Radioterapia preoperatoria en cáncer de mama como estrategia terapéutica, a propósito de un caso / Preoperative radiotherapy in breast cancer as a therapeutic strategy, case report

Múltiples estrategias terapéuticas se han desarrollado con el objetivo de optimizar el tratamiento del cáncer de mama, especialmente antes de ir a quirófano, desde la introducción de la quimioterapia preoperatoria por Fisher. Una de estas ha sido la radioterapia, la cual tiene beneficios claros en esa patología, pues reduce a la mitad el riesgo de recurrencia, y disminuye la muerte por cáncer de mama en aproximadamente una sexta parte después de cirugía conservadora. Aunque no se suele considerar antes de la cirugía, el uso de radioterapia preoperatoria en cáncer de mama, no es nuevo, y se ha demostrado que esta alternativa terapéutica es factible, bien tolerada y asociada a una tasa de respuesta patológica completa del 10 % -40 %. Se presenta el caso de una paciente con cáncer de mama metastásico, quien recibió múltiples esquemas de quimioterapia y a quien se le planteó radioterapia preoperatoria, recibiendo la misma con muy buena respuesta, sin aumentar la dificultad técnica para la realización de la intervención quirúrgica, y sin complicaciones asociadas a la herida operatoria. En la actualidad, existen pocos estudios clínicos sobre radioterapia preoperatoria, y su efecto en las pacientes con cáncer de mama localmente avanzado, es controvertido. Al observar en la biopsia definitiva respuesta patológica completa, es un indicio de cómo la radioterapia preoperatoria en cáncer de mama podría ser una opción en casos complejos con poca respuesta a la terapia convencional(AU)

Multiple therapeutic strategies have been developed with the aim of optimizing breast cancer (BC) treatment, especially preoperatively since the introduction of preoperative chemotherapy by Fisher. One of these has been radiation therapy (RT), which has clear benefits in breast cancer, halving the risk of recurrence andreducing breast cancer death byapproxmatelyone-sixth after breast-conserving surgery. Although not often considered for use prior to surgery, the use of preoperativeradiotherapy in localized breast cancer is not new andhas demonstrated that this therapeutic alternative is feasible, well tolerated and associated with a pathologic complete response rate of 10-40%. We present the case of a patient with metastatic breast cancer who received multiple chemotherapy schedules and who was considered preoperative radiotherapy, receiving the same with very good response, without increasing the technical difficulty for the performance of surgery, and without complications associated with the operative wound. At present, there are few clinical studies on preoperative radiotherapy, and its effect in patients with locally advanced breast cancer is controversial. And although this is a single case, observing a complete pathologic response in the definitive biopsy gives us a great indication of how preoperative radiotherapy in breast cancer could be an option in complex cases with little response to conventional therapy(AU)

AZD1775 and anti-PD-1 antibody synergistically sensitize hepatoma to radiotherapy / 中华医学杂志(英文版)

BACKGROUND@#Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.@*METHODS@#The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro . A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry.@*RESULTS@#Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro . AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 + /CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion.@*CONCLUSIONS@#This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

TRIP13 Enhances Radioresistance of Lung Adenocarcinoma Cells through the Homologous Recombination Pathway / 中国肺癌杂志

BACKGROUND@#Radiation therapy is one of the most common treatments for non-small cell lung cancer (NSCLC). However, the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients, and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge. This study aimed to identify the molecules associated with radioresistance in lung adenocarcinoma (LUAD), identified thyroid hormone receptor interactor 13 (TRIP13) as the main target initially, and explored whether TRIP13 is related to radioresistance in LUAD and the specific mechanism, with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic.@*METHODS@#Three datasets, GSE18842, GSE19188 and GSE33532, were selected from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (|log FC|>1.5, P<0.05) in each of the three datasets using the R 4.1.3 software, and then Venn diagram was used to find out the differentially expressed genes common to the three datasets. The screened differential genes were then subjected to protein-protein interaction (PPI) analysis and module analysis with the help of STRING online tool and Cytoscape software, and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database, and the TRIP13 gene was identified as the main molecule for subsequent studies. Subsequently, the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line, H292DR. The radioresistance of H292DR cells was verified using cell counting kit-8 (CCK-8) assay and clone formation assay. The expression levels of TRIP13 in H292 and H292DR cells were measured by Western blot. Small interfering RNA (siRNA) was used to silence the expression of TRIP13 in H292DR cells and Western blot assay was performed. The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing, followed by the detection of changes in the expression levels of proteins closely related to homologous recombination, such as ataxia telangiectasia mutated (ATM) protein.@*RESULTS@#Screening of multiple GEO datasets, validation of external datasets and survival analysis revealed that TRIP13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy. And the results of gene set enrichment analysis (GSEA) of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy. Experimentally, TRIP13 expression was found to be upregulated in H292DR, and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation.@*CONCLUSIONS@#TRIP13 is associated with poor prognosis in LUAD patients treated with radiation, possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.

