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1.
Radiat Prot Dosimetry ; 200(8): 802-807, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38773775

RESUMO

Interventional cardiology is characterized by high radiation exposure for both the patient and the operator. Adequate shielding and monitoring of the operator are fundamental to comply with radiation protection principles. In a previous work, the effect on the dose of the dosemeter position on the chest was studied. In this paper, the investigation has been completed, employing an anthropomorphic thorax phantom, equipped with arms. Although there are differences between the Monte Carlo simulations and the measurements, similar trends are observed, showing that the reduction in dose, due to the arms, is between 20 and 60%, compared with the situation without arms. For that reason, considering a dosemeter placed on the chest, the upper position, which is the least affected by the arms, should be preferred while the extreme lateral position, near the armpit, should be avoided.


Assuntos
Simulação por Computador , Método de Monte Carlo , Exposição Ocupacional , Imagens de Fantasmas , Roupa de Proteção , Doses de Radiação , Monitoramento de Radiação , Proteção Radiológica , Humanos , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Proteção Radiológica/métodos , Monitoramento de Radiação/métodos , Cardiologia/métodos , Corpo Clínico , Tórax/efeitos da radiação
2.
J Appl Clin Med Phys ; 25(7): e14389, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38778565

RESUMO

PURPOSE: The aim of this study was to compare the organ doses assessed through a digital phantom-based and a patient specific-based dosimetric tool in adult routine thorax computed tomography (CT) examinations with reference to physical dose measurements performed in anthropomorphic phantoms. METHODS: Two Monte Carlo based dose calculation tools were used to assess organ doses in routine adult thorax CT examinations. These were a digital phantom-based dosimetry tool (NCICT, National Cancer Institute, USA) and a patient-specific individualized dosimetry tool (ImpactMC, CT Imaging GmbH, Germany). Digital phantoms and patients were classified in four groups according to their water equivalent diameter (Dw). Normalized to volume computed tomography dose index (CTDIvol), organ dose was assessed for lungs, esophagus, heart, breast, active bone marrow, and skin. Organ doses were compared to measurements performed using thermoluminescent detectors (TLDs) in two physical anthropomorphic phantoms that simulate the average adult individual as a male (Alderson Research Labs, USA) and as a female (ATOM Phantoms, USA). RESULTS: The average percent difference of NCICT to TLD and ImpactMC to TLD dose measurements across all organs in both sexes was 13% and 6%, respectively. The average ± 1 standard deviation in dose values across all organs with NCICT, ImpactMC, and TLDs was ± 0.06 (mGy/mGy), ± 0.19 (mGy/mGy), and ± 0.13 (mGy/mGy), respectively. Organ doses decreased with increasing Dw in both NCICT and ImpactMC. CONCLUSION: Organ doses estimated with ImpactMC were in closer agreement to TLDs compared to NCICT. This may be attributed to the inherent property of ImpactMC methodology to generate phantoms that resemble the realistic anatomy of the examined patient as opposed to NCICT methodology that incorporates an anatomical discrepancy between phantoms and patients.


Assuntos
Método de Monte Carlo , Órgãos em Risco , Imagens de Fantasmas , Doses de Radiação , Radiografia Torácica , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Masculino , Feminino , Adulto , Órgãos em Risco/efeitos da radiação , Radiografia Torácica/métodos , Radiometria/métodos , Tórax/diagnóstico por imagem , Tórax/efeitos da radiação , Processamento de Imagem Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/métodos
3.
Femina ; 51(7): 390-399, 20230730. ilus
Artigo em Português | LILACS | ID: biblio-1512437

RESUMO

Objetivo: Apresentar a atualização das recomendações do Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, da Sociedade Brasileira de Mastologia e da Federação Brasileira das Associações de Ginecologia e Obstetrícia para o rastreamento do câncer de mama no Brasil. Materiais e Métodos: Foram feitas buscas das evidências científicas publicadas nas bases Medline, EMBASE, Cochrane Library, EBSCO, CINAHL e Lilacs, entre janeiro de 2012 e julho de 2022. As recomendações foram baseadas nessas evidências, mediante consenso da comissão de especialistas das três entidades. Recomendações: O rastreamento mamográfico anual é recomendado para as mulheres de risco habitual entre 40 e 74 anos. Acima de 75 anos, deve ser reservado para as que tenham expectativa de vida maior que sete anos. Mulheres com risco maior que o habitual, entre elas as com mamas densas, com história pessoal de hiperplasia lobular atípica, carcinoma lobular in situ clássico, hiperplasia ductal atípica, tratamento de câncer de mama ou de irradiação no tórax antes dos 30 anos ou, ainda, portadoras de mutação genética ou com forte história familiar, beneficiam-se do rastreamento complementar, sendo consideradas de forma individualizada. A tomossíntese é uma evolução da mamografia e deve ser considerada no rastreamento, sempre que acessível e disponível. (AU)


