Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 544
Filtrar
1.
Neural Netw ; 128: 216-233, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32447265

RESUMO

In this paper, we proposed nested encoder-decoder architecture named T-Net. T-Net consists of several small encoder-decoders for each block constituting convolutional network. T-Net overcomes the limitation that U-Net can only have a single set of the concatenate layer between encoder and decoder block. To be more precise, the U-Net symmetrically forms the concatenate layers, so the low-level feature of the encoder is connected to the latter part of the decoder, and the high-level feature is connected to the beginning of the decoder. T-Net arranges the pooling and up-sampling appropriately during the encoding process, and likewise during the decoding process so that feature-maps of various sizes are obtained in a single block. As a result, all features from the low-level to the high-level extracted from the encoder are delivered from the beginning of the decoder to predict a more accurate mask. We evaluated T-Net for the problem of segmenting three main vessels in coronary angiography images. The experiment consisted of a comparison of U-Net and T-Nets under the same conditions, and an optimized T-Net for the main vessel segmentation. As a result, T-Net recorded a Dice Similarity Coefficient score (DSC) of 83.77%, 10.69% higher than that of U-Net, and the optimized T-Net recorded a DSC of 88.97% which was 15.89% higher than that of U-Net. In addition, we visualized the weight activation of the convolutional layer of T-Net and U-Net to show that T-Net actually predicts the mask from earlier decoders. Therefore, we expect that T-Net can be effectively applied to other similar medical image segmentation problems.

2.
Korean J Radiol ; 21(6): 660-669, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32410405

RESUMO

OBJECTIVE: To evaluate the accuracy of a deep learning-based automated segmentation of the left ventricle (LV) myocardium using cardiac CT. MATERIALS AND METHODS: To develop a fully automated algorithm, 100 subjects with coronary artery disease were randomly selected as a development set (50 training / 20 validation / 30 internal test). An experienced cardiac radiologist generated the manual segmentation of the development set. The trained model was evaluated using 1000 validation set generated by an experienced technician. Visual assessment was performed to compare the manual and automatic segmentations. In a quantitative analysis, sensitivity and specificity were calculated according to the number of pixels where two three-dimensional masks of the manual and deep learning segmentations overlapped. Similarity indices, such as the Dice similarity coefficient (DSC), were used to evaluate the margin of each segmented masks. RESULTS: The sensitivity and specificity of automated segmentation for each segment (1-16 segments) were high (85.5-100.0%). The DSC was 88.3 ± 6.2%. Among randomly selected 100 cases, all manual segmentation and deep learning masks for visual analysis were classified as very accurate to mostly accurate and there were no inaccurate cases (manual vs. deep learning: very accurate, 31 vs. 53; accurate, 64 vs. 39; mostly accurate, 15 vs. 8). The number of very accurate cases for deep learning masks was greater than that for manually segmented masks. CONCLUSION: We present deep learning-based automatic segmentation of the LV myocardium and the results are comparable to manual segmentation data with high sensitivity, specificity, and high similarity scores.

3.
Am J Clin Nutr ; 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32453399

RESUMO

BACKGROUND: There are limited data regarding the relation between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in the asymptomatic healthy population without kidney dysfunction. OBJECTIVES: We aimed to investigate the relation between SPC and characteristics of atherosclerotic plaques and cardiac events according to SPCs using a large cohort of asymptomatic Korean individuals. METHODS: We evaluated 6329 asymptomatic Korean individuals [mean age: 53.6 ± 7.6 y, 4611 men (72.9%)] without kidney dysfunction and coronary artery disease who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Study participants were stratified into quartiles according to their SPCs (≤3.0, 3.1-3.3, 3.4-3.7, ≥3.8 mg/dL). The degree and extent of subclinical coronary atherosclerosis were evaluated with CCTA. Stenosis of diameter ≥50% was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, and coronary revascularization. RESULTS: After adjustment for cardiovascular disease risk factors, the risk of any atherosclerotic plaque was significantly higher with increasing SPC quartiles (P = 0.001). In particular, the risk of calcified plaque increased in the second (OR: 1.27; 95% CI: 1.07, 1.51; P = 0.006), third (OR: 1.39; 95% CI: 1.17, 1.64; P < 0.001), and fourth SPC quartiles (OR: 1.50; 95% CI: 1.24, 1.82; P < 0.001) compared with that in the first quartile. However, there were no significant differences in the adjusted ORs for noncalcified plaque, mixed plaque, or significant stenosis. During a follow-up of median 5.4 y, there was no significant difference in cardiac events between the SPC quartiles. CONCLUSIONS: In asymptomatic Korean individuals without kidney dysfunction, a high SPC was an independent predictor of calcified plaques without any difference in cardiac events. Further long-term prospective studies are required to validate these results.