Effect of Survivin Down-Regulation by Egr1-Survivin shRNA Combined with Radiotherapy on Radiosensitivity of Esophageal Squamous Carcinoma / Efecto de la Regulación Negativa de Survivina por shRNA de Egr1-Survivina Combinado con Radioterapia sobre la Radiosensibilidad del Carcinoma Escamoso de Esófago

SUMMARY: This study is to investigate the effect of survivin down-regulation by Egr1-survivin shRNA combined with radiotherapy on the apoptosis and radiosensitivity of esophageal squamous cell carcinoma ECA109 and KYSE150 cells. ECA109 and KYSE150 cells were transfected with Egr1-survivin shRNA, and then treated with radiotherapy. After 24 h, the mRNA and protein levels of Egr1-survivin were detected by qPCR and Western-Blot. Cell cycle and apoptosis were detected by flow cytometry. Western blot also detected levels of cleavaged Caspase 3 and Caspase 9. YM155 was used as a positive control to inhibit survivin expression. The levels of survivin mRNA and protein in ECA109 and KYSE150 cells treated with Egr1-survivin shRNA combined with radiotherapy were significantly lower than those of the blank control group, the empty vector control group, and, the YM155 + radiotherapy group (P<0.05). Meanwhile, after survivin down-regulation, the ratio of G2 to S phase of ECA109 and KYSE150 cells increased significantly, leading to significant G2 and S phase arrest. Additionally, apoptosis of ECA109 and KYSE150 cells increased significantly (P <0.01). Further, protein levels of cleavaged Caspase 3 and Caspase 9 significantly increased in Egr1-survivin shRNA combined with radiotherapy group. Egr1-survivin shRNA combined with radiotherapy can down-regulate survivin expression, which further increases the apoptosis, and enhances the radiosensitivity of ECA109 and KYSE150 cells.

Este estudio tuvo como objetivo investigar el efecto de la regulación negativa de survivina por el shRNA de Egr1-survivina combinado con radioterapia sobre la apoptosis y la radiosensibilidad del carcinoma de células escamosas de esófago Células ECA109 y KYSE150. Las células ECA109 y KYSE150 se transfectaron con shRNA de survivina Egr1 y luego se trataron con radioterapia. Después de 24 h, los niveles de ARNm y proteína de Egr1-survivina se detectaron mediante qPCR y Western-Blot. El ciclo celular y la apoptosis se detectaron mediante citometría de flujo. La transferencia Western también detectó niveles de Caspasa 3 y Caspasa 9 escindidas. Se usó YM155 como control positivo para inhibir la expresión de survivina. Los niveles de ARNm y proteína de survivina en células ECA109 y KYSE150 tratadas con shRNA de survivina Egr1 combinado con radioterapia fueron significativamente más bajos que los del grupo control en blanco, el grupo control de vector vacío y el grupo de radioterapia YM155 + (P <0,05). Mientras tanto, después de la regulación negativa de survivina, la proporción entre las fases G2 y S de las células ECA109 y KYSE150 aumentó significativamente, lo que llevó a una detención significativa de las fases G2 y S. Además, la apoptosis de las células ECA109 y KYSE150 aumentó significativamente (P <0,01). Además, los niveles de proteína de Caspasa 3 y Caspasa 9 escindidas aumentaron significativamente en el shRNA de Egr1- survivina combinado con el grupo de radioterapia. El shRNA de survivina de Egr1 combinado con radioterapia puede regular negativamente la expresión de survivina, lo que aumenta aún más la apoptosis y mejora la radiosensibilidad de las células ECA109 y KYSE150.

Alterações bucais associadas ao tratamento antineoplásico e a importância da assistência odontológica ao paciente oncológico: uma revisão integrativa / Oral alterations associated with antineoplastic treatment and the importance of dental care for oncology patients: an integrative review / Alteraciones orales asociadas al tratamiento antineoplásico y la importancia de la atención dental en pacientes oncológicos: una revisión integrativa

O tratamento oncológico por meio da quimioterapia e radioterapia consiste em destruir ou impedir o crescimento das células tumorais, visando a cura ou controle da doença. No entanto, esses tratamentos podem ocasionar danos às células saudáveis e consequentes efeitos colaterais, especialmente na cavidade oral, causando alterações como: mucosite, xerostomia, disgeusia, infecções orais, trismo e osteorradionecrose. Objetivo:Sumarizar estudos sobre a importância da prevenção ecuidado das alterações bucais no manejo odontológico a pacientes em tratamento oncológico.Metodologia:Revisão integrativa, a partir da identificação do tema e elaboração da questão norteadora com busca sistematizada da literatura realizada entre os meses de setembro e novembro de 2022. Foram realizadas buscasnas bases de dados da Biblioteca Virtual em Saúde, Google Acadêmicoe PubMed, excluindo-se artigos publicados há mais de cinco anos.Resultados:Obteve-se uma amostra final de seteestudos, após aplicação dos critérios de inclusão e exclusão.Houve concordância entre todos eles acerca das alterações bucais durante o tratamento oncológico, enfatizando a necessidade de assistência odontológica nesses pacientes antes, durante e após a terapia antineoplásica, além deminimizar efeitos desta intervenção. Conclusões:A atuação do cirurgião-dentista no cuidado aos pacientes oncológicos tem grande relevância, uma vez que as condições de saúde bucal impactam a qualidade de vida desses indivíduos. Em suma, o presente estudo contribuino entendimento das alterações bucais e cuidados para o bem-estar do paciente (AU).

