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1.
Cytokine ; 137: 155312, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33128927

RESUMO

BACKGROUND: COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered. METHODOLOGY: The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results. RESULTS: Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)). CONCLUSION: Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.


Assuntos
/radioterapia , Terapia com Luz de Baixa Intensidade , Pulmão/efeitos da radiação , Pneumonia/radioterapia , /sangue , Citocinas/metabolismo , Humanos , Pulmão/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Pneumonia/imunologia , Pneumonia/fisiopatologia , PubMed , Edema Pulmonar/imunologia , Edema Pulmonar/fisiopatologia , Edema Pulmonar/radioterapia , Espécies Reativas de Oxigênio/metabolismo , /radioterapia
2.
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
/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 , /terapia , 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 , /efeitos da radiação , Tórax/patologia , Tórax/efeitos da radiação , Tórax/virologia
3.
Phys Med ; 80: 119-124, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33171381

RESUMO

PURPOSE: The aim of this work was to evaluate the dosimetric impact of high-resolution thorax CT during COVID-19 outbreak in the University Hospital of Parma. In two months we have performed a huge number of thorax CT scans collecting effective and equivalent organ doses and evaluating also the lifetime attributable risk (LAR) of lung and other major cancers. MATERIALS AND METHOD: From February 24th to April 28th, 3224 high-resolution thorax CT were acquired. For all patients we have examined the volumetric computed tomography dose index (CTDIvol), the dose length product (DLP), the size-specific dose estimate (SSDE) and effective dose (E103) using a dose tracking software (Radimetrics Bayer HealthCare). From the equivalent dose to organs for each patient, LAR for lung and major cancers were estimated following the method proposed in BEIR VII which considers age and sex differences. RESULTS: Study population included 3224 patients, 1843 male and 1381 female, with an average age of 67 years. The average CTDIvol, SSDE and DLP, and E103 were 6.8 mGy, 8.7 mGy, 239 mGy·cm and 4.4 mSv respectively. The average LAR of all solid cancers was 2.1 cases per 10,000 patients, while the average LAR of leukemia was 0.2 cases per 10,000 patients. For both male and female the organ with a major cancer risk was lung. CONCLUSIONS: Despite the impressive increment in thoracic CT examinations due to COVID-19 outbreak, the high resolution low dose protocol used in our hospital guaranteed low doses and very low risk estimation in terms of LAR.


Assuntos
/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Radiometria/métodos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Surtos de Doenças , Feminino , Humanos , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Doses de Radiação , Medição de Risco , Fatores Sexuais , Software
4.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 623-628, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33210491

RESUMO

Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced pulmonary fibrosis (RIPF), is a side effect of radiotherapy for lung cancer and esophageal cancer. Pulmonary macrophages, as a kind of natural immune cells maintaining lung homeostasis, play a key role in the whole pathological process of RILI. In the early stage of RILI, classically activated M1 macrophages secrete proinflammatory cytokines to induce inflammation and produce massive reactive oxygen species (ROS) through ROS-induced cascade to further impair lung tissue. In the later stage of RILI, alternatively activated M2 macrophages secrete profibrotic cytokines to promote the development of RIPF. The roles of macrophage in the pathogenesis of RILI and the related potential clinical applications are summarized in this review.


Assuntos
Lesão Pulmonar , Pulmão , Macrófagos , Lesões por Radiação , Radioterapia , Humanos , Pulmão/efeitos da radiação , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Macrófagos/metabolismo , Pneumonite por Radiação/etiologia , Radioterapia/efeitos adversos
5.
PLoS One ; 15(10): e0238704, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33035214