Objective: To present the update of the recommendations of the Brazilian College of Radiology, the Brazilian Society of Mastology and the Brazilian Federation of Gynecology and Obstetrics Associations for breast cancer screening in Brazil. Materials and Methods: Scientific evidence published in Medline, Embase, Cochrane Library, Ebsco, Cinahl and Lilacs between January 2012 and July 2022 was searched. Recommendations were based on this evidence, by consensus of the expert committee of the three entities. Recommendations: Annual mammographic screening is recommended for women aged between 40 and 74 years old. Above 75 years should be reserved for those with a life expectancy greater than seven years. Women at higher than usual risk, including those with dense breasts, a personal history of atypical lobular hyperplasia, classic lobular carcinoma in situ, atypical ductal hyperplasia, treatment for breast câncer, chest irradiation before age 30, carriers of genetic mutation or with a strong family history, benefit from complementary screening, being considered individually. Tomosynthesis is an evolution of mammography and should be considered in screening, whenever accessible and available. (AU)


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/prevenção & controle , Programas de Rastreamento/efeitos adversos , Qualidade de Vida , Tórax/efeitos da radiação , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Mamografia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos de Coortes , Saúde da Mulher , Revisão Sistemática
4.
Food Funct ; 14(3): 1545-1559, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36655677

RESUMO

Radiation-induced lung injury (RILI) is one of the most prominent complications of thoracic radiotherapy for which effective therapy is still lacking. This study investigates the nutraceutical potential of the culinary spice Amomum subulatum in mitigating thoracic radiation-induced pneumonitis (RP) and pulmonary fibrosis (PF). Mouse models of RP and PF were established by whole thorax irradiation at a dose of 25 gray. C57BL/6 mice were administered with 250 mg per kg body weight of methanolic extract of A. subulatum dry fruits (MEAS) for four consecutive weeks and observed for changes in lung tissue antioxidant activities, oxidative stress parameters, and expression of antioxidant, inflammation, and fibrosis-related genes by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR analysis, and histology analysis. MEAS administration reduced radiation-induced oxidative stress by enhancing the expression of Nrf2 and its target genes. Irradiation increased gene expression of inflammatory mediators and lung histology further confirmed the characteristics of RP, which were reduced by MEAS treatment. Immunohistochemistry analysis revealed the potential of MEAS in reducing the radiation-induced elevation of cyclooxygenase 2 expression in the lungs. The late sequel of RILI was manifested as PF, characterized by the elevated expression of pro-fibrotic genes and increased collagen content. However, MEAS administration markedly reduced radiation-induced fibrotic changes in the lungs. These effects might be attributed to the synergistic effect of bioactive polyphenols in MEAS with antioxidant, anti-inflammatory, and anti-fibrotic efficacies. Taken together, this study demonstrates the potential of MEAS in mitigating RILI, suggesting the possible nutraceutical application of A. subulatum against radiation toxicities.


Assuntos
Amomum , Lesão Pulmonar , Fibrose Pulmonar , Lesões por Radiação , Pneumonite por Radiação , Animais , Camundongos , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Camundongos Endogâmicos C57BL , Pulmão , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/etiologia , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/metabolismo , Pneumonite por Radiação/patologia , Lesões por Radiação/tratamento farmacológico , Fibrose , Tórax/metabolismo , Tórax/patologia , Tórax/efeitos da radiação
5.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576128

RESUMO

Radiation-induced abscopal effect (RIAE) outside of radiation field is becoming more attractive. However, the underlying mechanisms are still obscure. This work investigated the deleterious effect of thoracic irradiation (Th-IR) on distant bone marrow and associated signaling factors by irradiating the right thorax of mice with fractionated doses (8 Gy × 3). It was found that this localized Th-IR increased apoptosis of bone marrow cells and micronucleus formation of bone marrow polychromatic erythrocytes after irradiation. Tandem mass tagging (TMT) analysis and ELISA assay showed that the concentrations of TNF-α and serum amyloid A (SAA) in the mice were significantly increased after Th-IR. An immunohistochemistry assay revealed a robust increase in SAA expression in the liver rather than in the lungs after Th-IR. In vitro experiments demonstrated that TNF-α induced SAA expression in mouse hepatoma Hepa1-6 cells, and these two signaling factors induced DNA damage in bone marrow mesenchymal stem cells (BMSCs) by increasing reactive oxygen species (ROS). On the other hand, injection with TNF-α inhibitor before Th-IR reduced the secretion of SAA and attenuated the abscopal damage in bone marrow. ROS scavenger NAC could also mitigated Th-IR/SAA-induced bone marrow damage in mice. Our findings indicated that Th-IR triggered TNF-α release from lung, which further promoted SAA secretion from liver in a manner of cascade reaction. Consequently, these signaling factors resulted in induction of abscopal damage on bone marrow of mice.


