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1.
Int J Med Sci ; 17(16): 2561-2569, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029098

RESUMO

Background: During the outbreak period of COVID-19 pneumonia, cancer patients have been neglected and in greater danger. Furthermore, the differential diagnosis between COVID-19 pneumonia and radiation pneumonitis in cancer patients remains a challenge. This study determined their clinical presentations and radiological features in order to early diagnose and separate COVID-19 pneumonia from radiation pneumonitis patients promptly. Methods and Findings: From January 21, 2020 to February 18, 2020, 112 patients diagnosed with suspected COVID-19 were selected consecutively. A retrospective analysis including all patients' presenting was performed. Four patients from 112 suspected individals were selected, including 2 males and 2 females with a median age of 54 years (range 39-64 years). After repeated pharyngeal swab nucleic acid tests, 1 case was confirmed and 3 cases were excluded from COVID-19 pneumonia. Despite the comparable morphologic characteristics of lung CT imaging, the location, extent, and distribution of lung lesions between COVID-19 pneumonia and radiation pneumonitis differed significantly. Conclusions: Lung CT imaging combined with clinical and laboratory findings can facilitate early diagnosis and appropriate management of COVID-19 pneumonia with a history of malignancy and radiation therapy.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Diagnóstico Diferencial , Neoplasias/radioterapia , Pneumonia Viral/diagnóstico por imagem , Pneumonite por Radiação/diagnóstico por imagem , Adulto , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias/virologia , Pandemias , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
2.
Medicine (Baltimore) ; 99(38): e21964, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957314

RESUMO

BACKGROUND: The aim of this study was to investigate the link between heart dose and overall survival, the link between heart dose and cardiac events and whether radiation-induced heart diseases were associated with overall survival in lung cancer radiotherapy. METHODS: We performed a literature search by using Pubmed, Embase, China National Knowledge Infrastructure (CNKI) databases. Pairs of reviewers independently screened literature according to the inclusion criteria, extracted data, assessed methodological quality, and publication bias. The primary end points included overall survival and cardiac events. I was calculated in a heterogeneity assessment. Publication bias was evaluated by using Begg funnel plot and Egger test. RESULTS: Ten studies including 1 randomized controlled trial, 3 post hoc analysis of prospective trials, and 6 cohort studies were identified. The meta-analysis showed that heart volume receiving ≥5 Gy (HV5) (hazard ratio [HR] = 1.01; 95% confidence interval [CI]: 1.00-1.01), heart volume receiving ≥30 Gy (HV30) (HR = 1.01; 95% CI: 1.00-1.02), heart volume receiving ≥50 Gy (HV50) (HR = 1.05; 95%CI: 1.00-1.10), and mean heart dose (MHD) (HR = 1.01; 95%CI:1.00-1.02) all were associated with worse overall survival. In addition, the MHD (HR = 1.03; 95% CI: 1.02-1.05), HV5 (HR = 1.02; 95% CI: 1.01-1.03), and HV30 (HR = 1.02; 95% CI: 1.01-1.03) were significantly associated with all grade cardiac events. Meanwhile, compared with those who did not receive radiotherapy, the radiotherapy group experienced a significantly increased risk for cardiac-specific mortality (HR = 1.297; 95% CI: 1.213-1.387). However, the results did not show that cardiac events were associated with overall survival in lung cancer radiotherapy (HR = 1.472; 95% CI: 0.988-2.193). CONCLUSION: Exposure of the heart to radiation increased the risk of cardiac events during radiotherapy for lung cancer. Meanwhile, heart dose including HV5 and HV30 were predictors of overall survival in lung cancer radiotherapy. It is necessary to constrain the heart dose when perform thoracic radiation therapy to decrease the incidence of cardiac events and improve the overall survival.


Assuntos
Volume Cardíaco/efeitos da radiação , Cardiopatias/etiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/epidemiologia , Cardiopatias/mortalidade , Estudos Prospectivos , Doses de Radiação , Lesões por Radiação/mortalidade
3.
Anticancer Res ; 40(10): 5895-5899, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988920