RESUMO

The aim of this work was to use TOPAS Monte Carlo simulations to model the effect of magnetic fields on dose distributions in brachytherapy lung treatments, under ideal and clinical conditions. Idealistic studies were modeled consisting of either a monoenergetic electron source of 432 keV, or a polyenergetic electron source using the spectrum of secondary electrons produced by 192Ir gamma-ray irradiation. The electron source was positioned in the center of a homogeneous, lung tissue phantom (ρ = 0.26 g/cm3). Conversely, the clinical study was simulated using the VariSource VS2000 192Ir source in a patient with a lung tumor. Three contoured volumes were considered: the tumor, the planning tumor volume (PTV), and the lung. In all studies, dose distributions were calculated in the presence or absence of a constant magnetic field of 3T. Also, TG-43 parameters were calculated for the VariSource and compared with published data from EGS-brachy (EGSnrc) and PENELOPE. The magnetic field affected the dose distributions in the idealistic studies. For the monoenergetic and poly-energetic studies, the radial distance of the 10% iso-dose line was reduced in the presence of the magnetic field by 64.9% and 24.6%, respectively. For the clinical study, the magnetic field caused differences of 10% on average in the patient dose distributions. Nevertheless, differences in dose-volume histograms were below 2%. Finally, for TG-43 parameters, the dose-rate constant from TOPAS differed by 0.09% ± 0.33% and 0.18% ± 0.33% with respect to EGS-brachy and PENELOPE, respectively. The geometry and anisotropy functions differed within 1.2% ± 1.1%, and within 0.0% ± 0.3%, respectively. The Lorentz forces inside a 3T magnetic resonance machine during 192Ir brachytherapy treatment of the lung are not large enough to affect the tumor dose distributions significantly, as expected. Nevertheless, large local differences were found in the lung tissue. Applications of this effect are therefore limited by the fact that meaningful differences appeared only in regions containing air, which is not abundant inside the human.


Assuntos
Braquiterapia/métodos , Neoplasias Pulmonares/radioterapia , Pulmão/efeitos da radiação , Campos Magnéticos , Braquiterapia/estatística & dados numéricos , Simulação por Computador , Relação Dose-Resposta à Radiação , Elétrons , Humanos , Radioisótopos de Irídio/administração & dosagem , Radioisótopos de Irídio/farmacocinética , Radioisótopos de Irídio/uso terapêutico , Imagem por Ressonância Magnética , Método de Monte Carlo , Imagens de Fantasmas , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Distribuição Tecidual
6.
Radiat Res ; 194(4): 411-430, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-32936898

RESUMO

In the event of a major accidental or intentional radiation exposure incident, the affected population could suffer from total- or partial-body exposures to ionizing radiation with acute exposure to organs that would produce life-threatening injury. Therefore, it is necessary to identify markers capable of predicting organ-specific damage so that appropriate directed or encompassing therapies can be applied. In the current work, gene expression changes in response to total-body irradiation (TBI) were identified in heart, lungs and liver tissue of Göttingen minipigs. Animals received 1.7, 1.9, 2.1 or 2.3 Gy TBI and were followed for 45 days. Organ samples were collected at the end of day 45 or sooner if the animal displayed morbidity necessitating euthanasia. Our findings indicate that different organs respond to TBI in a very specific and distinct manner. We also found that the liver was the most affected organ in terms of gene expression changes, and that lipid metabolic pathways were the most deregulated in the liver samples of non-survivors (survival time <45 days). We identified organ-specific gene expression signatures that accurately differentiated non-survivors from survivors and control animals, irrespective of dose and time postirradiation. At what point did these radiation-induced injury markers manifest and how this information could be used for applying intervention therapies are under investigation.


