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PURPOSE: Proton stereotactic radiosurgery (PSRS) has emerged as an innovative proton therapy modality aimed at achieving precise dose delivery with minimal impact on healthy tissues. This study explores the dosimetric outcomes of PSRS in comparison to traditional intensity-modulated proton therapy (IMPT) by focusing on cases with small target volumes. A custom-made aperture system designed for proton therapy, specifically tailored to small target volumes, was developed and implemented for this investigation. METHODS: A prerequisite mechanical validation through an isocentricity test precedes dosimetric assessments, ensuring the seamless integration of mechanical and dosimetry analyses. Five patients were enrolled in the study, including two with choroid melanoma and three with arteriovenous malformations (AVM). Two treatment plans were meticulously executed for each patient, one utilizing a collimated aperture and the other without. Both plans were subjected to robust optimization, maintaining identical beam arrangements and consistent optimization parameters to account for setup errors of 2 mm and range uncertainties of 3.5%. Plan evaluation metrics encompassing the Heterogeneity Index (HI), Paddick Conformity Index (CIPaddick), Gradient Index (GI), and the R50% index to evaluate alterations in low-dose volume distribution. RESULTS: The comparative analysis between PSRS and traditional PBS treatment revealed no significant differences in plan outcomes, with both modalities demonstrating comparable target coverage. However, collimated apertures resulted in discernible improvements in dose conformity, dose fall-off, and reduced low-dose volume. CONCLUSIONS: This study underscores the advantageous impact of the aperture system on proton therapy, particularly in cases involving small target volumes.
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Órgãos em Risco , Terapia com Prótons , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Radiocirurgia/métodos , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco/efeitos da radiação , Melanoma/radioterapia , Melanoma/cirurgiaRESUMO
BACKGROUND: The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. OBJECTIVE: To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. METHOD: The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. RESULTS: The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. CONCLUSION: The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3âcm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.
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Elétrons , Imagens de Fantasmas , Radiometria , Dosagem Radioterapêutica , Radiometria/métodos , Radiometria/instrumentação , Humanos , Queloide/radioterapiaRESUMO
PURPOSE: Pediatric diffuse malignant glioma located in the brainstem was officially named "diffuse midline glioma" (DMG) by the World Health Organization in 2016. For this disease, radical surgery is not beneficial, and the only major treatment strategy is radiotherapy. However, the dose limitations to brainstem tissue mean that treatment by radiotherapy can only control and not eradicate the tumors, and there is no effective treatment for recurrence, resulting in short overall survival of 6-12 months. This paper reports our experience with boron neutron capture therapy (BNCT), a new treatment process, and its efficacy in treating children with recurrent DMG. METHODS: From September 2019 to July 2022, we treated 6 children affected by recurrent DMG. With the collaboration of Taipei Veteran General Hospital (TVGH) and National Tsing-Hua University (NTHU), each patient received two sessions of BNCT within 1 month. RESULTS: Among the six patients, three showed partial response and the rest had stable disease after the treatment. The overall survival and recurrence-free survival duration after treatment were 6.39 and 4.35 months, respectively. None of the patients developed severe side effects, and only one patient developed brain necrosis, which was most likely resulted from previous hypofractionated radiotherapy received. CONCLUSION: BNCT elicited sufficient tumor response with low normal tissue toxicity; it may benefit vulnerable pediatric patients with DMG.
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Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Glioma , Humanos , Criança , Neoplasias Encefálicas/radioterapia , Terapia por Captura de Nêutron de Boro/efeitos adversos , Terapia por Captura de Nêutron de Boro/métodos , Glioma/radioterapia , Resultado do Tratamento , Recidiva Local de Neoplasia/patologiaRESUMO
This paper discusses the feasibility of a monitoring program for the quality assurance status of activity meters. We sent a questionnaire to clinical nuclear medicine departments of medical institutions, requesting information on their activity meters and quality assurance practices. On-site visits were conducted with exemption-level standard sources (Co-57, Cs-137 and Ba-133) for dose calibrators in nuclear medicine departments including physical inspection, accuracy and reproducibility. A method offering a quick check on the detection efficiency of the space dimension inside the activity meters was also introduced. For dose calibrator quality assurance, the daily checks had the highest implementation. However, annual checks and upon acceptance/after a repair check were reduced to 50% and 44%, respectively. The accuracy results of dose calibrators showed that all models exceeded the ±10% criteria with Co-57 and Cs-137 sources. The reproducibility results showed that some models exceeded the ±5% criteria with Co-57 and Cs-137 sources. The appropriate application of exemption-level standard sources considering the uncertainty that affects the measurement is discussed.