RESUMO

BACKGROUND: Randomized controlled trials had demonstrated local therapy, such as radiotherapy, can improve outcomes of patients with lung cancer with oligometastatic disease (OMD). However, the definition of OMD is not uniform and the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) proposed a new classification in 2020 comprising nine subtypes. Therefore, we aimed to investigate the prognostic significance of this European classification for patients with lung OMD treated with definitive radical radiotherapy. PATIENTS AND METHODS: We identified eligible patients via an in-house database. Patient, disease, and treatment characteristics, as well as outcomes, were obtained via chart review plus peer review. Overall and progression-free survival were estimated via the Kaplan-Meier method. Log-rank test was used in univariate analysis and Cox regression in multivariable analyses to investigate the prognostic significance of the subtypes of OMD. RESULTS: We identified 35 eligible patients with six different OMD subtypes treated from 2011 to 2019. After a median follow-up of 23 (range=2-88) months, the median progression-free and overall survival were 11 and 38 months, respectively. The prognosis for patients with the subtype 'induced oligoprogression' was statistically worse than for those without in both univariate (p=0.02) and multivariate (adjusted hazard ratio for death=4.8, 95% confidence interval=1.4-16.2, p=0.01) analyses. CONCLUSION: We found the subtype with induced oligoprogression in the European classification to be associated with worse survival. Further studies are needed to confirm our finding.


Assuntos
Neoplasias Pulmonares/radioterapia , Prognóstico , Radioterapia (Especialidade)/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos
4.
Anticancer Res ; 40(10): 5901-5907, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988921

RESUMO

BACKGROUND/AIM: To assess predictors of local control (LC) for stereotactic ablative radiotherapy (SAbR) in pulmonary oligometastatic disease (OMD) from gastrointestinal (GI) malignancies. PATIENTS AND METHODS: Patients with pulmonary OMD treated with SAbR from January 2016 to December 2018 were included in this observational analysis. Primary endpoint was LC. Uni- and multivariate analyses to assess variable correlations were conducted. RESULTS: Thirty-seven patients and 59 lung metastases were evaluated. The delivered dose was 30-60 Gy in 3-8 fractions. After a median follow-up of 23.0 months (range=6.3-50.4 months), LC rate at 1/2 years was 89.7%/85.0%, and increased to 96.0%/91.0% for lesions treated with a biologically effective dose (BED10) ≥100 Gy (p=0.03). RECIST response at 6 months was predictive for LC (p=0.002). CONCLUSION: SAbR is an effective option for pulmonary OMD from GI malignancies. A BED10 ≥100 Gy and radiological response at 6 months can affect LC.


Assuntos
Neoplasias Gastrointestinais/radioterapia , Neoplasias Gastrointestinais/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta à Radiação , Feminino , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Radiocirurgia/métodos
5.
Medicine (Baltimore) ; 99(34): e21715, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846789

RESUMO

BACKGROUND: Stereotactic body radiotherapy (SBRT) superseded conventional radiotherapy (CRT) for the treatment of patients with inoperable early stage non-small cell lung cancer (NSCLC) over a decade ago. However, the direct comparisons of the outcomes of SBRT and CRT remain controversial. This meta-analysis was performed to compare the survival and safety of SBRT and CRT in patients with inoperable stage I NSCLC. METHODS: We systematically searched the Cochrane Library, Embase, PubMed, Web of Science, Ovid MEDLINE, ScienceDirect, Scopus and Google Scholar for relevant articles. Overall survival (OS), progression-free survival (PFS), lung cancer-specific survival (LCSS), local control rate (LCR) and adverse effects (AEs) were the primary outcomes. RESULTS: We identified 11,110 articles, 17 of which were eventually included in this study; these 17 articles had 17,973 patients (SBRT: 7395; CRT: 10,578). Compared to CRT for the treatment of inoperable stage I NSCLC, SBRT had superior survival in terms of OS (hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.62-0.70, P < .00001), LCSS (HR: 0.42 [0.35-0.50], P < .00001), and PFS (HR: 0.34 [0.25-0.48], P < .00001). The 4-year OS rate (OSR); 4-year LCSS rate (LCSSR); 3-year local control rate (LCR); 5-year PFS rate (PFSR) with SBRT were all higher than those with CRT. With regard to all-grade AEs, the SBRT group had a significantly lower rate of dyspnea, esophagitis and radiation pneumonitis; no significant difference was found in grade 3-5 AEs (risk ratio [RR]: 0.68 [0.30-1.53], P = .35). CONCLUSIONS: With better survival and a lower rate of dyspnea, esophagitis and radiation pneumonitis than CRT, SBRT appears to be more suitable for patients with inoperable stage I NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Fatores Etários , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Lesões por Radiação/epidemiologia , Radiocirurgia/efeitos adversos , Taxa de Sobrevida
6.
Medicine (Baltimore) ; 99(34): e21800, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846816