Assuntos
Perfilação da Expressão Gênica , Coração/efeitos da radiação , Fígado/efeitos da radiação , Pulmão/efeitos da radiação , Lesões Experimentais por Radiação/genética , Irradiação Corporal Total/efeitos adversos , Animais , Apelina/fisiologia , Radioisótopos de Cobalto , Sistemas Computacionais , Relação Dose-Resposta à Radiação , Endotélio Vascular/embriologia , Endotélio Vascular/efeitos da radiação , Raios gama/efeitos adversos , Sistema Imunitário/efeitos da radiação , Estimativa de Kaplan-Meier , Metabolismo dos Lipídeos/efeitos da radiação , Fígado/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Miocárdio/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Especificidade de Órgãos , Imagens de Fantasmas , Lesões Experimentais por Radiação/etiologia , Transdução de Sinais/efeitos da radiação , Suínos , Porco Miniatura
7.
PLoS One ; 15(8): e0237434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797096

RESUMO

OBJECTIVES: To systematically evaluate the influence of acquisition settings in conjunction with raw-data based iterative image reconstruction (IR) on lung densitometry based on multi-row detector computed tomography (CT) in an anthropomorphic chest phantom. MATERIALS AND METHODS: Ten porcine heart-lung explants were mounted in an ex vivo chest phantom shell, six with highly and four with low attenuating chest wall. CT (Somatom Definition Flash, Siemens Healthineers) was performed at 120kVp and 80kVp, each combined with current-time products of 120, 60, 30, and 12mAs, and was reconstructed with filtered back projection (FBP) and IR (Safire, Siemens Healthineers). Mean lung density (LD), air density (AD) and noise were measured by semi-automated region-of interest (ROI) analysis, with 120kVp/120 mAs serving as the standard of reference. RESULTS: Using IR, noise in lung parenchyma was reduced by ~ 31% at high attenuating chest wall and by ~ 22% at low attenuating chest wall compared to FBP, respectively (p<0.05). IR induced changes in the order of ±1 HU to mean absolute LD and AD compared to corresponding FBP reconstructions which were statistically significant (p<0.05). CONCLUSIONS: Densitometry is influenced by acquisition parameters and reconstruction algorithms to a degree that may be clinically negligible. However, in longitudinal studies and clinical research identical protocols and potentially other measures for calibration may be required.


Assuntos
Pulmão/fisiologia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X , Algoritmos , Animais , Antropometria , Densitometria , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Exposição à Radiação , Razão Sinal-Ruído , Suínos , Tórax/diagnóstico por imagem
8.
Free Radic Res ; 54(7): 540-555, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32842802

RESUMO

Radiotherapy is an important treatment regime for lung cancer, worldwide. However, radiation-induced pneumonitis and fibrosis are the treatment-limiting toxicities among patients who have undergone radiotherapy. The epithelial cells via epithelial to mesenchymal transition [EMT] acquires mesenchymal phenotype, which ultimately leads to fibrosis. Many investigations are focussed on understanding the signalling pathways mediating in EMT, however, the role of histone methylation is less understood in radiation-induced lung EMT. In the present study, we analysed the effect of vanillin, an antioxidant, on histone methylation during radiation-induced EMT. The thoracic region of Wistar rats was irradiated with a fractionated dose of X-ray (3 Gy/day) for two weeks (total of 30 Gy). The irradiated animals were sacrificed at the 8th and 16th weeks and tissues were used for analyses. Our data showed that radiation decreased the level of antioxidant enzymes such as SOD, catalase and reduced glutathione that would ultimately enhance oxidative stress in the tissues. Histopathological analysis revealed that radiation increased the infiltration of inflammatory cells to the tissue injury site. Total global histone methylation was increased upon irradiation, which was effectively prevented by vanillin administration. Vanillin enhanced E-cadherin expression and decreased the mesenchymal markers N-cadherin and vimentin in the irradiated lung tissue. The ChIP-qPCR analysis suggested that snail expression in the nucleus might involve in the enrichment of suppressive marker H3K9me3 on the E-cadherin promoter. Finally, we suggested that vanillin administration decreased radiation-induced oxidative stress and EMT expression. Additionally, irradiation increased the H3K9 methylation status with nuclear translocation of snail during lung EMT.