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Radioisótopos de Césio , Reprodutibilidade dos Testes , IncertezaRESUMO
Hepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Sorafenib, a multikinase inhibitor, is the first-line drug approved by the Food and Drug Administration (FDA) for the treatment of patients with advanced HCC. However, most patients who continuously receive sorafenib may acquire resistance to this drug. Therefore, it is important to develop a new compound to treat liver cancer and sorafenib-resistant liver cancer. Barbituric acid derivatives have been used as antiasthmatic drugs in the clinic. We previously reported that a novel barbituric acid derivative inhibited carbon tetrachloride-induced liver fibrosis in mice, but its effects on liver cancer remain unknown. Thus, the purpose of this study was to investigate the antitumor effect of barbituric acid derivatives on HCC cells and sorafenib-resistant HCC cells (HCC-SRs). Our findings reveal that one of the barbituric acid derivatives, BA-5, significantly inhibited HCC and HCC-SR cell viability in a dose- and time-dependent manner. Therefore, compound BA-5 was selected for further experiments. Western blot data revealed that BA-5 treatment decreased the phosphorylation of AKT/p70s6k without affecting the MAPK pathway and increased cleaved PARP and cleaved caspase-7 in both HCC and HCC-SR cells. Since epithelial-mesenchymal transition plays a significant role in regulating cancer invasion and migration, we used the wound healing assay to evaluate the antimigratory effect of compound BA-5. The results showed that BA-5 treatment inhibited HCC and HCC-SR cell migration and reduced Vimentin protein expression. These results were confirmed by microarray analysis showing that BA-5 treatment influenced cancer cell motility and growth-related pathways. In the xenograft mouse model experiment, BA-5 administration significantly inhibited HCC cancer cell growth in mice. Furthermore, the combination of BA-5 with a low dose of regorafenib synergistically inhibited HCC-SR cell proliferation. In conclusion, our study showed that the barbituric acid derivative BA-5 is a new candidate for HCC and sorafenib-resistant HCC therapy.
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Antineoplásicos/farmacologia , Barbitúricos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Barbitúricos/administração & dosagem , Barbitúricos/química , Carcinoma Hepatocelular/patologia , Caspase 7/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Perfilação da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Compostos de Fenilureia/administração & dosagem , Poli(ADP-Ribose) Polimerase-1/metabolismo , Piridinas/administração & dosagem , Vimentina/metabolismo , Cicatrização/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To evaluate the effects of body mass index (BMI) and weight change during radiotherapy on the development of toxicity in patients with locally advanced cervical cancer (LACC) treated with intensity-modulated radiotherapy (IMRT). METHODS: A total of 245 patients were analyzed after undergoing definitive IMRT treatment between 2004 and 2015 for stage IB2 to stage IVA LACC. The patients were divided into 3 groups: underweight (BMI <18.5 kg/m), normal weight (BMI 18.5-24.9 kg/m), and overweight (BMI ≥25.0 kg/m). The relationships between toxicity, clinical factors, and the bowel dose-volume histogram were analyzed. V45 indicated the bowel volume that received a radiation dose of 45 Gy. RESULTS: The median follow-up period was 63 months. The V45 was similar among the 3 groups. The 5-year rates of grade 3 or higher late gastrointestinal toxicities were 18.6%, 4.0%, and 4.2% for the underweight, normal weight, and overweight groups, respectively (P = 0.002). In the multivariable analysis, underweight (hazard ratio, 13.99; 95% confidence interval, 3.22-60.82; P < 0.001) and weight loss (> -5%) (hazard ratio, 5.91; 95% confidence interval, 1.75-19.98; P = 0.004) were significant predictors of grade 3 or higher-grade late gastrointestinal toxicities. CONCLUSION: A BMI of less than 18.5 kg/m and weight loss (> -5%) were associated with a higher risk of grade ≥3 or higher late gastrointestinal toxicity in patients with LACC treated with definitive IMRT. Future research on the development of a standardized and structured approach to improve the therapeutic ratio for the supportive care of patients with LACC is needed.