Oncologicaltreatment through chemotherapy and radiotherapy consists of destroying or preventing the growth of tumor cells, aiming at curing or controlling the disease. However, these treatments can cause damage to healthy cells and consequent side effects, especially in the oral cavity, causing changes such as: mucositis, xerostomia, dysgeusia, oral infections, trismus and osteoradionecrosis. Objective:To summarize studies on the importance of prevention and care for oral changes in the dental management for patients undergoing oncologicaltreatment.Methodology:Integrative reviewfrom theidentification of the theme and elaboration of the guiding question with a systematic search of the literature carried out between September and November 2022. They were carried out searchesin the Virtual Health Librarydatabase, Google Scholar and PubMed, excluding articles published more than five years ago.Results:A final sample of 07 studies was obtained, after applying the inclusion and exclusion criteria. There was agreement among all of them about oral changes during cancer treatment, emphasizing the need for dental care in these patients before, during and after antineoplastic therapy, in addition to minimizing the effects of this intervention.Conclusions:The performance of the dental surgeon in the care of cancer patients is of great relevance, since oral health conditions impact the quality of life of these individuals. In short, the presentstudy contributesto the of oral changesand care for the patient's well-being (AU).

El tratamiento oncológicopor mediodequimioterapia y radioterapia consiste en destruir o impedir el crecimiento de las células tumorales, visando lacurar o controla de la enfermedad. Sin embargo, estos tratamientos pueden causar daño a las células sanasy en consecuenciaefectos secundarios, especialmenteen la cavidad oral, causandoalteraciones como: mucositis, xerostomía, disgeusia, infecciones orales, trismoy osteorradionecrosis.Objetivo: Resumir estudios acerca de la importancia de la prevención y cuidados de las alteracionesorales en el manejo dental apacientes en tratamiento oncológico.Metodología: Revisión integrativa, apartir de la identificación detema y elaboración de la pregunta guía con buscasistematizadade la literatura realizada entre los meses de septiembre y noviembre de 2022. Fueron realizadas búsquedas en las bases de datos de la Biblioteca Virtual en Salud, Google Académico y PubMed, excluyéndoseartículos publicados hace más de cinco años. Resultados: Se obtuvo una muestra final de siete estudios, después aplicaciones de los criterios de inclusión y exclusión. Hubo concordancia entre todos acerca de las alteracionesorales durante el tratamiento oncológico, enfatizando la necesidad de asistencia odontológica en esespacientes antes, durante y después de la terapia antineoplásica, además de minimizar efectos de esta intervención.Conclusiones: La actuación del cirujano dentistaen el cuidado a lospacientes oncológicos tienegran relevancia, una vez que las condiciones de salud oral impactan la calidad de vida de los individuos. En suma, el presente estudio contribuyeen el entendimientode las alteraciones orales y cuidados para el bienestar del paciente (AU).

Uso de imágenes KV CBCT del acelerador lineal Halcyon para la planificación de tratamientos de metástasis óseas con intensión paliativa / Use of KV CBCT images from the Halcyon linear accelerator for treatment planning of bone metastases with palliative intent

Las nuevas tecnologías para el tratamiento del cáncer con radiación ionizante tienen especial interés en mejorar la calidad de las imágenes para el posicionamiento adecuado del paciente con sistemas de radioterapia guiada por imagen IGRT. El sistema Halcyon cuenta con imágenes de tomografía computarizada de haz de cono CBCT. Estas imágenes podrían ser una opción para escenarios donde no se cuente con una Tomografía Computarizada CT o el equipo se encuentre en reparación o mantenimiento especialmente para escenarios de intensión paliativa. La diferencia en la distribución de dosis en imágenes CT y CBCT fue analizada en este estudio. Los resultados mostraron diferencias en las unidades Hounsfield UH, aunque no fueron estadísticamente significativas, el volumen irradiado mostro diferencias máximas de 3,92% que no supera el 4% permitido para tratamientos de intensión paliativa. En cuanto a las dosis dispersas al tejido sano la diferencia tampoco supera el 4%. Nuestro estudio mostro que las imágenes CBCT pueden ser una alternativa para el tratamiento de metástasis óseas, sin embargo, estas imágenes todavía no pueden remplazar las imágenes CT utilizadas para el cálculo de dosis en radioterapia

New technologies for the treatment of cancer with ionizing radiation are of particular interest in improving image quality for proper patient positioning with image-guided radiation therapy IGRT systems. IGRT image-guided radiation therapy systems. The Halcyon system features cone beam computed tomography CBCT imaging. These images could be an option for scenarios where a CT scan is not available or the equipment is under repair or maintenance especially for is under repair or maintenance, especially for palliative scenarios. The difference in the The difference in dose distribution in CT and CBCT images was analyzed in this study. The results showed differences in Hounsfield UH units, although not statistically significant, the irradiated volume showed maximum differences of 3.92%, which is the maximum difference of 3.92%. Differences of 3.92%, which does not exceed the 4% allowed for palliative treatments. As for the doses dispersed to healthy tissue the difference does not exceed the 4% allowed for palliative treatments. Our study showed that CBCT imaging can be an alternative for the treatment of metastases. an alternative for the treatment of bone metastases, however, these images cannot yet replace the CT images used for dose calculation. CT images used for dose calculation in radiotherapy

Sarcoma de Ewing multifocal: presentación de un caso pediátrico / Multifocal Ewing sarcoma: presentation of a pediatric case / Sarcoma de Ewing Multifocal: apresentação de um caso pediátrico

