC and indicate that proteomics data can contribute to determining OSCC prognosis.The development and progression of oral cavity squamous cell carcinoma (OSCC) involves complex cellular mechanisms that contribute to the low five-year survival rate of approximately 20% among diagnosed patients. However, the biological processes essential to tumor progression are not completely understood. Therefore, detecting alterations in the salivary proteome may assist in elucidating the cellular mechanisms modulated in OSCC and improve the clinical prognosis of the disease. The proteome of whole saliva and salivary extracellular vesicles (EVs) from patients with OSCC and healthy individuals were analyzed by LC-MS/MS and label-free protein quantification. Proteome data analysis was performed using statistical, machine learning and feature selection methods with additional functional annotation. Biological processes related to immune responses, peptidase inhibitor activity, iron coordination and protease binding were overrepresented in the group of differentially expressed proteins. Proteins related to the inflammatory system, transport of metals and cellular growth and proliferation were identified in the proteome of salivary EVs. The proteomics data were robust and could classify OSCC with 90% accuracy. The saliva proteome analysis revealed that immune processes are related to the presence of OSCC and indicate that proteomics data can contribute to determining OSCC prognosis5FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2009/54067-3; 2010/19278-0470549/2011-4; 301702/2011-0; 470268/2013-1

Integrative analysis to select cancer candidate biomarkers to targeted validation

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOTargeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS.Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS6414363543652FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2009/54067-3; 2010/19278-0; 2011/22421-2; 2009/53839-2470567/2009-0; 470549/2011-4; 301702/2011-0; 470268/2013-

Obturator Prostheses For Melanotic Neuroectodermal Tumor Of Infancy In The Maxilla.

Melanotic neuroectodermal tumor of infancy frequently affects the maxilla. A communication between the oral and nasal cavities can be created by surgery. The authors rehabilitated a young patient with obturator prostheses to correct feeding. The association of the obturators with orthodontic devices provided proper maxillary growth and eruption of teeth. The outcomes were very satisfactory after a 3-year follow-up, and dental implants are planned.27e64-6

Osteonecrosis of the mandible associated with bevacizumab therapy

Bevacizumab is a humanized antibody that blocks vascular endothelial growth factor and is of great value for the treatment of advanced cancer. Several adverse effects following its administration have been reported. To date, only 8 cases of osteonecrosis of the jaws associated with bevacizumab (without any association with bisphosphonates) have been reported. The aim of this article was to describe an original case of bevacizumab-related osteonecrosis of the jaw. A 61-year-old man diagnosed with advanced renal cell carcinoma was undergoing treatment with intravenous bevacizumab and temsirolimus when he spontaneously developed mandible osteonecrosis, which resolved after 3 months of conservative management. The present case reinforces recent speculation that the anti-angiogenic properties of bevacizumab may represent a potential new source of osteonecrosis of the jaws in patients undergoing cancer treatment. Multidisciplinary teams in cancer care should be aware of the possible association between osteonecrosis of the jaw and bevacizumab therapy.Bevacizumab is a humanized antibody that blocks vascular endothelial growth factor and is of great value for the treatment of advanced cancer. Several adverse effects following its administration have been reported. To date, only 8 cases of osteonecrosis of the jaws associatedwith bevacizumab (without any association with bisphosphonates) have been reported. The aim of this article was to describe an original case of bevacizumab-related osteonecrosis of the jaw. A 61-year-old man diagnosed with advanced renal cell carcinoma was undergoing treatment with intravenous bevacizumab and temsirolimus when he spontaneously developed mandible osteonecrosis, which resolved after 3 months of conservative management. The present case reinforces recent speculation that the anti-angiogenic properties of bevacizumabmay represent a potential new source of osteonecrosis of the jaws in patients undergoing cancer treatment. Multidisciplinary teams in cancer care should be aware of the possible association between osteonecrosis of the jaw and bevacizumab therapy1156e32e3

Is photobiomodulation therapy effective in reducing pain caused by toxicities related to head and neck cancer treatment? : a systematic review