Assuntos
Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos da radiação , Fracionamento da Dose de Radiação , Proteína Amiloide A Sérica/metabolismo , Tórax/efeitos da radiação , Fator de Necrose Tumoral alfa/metabolismo , Acetilcisteína/farmacologia , Animais , Proteínas Sanguíneas/metabolismo , Ciclo Celular/efeitos da radiação , Dano ao DNA , Sequestradores de Radicais Livres/farmacologia , Lesão Pulmonar/patologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos da radiação , Camundongos Endogâmicos C57BL , Proteômica , Espécies Reativas de Oxigênio/metabolismo
6.
Health Phys ; 121(4): 331-344, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34546215

RESUMO

ABSTRACT: To study the molecular and cellular mechanisms of radiation-induced lung injury (RILI) in a non-human primate model, Rhesus macaques were irradiated with lethal doses of radiation to the whole thorax. A subset of the irradiated animals was treated with AEOL 10150, a potent catalytic scavenger of reactive oxygen and nitrogen species. Lung tissues were collected at necropsy for molecular and immunohistochemical (IHC) studies. Microarray expression profiling in the irradiated lung tissues identified differentially expressed genes (DEGs) and pathways important in innate immunity. The elevated expression of cytokines (CCL2, CCL11, IL-8), complement factors (CFB, C3), apoptosis-related molecules (p53, PTEN, Bax, p21, MDM2, c-Caspase 3), and adhesion molecules (fibronectin, integrin ß6, ICAM-1) were further studied using real-time PCR, Western blot, or IHC. Oxidative stress and pulmonary inflammatory cell infiltration were increased in the irradiated lungs. Treatment with AEOL 10150 significantly decreased oxidative stress and monocyte/macrophage infiltration. Cytokine/chemokine-induced excessive innate immune response after thoracic irradiation plays an important role in RILI. To our knowledge, this is the first study to highlight the role of cytokine/chemokine-induced innate immune responses in radiation-induced pulmonary toxicity in a NHP model.


Assuntos
Pulmão , Tórax , Animais , Imunidade Inata , Pulmão/efeitos da radiação , Macaca mulatta , Metaloporfirinas , Tórax/efeitos da radiação
7.
Radiat Res ; 196(3): 297-305, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34129665

RESUMO

Survival from partial-body irradiation (PBI) may be limited by the development of the late lung injury response of pneumonitis. Herein we investigated the hypothesis that acute hematopoietic depletion alters the onset and severity of lung disease in a mouse model. To establish depletion, C3H/HeJ mice received 8 Gy PBI with shielding of only the tibiae, ankles and feet. One week after irradiation, blood lymphocyte and neutrophil counts were each significantly reduced (P < 0.04) in these mice compared to levels in untreated controls or in mice receiving 16 Gy to the whole thorax only. All 8 Gy PBI mice survived to the experimental end point of 16 weeks postirradiation. To determine whether the hematopoietic depletion affects lung disease, groups of mice received 8 Gy PBI plus 8 Gy whole-thorax irradiation (total lung dose of 16 Gy) or 16 Gy whole-thorax irradiation only. The weight loss, survival to onset of respiratory distress (P = 0.17) and pneumonitis score (P = 0.96) of mice that received 8 Gy PBI plus 8 Gy whole-thorax irradiation were not significantly different from those of mice receiving 16 Gy whole-thorax irradiation only. Mice in respiratory distress from PBI plus whole-thorax irradiation had significantly reduced (P = 0.02) blood monocyte counts compared to levels in distressed, whole-thorax irradiated mice, and symptomatic pneumonitis was associated with increased blood neutrophil counts (P = 0.04) relative to measures from irradiated, non-distressed mice. In conclusion, survivable acute hematopoietic depletion by partial-body irradiation did not alter the onset or severity of lethal pneumonitis in the C3H/HeJ mouse model.