RESUMO

Delineation of organs at risk (OARs) is important but time consuming for radiotherapy planning. Automatic segmentation of OARs based on convolutional neural network (CNN) has been established for lung cancer patients at our institution. The aim of this study is to compare automatic segmentation based on CNN (AS-CNN) with automatic segmentation based on atlas (AS-Atlas) in terms of the efficiency and accuracy of OARs contouring.The OARs, including the lungs, esophagus, heart, liver, and spinal cord, of 19 non-small cell lung cancer patients were delineated using three methods: AS-CNN, AS-Atlas in the Pinnacle-software, and manual delineation (MD) by a senior radiation oncologist. MD was used as the ground-truth reference, and the segmentation efficiency was evaluated by the time spent per patient. The accuracy was evaluated using the Mean surface distance (MSD) and Dice similarity coefficient (DSC). The paired t-test or Wilcoxon signed-rank test was used to compare these indexes between the 2 automatic segmentation models.In the 19 testing cases, both AS-CNN and AS-Atlas saved substantial time compared with MD. AS-CNN was more efficient than AS-Atlas (1.6 min vs 2.4 min, P < .001). In terms of the accuracy, AS-CNN performed well in the esophagus, with a DSC of 73.2%. AS-CNN was better than AS-Atlas in segmenting the left lung (DSC: 94.8% vs 93.2%, P = .01; MSD: 1.10 cm vs 1.73 cm, P < .001) and heart (DSC: 89.3% vs 85.8%, P = .05; MSD: 1.65 cm vs 3.66 cm, P < .001). Furthermore, AS-CNN exhibited superior performance in segmenting the liver (DSC: 93.7% vs 93.6%, P = .81; MSD: 2.03 cm VS 2.11 cm, P = .66). The results obtained from AS-CNN and AS-Atlas were similar in segmenting the right lung. However, the performance of AS-CNN in the spinal cord was inferior to that of AS-Atlas (DSC: 82.1% vs 86.8%, P = .01; MSD: 0.87 cm vs 0.66 cm, P = .01).Our study demonstrated that AS-CNN significantly reduced the contouring time and outperformed AS-Atlas in most cases. AS-CNN can potentially be used for OARs segmentation in patients with pathological N2 (pN2) non-small cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Redes Neurais de Computação , Órgãos em Risco , Planejamento da Radioterapia Assistida por Computador/métodos , Esôfago , Coração , Humanos , Fígado , Pulmão , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medula Espinal , Fatores de Tempo
7.
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
8.
Cancer Radiother ; 24(6-7): 554-558, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32828666

RESUMO

The management of metastatic lung cancers, either of the small-cell (SCLC) or the non-small cell (NSCLC) subtype, largely based on systemic treatments so far, has been the subject of breakthrough advances over the past few years, with notably the wide use of immunotherapy changing the landscape of these harmful prognosis diseases. In parallel with this major progress, the increasing use of radiotherapy (RT) for the treatment of the primary thoracic lesion±the distant lesions, may contribute to improving the condition of these metastatic patients, both in terms of progression-free survival (PFS) and overall survival (OS). This review proposes to summarize and explain the findings provided by the different studies published in the last years experiencing RT of the primary tumor in metastatic lung cancers, either associated or not with the local ablative treatment of a low number of distant lesions. It will also expose the respective limits encountered in these studies and, in the light of all these elements, suggests various promising issues and fields of research for the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/patologia , Previsões , Humanos , Neoplasias Pulmonares/patologia , Metástase Neoplásica/radioterapia
9.
Cancer Radiother ; 24(6-7): 513-522, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32830055

RESUMO

Stereotactic radiotherapy is a fundamental change from the conventional fractionated radiotherapy and represents a new therapeutic indication. Stereotactic radiotherapy is now a standard of care for inoperable patients or patients who refuse surgery. The results are encouraging with local control and survival rates very high in selected populations. The rate of late toxicity remains acceptable. Good tolerability makes it appropriate even for elderly and frail patients. In these fragile patients or in certain specific clinical situations, different surgical, radiotherapy or interventional radiology attitudes can be discussed on a case-by-case basis. These situations are considered in this article for the pulmonary, hepatic and prostatic localizations.


