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1.
Cancer Radiother ; 23(6-7): 658-661, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471252

RESUMO

Stereotactic radiotherapy represents a fundamental change in the practice of radiotherapy of lung cancers. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Stereotactic radiotherapy can be realized either by a dedicated accelerator (CyberKnife®) or by a conventional accelerator associated with specific systems. The two modalities deliver a very precise irradiation whose very good results published to date are similar. Some technical characteristics specific to each type of linear accelerator could guide the choice according to the target volume treated.


Assuntos
Neoplasias Pulmonares/radioterapia , Aceleradores de Partículas , Radiocirurgia/instrumentação , Humanos , Movimentos dos Órgãos , Órgãos em Risco/efeitos da radiação , Radiocirurgia/métodos , Respiração , Resultado do Tratamento
2.
Cancer Radiother ; 23(6-7): 720-731, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471255

RESUMO

Stereotactic radiotherapy (or Stereotactic body radiotherapy [SBRT]) is a technique currently well established in the therapeutic arsenal for the management of bronchial cancers. It represents the standard treatment for inoperable patients or who refuses surgery. It is well tolerated, especially in elderly and frail patients, and the current issue is to define its indications in operated patients, based on retrospective and randomized trials comparing stereotactic radiotherapy and surgery, with results equivalents. This work analyzes in detail the different aspects of pulmonary stereotactic radiotherapy and suggests arguments that help in the therapeutic choice between surgery and stereotaxic irradiation. In all cases, the therapeutic decision must be discussed in a multidisciplinary consultation meeting, while informing the patient of the possible therapeutic options.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Tomada de Decisão Clínica , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Equipolência Terapêutica
3.
Cancer Radiother ; 23(6-7): 701-707, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31501024

RESUMO

Lung cancer treatment is a heavy workload for radiation oncologist and that field showed many evolutions over the last two decades. The issue about target volume was raised when treatment delivery became more precise with the development of three-dimensional conformal radiotherapy. Initially based upon surgical series, numerous retrospective and prospective studies aimed to evaluate the risk of elective nodal failure of involved-field radiotherapy compared to standard large field elective nodal irradiation. In every setting, locally advanced non-small cell lung cancer, localized non-small cell lung cancer, localized small cell lung cancer, exclusive chemoradiation or postoperative radiotherapy, most of the studies showed no significant difference between involved-field radiotherapy or elective nodal irradiation with elective nodal failure rate under 5% at 2 years, provided staging had been done with modern imaging and diagnostic techniques (positron emission tomography scan, endoscopy, etc.). Moreover, if reducing irradiated volumes are safe regarding recurrences, involved-field radiotherapy allowed dose escalation while reducing acute and late oesophageal, cardiac and pulmonary toxicities. Consequently, major clinical trials involving radiotherapy initiated in the last two decades and international clinical guidelines recommended omission of elective nodal irradiation in favour of in-field radiotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Irradiação Linfática/métodos , Radioterapia Conformacional/métodos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia por Emissão de Pósitrons , Radioterapia/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Toracoscopia
4.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
6.
Cancer Radiother ; 23(6-7): 486-495, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31501025

RESUMO

The basis of treatment of primary disease in case of metastatic cancer at diagnosis is based on the knowledge of the natural history of the disease, the biology of the primary tumour and its metastases, advances in modern radiotherapy techniques (modulated intensity, stereotactic radiotherapy) in order to improve the survival of patients with advanced disease. The clinical concept of oligometastatic disease at diagnosis has repositioned the interest of local treatment for primitive disease because these patients have a slower evolutionary profile than metastatic disease extended from the outset. This article reviews the indication of radiotherapy as a local treatment for primary cancer in a de novo metastatic diagnosed disease in the case of breast cancer, non-small cell lung cancer and prostate cancer.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Neoplasias da Próstata/radioterapia , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica , Estudos Prospectivos , Neoplasias da Próstata/patologia , Estudos Retrospectivos
7.
J Cancer Res Clin Oncol ; 145(11): 2813-2822, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31492985