Assuntos
Pancitopenia/etiologia , Lesões Experimentais por Radiação/terapia , Pneumonite por Radiação/prevenção & controle , Animais , Progressão da Doença , Feminino , Inflamação/prevenção & controle , Contagem de Leucócitos , Pulmão/patologia , Pulmão/efeitos da radiação , Camundongos , Camundongos Endogâmicos C3H , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/etiologia , Pneumonite por Radiação/sangue , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/patologia , Tórax/efeitos da radiação , Redução de Peso/efeitos da radiação
8.
J Radiat Res ; 62(4): 669-675, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34121123

RESUMO

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P < 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Cuidados Paliativos , Pneumonia/epidemiologia , Pneumonia/etiologia , Tórax/efeitos da radiação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Curva ROC , Fatores de Risco , Tomografia Computadorizada por Raios X
9.
Radiat Oncol ; 16(1): 70, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849579

RESUMO

BACKGROUND: Previous studies have found that patients with subclinical interstitial lung disease (ILD) are highly susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy. In the present study we aimed to evaluate the incidence of and risk factors for RP after thoracic intensity-modulated radiation therapy in lung cancer patients with subclinical ILD. METHODS: We retrospectively analyzed data from lung cancer patients with subclinical ILD who were treated with thoracic intensity-modulated radiation therapy with a prescribed dose of ≥ 50 Gy in our institution between January 2016 and December 2017. RESULTS: Eighty-seven consecutive lung cancer patients with subclinical ILD were selected for the study. The median follow-up period was 14.0 months. The cumulative incidence of grades ≥ 2 and ≥ 3 RP at one year was 51.0% and 20.9%, respectively. In the multivariate analysis, a mean lung dose ≥ 12 Gy was a significant risk factor for grade ≥ 2 RP (p = 0.049). Chemotherapy with gemcitabine in the past, V5 ≥ 50%, and subclinical ILD involving ≥ 25% of the lung volume were significantly associated with grade ≥ 3 RP (p = 0.046, p = 0.040, and p = 0.024, respectively). CONCLUSION: Mean lung dose is a significant risk factor for grade ≥ 2 RP. Lung cancer patients who have received chemotherapy with gemcitabine in the past, V5 ≥ 50%, and those with subclinical ILD involving ≥ 25% of lung volume have an increased risk of grade ≥ 3 RP in lung cancer patients with subclinical ILD.


Assuntos
Doenças Pulmonares Intersticiais/radioterapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/radioterapia , Pneumonite por Radiação/etiologia , Radioterapia/métodos , Tórax/efeitos da radiação , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Progressão da Doença , Relação Dose-Resposta à Radiação , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Gencitabina
10.
Front Immunol ; 12: 627197, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859637

RESUMO

Background: The combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment. Methods: An electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software. Results: Eleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed. Conclusion: Most AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Radioterapia/efeitos adversos , Tórax/efeitos da radiação
11.
PLoS One ; 16(4): e0250490, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33891632

RESUMO

The objective of this study is to identify essential aspects influencing radiation dose in computed tomography [CT] of the chest, abdomen and pelvis by intraindividual comparison of imaging parameters and patient related factors. All patients receiving at least two consecutive CT examinations for tumor staging or follow-up within a period of 22 months were included in this retrospective study. Different CT dose estimates (computed tomography dose index [CTDIvol], dose length product [DLP], size-specific dose estimate [SSDE]) were correlated with patient's body mass index [BMI], scan length and technical parameters (tube current, tube voltage, pitch, noise level, level of iterative reconstruction). Repeated-measures-analysis was initiated with focus on response variables (CTDIvol, DLP, SSDE) and possible factors (age, BMI, noise, scan length, peak kilovoltage [kVp], tube current, pitch, adaptive statistical iterative reconstruction [ASIR]). A univariate-linear-mixed-model with repeated-measures-analysis followed by Bonferroni adjustments was used to find associations between CT imaging parameters, BMI and dose estimates followed by a subsequent multivariate-mixed-model with repeated-measures-analysis with Bonferroni adjustments for significant parameters. A p-value <0.05 was considered statistically significant. We found all dose estimates in all imaging regions were substantially affected by tube current. The iterative reconstruction significantly influenced all dose estimates in the thoracoabdominopelvic scans as well as DLP and SSDE in chest-CT. Pitch factor affected all dose parameters in the thoracoabdominopelvic CT group. These results provide further evidence that tube current has a pivotal role and potential in radiation dose management. The use of iterative reconstruction algorithms can substantially decrease radiation dose especially in thoracoabdominopelvic and chest-CT-scans. Pitch factor should be kept at a level of ≥1.0 in order to reduce radiation dose.