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Índice de Massa Corporal , Gastroenteropatias/etiologia , Lesões por Radiação/etiologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Glycine N-methyltransferase (GNMT) is abundantly expressed in the normal liver but is down-regulated in liver cancer tissues. GNMT knockout (Gnmt-/-) mice can spontaneously develop chronic hepatitis, fatty liver, and liver cancer. We previously demonstrated that hepatic GNMT is decreased in high-fat-diet-induced type 2 diabetes mellitus, but its contribution to metabolic syndrome is unclear. Here we show that GNMT modulates key aspects of metabolic syndrome in mice. METHODS: Eleven-week-old Gnmt-/- and wild-type (WT) mice with a C57BL/6 genetic background were used in this study. The metabolic defects of GNMT deficiency were measured by glucose and insulin tolerance tests, lipid homeostasis, gluconeogenesis, and insulin signaling. RESULTS: Gnmt-/- mice, especially females, exhibited glucose intolerance and insulin resistance. However, their body fat and lean mass, food and water intakes, and energy expenditure did not differ from those of WT mice. In addition, glucose-stimulated insulin secretion and insulin-stimulated glucagon secretion were normal in the serum and pancreatic islets of Gnmt-/- mice. Importantly, we found that GNMT deficiency increased lipogenesis and triglycerides in the liver. The elevated triglycerides disrupted the ability of insulin to induce Akt and S6 ribosomal protein phosphorylation, and then triggered insulin resistance and gluconeogenesis in female Gnmt-/- mice. CONCLUSIONS: Our data indicate that hepatic GNMT regulates lipid and glucose homeostasis, and provide insight into the development of insulin resistance through modulating the PI3K/Akt pathway.
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Gluconeogênese , Glicina N-Metiltransferase/deficiência , Glicina N-Metiltransferase/genética , Insulina/metabolismo , Fígado/enzimologia , Síndrome Metabólica/genética , Transdução de Sinais , Animais , Feminino , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
In chronic liver diseases, regardless of their etiology, the development of fibrosis is the first step toward the progression to cirrhosis, portal hypertension, and hepatocellular carcinoma. Hepatic stellate cells (HSCs) are the main profibrogenic cells that promote the pathogenesis of liver fibrosis, and so it is important to identify the molecules that regulate HSCs activation and liver fibrosis. Niemann-Pick type C2 (NPC2) protein plays an important role in the regulation of intracellular cholesterol homeostasis by directly binding with free cholesterol. However, the roles of NPC2 in HSCs activation and liver fibrosis have not been explored in detail. Since a high-cholesterol diet exacerbates liver fibrosis progression in both rodents and humans, we propose that the expression of NPC2 affects free cholesterol metabolism and regulates HSCs activation. In this study, we found that NPC2 is decreased in both thioacetamide- and carbon tetrachloride-induced liver fibrosis tissues. In addition, NPC2 is expressed in quiescent HSCs, but its activation status is down-regulated. Knockdown of NPC2 in HSC-T6 cells resulted in marked increases in transforming growth factor-ß1 (TGF-ß1)-induced collagen type 1 α1 (Col1a1), α-smooth muscle actin (α-SMA) expression, and Smad2 phosphorylation. In contrast, NPC2 overexpression decreased TGF-ß1-induced HSCs activation. We further demonstrated that NPC2 deficiency significantly increased the accumulation of free cholesterol in HSCs, increasing Col1a1 and α-SMA expression and activating Smad2, and leading to sensitization of HSCs to TGF-ß1 activation. In contrast, overexpression of NPC2 decreased U18666A-induced free cholesterol accumulation and inhibited the subsequent HSCs activation. In conclusion, our study has demonstrated that NPC2 plays an important role in HSCs activation by regulating the accumulation of free cholesterol. NPC2 overexpression may thus represent a new treatment strategy for liver fibrosis.