RESUMO

BACKGROUND: Stereotactic body radiotherapy (SBRT) can achieve high tumour control with limited toxicity for inoperable early stage non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: The German Epidemiologic Cancer Registries from the Robert-Koch Institute were assessed. Periods according to the availability of SBRT were: (1) 2000-2003 (pre-SBRT); (2) 2004-2007 (interim); and (3) 2007-2014 (broad availability of SBRT). To assess the association of cancer-related parameters with mortality, hazard ratios (HR) from Cox proportional hazards models were computed. To evaluate the change of treatment-related mortality, we performed interaction analyses and the relative excess risk due to interaction (RERI, additive scale) was computed. RESULTS: A total of 16,292 patients with UICC stage I NSCLC diagnosed between 2000 and 2014 were analysed. Radiotherapy utilization increased from 5% in pre-SBRT era to 8.8% after 2007. In univariate analyses, survival in the whole cohort improved only marginally when 2000-2003 is compared to 2004-2007 (HR 0.92, 95% CI 0.85-1.01) or 2008-2014 (HR 0.93, 95% CI 0.86-1.01). Comparing surgery/radiotherapy, mortality in the radiotherapy group started from a 3.5-fold risk in 2000-2003 to 2.6 after 2007. The interaction analysis revealed a stronger improvement for radiotherapy (multiplicative scale for 2000-2003 vs. > 2007: 0.74, 95% CI 0.58-0.94). On an additive scale, treatment × period interaction revealed an RERI for 2000-2003 vs. > 2007 of - 1.18 (95% CI - 1.8, - 0.55). CONCLUSIONS: Using population-based data, we observed a survival improvement in stage I lung cancer over time. With an increasing utilization of radiotherapy, a stronger improvement occurred in patients treated with radiotherapy when compared to surgery.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Radiocirurgia/mortalidade , Radioterapia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
9.
Cancer Radiother ; 23(6-7): 592-608, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31427077

RESUMO

Adaptive radiotherapy (ART) is a complexe image-guided radiotherapy modality that comprises multiple planning to account for anatomical variations occurring during irradiation. Schematically, two strategies of RTA can be distinguished and combined according to tumor locations. One or more replanning can be proposed to correct systematic variations such as tumor shrinkage. A library of treatment plans with day-to-day plan selection from cone-beam CT imaging can also be proposed to correct random variations such as uterine motion or bladder/rectum volume changes. Because of strong anatomical variations occurring during irradiation, RTA appears therefore particularly justified in head and neck, lung, bladder, cervical and rectum and pancreas tumors, and to a lesser extent for prostate tumors and other digestive tumors. For these tumor locations, ART provides a fairly clear dosimetric benefit but a clinical benefit not yet formally demonstrated. ART cannot be proposed in a routine practice but must be evaluated medico-economically in the context of prospective trials. A rigorous quality control must be associated.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Feminino , Neoplasias Gastrointestinais/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Neoplasias Otorrinolaringológicas/radioterapia , Neoplasias da Próstata/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias do Colo do Útero/radioterapia
10.
BMC Infect Dis ; 19(1): 710, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405376

RESUMO

BACKGROUND: Pulmonary Cryptococcosis (PC) is diagnosed with increasing incidence in recent years, but it does not commonly involve the pleural space. Here, we report a HIV-negative case with advanced stage IIIB non-small cell lung cancer (NSCLC) treated with radiation therapy presented with dyspnea, a new PET-positive lung mass and bilateral pleural effusion suspecting progressive cancer. However, the patient has been diagnosed as pulmonary cryptococcal infection and successfully treated with oral fluconazole therapy. CASE PRESENTATION: A 77-year-old male with advanced stage non-small cell lung cancer treated with combined chemo-radiation therapy who presented with progressive dyspnea, a new PET-positive left lower lobe lung mass and bilateral pleural effusions. Initial diagnostic thoracentesis and bronchoscopy yielded no cancer, but instead found yeast forms consistent with cryptococcal organisms in the transbronchial biopsies of the left lower lobe lung mass. Subsequent to this, the previously collected pleural fluid culture showed growth of Cryptococcus neoformans. The same sample of pleural effusion was tested and was found to be positive for crytococcal antigen (CrAg) by a lateral flow assay (LFA). The patient has been treated with oral fluconazole therapy resulting in gradual resolution of the nodular infiltrates. CONCLUSION: PC should be considered in immunosuppressed cancer patients. Additionally, concomitant pleural involvement in pulmonary cryptococcal infections may occur. The incidence of false positive 18FDG-PET scans in granulomatous infections and the use of CrAg testing in pleural fluid to aid in diagnosis are reviewed.