Assuntos
Antígenos CD/metabolismo , Benzaldeídos/metabolismo , Caderinas/metabolismo , Histonas/metabolismo , Pulmão/efeitos da radiação , Células A549 , Animais , Antígenos CD/genética , Caderinas/genética , Transição Epitelial-Mesenquimal , Feminino , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Metilação/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Regiões Promotoras Genéticas , Ratos , Ratos Wistar
9.
Sci Rep ; 10(1): 10559, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601297

RESUMO

Multiple competing normal tissue complication probability (NTCP) models have been proposed for predicting symptomatic radiation-induced lung injury in human. In this paper we tested the efficacy of four common NTCP models applied quantitatively to sub-clinical X-ray computed tomography (CT)-density changes in the lung following radiotherapy. Radiotherapy planning datasets and follow-up chest CTs were obtained in eight patients treated for targets within the lung or hilar region. Image pixel-wise radiation dose exposure versus change in observable CT Hounsfield units was recorded for early (2-5 months) and late (6-9 months) time-points. Four NTCP models, Lyman, Logistic, Weibull and Poisson, were fit to the population data. The quality of fits was assessed by five statistical criteria. All four models fit the data significantly (p < 0.05) well at early, late and cumulative time points. The Lyman model fitted best for early effects while the Weibull Model fitted best for late effects. No significant difference was found between the fits of the models and with respect to parameters D50 and γ50. The D50 estimates were more robust than γ50 to image registration error. For analyzing population-based sub-clinical CT pixel intensity-based dose response, all four models performed well.


Assuntos
Lesão Pulmonar/prevenção & controle , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Biologia Computacional/métodos , Simulação por Computador , Relação Dose-Resposta à Radiação , Feminino , Previsões/métodos , Humanos , Pulmão/efeitos da radiação , Pneumopatias , Masculino , Probabilidade , Lesões por Radiação/etiologia , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
10.
Sci Rep ; 10(1): 11191, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636439

RESUMO

Radiation doses to the heart are potentially high in patients undergoing radiotherapy for thymoma or thymic carcinoma because of their origin site and propensity for pericardial invasion. We investigated potential relationships between radiation pneumonitis (RP) and the dosimetric parameters of lung and heart substructures in patients with thymic epithelial tumors. This retrospective study included 70 consecutive patients who received definitive or postoperative radiotherapy at a median dose of 58.3 Gy. Heart substructures were delineated according to a published atlas. The primary end point of ≥ grade 2 RP was observed in 13 patients (19%) despite a low lung dose; median lung V20 (i.e. percentage of the volume receiving at least 20 Gy) was only 16.6%. In a univariate analysis, four lung parameters, heart V35, three pulmonary artery (PA) parameters, two left ventricle parameters, and left atrium V35 were associated with the development of RP. In a multivariate analysis, only PA V35 remained significant (hazard ratio 1.04; 95% CI 1.01-1.07, p = 0.007). PA V35 of the RP versus non-RP groups were 84.2% versus 60.0% (p = 0.003). The moderate dose sparing of PA could be a candidate as a planning constraint for reducing the risk of RP in thoracic radiotherapy.


Assuntos
Carcinoma/radioterapia , Coração/efeitos da radiação , Doses de Radiação , Pneumonite por Radiação/etiologia , Timoma/radioterapia , Neoplasias do Timo/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Pneumonite por Radiação/epidemiologia
11.
Sci Rep ; 10(1): 11158, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32636458

RESUMO

The goal of this study was to develop a potential druggable target for lung injury after SABR through the small animal model. Utilising the model, a radiation dose of 70 Gy or 90 Gy was focally (small volume) delivered to the left lung of mice. The highly expressed phosphorylation form of C-Raf was discovered through a protein array experiment, with the protein being extracted from the area of radiated mouse lung tissue, and was confirmed by IHC and western blot. C-Raf activation, along with morphological change and EMT (Epithelial to Mesenchymal Transition) marker expression, was observed after radiation to the mouse type II alveolar cell line MLE-12. C-Raf inhibitor GW5074 was able to reverse the EMT in cells effectively, and was found to be dependent on Twist1 expression. In the animal experiment, pretreatment of GW5074 alleviated EMT and lung injury after 70 Gy radiation was focally delivered to the lung of mice. Conclusively, these results demonstrate that C-Raf inhibitor GW5074 inhibits high-dose small-volume radiation-induced EMT via the C-Raf/Twist1 signalling pathway in mice. Therefore, pharmacological C-Raf inhibitors may be used effectively as inhibitors of SABR-induced lung fibrosis.