Introducción: el Sarcoma de Ewing es una neoplasia maligna de origen mesenquimático. Al momento del diagnóstico el 75% se presentan en forma localizada. Objetivo: comunicar un caso que por su presentación multifocal, generó dificultades diagnósticas. Caso clínico: niña de 6 años. Consulta por traumatismo de mano derecha tras caída de su altura 24 horas previas, constatándose en mano y puño derecho edema, calor y eritema, movilidad conservada. No fiebre. Radiografía: aumento del diámetro del tercer metacarpiano, imagen esmerilada, no trazos de fracturas. Ingresa con planteo de celulitis. Anemia leve microcítica, hipocrómica. Proteína C reactiva 82 mg/l. Recibe clindamicina intravenosa 72 horas, completa 14 días vía oral. Persistencia de alteraciones en puño y mano derecha, agrega tumoración de raíz nasal con desviación del eje, indolora. Fosfatasa alcalina, lactato deshidrogenasa, fosfatemia, calcemia normales. Resonancia magnética: alteración morfoestructural de radio, olecranon y tercer metacarpiano, fractura de olecranon y radio, reacción perióstica. Pet-Scan: lesión extensa ósea en macizo facial, tibias, cúbitos, humero derecho y clavícula. Biopsia 3er metacarpiano: tumor de células pequeñas, redondas azules, CD99 y vimentina positivo. Comienza poliquimioterapia y radioterapia sin complicaciones. Conclusiones: es frecuente que las manifestaciones clínicas iniciales sean confundidas con entidades más frecuentes, como post-traumáticas y/o inflamatorias, tal como ocurrió en este caso. Posteriormente, la aparición de nuevas lesiones y compromiso del estado general orientó el abordaje diagnóstico de la patología tumoral. La confirmación exige el estudio anatomopatológico con estudio inmunohistoquímico. La presencia de metástasis óseas constituye un factor de mal pronóstico y dificulta el abordaje terapéutico.

Introduction: Ewing's sarcoma is a malignant neoplasm of mesenchymal origin. At the time of diagnosis 75% of the cases are localized. Objective: to report a case that, due to its multifocal presentation, generated diagnostic difficulties. Clinical case: 6-year-old girl. She consulted for right hand trauma after a fall from her height 24 hours earlier, with edema, warmth and erythema in the right hand and fist, with preserved mobility. No fever. X-ray: increase in the diameter of the 3rd metacarpal, frosted image, no traces of fractures. Admitted with cellulitis. Mild microcytic anemia, hypochromic. C-reactive protein 82mg/l. Receives intravenous clindamycin 72 hours, completes 14 days orally. Persistence of alterations in fist and right hand, adds tumor of nasal root with deviation of the axis, painless. Alkaline phosphatase, lactate dehydrogenase, phosphatemia, normal calcemia. MRI: morphostructural alteration of radius, olecranon and 3rd metacarpal, fracture of olecranon and radius, periosteal reaction. Pet-Scan: extensive bone lesion in facial mass, tibiae, ulnae, right humerus and clavicle. Biopsy 3rd metacarpal: small cell tumor, blue round, CD 99 and vimentin positive. Polychemotherapy and radiotherapy were started without complications. Conclusions: it is frequent that the initial clinical manifestations are confused with more frequent entities, such as post-traumatic and/or inflammatory, as occurred in this case. Subsequently, the appearance of new lesions and compromise of the general condition guided the diagnostic approach of the tumor pathology. Confirmation requires anatomopathological study with immunohistochemical study. The presence of bone metastases constitutes a poor prognostic factor and hinders the therapeutic approach.

Introdução: O sarcoma de Ewing é um neoplasma maligno de origem mesenquimatosa. No momento do diagnóstico, 75% dos casos são localizados. Objetivo: Relatar um caso que, devido a sua apresentação multifocal, causou dificuldades diagnósticas. Caso clínico: Menina de 6 anos. Ela consultou por traumatismo à mão direita após cair de sua altura 24 horas antes, com edema, calor e eritema na mão direita e punho, com mobilidade preservada. Sem febre. Raio-X: aumento do diâmetro do 3º metacarpo, imagem fosca, sem vestígios de fraturas. Admitido com a sugestão de celulite. Anemia microcítica leve, hipocrómica. Proteína C reativa 82mg/l. Recebe clindamicina intravenosa por 72 horas, completa 14 dias por via oral. Persistência de alterações no punho e mão direita, tumor indolor da raiz nasal com desvio do eixo. Fosfatase alcalina, desidrogenase láctica, fosfataemia, calcemia normal. IRM: alteração morfo-estrutural do rádio, olecrânio e 3º metacarpo, fratura do olecrânio e do rádio, reação periosteal. Pet-Scan: extensa lesão óssea na massa facial, tíbia, ulnae, úmero direito e clavícula. Biópsia do 3º metacarpo: tumor de pequenas células, redondo azul, CD 99 e vimentina positiva. Ela iniciou a poli-quimioterapia e radioterapia sem complicações. Conclusões: É comum que as manifestações clínicas iniciais sejam confundidas com entidades mais freqüentes, tais como pós-traumáticas e/ou inflamatórias, como ocorreu neste caso. Posteriormente, o aparecimento de novas lesões e o envolvimento do quadro geral levaram a uma abordagem diagnóstica da patologia tumoral. A confirmação requer um estudo anatomopatológico com estudo imuno-histoquímico. A presença de metástases ósseas é um fator de mau prognóstico e dificulta a abordagem terapêutica.