Assuntos
Criptococose/diagnóstico por imagem , Criptococose/microbiologia , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/microbiologia , Derrame Pleural/microbiologia , Administração Oral , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Criptococose/tratamento farmacológico , Cryptococcus neoformans/patogenicidade , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/radioterapia , Masculino , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Tomografia por Emissão de Pósitrons
11.
Cancer Sci ; 110(11): 3553-3564, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31464032

RESUMO

To determine the therapeutic efficacy and safety of risk-adapted stereotactic body radiation therapy (SBRT) schedules for patients with early-stage central and ultra-central inoperable non-small cell lung cancer. From 2006 to 2015, 80 inoperable T1-2N0M0 NSCLC patients were treated with two median dose levels: 60 Gy in six fractions (range, 48-60 Gy in 4-8 fractions) prescribed to the 74% isodose line (range, 58%-79%) for central lesions (ie within 2 cm of, but not abutting, the proximal bronchial tree; n = 43), and 56 Gy in seven fractions (range, 48-60 Gy in 5-10 fractions) prescribed to the 74% isodose line (range, 60%-80%) for ultra-central lesions (ie abutting the proximal bronchial tree; n = 37) on consecutive days. Primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), tumor local control rate (LC), and toxicity. Median OS and PFS were 64.47 and 32.10 months (respectively) for ultra-central patients, and not reached for central patients. Median time to local failure, regional failure, and any distant failures for central versus ultra-central lesions were: 27.37 versus 26.07 months, 20.90 versus 12.53 months, and 20.85 versus 15.53 months, respectively, all P < .05. Multivariate analyses showed that tumor categorization (ultra-central) and planning target volume ≥52.76 mL were poor prognostic factors of OS, PFS, and LC, respectively (all P < .05). There was one grade 5 toxicity; all other toxicities were grade 1-2. Our results showed that ultra-central tumors have a poor OS, PFS, and LC compared with central patients because of the use of risk-adapted SBRT schedules that allow for equal and favorable toxicity profiles.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Intervalo Livre de Progressão , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento
12.
Medicine (Baltimore) ; 98(35): e17020, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464961

RESUMO

The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques.We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS.We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS.There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Dosagem Radioterapêutica , Fatores Etários , Idoso , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos
13.
J Cancer Res Clin Oncol ; 145(10): 2605-2612, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31410604

RESUMO

BACKGROUNDS: This study was designed to evaluate the role of thoracic radiotherapy (TRT) in a selected patient population with oligometastatic extensive stage small-cell lung cancer (ES-SCLC) without brain or liver involved. The underlying hypothesis was that TRT will improve outcomes in this favorable patient population. METHODS: 305 patients were included in an institutional review board (IRB)-approved study, of which 105 received TRT after chemotherapy (ChT) and 200 received ChT alone. The survival outcomes were compared between ChT+TRT group and ChT-alone group in patients with oligometastasis without brain or liver involved and patients with brain/liver/multimetastasis, respectively. RESULTS: The 1-year, 2-year and 5-year overall survival (OS) for all patients were 60.3%, 23.9% and 1.6%, respectively. The addition of TRT significantly improved PFS in total patients than ChT alone (14.5 months vs. 10.1 months, p = 0.006), but the OS benefit was not significant (17.8 months vs. 16.5 months, p = 0.061). For patients with oligometastasis (n = 118), TRT offered significant progression free survival (PFS) (16.5 months vs. 9.1 months, p = 0.005) and OS (19.2 months vs. 15.6 months, p = 0.039) benefits. However, for patients with brain/liver/multimetastasis, the PFS and OS were not improved with TRT (p = 0.49, p = 0.811). CONCLUSIONS: TRT provided significant PFS and OS benefits in patients with oligometastatic ES-SCLC without brain or liver involved. The consolidative TRT is a reasonable treatment option for this favorable patient population.