Assuntos
Transição Epitelial-Mesenquimal/efeitos da radiação , Indóis/farmacologia , Pulmão/efeitos da radiação , Fenóis/farmacologia , Proteínas Proto-Oncogênicas c-raf/metabolismo , Radiocirurgia , Animais , Western Blotting , Relação Dose-Resposta à Radiação , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-raf/antagonistas & inibidores , Doses de Radiação , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/prevenção & controle , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos
12.
PLoS One ; 15(7): e0236350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687531

RESUMO

PURPOSE: We evaluated that early metabolic response determined by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiotherapy (RT), predicts outcomes in non-small cell lung cancer. MATERIAL AND METHODS: Twenty-eight patients evaluated using pretreatment 18F-FDG-PET/CT (PETpre) and interim 18F-FDG-PET/CT (PETinterim) after 11 fractions of RT were retrospectively reviewed. Maximum standardized uptake value (SUVmax) was calculated for primary lesion. Predictive value of gross tumor volume (ΔGTV) and SUVmax (ΔSUVmax) changes was evaluated for locoregional control (LRC), distant failure (DF), and overall survival (OS). Metabolic responders were patients with ΔSUVmax >40%. RESULTS: Metabolic responders showed better trends in 1-year LRC (90.9%) than non-responders (47.1%) (p = 0.086). Patients with large GTVpre (≥120 cc) demonstrated poor LRC (hazard ratio 4.14, p = 0.022), while metabolic non-responders with small GTVpre (<120 cc) and metabolic responders with large GTVpre both had 1-year LRC rates of 75.0%. Reduction of 25% in GTV was not associated with LRC; however, metabolic responders without a GTV response showed better 1-year LRC (83.3%) than metabolic non-responders with a reduction in GTV (42.9%). Metabolic responders showed lower 1-year DF (16.7%) than non-responders (50.0%) (p = 0.025). An ΔSUVmax threshold of 40% yielded accuracy of 64% for predicting LRC, 75% for DF, and 54% for OS. However, ΔGTV > 25% demonstrated inferior diagnostic values than metabolic response. CONCLUSIONS: Changes in tumor metabolism diagnosed using PETinterim during RT better predicted treatment responses, recurrences, and prognosis than other factors historically used.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia , Neoplasias Pulmonares/terapia , Pulmão/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Seguimentos , Humanos , Pulmão/patologia , Pulmão/efeitos da radiação , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação
13.
Int J Radiat Oncol Biol Phys ; 108(5): 1134-1139, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32707264

RESUMO

PURPOSE: The COVID-19 outbreak is affecting people worldwide. Many infected patients have respiratory involvement that may progress to acute respiratory distress syndrome. This pilot study aimed to evaluate the clinical efficacy of low-dose whole-lung radiation therapy in patients with COVID-19 pneumonia. METHODS AND MATERIALS: In this clinical trial, conducted in Iran, we enrolled patients with COVID-19 who were older than 60 years and hospitalized to receive supplementary oxygen for their documented pneumonia. Participants were treated with whole-lung irradiation in a single fraction of 0.5 Gy plus the national protocol for the management of COVID-19. Vital signs (including blood oxygenation and body temperature) and laboratory findings (interleukin-6 and C-reactive peptide) were recorded before and after irradiation. RESULTS: Between May 21, 2020 and June 24, 2020, 5 patients received whole-lung irradiation. They were followed for 5 to 7 days to evaluate the response to treatment and toxicities. The clinical and paraclinical findings of 4 of the 5 patients (patient 4 worsened and died on day 3) improved on the first day of irradiation. Patient 3 opted out of the trial on the third day after irradiation. The mean time to discharge was 6 days for the other 3 patients. No acute radiation-induced toxicity was recorded. CONCLUSIONS: With a response rate of 80%, whole-lung irradiation in a single fraction of 0.5 Gy had encouraging results in oxygen-dependent patients with COVID-19 pneumonia.