Multiple Myeloma (Part 1) - Update on Epidemiology, Diagnostic Criteria, Systemic Treatment and Prognosis / Mieloma múltiplo (Parte 1) - Atualização sobre epidemiología, critérios diagnósticos, tratamento sistêmico e prognóstico

Abstract Multiple myeloma (MM) is a hematological malignancy characterized by unregulated and clonal proliferation of plasma cells in the bone marrow; these cells produce and secrete an anomalous monoclonal immunoglobulin, or a fragment of this, called M protein. The clinical manifestations of MM result from the proliferation of these plasmocytes, the excessive production of monoclonal immunoglobulin and the suppression of normal humoral immunity, leading to hypercalcemia, bone destruction, renal failure, suppression of hematopoiesis and humoral immunity, increasing the risk for the development of infections. The increase in life expectancy of the world population led to a concomitant increase in the prevalence of MM, a pathology that usually affects the elderly population. The aim of this review is to update the reader on epidemiology, diagnostic criteria, differential diagnosis with other monoclonal gam-mopathies, systemic treatment and prognosis of MM.

Resumo O mieloma múltiplo (MM) constitui neoplasia maligna de origem hematológica caracterizada pela proliferação desregulada e clonal de plasmócitos na medula óssea; estas células produzem e secretam imunoglobulina monoclonal anômala, ou um fragmento desta, denominado proteína M. As manifestações clínicas do MM decorrem da proliferação destes plasmócitos, da produção excessiva de imunoglobulina monoclonal e da supressão da imunidade humoral normal, levando à hipercalcemia, destruição óssea, insuficiência renal, supressão da hematopoiese e da imunidade humoral,aumentandooriscoparaodesenvolvimento de infecções. O aumento na expectativa de vida da população mundial levou a concomitante incremento na prevalência do MM, patologia que habitualmente acomete a população idosa. O objetivo desta revisão é atualizar o leitor sobre a epidemiologia, critérios diagnósticos, diagnóstico diferencial com outras gamopatias monoclonais, tratamento sistêmico e prognóstico do MM.

Update in Imaging Evaluation of Bone and Soft Tissue Sarcomas / Atualização na avaliação por imagens dos sarcomas ósseos e das partes moles

Abstract The evolution in imaging evaluation of musculoskeletal sarcomas contributed to a significant improvement in the prognosis and survival of patients with these neoplasms. The precise characterization of these lesions, using the most appropriate imaging modalities to each clinical condition presented, is of paramount importance in the design of the therapeutic approach to be instituted, with a direct impact on clinical outcomes. The present article seeks to update the reader regarding imaging methodologies in the context of local and systemic evaluation of bone sarcomas and soft tissues.

Resumo A evolução na avaliação por imagens dos sarcomas musculoesqueléticos contribuiu para melhora significativa no prognóstico e na sobrevida dos portadores destas neoplasias. A caracterização precisa destas lesões, mediante utilização das modalidades de imagem mais adequadas a cada condição clínica apresentada, é de suma importância no delineamento da abordagem terapêutica a ser instituída, com impacto direto sobre os desfechos clínicos. O presente artigo busca atualizar o leitor a propósito das metodologias de imagem no contexto da avaliação local e sistêmica dos sarcomas ósseos e das partes moles.

Effect of Shengmai Yin on Epithelial-Mesenchymal Transition of Nasopharyngeal Carcinoma Radioresistant Cells / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R.@*METHODS@#Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label.@*RESULTS@#The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results.@*CONCLUSIONS@#SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.

The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis / 中华肿瘤杂志

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Análise Epidemiológica, Clínica e Patológica de Crianças com Neoplasias do Sistema Nervoso Central Tratadas com Radioterapia no Instituto Nacional de Câncer / Epidemiological, Clinical, and Pathological Analysis of Children with Central Nervous System Neoplasms Treated with Radiotherapy at the National Cancer Institute / Análisis Epidemiológico, Clínico y Patológico de Niños con Neoplasias del Sistema Nervioso Central Tratados con Radioterapia en el Instituto Nacional de Cáncer

Introdução: As neoplasias de sistema nervoso central representam 21% do câncer infantojuvenil, sendo a principal causa de morte nessa população em países desenvolvidos. Avanços na neuroimagem têm melhorado seu diagnóstico, e a combinação de terapias tem permitido a cura, com maior preservação neurológica. A cirurgia é o principal tratamento, frequentemente combinada com radioterapia e quimioterapia. Objetivo: Descrever achados socioeconômicos, sinais e sintomas, e aspectos histológicos dos tumores cerebrais pediátricos, tratados com radioterapia. Método: Estudo transversal e descritivo, utilizando prontuários de 257 crianças e adolescentes portadores de neoplasias de sistema nervoso central, tratados com radioterapia no Instituto Nacional de Câncer, no Rio de Janeiro, de 2012 a 2020. As variáveis foram divididas em sociodemográficas, clínicas e patológicas. Resultados: Crianças brancas do sexo masculino foram as mais prevalentes, com mediana de idade de 7,5 anos no diagnóstico e de 8,0 anos na radioterapia. A maioria possuía casa própria com infraestrutura básica e renda familiar de até um salário-mínimo. Os sintomas mais comuns foram cefaleia, vômitos e alterações na marcha, variando de acordo com a localização do tumor e a idade da criança. A radioterapia foi utilizada em 64% dos pacientes, principalmente para meduloblastoma, tumores de tronco cerebral e ependimoma anaplásico. Conclusão: Estudos específicos sobre crianças e adolescentes com neoplasias cerebrais tratados com radioterapia são raros na literatura. Quando comparados com a população em geral, apresentam perfis sociodemográficos e clínicos semelhantes, com diferenças notáveis apenas na frequência dos tipos tumorais