Assuntos
Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Radioterapia/efeitos adversos , Radioterapia/métodos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/radioterapia , Resultado do Tratamento
14.
Br J Radiol ; 92(1103): 20190174, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364397

RESUMO

OBJECTIVE: The effect of functional lung avoidance planning on radiation dose-dependent changes in regional lung perfusion is unknown. We characterized dose-perfusion response on longitudinal perfusion single photon emission computed tomography (SPECT)/CT in two cohorts of lung cancer patients treated with and without functional lung avoidance techniques. METHODS: The study included 28 primary lung cancer patients: 20 from interventional (NCT02773238) (FLARE-RT) and eight from observational (NCT01982123) (LUNG-RT) clinical trials. FLARE-RT treatment plans included perfused lung dose constraints while LUNG-RT plans adhered to clinical standards. Pre- and 3 month post-treatment macro-aggregated albumin (MAA) SPECT/CT scans were rigidly co-registered to planning four-dimensional CT scans. Tumour-subtracted lung dose was converted to EQD2 and sorted into 5 Gy bins. Mean dose and percent change between pre/post-RT MAA-SPECT uptake (%ΔPERF), normalized to total tumour-subtracted lung uptake, were calculated in each binned dose region. Perfusion frequency histograms of pre/post-RT MAA-SPECT were analyzed. Dose-response data were parameterized by sigmoid logistic functions to estimate maximum perfusion increase (%ΔPERFmaxincrease), maximum perfusion decrease (%ΔPERFmaxdecrease), dose midpoint (Dmid), and dose-response slope (k). RESULTS: Differences in MAA perfusion frequency distribution shape between time points were observed in 11/20 (55%) FLARE-RT and 2/8 (25%) LUNG-RT patients (p < 0.05). FLARE-RT dose response was characterized by >10% perfusion increase in the 0-5 Gy dose bin for 8/20 patients (%ΔPERFmaxincrease = 10-40%), which was not observed in any LUNG-RT patients (p = 0.03). The dose midpoint Dmid at which relative perfusion declined by 50% trended higher in FLARE-RT compared to LUNG-RT cohorts (35 GyEQD2 vs 21 GyEQD2, p = 0.09), while the dose-response slope k was similar between FLARE-RT and LUNG-RT cohorts (3.1-3.2, p = 0.86). CONCLUSION: Functional lung avoidance planning may promote increased post-treatment perfusion in low dose regions for select patients, though inter-patient variability remains high in unbalanced cohorts. These preliminary findings form testable hypotheses that warrant subsequent validation in larger cohorts within randomized or case-matched control investigations. ADVANCES IN KNOWLEDGE: This novel preliminary study reports differences in dose-response relationships between patients receiving functional lung avoidance radiation therapy (FLARE-RT) and those receiving conventionally planned radiation therapy (LUNG-RT). Following further validation and testing of these effects in larger patient populations, individualized estimation of regional lung perfusion dose-response may help refine future risk-adaptive strategies to minimize lung function deficits and toxicity incidence.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta à Radiação , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão/métodos , Estudos Prospectivos , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada de Emissão de Fóton Único/métodos
15.
Medicine (Baltimore) ; 98(29): e16427, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335695