Assuntos
/radioterapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Irã (Geográfico) , Pulmão/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Dosagem Radioterapêutica , Resultado do Tratamento
14.
J Cancer Res Clin Oncol ; 146(9): 2267-2276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32514629

RESUMO

BACKGROUND: To investigate the role of intensity-modulated proton therapy (IMPT) compared to volumetric modulated arc therapy (VMAT) for the radiation treatment of thymoma cancer. METHODS: Twenty patients were retrospectively planned for IMPT [with (IMPT_R1 or IMPT_R2 according to the approach adopted) and without robust optimization] and VMAT. The results were compared according to dose-volume metrics on the clinical and planning target volumes (CTV and PTV) and the main organs at risk (heart, breasts, lungs, spinal cord and oesophagus). Estimates of the excess absolute risk (EAR) of secondary cancer induction were determined for the oesophagus, the breasts and the composite lungs. For the heart, the relative risk (RR) of chronic heart failure (CHF) was assessed. RESULTS: IMPT and VMAT plans resulted equivalent in terms of target coverage for both the CTV and the PTV. The CTV homogeneity index resulted in 0.03 ± 0.01 and 0.04 ± 0.01 for VMAT and all IMPT plans, respectively. The conformality index resulted in 1.1 ± 0.1 and 1.2 ± 0.1 for VMAT and all IMPT plans. The mean dose to the breasts resulted in 10.5 ± 5.0, 4.5 ± 3.4, 4.7 ± 3.5 and 4.6 ± 3.4 Gy for VMAT, IMPT, IMPT_R1 and IMPT_R2. For the lungs, the mean dose was 9.6 ± 2.3, 3.5 ± 1.5, 3.6 ± 1.6 and 3.8 ± 1.4 Gy; for the heart: 8.7 ± 4.4, 4.3 ± 1.9, 4.5 ± 2.0 and 4.4 ± 2.4 Gy and for the oesophagus 8.2 ± 3.5, 2.2 ± 3.4, 2.4 ± 3.6 and 2.5 ± 3.5 Gy. The RR for CHF was 1.6 ± 0.3 for VMAT and 1.3 ± 0.2 for IMPT (R1 or R2). The EAR was 3.6 ± 0.v vs 1.0 ± 0.6 or 1.2 ± 0.6 (excess cases/10,000 patients year) for the oesophagus; 17.4 ± 6.5 vs 5.7 ± 3.2 or 6.1 ± 3.8 for the breasts and 24.8 ± 4.3 vs 8.1 ± 2.7 or 8.7 ± 2.3 for the composite lungs for VMAT and IMPT_R, respectively. CONCLUSION: The data from this in-silico study suggest that intensity-modulated proton therapy could be significantly advantageous in the treatment of thymoma patients with particular emphasis to a substantial reduction of the risk of cardiac failure and secondary cancer induction. Robust planning is a technical pre-requisite for the safety of the delivery.