Introduction: Central nervous system neoplasms account for 21% of pediatric cancer cases and are the leading cause of death in this population in developed countries. Advances in neuroimaging have improved diagnosis, and combination therapies have ensured the cure with greater neurological preservation. Surgery is the primary treatment, often combined with radiation therapy and chemotherapy. Objective: To describe socioeconomic findings, signs and symptoms, and histological aspects of pediatric brain tumors treated with radiation therapy. Method: A cross-sectional and descriptive study was conducted with 257 children and adolescents utilizing medical records with central nervous system neoplasms treated with radiotherapy at the National Cancer Institute, Rio de Janeiro, from 2012 to 2020. The variables were divided into sociodemographic, clinical, and pathological categories. Results: White male children were the most prevalent, with a median age at diagnosis of 7.5 years and at radiotherapy, of 8.0 years. The majority had their own home with basic infrastructure and family income of up to one minimum wage. The most common symptoms were headache, vomiting, and gait disorders, varying according to tumor location and child's age. Radiation therapy was used in 64% of patients, mainly for medulloblastoma, brainstem tumors, and anaplastic ependymoma. Conclusion: Specific studies on children and adolescents with brain neoplasms treated with radiotherapy are rare in the literature. When compared with the general population, they present similar sociodemographic and clinical profiles, with remarkable differences only in the frequency of tumor types

Introducción: Las neoplasias del sistema nervioso central representan el 21% del cáncer infantil y juvenil, siendo la principal causa de muerte en esta población en países desarrollados. Los avances en neuroimagen han mejorado su diagnóstico y la combinación de terapias viene permitiendo la cura, con una mayor preservación neurológica. La cirugía es el tratamiento principal, a menudo combinada con radioterapia y quimioterapia. Objetivo: Describir los hallazgos socioeconómicos, los signos y síntomas, y los aspectos histológicos de los tumores cerebrales pediátricos tratados con radioterapia. Método: Estudio transversal y descriptivo utilizando las historias clínicas de 257 niños y adolescentes con neoplasias del sistema nervioso central, que fueron tratados con radioterapia en el Instituto Nacional del Cáncer en Río de Janeiro entre 2012 y 2020. Las variables se dividieron en sociodemográficas, clínicas y patológicas. Resultado: Los niños blancos y de sexo masculino fueron los más prevalentes, con una mediana de edad de 7,5 años en el momento del diagnóstico y de 8,0 años en el momento de la radioterapia. La mayoría poseía una vivienda propia con infraestructura básica y un ingreso familiar de hasta un salario mínimo. Los síntomas más comunes fueron dolor de cabeza, vómitos y alteraciones en la marcha, que variaban según la ubicación del tumor y la edad del niño. Se utilizó radioterapia en el 64% de los pacientes, principalmente para meduloblastoma, tumores del tronco cerebral y ependimoma anaplásico. Conclusión: Los estudios específicos sobre niños y adolescentes con neoplasias cerebrales tratados con radioterapia son raros en la literatura. Cuando se comparan con la población en general, presentan perfiles sociodemográficos y clínicos similares, con diferencias notables solo en la frecuencia de los tipos tumorales

Study on the sensitivity of a volumetric modulated arc therapy plan verification equipment on multi-leaf collimator opening and closing errors and its gamma pass rate limit / 生物医学工程学杂志

To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.

Neoadjuvant radiohormonal therapy for oligo-metastatic prostate cancer: safety and efficacy outcomes from an open-label, dose-escalation, single-center, phase I/II clinical trial / 医学前沿

To evaluate the safety and efficacy of neoadjuvant radiohormonal therapy for oligometastatic prostate cancer (OMPC), we conducted a 3 + 3 dose escalation, prospective, phase I/II, single-arm clinical trial (CHiCTR1900025743), in which long-term neoadjuvant androgen deprivation was adopted 1 month before radiotherapy, comprising intensity modulated radiotherapy to the pelvis, and stereotactic body radiation therapy to all extra-pelvic bone metastases for 4-7 weeks, at 39.6, 45, 50.4, and 54 Gy. Robotic-assisted radical prostatectomy was performed after 5-14 weeks. The primary outcome was treatment-related toxicities and adverse events; secondary outcomes were radiological treatment response, positive surgical margin (pSM), postoperative prostate-specific antigen (PSA), pathological down-grading and tumor regression grade, and survival parameters. Twelve patients were recruited from March 2019 to February 2020, aging 66.2 years in average (range, 52-80). Median baseline PSA was 62.0 ng/mL. All underwent RARP successfully without open conversions. Ten patients recorded pathological tumor down-staging (83.3%), and 5 (41.7%) with cN1 recorded negative regional lymph nodes on final pathology. 66.7% (8/12) recorded tumor regression grading (TRG) -I and 25% (3/12) recorded TRG-II. Median follow-up was 16.5 months. Mean radiological progression-free survival (RPFS) was 21.3 months, with 2-year RPFS of 83.3%. In all, neoadjuvant radiohormonal therapy is well tolerated for oligometastatic prostate cancer.