Assuntos
Meios de Contraste/administração & dosagem , Neoplasias Induzidas por Radiação/epidemiologia , Doses de Radiação , Tomografia Computadorizada por Raios X/efeitos adversos , Abdome/patologia , Abdome/efeitos da radiação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Índice de Massa Corporal , Meios de Contraste/efeitos adversos , Testes Diagnósticos de Rotina , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/prevenção & controle , Pelve/diagnóstico por imagem , Pelve/patologia , Pelve/efeitos da radiação , Interpretação de Imagem Radiográfica Assistida por Computador/normas , Razão Sinal-Ruído , Tórax/diagnóstico por imagem , Tórax/efeitos da radiação , Adulto Jovem
12.
Br J Cancer ; 124(11): 1809-1819, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33742147

RESUMO

BACKGROUND: The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model. METHODS: To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology. RESULTS: Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity. CONCLUSIONS: The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Modelos Animais de Doenças , Feminino , Neoplasias Pulmonares/patologia , Camundongos , Ftalazinas/farmacologia , Piperazinas/farmacologia , Radiossensibilizantes/uso terapêutico , Índice Terapêutico , Tórax/efeitos da radiação , Resultado do Tratamento
13.
J Radiat Res ; 62(2): 236-248, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33616187

RESUMO

The lung is sensitive to radiation and exhibits several phases of injury, with an initial phase of radiation-induced pneumonitis followed by delayed and irreversible fibrosis. The angiotensin-converting enzyme inhibitor captopril has been demonstrated to mitigate radiation lung injury and to improve survival in animal models of thoracic irradiation, but the mechanism remains poorly understood. Here we investigated the effect of captopril on early inflammatory events in the lung in female CBA/J mice exposed to thoracic X-ray irradiation of 17-17.9 Gy (0.5-0.745 Gy min-1). For whole-body + thoracic irradiation, mice were exposed to 7.5 Gy (0.6 Gy min-1) total-body 60Co irradiation and 9.5 Gy thoracic irradiation. Captopril was administered orally (110 mg kg-1 day-1) in the drinking water, initiated 4 h through to150 days post-irradiation. Captopril treatment increased survival from thoracic irradiation to 75% at 150 days compared with 0% survival in vehicle-treated animals. Survival was characterized by a significant decrease in radiation-induced pneumonitis and fibrosis. Investigation of early inflammatory events showed that captopril significantly attenuated macrophage accumulation and decreased the synthesis of radiation-induced interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) pro-inflammatory cytokines in the lungs of irradiated mice. Suppression of IL-1ß and TNF-α correlated with an increase of the anti-inflammatory cytokine IL-10 in the spleen with captopril treatment. We also found that captopril decreased markers for radiation-induced accelerated senescence in the lung tissue. Our data suggest that suppression of inflammation and senescence markers, combined with an increase of anti-inflammatory factors, are a part of the mechanism for captopril-induced survival in thoracic irradiated mice.


Assuntos
Envelhecimento/patologia , Captopril/uso terapêutico , Pneumonia/tratamento farmacológico , Tórax/efeitos da radiação , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Biomarcadores/metabolismo , Captopril/farmacologia , Citocinas/metabolismo , Feminino , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/patologia , Macrófagos Alveolares/efeitos da radiação , Camundongos Endogâmicos CBA , Fibrose Pulmonar/patologia , Baço/efeitos dos fármacos , Baço/efeitos da radiação , Análise de Sobrevida , Irradiação Corporal Total , Raios X
14.
Diagn Interv Radiol ; 27(1): 147-151, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33475510

RESUMO

PURPOSE: We aimed to obtain typical values for head, neck, chest, and abdominal computed tomography (CT) examinations from routine patients in 2018, and to review our data with national and international diagnostic reference levels (DRLs). METHODS: Single-phase head, neck, chest, and abdominal CT scans of adults performed in 64-slice CT in 2018 were included in this study. Radiation dose parameters of CT scans were obtained from the picture archiving and communication system of our hospital. Volumetric CT dose index (CTDIvol) and dose length product (DLP) values were recorded. Effective dose (ED) and scan length was calculated. A 16 cm diameter phantom is referenced for head CT, and 32 cm diameter phantom is referenced for neck, chest, and abdominal CT. Descriptive statistics of the variables were given according to the normality testing. RESULTS: Median CTDIvol value was 53 mGy for the head, 13.1 mGy for the neck, 8.3 mGy for the chest, and 8.6 mGy for the abdomen. Median DLP value was 988 mGy.cm for the head, 299 mGy.cm for the neck, 314 mGy.cm for the chest, and 457 mGy.cm for the abdomen. Median ED value was 2.07 mSv for the head, 1.76 mSv for the neck, 4.4 mSv for the chest, and 6.8 mSv for the abdomen. Considering national DRLs, median CTDIvol values of head, chest, and abdomen were lower, whereas median DLP and ED values of head and chest were higher. For the abdomen, the median DLP and ED values were lower. CONCLUSION: Overall radiation dose parameters obtained in this study points out the need for optimization of head CT examinations in our institution.