Assuntos
Timoma/radioterapia , Neoplasias do Timo/radioterapia , Esôfago/efeitos da radiação , Feminino , Humanos , Pulmão/efeitos da radiação , Masculino , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Estudos Retrospectivos
15.
J Cancer Res Clin Oncol ; 146(9): 2289-2297, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32524292

RESUMO

INTRODUCTION: Biliary tract cancers (BTC) are rare malignancies arising from biliary system. Systemic therapy is the cornerstone for stage IV disease, with poor overall survival (OS). Evidence is lacking about safety and efficacy of local ablative treatments, such as surgery and stereotactic body radiotherapy (SBRT) in the context of metastatic BTC (mBTC). MATERIALS AND METHODS: We retrospectively analyzed clinical outcomes for a cohort of mBTC patients treated with SBRT for oligometastatic disease. Inclusion criteria were 1-5 distant metastases; SBRT with a dose/fraction of a least 5 Gy to a biological effective dose (BED) of at least 40 Gy considering an α/ß of 10 Gy. Analyzed outcomes included local control (LC), distant progression-free survival (DPFS), PFS, and OS. RESULTS: 51 patients meeting the inclusion criteria. Primary tumor sites were intrahepatic cholangiocarcinoma (35%), extrahepatic cholangiocarcinoma (31%), ampullary adenocarcinoma (20%), gallbladder adenocarcinoma (14%). 21 patients were treated on liver lesions, 17 on nodal metastasis, 5 patients on lung lesions, 4 patients on recurrence along the extrahepatic bile duct. After a median follow-up of 14 months median OS was 13.7 months, 1- and 2-year OS were 58% and 41%, respectively. Node and lung as metastatic sites were associated with a longer OS (p < 0.001). Median LC was 26.8 months, and intrahepatic cholangiocarcinoma was associated with longer LC (p = 0.036). Median DPFS was 11 months, with 1- and 2-year DPFS of 48% and 27.8%, respectively. Ten patients reported grade 1-2 toxicity and 2 cases of acute G3 biliary obstruction. CONCLUSIONS: Stereotactic body radiotherapy (SBRT) is feasible in the context of mBTC. OS and PFS results are promising, considering that our patients were heavily pre-treated with systemic therapy. Patients with nodal or lung relapse have better prognosis. Distant relapses remain the main pattern of failure, but treatment of all metastatic sites seems to improve DMFS.


Assuntos
Neoplasias dos Ductos Biliares/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radiocirurgia/efeitos adversos , Radioterapia/efeitos adversos , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares Intra-Hepáticos/efeitos da radiação , Colangiocarcinoma/radioterapia , Feminino , Humanos , Pulmão/efeitos da radiação , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Radiocirurgia/métodos , Estudos Retrospectivos , Resultado do Tratamento
16.
Cancer Radiother ; 24(5): 379-387, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534799

RESUMO

The increasing use of stereotactic body radiation therapy for lung tumours comes along with new post-therapeutic imaging findings that should be known by physicians involved in patient follow-up. Radiation-induced lung injury is much more frequent than after conventional radiation therapy, it can also be delayed and has a different radiological presentation. Radiation-induced lung injury after stereotactic body radiation therapy involves the lung parenchyma surrounding the target tumour and appears as a dynamic process continuing for years after completion of the treatment. Thus, the radiological pattern and the severity of radiation-induced lung injury are prone to changes during follow-up, which can make it difficult to differentiate from local recurrence. Contrary to radiation-induced lung injury, local recurrence after stereotactic body radiation therapy is rare. Other complications mainly depend on tumour location and include airway complications, rib fractures and organizing pneumonia. The aim of this article is to provide a wide overview of radiological changes occurring after SBRT for lung tumours. Awareness of changes following stereotactic body radiation therapy should help avoiding unnecessary interventions for pseudo tumoral presentations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Lesão Pulmonar/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Pulmão/efeitos da radiação , Lesões por Radiação/diagnóstico por imagem , Radiocirurgia/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Diagnóstico Diferencial , Seguimentos , Humanos , Pulmão/diagnóstico por imagem , Lesão Pulmonar/etiologia , Neoplasias Pulmonares/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Lesões por Radiação/etiologia , Pneumonite por Radiação/diagnóstico por imagem , Radiocirurgia/efeitos adversos , Fatores de Tempo
17.
Phys Med Biol ; 65(15): 155019, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32554879