A single-center, retrospective analysis of relapse and progression patterns of primary central nervous system lymphoma: can whole brain radiotherapy be replaced? / 南方医科大学学报

OBJECTIVE@#To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment.@*METHODS@#This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions.@*RESULTS@#MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area.@*CONCLUSIONS@#Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.

Quantitative evaluation of radiotherapy plan in precise external beam radiotherapy process management for cervical cancer / 南方医科大学学报

OBJECTIVE@#To identify the problems in clinical radiotherapy planning for cervical cancer through quantitative evaluation of the radiotherapy plans to improve the quality of the plans and the radiotherapy process.@*METHODS@#We selected the clinically approved and administered radiotherapy plans for 227 cervical cancer patients undergoing external radiotherapy at Sun Yat-sen University Cancer Center from May, 2019 to January, 2022. These plans were transferred from the treatment planning system to the Plan IQTM workstation. The plan quality metrics were determined based on the guidelines of ICRU83 report, the GEC-ESTRO Working Group, and the clinical requirements of our center and were approved by a senior clinician. The problems in the radiotherapy plans were summarized and documented, and those with low scores were re-planned and the differences were analyzed.@*RESULTS@#We identified several problems in the 277 plans by quantitative evaluation. Inappropriate target volume selection (with scores < 60) in terms of GTV, PGTV (CI) and PGTV (V66 Gy) was found in 10.6%, 65.2%, and 1% of the plans, respectively; and the PGTV (CI), GTV, and PCTV (D98%, HI) had a score of 0 in 0.4%, 10.1%, 0.4%, 0.4% of the plans, respectively. The problems in the organs at risk (OARs) involved mainly the intestines (the rectum, small intestine, and colon), found in 20.7% of the plans, and in occasional cases, the rectum, small intestine, colon, kidney, and the femoral head had a score of 0. Senior planners showed significantly better performance than junior planners in PGTV (V60 Gy, D98%), PCTV (CI), and CTV (D98%) (P≤0.046) especially in terms of spinal cord and small intestine protection (P≤0.034). The bowel (the rectum, small intestine and colon) dose was significantly lower in the prone plans than supine plans (P < 0.05), and targets coverage all met clinical requirements. Twenty radiotherapy plans with low scores were selected for re-planning. The re-planned plans had significantly higher GTV (Dmin) and PTV (V45 Gy, D98%) (P < 0.05) with significantly reduced doses of the small intestines (V40 Gy vs V30 Gy), the colon (V40 Gy vs V30 Gy), and the bladder (D35%) (P < 0.05).@*CONCLUSION@#Quantitative evaluation of the radiotherapy plans can not only improve the quality of radiotherapy plan, but also facilitate risk management of the radiotherapy process.

Deep learning-based dose prediction in radiotherapy planning for head and neck cancer / 南方医科大学学报

OBJECTIVE@#To propose an deep learning-based algorithm for automatic prediction of dose distribution in radiotherapy planning for head and neck cancer.@*METHODS@#We propose a novel beam dose decomposition learning (BDDL) method designed on a cascade network. The delivery matter of beam through the planning target volume (PTV) was fitted with the pre-defined beam angles, which served as an input to the convolution neural network (CNN). The output of the network was decomposed into multiple sub-fractions of dose distribution along the beam directions to carry out a complex task by performing multiple simpler sub-tasks, thus allowing the model more focused on extracting the local features. The subfractions of dose distribution map were merged into a distribution map using the proposed multi-voting mechanism. We also introduced dose distribution features of the regions-of-interest (ROIs) and boundary map as the loss function during the training phase to serve as constraining factors of the network when extracting features of the ROIs and areas of dose boundary. Public datasets of radiotherapy planning for head and neck cancer were used for obtaining the accuracy of dose distribution of the BDDL method and for implementing the ablation study of the proposed method.@*RESULTS@#The BDDL method achieved a Dose score of 2.166 and a DVH score of 1.178 (P < 0.05), demonstrating its superior prediction accuracy to that of current state-ofthe-art (SOTA) methods. Compared with the C3D method, which was in the first place in OpenKBP-2020 Challenge, the BDDL method improved the Dose score and DVH score by 26.3% and 30%, respectively. The results of the ablation study also demonstrated the effectiveness of each key component of the BDDL method.@*CONCLUSION@#The BDDL method utilizes the prior knowledge of the delivery matter of beam and dose distribution in the ROIs to establish a dose prediction model. Compared with the existing methods, the proposed method is interpretable and reliable and can be potentially applied in clinical radiotherapy.

Feasibility Study of Beam Angle Optimization Based on Scripts in Automated-planning for Liver Cancer / 中国医疗器械杂志

OBJECTIVE@#To study the feasibility and potential benefits of beam angle optimization (BAO) to automated planning in liver cancer.@*METHODS@#An approach of beam angle sampling is proposed to implement BAO along with the module Auto-planning in treatment planning system (TPS) Pinnacle. An in-house developed plan quality metric (PQM) is taken as the preferred evaluating method during the sampling. The process is driven automatically by in-house made Pinnacle scripts both in sampling and scoring. In addition, dosimetry analysis and physician's opinion are also performed as the supplementary and compared with the result of PQM.@*RESULTS@#It is revealed by the numerical analysis of PQM scores that only 15% patients whose superior trials evaluated by PQM are also the initial trials. Gantry optimization can bring benefit to plan quality along with auto-planning in liver cancer. Similar results are provided by both dose comparison and physician's opinion.@*CONCLUSIONS@#It is possible to introduce a full automated approach of beam angle optimization to automated planning process. The advantages of this procedure can be observed both in numerical analysis and physician's opinion.