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Proteínas de Transporte/metabolismo , Colesterol/metabolismo , Glicoproteínas/metabolismo , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Animais , Western Blotting , Tetracloreto de Carbono/toxicidade , Modelos Animais de Doenças , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Humanos , Técnicas Imunoenzimáticas , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Tioacetamida/toxicidade , Fator de Crescimento Transformador beta1/farmacologia , Proteínas de Transporte VesicularRESUMO
Primary hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related death. It is important to identify new targets for early diagnosis and treatment of HCC. Niemann-Pick type C2 (NPC2) plays an important role in the regulation of intracellular cholesterol homeostasis via direct binding with free cholesterol. However, little is known about the significance of NPC2 in HCC tumorigenesis. In this study, we showed that NPC2 is abundantly expressed in normal liver, but is downregulated in human HCC tissues. The patients with NPC2 downregulation expressed much higher α-fetoprotein, multiple tumor type, vascular invasion, later pathological stage and shorter survival rate. Knockdown NPC2 in liver cancer cell lines promote cell proliferation, migration and xenograft tumorigenesis. In contrast, NPC2 overexpression inhibits HuH7 promoted tumor growth. Furthermore, administration of hepatotropic adeno-associated virus 8 (AAV8) delivered NPC2 decreased the inflammatory infiltration, the expression of two early HCC markers-glypican 3 and survivin and suppressed the spontaneous HCC development in mice. To identify the NPC2-dependent mechanism, we emphasized on the status of MAPK/ERK signaling. MEK1/2 inhibitor treatment demonstrated that the expression of NPC2 affected the activation of ERK1/2 but not MEK1/2. In addition, cholesterol trafficking inhibitor treatment did not alter the cell proliferation and the activation of MEK/ERK. In conclusion, our study demonstrates that NPC2 may play an important role in negatively regulate cell proliferation and ERK1/2 activation that were independent of cholesterol accumulation. AAV-NPC2 may thus represent a new treatment strategy for liver cancer.
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Proteínas de Transporte/genética , Glicoproteínas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Feminino , Células HEK293 , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Taxa de Sobrevida , Proteínas de Transporte Vesicular , alfa-Fetoproteínas/genéticaRESUMO
This study uses Monte Carlo simulation and experimental measurements to develop a predictive model for estimating the external dose rate associated with permanent radioactive source implantation in prostate cancer patients. The objective is to estimate the accuracy of the patient's external dose rate measurement. First, I-125 radioactive sources were implanted into Mylar window water phantoms to simulate the permanent implantation of these sources in patients. Water phantom experimental measurement was combined with Monte Carlo simulation to develop predictive equations, whose performance was verified against external clinical data. The model's accuracy in predicting the external dose rate in patients with permanently implanted I-125 radioactive sources was high (R2 = 0.999). A comparative analysis of the experimental measurements and the Monte Carlo simulations revealed that the maximum discrepancy between the measured and calculated values for the water phantom was less than 5.00%. The model is practical for radiation safety assessments, enabling the evaluation of radiation exposure risks to individuals around patients with permanently implanted I-125 radioactive sources.
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BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however, no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for 1 patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection before radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.