Assuntos
Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/radioterapia , Neoplasias da Próstata/radioterapia , Radiocirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/cirurgia , Masculino , Guias de Prática Clínica como Assunto , Neoplasias da Próstata/cirurgia
10.
Cancer Radiother ; 24(6-7): 635-644, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32859466

RESUMO

Adaptive radiotherapy (ART) corresponds to various replanning strategies aiming to correct for anatomical variations occurring during the course of radiotherapy. The goal of the article was to report the rational, feasibility and benefit of using PET and/or MRI to guide this ART strategy in various tumor localizations. The anatomical modifications defined by scanner taking into account tumour mobility and volume variation are not always sufficient to optimise treatment. The contribution of functional imaging by PET or the precision of soft tissue by MRI makes it possible to consider optimized ART. Today, the most important data for both PET and MRI are for lung, head and neck, cervical and prostate cancers. PET and MRI guided ART appears feasible and safe, however in a very limited clinical experience. Phase I/II studies should be therefore performed, before proposing cost-effectiveness comparisons in randomized trials and before using the approach in routine practice.


Assuntos
Imagem por Ressonância Magnética , Neoplasias/radioterapia , Tomografia por Emissão de Pósitrons , Radioterapia Guiada por Imagem/métodos , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias do Colo do Útero/radioterapia
11.
Medicine (Baltimore) ; 99(27): e20518, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629632

RESUMO

INTRODUCTION: The optimal dose and fractionation of thoracic radiotherapy (RT) for limited-disease small-cell lung cancer (LD-SCLC) remain controversial. This meta-analysis was performed to compare the efficacy and RT toxicity between twice-daily thoracic RT (45 Gy with 1.5 Gy twice daily) and higher-dose once-daily RT (60-72 Gy with 1.8 Gy/2 Gy once daily) administered with chemotherapy in LD-SCLC patients. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched up to March 19, 2020 for studies that compared twice-daily thoracic RT (45 Gy with 1.5 Gy twice daily over 3 weeks) with higher-dose once-daily RT (60-72 Gy with 1.8 Gy/2 Gy once daily over 6-8 weeks) in LD-SCLC patients. RESULTS: Five studies involving 13,726 patients were included in this analysis. Compared with the once-daily thoracic RT group, the 1-year overall survival (OS) rate (P < .001), the 2-year OS rate (P < .001), the 5-year OS rate (P < .001), the mOS (P < .001), and the 1-year LRFS rate (P = .048) were significantly improved in the twice-daily RT group. The toxic effects of RT (esophagitis: P = .293; pneumonitis: P = .103) were similar in both groups. CONCLUSION: Compared with the higher-dose once-daily regimen, the twice-daily thoracic radiotherapy regimen improved efficacy but did not increase RT toxicity in LD-SCLC patients.


Assuntos
Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Humanos , Dosagem Radioterapêutica , Resultado do Tratamento
12.
Cancer Radiother ; 24(5): 444-452, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32620457

RESUMO

The aim of the present paper is to systematically review all available literature on preradiotherapy high uptake areas (hotspots) as a potential target for dose escalation in different tumour sites, and to understand the potential role and limitations of fluorodeoxyglucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) in this context. An electronic database (Medline) search was conducted to identify articles reporting on a correlation between high tracer uptake on pretreatment PET and preferential sites of local recurrence after radiotherapy. Search was limited to English language. No date range limitation was applied. Among 45 studies initially identified, nine series matching with inclusion criteria have finally been retained from the literature after reviewing (5 retrospective and 4 prospective). Primary tumour locations were head-neck (n=2), lung (n=4), oesophageal (n=2) and rectal (n=1) areas. Overlaps between FDG hotspot on preradiotherapy PET/CT and site of local recurrence on post-treatment scan showed good to excellent agreement. Only studies on head-neck cancer reported moderate agreement probably explained by the lack of reproducibility of the patients positioning between pre- and post-treatment FDG-PET/CT; and by the rigid registration process of images limited by post-therapeutic changes that highly affect anatomical landmarks. FDG hotspot-guided radiotherapy may allow dose escalation in respecting a robust methodology (treatment position, co-registration method, four-dimensional PET).