Assuntos
Tórax , Tomografia Computadorizada por Raios X , Abdome/efeitos da radiação , Adulto , Cabeça/efeitos da radiação , Humanos , Doses de Radiação , Valores de Referência , Tórax/efeitos da radiação
15.
Int J Radiat Oncol Biol Phys ; 109(4): 946-952, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33223046

RESUMO

PURPOSE: The effects of thoracic radiation therapy (RT) on physical functioning and quality of life (QoL) are incompletely defined. We determined the associations between thoracic RT dose volume metrics, physical activity, and QoL in patients with cancer. METHODS AND MATERIALS: Participants with breast cancer, lung cancer, or mediastinal lymphoma treated with radiation with or without chemotherapy were enrolled in a prospective, longitudinal cohort study. Data were collected pre-RT, immediately post-RT, and 5 to 9 months post-RT. At each timepoint, self-reported physical activity was assessed via the Godin-Shephard Leisure-Time Physical Activity Questionnaire, and QoL metrics were assessed via Functional Assessment of Chronic Illness Therapy Fatigue and Dyspnea Scales. Multivariable adjusted linear regression models were stratified by breast cancer alone and lung cancer and lymphoma combined. RESULTS: One hundred thirty participants were included in the study. In breast cancer (n = 80), each 1-Gy increase in mean heart dose was associated with worse Functional Assessment of Chronic Illness Therapy Fatigue scores (-1.0; 95% confidence interval [CI], -1.9 to -0.2; P = .021); similar associations were observed between V5 and fatigue (-2.5; 95% CI, -4.4 to -0.6; P = .010 for each 10% increase in V5). In lung cancer and lymphoma (n = 50), each 10% increase in V5 was associated with decreased physical activity (Godin-Shephard Leisure-Time Physical Activity Questionnaire score -2.3; 95% CI, -4.3 to -0.4; P = .017). Although the associations between baseline levels of physical activity and fatigue and dyspnea were of borderline significance in breast cancer alone (P < .10), increased physical activity over time was associated with improvements in fatigue and dyspnea across all cancer types (P < .05 for all). CONCLUSIONS: Higher cardiac RT dose was associated with worse fatigue and physical activity across breast cancer, lung cancer, and mediastinal lymphoma. Longitudinal increases in physical activity were associated with concurrent improvements in QoL measures. Strategies to increase physical activity and decrease cardiac RT dose may improve physical functioning and QoL for patients with cancer.


Assuntos
Neoplasias da Mama/radioterapia , Exercício Físico , Neoplasias Pulmonares/radioterapia , Linfoma/radioterapia , Neoplasias do Mediastino/radioterapia , Qualidade de Vida , Tórax/efeitos da radiação , Adulto , Idoso , Neoplasias da Mama/psicologia , Feminino , Humanos , Estudos Longitudinais , Neoplasias Pulmonares/psicologia , Linfoma/psicologia , Masculino , Neoplasias do Mediastino/psicologia , Pessoa de Meia-Idade , Estudos Prospectivos
16.
J Radiat Res ; 62(1): 119-132, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33302295

RESUMO

The contribution of type II alveolar epithelial stem cells (AEC II) to radiation-induced lung fibrosis (RILF) is largely unknown. Cell differentiation phenotypes are determined by the balance between Lin28 and lethal-7 microRNA (let-7 miRNA). Lin28 is activated by ß-catenin. The aim of this study was to track AEC II phenotypes at different phases of injury following thoracic irradiation and examine the expression of ß-catenin, Lin28 and let-7 to identify their role in AEC II differentiation. Results showed that coexpression of prosurfactant protein C (proSP-C, an AEC II biomarker) and HOPX (homeobox only protein X, an AEC I biomarker) or vimentin (a differentiation marker) was detected in AEC II post-irradiation. The protein expression levels of HOPX and proSP-C were significantly downregulated, but vimentin was significantly upregulated following irradiation. The expression of E-cadherin, which prevents ß-catenin from translocating to the nucleus, was downregulated, and the expression of ß-catenin and Lin28 was upregulated after irradiation (P < 0.05 to P < 0.001). Four let-7 miRNA members (a, b, c and d) were upregulated in irradiated lungs (P < 0.05 to P < 0.001), but let-7d was significantly downregulated at 5 and 6 months (P < 0.001). The ratios of Lin28 to four let-7 members were low during the early phase of injury and were slightly higher after 2 months. Intriguingly, the Lin28/let-7d ratio was strikingly increased after 4 months. We concluded that ß-catenin contributed to RILF by promoting Lin28 expression, which increased the number of AEC II and the transcription of profibrotic molecules. In this study, the downregulation of let-7d miRNA by Lin28 resulted in the inability of AEC II to differentiate into type I alveolar epithelial cells (AEC I).