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Adenocarcinoma , Estudos de Viabilidade , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagem , Adenocarcinoma/radioterapia , Adenocarcinoma/diagnóstico por imagem , Masculino , Idoso , Pessoa de Meia-Idade , Feminino , Idoso de 80 Anos ou mais , Adulto , InjeçõesRESUMO
BACKGROUND AND PURPOSE: Hippocampal avoidance whole brain radiotherapy (HA-WBRT) is effective for controlling disease and preserving neuro-cognitive function for brain metastases. However, contouring and planning of HA-WBRT is complex and time-consuming. We designed and evaluated a pipeline using deep learning tools for a fully automated treatment planning workflow to generate HA-WBRT radiotherapy plans. MATERIALS AND METHODS: We retrospectively collected 50 adult patients who received HA-WBRT. Using RTOG- 0933 clinical trial protocol guidelines, all organs-at-risk (OARs) and the clinical target volume (CTV) were contoured by experienced radiation oncologists. A deep-learning segmentation model was designed and trained. Next, we developed a volumetric-modulated arc therapy (VMAT) auto-planning algorithm for 30 Gy in 10 fractions. Automated segmentations were evaluated using the Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95 % HD). Auto-plans were evaluated by the percentage of PTV volume that receives 30 Gy (V30Gy), conformity index (CI), and homogeneity index (HI) of planning target volume (PTV) and the minimum dose (D100%) and maximum dose (Dmax) for the hippocampus, Dmax for the lens, eyes, optic nerve, brain stem, and chiasm. RESULTS: We developed a deep-learning segmentation model and an auto-planning script. For the 10 cases in the independent test set, the overall average DSC and 95 % HD of contours were greater than 0.8 and less than 7 mm, respectively. All auto-plans met the RTOG- 0933 criteria. The HA-WBRT plan automatically created time was about 10 min. CONCLUSIONS: An artificial intelligence (AI)-assisted pipeline using deep learning tools can rapidly and accurately generate clinically acceptable HA-WBRT plans with minimal manual intervention and increase efficiency of this treatment for brain metastases.
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Neoplasias Encefálicas , Radioterapia de Intensidade Modulada , Adulto , Humanos , Inteligência Artificial , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Hipocampo , Tratamentos com Preservação do Órgão , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos RetrospectivosRESUMO
PURPOSE: Transmission-target x-ray tubes generate more x-rays than reflection thick-target x-ray tubes. A transmission x-ray tube combined with radiosensitizers has a better radiation enhancement effect. This study investigated the feasibility of using a transmission x-ray tube with radiosensitizers in clinical radiotherapy and its effect on radiation dose enhancement. METHODS: This study used MCNP6.2 to simulate the model of a transmission x-ray tube and Co-60 beam. The radiation enhancement effect of radiosensitizers was examined with iodine-127 (I-127), radioiodinated iododeoxyuridine (IUdR), and gold nanoparticles (GNPs). RESULTS: The study results showed that the dose enhancement factor (DEF) of the transmission x-ray tube with GNPs was 10.27, which was higher than that of I-127 (6.46) and IUdR (3.08). The DEF of the Co-60 beam with GNPs, I-127, and IUdR was 1.23, 1.19, and 1.2, respectively. The Auger electron flux of the transmission x-ray tube with GNPs was 1.19E+05 particles/cm2 . CONCLUSIONS: This study found that a transmission x-ray tube with appropriate radiosensitizers could produce a high rate of Auger electrons to fulfill the radiation enhancement effect, and this procedure has the potential to become a radiotherapy modality.
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Nanopartículas Metálicas , Radiossensibilizantes , Idoxuridina , Raios X , Método de Monte Carlo , Ouro , Nanopartículas Metálicas/uso terapêuticoRESUMO
BACKGROUND: Systemic therapy is the primary treatment for advanced thymic malignancies. However, there is an urgent need to improve clinical outcome. Personalized treatment based on predictive biomarkers is a potential approach to address this requirement. In this study, we aimed to show the correlation between drug sensitivity tests on CTCs-derived organoids and clinical response in patients with thymic malignancies. This approach carries the potential to create personalized cancer avatars and improve treatment outcome for patients. METHODS: We previously reported potential treatment outcome prediction with patient-derived organoids (cancer avatars) in patients with pancreatic ductal adenocarcinoma. To further investigate the feasibility of this approach in advanced thymic malignancies, we conducted a study in which 12 patients were enrolled and 21 liquid biopsies were performed. RESULTS: Cancer avatars were successfully derived in 16 out of 21 samples (success rate 76.2%). We found a sensitivity of 1.0 and specificity of 0.6 for drug sensitivity tests on the cancer avatars, and a two-tailed Fisher's exact test revealed a significant correlation between drug sensitivity tests and clinical responses (p = 0.0275). CONCLUSION: This study supports the potential of circulating tumor cell-derived organoids to inform personalized treatment for advanced thymic malignancies. Further validation of this proof of concept finding is ongoing.