RESUMO

BACKGROUND: Preclinical in vitro experiments demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) might have synergistic effect in combination with radiotherapy on Non-small cell lung cancer (NSCLC), but the clinical trials showed inconsistence results in NSCLC patients with EGFR status unknow or mutations. This study aimed to determine if added TKIs to Thoracic radiotherapy (TRT) improve primary disease response rate (RR) and survival outcomes in advanced or metastatic NSCLC. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library from January 2000 to December 2017 for eligible studies where patients received concurrent EGFR TKIs and TRT or CRT. Concerned outcomes were primary tumor RR, overall survival (OS), and adverse events (AEs). The meta-analysis was performed using Stata software (version 12.0). Random effects models were used to pool outcomes across studies. Sensitivity analysis was performed to determine if the results would be different. RESULTS: We found 16 prospective clinical trials with mature results for meta-analyses. Twelve studies including 446 patients reported the RR and survival outcomes of TRT combined TKIs. The CR, PR, SD, and PD, respectively, were 0.06 (95% CI 0.03-0.09, I = 0%), 0.44 (95% CI 0.38-0.49, I = 64.9%), 0.29 (95% CI 0.24-0.34, I = 78.4%), and 0.15 (95% CI 0.11-0.19, I = 84.2%). One- and 2-year OS, respectively, were 0.52 (95% CI 0.44-0.60, I = 38.8%) and 0.26 (95% CI 0.18-0.33, I = 0%). Four studies including 182 patients reported the RR and survival outcomes of CRT combined TKIs. The pooled CR, PR, SD, and PD, respectively, were 0.12 (95% CI 0.02-0.22, I = 69.1%), 0.41 (95% CI 0.27-0.55, I71.6%), 0.31 (95% CI 0.16-0.46, I = 79%), and 0.14 (95% CI -0.01-0.30, I = 87.8%). Only 1 study reported the survival event rate, 1- and 2-year OS, respectively, were 0.83 (95% CI 0.71-0.94) and 0.67 (95% CI 0.54-0.81). There were not severe adverse events (SAEs) reported either TRT combined TKIs or CRT combined TKIs. CONCLUSION: There is evidence, albeit of low quality, that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone, TRT alone or CRT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia/métodos , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares , Inibidores de Proteínas Quinases/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Estadiamento de Neoplasias , Resultado do Tratamento
17.
Medicine (Baltimore) ; 98(26): e16124, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31261531

RESUMO

BACKGROUND: The aim of this study is to assess the quality of reporting of thoracic (T) RT technique for curative intent treatment in prospective lung cancer trials. METHODS: We searched MEDLINE for eligible trials published from 1996 to 2016. We assessed the included trials' reports on whether they reported the RT dose prescription method; RT dose-planning procedures; algorithm for tissue inhomogeneity dose corrections; organs at risk dose constraints; target volume definition, simulation and/or motion management procedures; treatment verification procedures; total RT dose; fractionation schedule; conduct of quality assurance as well as presence or absence of deviations in RT treatment planning and delivery adequately. We performed univariable and multivariable logistic regression to determine the factors that may influence the quality of reporting. RESULTS: We found 85 eligible trial reports. Target volume definition, total RT dose, and fractionation schedules were reported adequately in more than 90% of the included trials. Algorithm for tissue inhomogeneity dose corrections, simulation and verification procedures, presence or absence of deviations in RT treatment planning and delivery were reported adequately in less than 20% of the included trials. Twenty-three trials (27%) reported 7 criteria or more adequately. Both univariable and multivariable logistic regression showed that trials with RT focused research question were more likely to have adequate quality in reporting (judged as adequate reporting in 7 criteria or more) than trials with non-RT focused question (odds ratio 4.11, 95% confidence interval 1.10 to 15.43, P value = .04). CONCLUSION: There is significant variability in the quality of reporting on thoracic radiotherapy treatment in prospective lung cancer trials. Future research should focus on developing consensus guidelines to standardize the reporting of radiotherapy technique in clinical trials.


Assuntos
Ensaios Clínicos como Assunto , Neoplasias Pulmonares/radioterapia , Projetos de Pesquisa , Ensaios Clínicos como Assunto/métodos , Humanos , Garantia da Qualidade dos Cuidados de Saúde
18.
Br J Radiol ; 92(1101): 20190184, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31287737

RESUMO

OBJECTIVES: In non-small cell lung cancer (NSCLC) patients, to establish whether the fractional volumes of irradiated anatomic or perfused lung differed between those with and without deteriorating lung function or radiation associated lung injury (RALI). METHODS: 48 patients undergoing radical radiotherapy for NSCLC had a radiotherapy-planning CT scan and single photon emission CT lung perfusion imaging (99mTc-labelled macroaggregate albumin). CT defined the anatomic and the single photon emission CT scan (co-registered with CT) identified the perfused (threshold 20 % of maximum) lung volumes. Fractional volumes of anatomic and perfused lung receiving more than 5, 10, 13, 20, 30, 40, 50 Gy were compared between patients with deteriorating (>median decline) vs stable (30, 40, 50 Gy). Fractional volumes of anatomic and perfused lung receiving > 10 Gy best predicted decline in FEV1 (Area under receiver operating characteristic curve (Az = 0.77 and 0.76 respectively); sensitivity/specificity 75%/81 and 80%/71%) for a 32.7% anatomic and 33.5% perfused volume cut-off. Irradiating an anatomic fractional volume of 4.7% to > 50 Gy had a sensitivity/specificity of 83%/89 % for indicating RALI (Az = 0.83). CONCLUSION: A 10-20 Gy radiation dose to anatomic or perfused lung results in decline in FEV1. A fractional anatomic volume of >5% receiving >50 Gy influences development of RALI. ADVANCES IN KNOWLEDGE: Extent of low-dose radiation to normal lung influences functional respiratory decline.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Lesões por Radiação/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Dosagem Radioterapêutica , Tomografia Computadorizada de Emissão de Fóton Único/métodos
19.
Life Sci ; 232: 116562, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201845