Assuntos
Células Epiteliais Alveolares/metabolismo , Redes Reguladoras de Genes , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/metabolismo , Células-Tronco/metabolismo , Tórax/efeitos da radiação , beta Catenina/metabolismo , Células Epiteliais Alveolares/efeitos da radiação , Animais , Biomarcadores/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos da radiação , Redes Reguladoras de Genes/efeitos da radiação , Proteínas de Homeodomínio/metabolismo , Pulmão/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Fenótipo , Proteína C Associada a Surfactante Pulmonar/metabolismo , Células-Tronco/efeitos da radiação , Vimentina/metabolismo , Raios X
17.
Strahlenther Onkol ; 197(5): 423-428, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33231713

RESUMO

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective treatment modality for inoperable early-stage lung cancer or metastatic lung lesions. Post-SBRT, acute radiological lung changes sometimes mimic tumor progression, so over-investigation may be applied. We aimed to reveal the interobserver agreement among physicians regarding acute radiographic changes on CT of the thorax obtained shortly after SBRT MATERIALS AND METHODS: Radiologic images of 20 lesions treated with SBRT were evaluated for acute lung changes. Two physicians, one senior and one junior, from diagnostic radiology, radiation oncology, nuclear medicine, and chest disease departments reviewed these images. The final interpretations were categorized as stable, regression/consolidation, progressive disease, and SBRT-related changes. The evaluations of the physicians were compared with the experienced reference radiation oncologist. The gold standard was accepted as the reference physician's final score. Unweighted Cohen's kappa (κ) coefficient was used for assessing interobserver agreement between physicians. RESULTS: The evaluations of the physicians were compared with the reference radiation oncologist. The strongest coherence coefficient was found with the senior radiation oncologist (κ: 0.72). The kappa coefficients between the junior radiation oncologist, junior nuclear medicine physician, and the reference physician were 0.61 and 0.55, respectively. The disciplines with the lowest kappa coefficients were junior chest disease and senior radiologist, and the kappa values were 0.37 and 0.44, respectively. CONCLUSION: Disciplines dealing with lung cancer treatment may not be aware of the various radiologic changes after SBRT or inexperienced in interpreting them from recurrence. Therefore, physicians must have detailed radiotherapy information such as planning target volume (PTV), dose/fractionation, etc. In addition, final evaluations should be performed in the multidisciplinary team dealing with the treatment of the patient.


Assuntos
Pulmão/efeitos da radiação , Variações Dependentes do Observador , Médicos/psicologia , Radiocirurgia , Tórax/efeitos da radiação , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Tomografia Computadorizada Quadridimensional , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Medicina Nuclear , Posicionamento do Paciente , Pneumologia , Radioterapia (Especialidade) , Radiologistas/psicologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Tórax/diagnóstico por imagem
18.
Int J Radiat Oncol Biol Phys ; 109(2): 425-435, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002543

RESUMO

PURPOSE: Consolidative thoracic radiation therapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer. We hypothesized that the addition of ipilimumab (IPI) and nivolumab (NIVO) after TRT would improve outcomes for patients with extensive stage small cell lung cancer. METHODS AND MATERIALS: Eligibility required stable disease or better after platinum doublet chemotherapy. Study therapy included consolidative TRT to 30 Gy in 10 fractions, targeting residual primary tumor and initially involved regional lymph nodes. Two weeks after TRT, patients received concurrent IPI (3 mg/kg) and NIVO (1 mg/kg) every 3 weeks for 4 doses followed by NIVO monotherapy (480 mg) every 4 weeks until progression or up to 1 year. RESULTS: The study enrolled 21 patients, with 6-month progression-free survival (PFS) of 24% (90% confidence interval [CI], 11%-40%) and a median PFS of 4.5 months (95% CI, 2.7%-4.6%). The 12-month overall survival (OS) was 48% (95% CI, 29%-64%) with a median OS of 11.7 months (95% CI, 4.7%-16.0%). Fifty-two percent of patients had ≥1 possibly related grade 3 to 4 immune-related adverse event. Grade 3 pulmonary and gastrointestinal immune-related adverse events were recorded in 19% and 24% of patients, respectively. Exploratory analysis showed increased cytotoxic T cell (CD3+CD8+) tumor infiltration was associated with favorable PFS (P = .01) and OS (P = .02). Reduction in peripheral blood CD3+CD8+ from baseline to after first dose of IPI/NIVO was associated with improved PFS (P = .02) and OS (P = .02). CONCLUSIONS: Consolidative IPI and NIVO after platinum-based chemotherapy and TRT demonstrated a toxicity profile consistent with the known adverse events attributable to IPI and NIVO. Although the study regimen did not significantly improve PFS, the OS was higher than historic expectations. CD3+CD8+ tumor infiltration and migration may identify patients most likely to have improved outcomes in small cell lung cancer.