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Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Neoplasias do Timo , Humanos , Projetos Piloto , Células Neoplásicas Circulantes/patologia , Neoplasias do Timo/patologia , Neoplasias Pancreáticas/patologia , Organoides/patologiaRESUMO
This study combined the use of radiation dosimeteric measurements and a custom-made anthropomorphic phantom in order to evaluate the accuracy of therapeutic dose calculations at the nasopharyngeal air-tissue interface. The doses at the nasopharyngeal air-tissue interface obtained utilizing the Pinnacle and TomoTherapy TPS, which are based on collapsed cone convolution superposition (CCCS) algorithms, were evaluated and measured under single 10 × 10 cm2, 2 × 2 cm2, two parallel opposed 2 × 2 cm2 and clinical fields for early stage of nasopharyngeal carcinoma by using EBT3, GR-200F, and TLD 100. At the air-tissue interface under a 10 × 10 cm2 field, the TPS dose calculation values were in good agreement with the dosimeter measurement with all differences within 3.5%. When measured the single field 2 × 2 cm2, the differences between the average dose were measured at the distal interface for EBT3, GR-200F, and TLD-100 and the calculation values were -15.8%, -16.4%, and -4.9%, respectively. When using the clinical techniques such as IMRT, VMAT, and tomotherapy, the measurement results at the interface for all three techniques did not imply under dose. Small-field sizes will lead to dose overestimation at the nasopharyngeal air-tissue interface due to electronic disequilibrium when using CCCS algorithms. However, under clinical applications of multiangle irradiation, the dose errors caused by this effect were not significant.
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Neoplasias Nasofaríngeas , Planejamento da Radioterapia Assistida por Computador , Algoritmos , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Nasofaringe , Imagens de Fantasmas , Radiometria/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
To develop a method of estimating surface dose in whole breast irradiation, we used an anthropomorphic phantom with accessories for the simulation of different breast sizes. The surface points, which are measured by TLDs, are set along with two main directions, superior-inferior and medial-lateral. The incident angle between the photon beam and the surface and the doses at 1 cm beneath the surface at every point are assessed by a computerized treatment planning system (cTPS). With the prescription dose of 200 cGy, the average surface doses under tangential irradiation are 97.73 (±14.96) cGy, 99.90 (±10.73) cGy, and 105.26 (±9.21) cGy for large, medium, and small breast volumes, respectively. The surface dose increased in the model of small breast volume without significance (p = 0.39). The linear analysis between surface dose and the incident angle is y = 0.5258x + 69.648, R2 = 0.7131 (x: incident angle and y: surface dose). We develop the percentage of skin surface dose with reference to a depth of 1 cm (PSDR1cm) to normalize the inhomogeneous dose. The relationship between incident angle and PSDR1cm is y = 0.1894x + 36.021, R2 = 0.6536 (x: incident angle and y: PSDR1cm) by linear analysis. In conclusion, the surface dose in whole breast irradiation could be estimated from this linear relationship between PSDR1cm and incident angle in daily clinical practice by cTPS. Further in vivo data should be studied to verify this formula.
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OBJECTIVE: Good bone quality is the key to avoiding osteoporotic fragility fractures and poor outcomes after lumbar instrumentation and fusion surgery. Although dual-energy x-ray absorptiometry (DEXA) screening is the current standard for evaluating osteoporosis, many patients lack DEXA measurements before undergoing lumbar spine surgery. The present study aimed to investigate the utility of using simple quantitative parameters generated with novel synthetic MRI to evaluate bone quality, as well as the correlations of these parameters with DEXA measurements. METHODS: This prospective study enrolled patients with symptomatic lumbar degenerative disease who underwent DEXA and conventional and synthetic MRI. The quantitative parameters generated with synthetic MRI were T1 map, T2 map, T1 intensity, proton density (PD), and vertebral bone quality (VBQ) score, and these parameters were correlated with T-score of the lumbar spine. RESULTS: There were 62 patients and 238 lumbar segments eligible for analysis. PD and VBQ score moderately correlated with T-score of the lumbar spine (r = -0.565 and -0.651, respectively; both p < 0.001). T1 intensity correlated fairly well with T-score (r = -0.411, p < 0.001). T1 and T2 correlated poorly with T-score. Receiver operating characteristic curve analysis demonstrated area under the curve values of 0.808 and 0.794 for detecting osteopenia/osteoporosis (T-score ≤ -1.0) and osteoporosis (T-score ≤ -2.5) with PD (both p < 0.001). CONCLUSIONS: PD and T1 intensity values generated with synthetic MRI demonstrated significant correlation with T-score. PD has excellent ability for predicting osteoporosis and osteopenia.