RESUMO

The novel coronavirus, SARS-CoV-2, that causes the COVID-19 disease currently has healthcare systems around the world dealing with unprecedented numbers of critically ill patients. One of the primary concerns associated with this illness is acute respiratory distress syndrome (ARDS) and the pneumonia that accompanies it. Historical literature dating back to the 1940s and earlier contains many reports of successful treatment of pneumonias with ionizing radiation. Although these were not randomized controlled trials, they do suggest a potential avenue for further investigation. Technical details in these reports however were limited. In this work we review the literature and identify details including nominal kilovoltage ranges, filtration, and focus-skin distances (FSDs). Using a freely available and benchmarked code, we generated spectra and used these as sources for Monte Carlo simulations using the EGSnrc software package. The approximate sources were projected through a radiologically anthropomorphic phantom to provide detailed dose distributions within a targeted lung volume (approximate right middle lobe). After accounting for the reported exposure levels, mean lung doses fell in a relatively narrow range: 30-80 cGy. Variation in patient dimensions and other details are expected to result in an uncertainty on the order of ± 20%. This result is consistent with the dose range expected to induce anti-inflammatory effects.


Assuntos
Pulmão/efeitos da radiação , Pneumonia/radioterapia , Doses de Radiação , Infecções por Coronavirus/complicações , Humanos , Método de Monte Carlo , Pandemias , Pneumonia/complicações , Pneumonia Viral/complicações , Dosagem Radioterapêutica
18.
Phys Med Biol ; 65(17): 175012, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32485691

RESUMO

Small-field dosimetry is central to the planning and delivery of radiotherapy to patients with cancer. Small-field dosimetry is beset by complex issues, such as loss of charged-particle equilibrium (CPE), source occlusion and electron-scattering effects in low-density tissues. The purpose of the present research is the elucidation of the fundamental physics of small fields through the computation of absorbed dose, kerma and fluence distributions in heterogeneous media using the Monte-Carlo (MC) method. Absorbed dose and kerma were computed using the DOSRZnrc MC user-code for beams with square field sizes ranging from 0.25 × 0.25 to 7 × 7 cm2 (for 6 MV 'full linac' geometry) and 0.25 × 0.25 to 16 × 16 cm2 (for 15 MV 'full linac' geometry). In the bone inhomogeneity the dose increases (vs. homogeneous water) for field sizes <1 × 1 cm2 at 6 MV and ⩽3 × 3 cm2 at 15 MV and decreases (vs. homogeneous water) for field sizes ⩾3 × 3 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV. In the lung inhomogeneity there is negligible decrease in dose compared to in uniform water for field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV, consistent with the Fano theorem. The near-unity value of the absorbed-dose to collision-kerma ratio, D/K col, at the centre of the bone and lung slabs in the heterogeneous phantom demonstrates that CPE is achieved in bone for field sizes >1 × 1 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV; CPE is achieved in lung at field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV. Electron-fluence perturbation factors for the 0.25 × 0.25 cm2 field were 1.231 and 1.403 for bone-to-water and 0.454 and 0.333 for lung-to-water at 6 and 15 MV, respectively. For field sizes large enough for quasi-CPE, the MC-derived dose-perturbation factors, lung-to-water, [Formula: see text] were close to unity; electron-fluence perturbation factors, lung-to-water, [Formula: see text] were ∼1.0, consistent with the Fano theorem. At 15 MV in the lung inhomogeneity the magnitude and also the 'shape' of the primary electron-fluence spectrum differ significantly from that in water. Beam penumbrae relative to water are narrower in the bone inhomogeneity and broader in the lung inhomogeneity for all field sizes.


Assuntos
Método de Monte Carlo , Fótons/uso terapêutico , Osso e Ossos/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Aceleradores de Partículas , Imagens de Fantasmas , Radiometria , Dosagem Radioterapêutica
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