Assuntos
Fluordesoxiglucose F18 , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Pontos de Referência Anatômicos/diagnóstico por imagem , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/radioterapia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Neoplasias/radioterapia , Posicionamento do Paciente , Estudos Prospectivos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/radioterapia , Estudos Retrospectivos
13.
PLoS One ; 15(7): e0236245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706818

RESUMO

We have previously demonstrated that endothelial targeting of gold nanoparticles followed by external beam irradiation can cause specific tumor vascular disruption in mouse models of cancer. The induced vascular damage may lead to changes in tumor physiology, including tumor hypoxia, thereby compromising future therapeutic interventions. In this study, we investigate the dynamic changes in tumor hypoxia mediated by targeted gold nanoparticles and clinical radiation therapy (RT). By using noninvasive whole-body fluorescence imaging, tumor hypoxia was measured at baseline, on day 2 and day 13, post-tumor vascular disruption. A 2.5-fold increase (P<0.05) in tumor hypoxia was measured two days after combined therapy, resolving by day 13. In addition, the combination of vascular-targeted gold nanoparticles and radiation therapy resulted in a significant (P<0.05) suppression of tumor growth. This is the first study to demonstrate the tumor hypoxic physiological response and recovery after delivery of vascular-targeted gold nanoparticles followed by clinical radiation therapy in a human non-small cell lung cancer athymic Foxn1nu mouse model.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nanopartículas Metálicas/uso terapêutico , Hipóxia Tumoral , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Ouro/uso terapêutico , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Camundongos , Camundongos Nus , Imagem Óptica/métodos , Hipóxia Tumoral/efeitos dos fármacos , Hipóxia Tumoral/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Int J Radiat Oncol Biol Phys ; 107(4): 631-640, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32589990

RESUMO

BACKGROUND: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. METHODS: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. RESULTS: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. CONCLUSION: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.


Assuntos
Consenso , Infecções por Coronavirus/epidemiologia , Neoplasias Pulmonares/radioterapia , Oncologia , Pandemias , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Sociedades Médicas , Humanos , Gestão de Riscos , Triagem
15.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32518630

RESUMO

Cancer in the elderly remains an evolving issue and a health challenge. Several improvements in the radiotherapy field allow the delivery of higher doses/fractions with a safe toxicity profile, permitting the reduction of radiation treatment protocols in the elderly. Regarding breast, prostate, and lung cancer, the under-representation of older patients in clinical trials limits the extension of treatment recommendations to elderly patients in routine clinical practice. Among the feasible alternatives to standard whole breast radiotherapy (WBRT) in older patients are shorter courses using higher hypofractionation (HF) and accelerated partial breast irradiation (APBI). The boost continues to be used in women at high risk of local recurrence but is less widely accepted for women at lower risk and patients over 70 years of age. Regarding prostate cancer, there are no published studies with a focus on the elderly. Current management decisions are based on life expectancy and geriatric assessment. Regimens of HF and ultra-HF protocols are feasible strategies for older patients. Several prospective non-randomized studies have documented the safe delivery of ultra-HF for patients with localized prostate cancer, and multiple phase III trials and meta-analyses have confirmed that the HF regimen should be offered with similar acute toxicity regardless of patient age and comorbidity. A recent pooled analysis from two randomized trials comparing surgery to stereotactic body radiation therapy (SBRT) in older adult patients with early stage non-small cell lung cancer did show comparable outcomes between surgery and SBRT. Elderly cancer patients are significantly under-represented in all clinical trials. Thus, the inclusion of older patients in clinical studies should be strongly encouraged to strengthen the evidence base for this age group. We suggest that the creation of oncogeriatric coordination units may promote individualized care protocols, avoid overtreatment with aggressive and unrecommended therapies, and support de-escalating treatment in elderly cancer patients.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Neoplasias da Próstata/radioterapia , Doses de Radiação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Cancer Treat Rev ; 88: 102025, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32512415

RESUMO

BACKGROUND: Prophylactic cranial irradiation (PCI) reduces brain metastasis incidence in lung cancer, however with risk of neurocognitive decline. Nevertheless, risk factors for neurocognitive decline after PCI remain unclear. METHODS: We systematically reviewed the PubMed database according to the PRISMA guideline. Inclusion criteria were: randomized clinical trials (RCTs) and observational/single arm trials evaluating PCI, including ≥20 patients, reporting neurocognitive test results for lung cancer. Primary aim: evaluate risk factors associated with neurocognitive decline after PCI. RESULTS: Twenty records were eligible (8 different RCTs, 8 observational studies), including 3553 patients in total (858 NSCLC, 2695 SCLC) of which 73.6% received PCI. Incidence of mild/moderate cognitive decline after PCI varied from 8 to 89% (grading not always provided); for those without PCI, this was 3.4-42%. Interestingly, 23-95% had baseline cognitive impairment. Risk factors were often not reported. In one trial, both age (>60 years) and higher PCI dose (36 Gy) including twice-daily PCI were associated with a higher risk of cognitive decline. In one trial, white matter abnormalities were more frequent in the concurrent or sandwiched PCI arm, but without significant neuropsychological differences. One trial identified hippocampal sparing PCI to limit the neurocognitive toxicities of PCI and another reported an association between hippocampal dose volume effects and memory decline. As neurocognition was a secondary endpoint in most RCTs, and was assessed by various instruments with often poor/moderate compliance, high-quality data is lacking. CONCLUSIONS: Age, PCI dose, regimen and timing might be associated with cognitive impairment after PCI in lung cancer patients, but high-quality data is lacking. Future PCI trials should collect and evaluate possible risk factors systematically.


Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Transtornos Cognitivos/etiologia , Irradiação Craniana/efeitos adversos , Neoplasias Pulmonares/radioterapia , Lesões por Radiação/etiologia , Irradiação Craniana/métodos , Humanos , Neoplasias Pulmonares/patologia , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
17.
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
18.
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
19.
Anticancer Res ; 40(5): 2537-2548, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366398

RESUMO

BACKGROUND/AIM: Radiotherapy-induced autophagy affects radiation-sensitivity and radiotherapy efficacy. Histone modifications also occur during radiotherapy. This study assessed radiotherapy effects on histone modification and autophagy in non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: NSCLC cells were subjected to γ-irradiation. Autophagy was detected using western blotting and acridine orange staining. Radiation effect on cell growth was evaluated by clonogenic assay. Histone modifications were assessed by western blotting. Next generation sequencings (NGSs) were conducted to identify histone modification target genes. RESULTS: Radio-protective autophagy and histone H4 lysine 20 trimethylation (H4K20me3) were up-regulated after irradiation. By NGSs, genes that are differentially expressed upon irradiation were identified, including the candidate H4K20me3 target gene GABARAPL1. Furthermore, we showed that GABARAPL1 is essential for the radiation-induced autophagy. CONCLUSION: Our findings revealed the regulatory axis of radiation-induced H4K20me3-GABARAPL1 in radio-protective autophagy. Modulation of this axis may be a new strategy to enhance radiotherapy efficacy in NSCLC.


Assuntos
Autofagia/efeitos da radiação , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Histonas/metabolismo , Neoplasias Pulmonares/metabolismo , Lisina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Linhagem Celular Tumoral , Epigênese Genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Metilação , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , RNA Interferente Pequeno/genética
20.
Clin Oncol (R Coll Radiol) ; 32(8): 481-489, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32405158

RESUMO

Patients treated with curative-intent lung radiotherapy are in the group at highest risk of severe complications and death from COVID-19. There is therefore an urgent need to reduce the risks associated with multiple hospital visits and their anti-cancer treatment. One recommendation is to consider alternative dose-fractionation schedules or radiotherapy techniques. This would also increase radiotherapy service capacity for operable patients with stage I-III lung cancer, who might be unable to have surgery during the pandemic. Here we identify reduced-fractionation for curative-intent radiotherapy regimes in lung cancer, from a literature search carried out between 20/03/2020 and 30/03/2020 as well as published and unpublished audits of hypofractionated regimes from UK centres. Evidence, practical considerations and limitations are discussed for early-stage NSCLC, stage III NSCLC, early-stage and locally advanced SCLC. We recommend discussion of this guidance document with other specialist lung MDT members to disseminate the potential changes to radiotherapy practices that could be made to reduce pressure on other departments such as thoracic surgery. It is also a crucial part of the consent process to ensure that the risks and benefits of undergoing cancer treatment during the COVID-19 pandemic and the uncertainties surrounding toxicity from reduced fractionation have been adequately discussed with patients. Furthermore, centres should document all deviations from standard protocols, and we urge all colleagues, where possible, to join national/international data collection initiatives (such as COVID-RT Lung) aimed at recording the impact of the COVID-19 pandemic on lung cancer treatment and outcomes.


Assuntos
Betacoronavirus , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Infecções por Coronavirus/complicações , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Pneumonia Viral/complicações , Guias de Prática Clínica como Assunto/normas , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma Pulmonar de Células não Pequenas/virologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/virologia , Humanos , Neoplasias Pulmonares/virologia , Metanálise como Assunto , Pandemias , Pneumonia Viral/virologia , Gestão de Riscos , Carcinoma de Pequenas Células do Pulmão/virologia , Revisões Sistemáticas como Assunto
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