Photobiomodulation therapy (PBMT) has been considered an effective method for preventing and managing certain cancer-related toxicities in head and neck cancer (HNC) patients treated with radiotherapy and chemotherapy. However, the potential effects of PBMT on pain control and analgesia resulting from these toxicities is still controversial. The aim of this systematic review was to compile available evidence of the effects of PMBT on pain control and reduced use of analgesics in HNC patients. We searched three indexed databases: MEDLINE/PubMed, Embase, and Scopus. The databases were reviewed up to and including December 2018. Only human clinical studies in English language were selected. Information was only available for mucositis and radiodermatitis. Fifteen out of 1112 studies met the inclusion criteria (14 for oral mucositis (OM) and 1 for radiodermatitis). From the 14 studies involving the prevention and treatment of OM, 10 had the study subjects compared to a placebo group. Of these 10 studies, all but 1 showed statistically significant difference related to pain control favoring the PBMT group. The study that compared PBMT with other treatment modality showed better results in pain control with PBMT. It appears that PBMT application frequency and potency impact on pain control. The only study involving the prevention and treatment of radiodermatitis was compared to placebo arm and showed statistically significant difference related to pain control favoring the PBMT group. Seven studies compared the need of analgesic medication between PBMT and placebo groups. Of these, five studies showed that the use of analgesic medication was significantly higher in the placebo group. The current evidence supports that PBMT is effective in pain control resulting from OM and radiodermatitis and may also reduce the need for analgesics. The evidence is not yet available of the effects of PBMT in other HNC treatment-related toxicities271140434054CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São PauloNão tem2018/02233-6; 2013/18402-8; 2012/06138-

PAPEL DA EQUIPE DE ODONTOLOGIA NA REDUÇÃO DA PNEUMONIA ASSOCIADA À VENTILAÇÃO MECÂNICA EM UNIDADE DE TERAPIA INTENSIVA DE UM CENTRO DE REFERÊNCIA EM ONCOLOGIA

Introdução/objetivo: A pneumonia Associada à Ventilação Mecânica (PAV) é uma das infecções hospitalares mais prevalentes em pacientes internados em Unidade de Terapia Intensiva (UTI). Tendo em vista a relação entre a presença de patógenos orais e o desenvolvimento de infecções respiratórias, o profissional habilitado em Odontologia Hospitalar, ao realizar procedimentos de prevenção, detecção e remoção de focos infecciosos orais, poderia contribuir na prevenção da PAV. O presente estudo tem como objetivo avaliar o papel da equipe de odontologia na redução da PAV em UTI oncológica. Método: Estudo retrospectivo de avaliação de intervenção, em hospital público oncológico universitário de São Paulo. Foram incluídos adultos internados em UTI sob ventilação mecânica (VM) há mais de 48 horas, de 01/2021 a 05/2023. Comparativo entre 2 UTIs que somam 70 leitos. Os pacientes da UTI A foram submetidos à intervenção da equipe de odontologia: avaliação da cavidade bucal e higiene oral (escova com sucção e clorexidina 0,12%) 1 × /dia; a enfermagem realizou higiene com swab oral e clorexidina 0,12% nos demais períodos. Os pacientes da UTI B foram atendidos pela odontologia sob demanda (pedido de interconsulta pelo intensivista) e a enfermagem realizou higienização oral 3 × /dia (swab oral e clorexidina 0,12%). Durante a intervenção, foi atualizado o protocolo de higiene oral em pacientes sob VM e realizado treinamento para a equipe assistencial das 2 UTIs, com participação da odontologia. O bundle de PAV seguiu sendo aplicado pela equipe assistencial nas UTIs. Períodos avaliados foram: pré intervenção (PrI) 01-08/2021, durante intervenção (DuI) 09/2021-06/2022 e pós (PoI) 07/2022-05/2023. Os desfechos avaliados foram densidade de incidência de PAV (DI PAV) e mortalidade nos 10 dias após o diagnóstico de PAV nos 3 períodos (PrI, DuI e PoI). Resultados: Foram identificados 74 casos de PAV (41 PrI, 13 DuI e 20 PoI). A DI PAV (1000 VM-dia) nos 3 períodos foi de 8,6 PrI, 2,5 DuI e 3,7 PoI. A DI PAV (1000 VM-dia) na UTI A foi de 10,0 no PrI para 2,6 DuI e 0,8 no PoI. Na UTI B também houve redução da média de DI PAV (1000 VM-dia) de 5,2 no PrI para 2,2 DuI, que não se manteve no PoI (5,4 PAV/1000 VM-dia). A mortalidade em 10 dias foi de 52,7% (70,7% PrI, 38,5% DuI e 35% PoI). Conclusão: O presente estudo demonstrou que a atuação da Odontologia Hospitalar na UTI pode contribuir na redução da incidência de PAV e da mortalidade associada em pacientes críticos oncológicos

Cost-effectiveness of photobiomodulation therapy for the prevention and management of cancer treatment toxicities: a systematic review

To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3–4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy. There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicitiesCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQnão tem2018/02233-6; 2018/23479-