Research Progress on the Protective Effect of Intestinal Flora on Radiation-induced Lung Injury in Thoracic Tumors / 中国肺癌杂志

Radiation therapy is one of the main treatment methods for patients with thoracic malignant tumors, which can effectively improve the survival rate of the patients. However, radiation therapy can also cause damage to normal tissues while treating tumors, leading to radiation-induced lung injury such as radiation pneumonia and pulmonary fibrosis. Radiation-induced lung injury is a complex pathophysiological process involving many factors, and its prevention and treatment is one of the difficult problems in the field of radiation medicine. Therefore, the search for sensitive predictors of radiation-induced lung injury can guide clinical radiotherapy and reduce the incidence of radiation-induced lung injury. With the in-depth study of intestinal flora, it can drive immune cells or metabolites to reach lung tissue through the circulatory system to play a role, and participate in the occurrence, development and treatment of lung diseases. At present, there are few studies on intestinal flora and radiation-induced lung injury. Therefore, this paper will comprehensively elaborate the interaction between intestinal flora and radiation-induced lung injury, so as to provide a new direction and strategy for studying the protective effect of intestinal flora on radiation-induced lung injury.
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Effect of low-level LASER therapy versus CAD/CAM Michigan splint on patients with Temporomandibular Muscle Disorders: a randomized clinical trial / Efeito da terapia LASER de baixa potência versus placa de Michigan CAD/CAM em pacientes com Distúrbios Temporomandibulares musculares: um ensaio clínico randomizado

Objective: This study aimed to evaluate the efficacy and sustainability of using low level LASER therapy and CAD/CAM Michigan splint on improving the range of mandibular movements, muscle activity and reducing the pain. Material and Methods: 56 female patients were randomly divided into two groups. Group A: Patients received applications of low-level LASER therapy using semiconductor InGaAsp diode LASER type 940 nm with continuous mode of operation, applied for 180 sec per session for 12 sessions. Group B: Patients received Michigan splint of 2 mm thickness constructed on their upper teeth, the splint was 3D digitally printed. Electromyography was used to evaluate muscle activity, visual analogue scale was used to evaluate the pain intensity, ARCUS digma facebow was used to evaluate range of mandibular movements, and maximum mouth opening was taken using a millimeter ruler. They were measured before the beginning of the treatment, and at three and six month follow-up periods. Results: The results revealed that both low-level LASER therapy and Michigan splint reduce the myofascial pain, improved the range of the mandibular movements, and the muscles activity, but the effect of the low-level LASER therapy was more profound and sustainable. After 6 months from the beginning of the treatment, changes in masseter muscle activity (P= 0.001; effect size= 1.757), pain intensity (P= 0.003; effect size= 3), and range of mandibular movement (P= 0.001, effect size= 1.729) differed significantly between the two groups. Conclusions: Low-level LASER therapy had a better and more sustainable effect on reducing the pain intensity and improving the muscle activity as well as the mandibular movement when compared to Michigan splint (AU)

Objetivo: Este estudo teve como objetivo avaliar a eficácia e a durabilidade do uso da terapia LASER de baixa potência e da placa de Michigan CAD/CAM na melhora da amplitude dos movimentos mandibulares, atividade muscular e redução da dor. Material e Métodos: 56 pacientes do sexo feminino foram divididos aleatoriamente em dois grupos. Grupo A: os pacientes receberam aplicações de terapia LASER de baixa potência utilizando diodo semicondutor InGaAsp LASER tipo 940 nm em modo contínuo de operação, aplicado por 180 segundos por sessão durante 12 sessões. Grupo B: os pacientes receberam a placa de Michigan com uma espessura de 2 mm confeccionada sobre a arcada superior, a placa foi impressa digitalmente em 3D. A eletromiografia foi utilizada para avaliar a atividade muscular, a escala visual analógica foi utilizada para avaliar a intensidade da dor, o arco facial ARCUS digma foi utilizado para determinar a amplitude dos movimentos mandibulares e a abertura máxima da boca foi medida com uma régua milimétrica. Todas as medidas foram realizadas antes do início do tratamento e nos períodos de acompanhamento de três e seis meses. Resultados: Os resultados revelaram que tanto a terapia LASER de baixa potência como a placa de Michigan reduziram a dor miofascial, aumentaram a amplitude dos movimentos mandibulares e melhoraram a atividade muscular, mas o efeito da terapia LASER de baixa potência foi mais profundo e duradouro. Após 6 meses do início do tratamento, as alterações na atividade do músculo masseter (P= 0. 001; tamanho do efeito= 1,757), intensidade da dor (P= 0,003; tamanho do efeito= 3), e amplitude de movimento mandibular (P= 0,001, tamanho do efeito= 1,729) diferiram significativamente entre os dois grupos. Conclusão: A terapia com LASER de baixa potência teve um efeito melhor e mais duradouro na redução da intensidade da dor e na melhora da atividade muscular, bem como do movimento mandibular, quando comparada à placa de Michigan(AU)