Assuntos
Ipilimumab/uso terapêutico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Nivolumabe/uso terapêutico , Platina/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tórax/efeitos da radiação
19.
Jpn J Clin Oncol ; 51(2): 279-286, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33049757

RESUMO

OBJECTIVES: Studies investigating the association between radiation therapy and the efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer have provided inconsistent results, likely due to relatively small cohort sizes. This study investigated the effect of previous thoracic radiation therapy on the efficacy of immune checkpoint inhibitor therapy in a large non-small-cell lung cancer cohort. PATIENTS AND METHODS: We conducted a retrospective cohort study using data from 531 non-small-cell lung cancer patients who received monotherapy with programmed cell death protein 1/programmed death-ligand 1 inhibitors at nine institutions. The effects of thoracic radiation therapy on the efficacy of immune checkpoint inhibitors were investigated. RESULTS: A total of 531 non-small-cell lung cancer patients treated with immune checkpoint inhibitors were included in this study. The progression-free survival period was significantly longer in patients that had received thoracic radiation therapy before immune checkpoint inhibitor therapy compared to those without previous thoracic radiation therapy (median progression-free survival 5.0 vs. 3.0 months, P = 0.0013). A multivariate analysis showed that thoracic radiation therapy was an independent predictive factor of improved progression-free survival (hazard ratio of progression-free survival: 0.79, P = 0.049). In contrast, extra-thoracic radiation therapy was associated with inferior outcomes (median progression-free survival 3.0 vs. 4.2 months, P = 0.0008). CONCLUSION: Previous thoracic radiation therapy, but not prior extra-thoracic radiation therapy, enhanced the efficacy of anti-programmed cell death protein 1/programmed death-ligand 1 therapy in non-small-cell lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Tórax/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/metabolismo , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
20.
PLoS One ; 15(12): e0244267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362199

RESUMO

BACKGROUND: Cardiovascular comorbidity anticipates poor prognosis of SARS-CoV-2 disease (COVID-19) and correlates with the systemic atherosclerotic transformation of the arterial vessels. The amount of aortic wall calcification (AWC) can be estimated on low-dose chest CT. We suggest quantification of AWC on the low-dose chest CT, which is initially performed for the diagnosis of COVID-19, to screen for patients at risk of severe COVID-19. METHODS: Seventy consecutive patients (46 in center 1, 24 in center 2) with parallel low-dose chest CT and positive RT-PCR for SARS-CoV-2 were included in our multi-center, multi-vendor study. The outcome was rated moderate (no hospitalization, hospitalization) and severe (ICU, tracheal intubation, death), the latter implying a requirement for intensive care treatment. The amount of AWC was quantified with the CT vendor's software. RESULTS: Of 70 included patients, 38 developed a moderate, and 32 a severe COVID-19. The average volume of AWC was significantly higher throughout the subgroup with severe COVID-19, when compared to moderate cases (771.7 mm3 (Q1 = 49.8 mm3, Q3 = 3065.5 mm3) vs. 0 mm3 (Q1 = 0 mm3, Q3 = 57.3 mm3)). Within multivariate regression analysis, including AWC, patient age and sex, as well as a cardiovascular comorbidity score, the volume of AWC was the only significant regressor for severe COVID-19 (p = 0.004). For AWC > 3000 mm3, the logistic regression predicts risk for a severe progression of 0.78. If there are no visually detectable AWC risk for severe progression is 0.13, only. CONCLUSION: AWC seems to be an independent biomarker for the prediction of severe progression and intensive care treatment of COVID-19 already at the time of patient admission to the hospital; verification in a larger multi-center, multi-vendor study is desired.


Assuntos
COVID-19/diagnóstico por imagem , Doses de Radiação , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Aorta Torácica/efeitos da radiação , Aorta Torácica/virologia , COVID-19/diagnóstico , COVID-19/terapia , COVID-19/virologia , Cuidados Críticos , Feminino , Hospitalização , Humanos , Intubação Intratraqueal/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/efeitos da radiação , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , SARS-CoV-2/patogenicidade , SARS-CoV-2/efeitos da radiação , Tórax/patologia , Tórax/efeitos da radiação , Tórax/virologia
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