RESUMO

AIMS: Lung cancer is one of the main causes of cancer-related deaths worldwide and radiotherapy is a major treatment of choice. However, radioresistance is a main reason for radiotherapy failure or tumor relapse. Here, we investigated possible mechanisms associated with cancer cell radioresistance. MATERIALS AND METHODS: We compared two newly derived cell lines, namely A549-IR3 and A549-IR6, which survived repeated (3 or 6 times) 4 Gy exposure of parental A549 lung cancer cell line. DNA repair ability, stemness and senescence were comparatively studied. KEY FINDINGS: A549-IR3 exhibited higher proliferation ability and radioresistance compared to parental and A549-IR6 cells. Enhanced radioresistance was not accompanied by chemoresistance to cisplatin or docetaxel. DNA repair kinetics (γΗ2ΑΧ expression) were similar in all cell lines. A549-IR3 cells exhibited a significant rise in stem cell markers (CD44, CD133, OCT4, SOX2 and NANOG) whereas A549-IR6 displayed an increased senescent population. SIGNIFICANCE: Cancer cells surviving after radiotherapy may follow two different escape pathways: selection for radioresistance resulting in regrowth, and in clinical terms relapse, or above an irradiation threshold, stem-cells die and cancer cells become senescent, leading the tumor to a state of dormancy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Células-Tronco Neoplásicas/efeitos da radiação , Células A549 , Envelhecimento/efeitos da radiação , Apoptose/efeitos da radiação , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Reparo do DNA , Humanos , Neoplasias Pulmonares/metabolismo , Recidiva Local de Neoplasia/genética , Células-Tronco Neoplásicas/metabolismo , Tolerância a Radiação
20.
Gene ; 710: 178-185, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31158449

RESUMO

In order to improve the therapeutic effect of non-small cell lung cancer (NSCLC), it is critical to combine radiation and gene therapy. Our study found that the activation of microRNA-9 (miR-9) conferred ionizing radiation (IR) sensitivity in cancer cells. Furthermore, increased microRNA-9 promoter methylation level was observed after IR. Our study combined the IR and microRNA-9 overexpression treatment which leads to a significant enhancement in the therapeutic efficiency in lung cancer both in vitro and in vivo. Therefore, it is plausible that microRNA-9 can be used as a novel therapeutic strategy of NSCLC. MTT assay was performed to detect the effect of microRNA-9 on the survival and growth of NSCLC cells. Flow cytometry results showed that microRNA-9 enhanced the apoptosis of NSCLC cells. Wound healing assay found that microRNA-9 can inhibit the migration of NSCLC cells and enhance the effect of radiation on the migration of NSCLC cells. In addition, bisulfate sequencing PCR was performed to analyze the methylation status of the microRNA-9 promoter. In order to determine the effect of microRNA-9 and its promoter methylation status on proliferation and radio-sensitivity in vivo, a subcutaneous tumor formation assay in nude mice was performed. Results have shown that microRNA-9 overexpression increased the radiosensitivity of A549 cells by inhibiting cell activity and migration, and by increasing apoptosis. In addition, the promoter methylation status of the microRNA-9 gene increased in response to ionizing radiation. Our study demonstrated that microRNA-9 enhanced radiosensitivity in NSCLC and this effect is highly regulated by its promoter methylation status. These results will help to clarify regulatory mechanisms of radiation resistance thus stimulate new methods for improving radiotherapy for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Metilação de DNA , Neoplasias Pulmonares/genética , MicroRNAs/genética , Tolerância a Radiação , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Epigênese Genética , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Regiões Promotoras Genéticas , Análise de Sequência de DNA
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