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Background: This study aims to establish and validate a predictive model based on radiomics features, clinical features, and radiation therapy (RT) dosimetric parameters for overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with RT for portal vein tumor thrombosis (PVTT). Methods: We retrospectively reviewed 131 patients. Patients were randomly divided into the training (n = 105) and validation (n = 26) cohorts. The clinical target volume was contoured on pre-RT computed tomography images and 48 textural features were extracted. The least absolute shrinkage and selection operator regression was used to determine the radiomics score (rad-score). A nomogram based on rad-score, clinical features, and dosimetric parameters was developed using the results of multivariate regression analysis. The predictive nomogram was evaluated using Harrell's concordance index (C-index), area under the curve (AUC), and calibration curve. Results: Two radiomics features were extracted to calculate the rad-score for the prediction of OS. The radiomics-based nomogram had better performance than the clinical nomogram for the prediction of OS, with a C-index of 0.73 (95% CI, 0.67-0.79) and an AUC of 0.71 (95% CI, 0.62-0.79). The predictive accuracy was assessed by a calibration curve. Conclusion: The radiomics-based predictive model significantly improved OS prediction in HCC patients treated with RT for PVTT.
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(1) Background: The purpose of this study was to evaluate the radiation awareness level of the public in Taiwan. (2) Methods: This study designed an online survey form to investigate the radiation awareness level with six topics: basic knowledge of radiation, environmental radiation, medical radiation, radiation protection, and university/corporate social responsibility. The score of respondents were converted into knowledge and responsibility indexes for the quantitative evaluation. Logistic regression was used to assess the correlation between the knowledge index and individual factors. Paired t-test was used to assess the significant difference in knowledge index between pre-training and post-training. (3) Results: The knowledge index of each job category reflected the proportion of radiation awareness of the job. The logistic regression result indicated that radiation-related people could get higher knowledge index. The paired t-test indicated that the knowledge index before and after class had significant differences in all question topics. (4) Conclusions: The public's awareness of medical radiation was the topic that needed to be strengthened the most-the responses with high knowledge index significantly correlated with their experience in radiation education training or radiation-related jobs. It significantly increased the knowledge index of radiation if the public received radiation education training.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Proteção Radiológica , Humanos , Taiwan , Inquéritos e Questionários , Modelos Logísticos , ConscientizaçãoRESUMO
BACKGROUND: Neoadjuvant chemoradiation therapy (NCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC); approximately 80% of patients do not achieve complete response. Identifying prognostic factors predictive of survival in these patients to guide further management is needed. The intratumoural lymphocytic response (ILR), peritumoural lymphocytic reaction (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PtLR) are correlated with the tumour microenvironment and cancer-related systemic inflammation. This study aimed to explore the ability of the ILR, PLR, NLR, and PtLR to predict survival in LARC patients without a complete response to NCRT. METHODS: Sixty-nine patients who underwent NCRT and surgery were retrospectively reviewed. The ILR and PLR were assessed in surgical specimens, and the NLR and PtLR were calculated using pre- and post-NCRT blood count data. The Kaplan-Meier method and Cox regression analyses were performed for survival analysis. RESULTS: A high PLR and high post-NCRT NLR and PtLR were significantly associated with better prognosis. Lymphovascular invasion (LVI), post-NCRT neutrophil count, and lymphocyte count were significant predictors of overall survival. LVI and the PLR were independent predictors of disease-free survival. CONCLUSIONS: NCRT-induced local and systemic immune responses are favourable prognostic predictors in LARC patients without complete response to NCRT.