4.
Anticancer Res ; 40(5): 2981-2987, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366452

RESUMO

BACKGROUND/AIM: Continuation maintenance therapy is standard for advanced nonsquamous non-small cell lung cancer; however, the optimal maintenance strategy has yet to be determined. PATIENTS AND METHODS: Patients without disease progression after four cycles of carboplatin (CBDCA)+ pemetrexed (PEM)+ bevacizumab (BEV) were randomized to maintenance therapy with BEV, PEM, or BEV+PEM. The primary endpoint was 1-year progression-free survival (PFS) rate. RESULTS: Of the 90 patients enrolled, 64 were randomly assigned to maintenance therapy. The 1-year PFS rate was 9.1% in the BEV arm, 19.1% in the PEM arm, and 19.1% in the BEV+PEM arm. The median PFS and overall survival (OS) were 4.0 and 43.1 months in the BEV arm, 4.5 and 32.0 months in the PEM arm, and 6.4 and 41.8 months in the BEV+PEM arm. CONCLUSION: The median PFS was numerically better in the BEV+PEM arm, but the median OS was not significantly different among the three arms.

5.
Circulation ; 141(18): 1437-1446, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32223567

RESUMO

BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents and coronary-artery bypass grafting (CABG) for left main coronary artery disease are highly debated. METHODS: In the PRECOMBAT trial (Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), patients with unprotected left main coronary artery disease were randomly assigned to undergo PCI with sirolimus-eluting stents (n=300) or CABG (n=300) in 13 hospitals in Korea from April 2004 to August 2009. The follow-up was extended to at least 10 years for all patients (median, 11.3 years). The primary outcome was the incidence of major adverse cardiac or cerebrovascular events (composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target-vessel revascularization). RESULTS: At 10 years, a primary outcome event occurred in 29.8% of the PCI group and in 24.7% of the CABG group (hazard ratio [HR] with PCI vs CABG, 1.25 [95% CI, 0.93-1.69]). The 10-year incidence of the composite of death, myocardial infarction, or stroke (18.2% vs 17.5%; HR 1.00 [95% CI, 0.70-1.44]) and all-cause mortality (14.5% vs 13.8%; HR 1.13 [95% CI, 0.75-1.70]) were not significantly different between the PCI and CABG groups. Ischemia-driven target-vessel revascularization was more frequent after PCI than after CABG (16.1% vs 8.0%; HR 1.98 [95% CI, 1.21-3.21). CONCLUSIONS: Ten-year follow-up of the PRECOMBAT trial of patients with left main coronary artery disease randomized to PCI or CABG did not demonstrate significant difference in the incidence of major adverse cardiac or cerebrovascular events. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03871127 and NCT00422968.

6.
PLoS One ; 15(4): e0231428, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267899

RESUMO

BACKGROUND: Homocysteine has been known as a risk factor for cardiovascular disease. This study sought to evaluate the influence of homocysteine on the risk of subclinical coronary atherosclerosis in asymptomatic individuals. METHODS: We reviewed 3,186 asymptomatic individuals (mean age 53.8 ± 8.0 years, 2,202 men [69.1%]) with no prior history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography (CCTA) and laboratory tests as part of a general health examination. The subjects were stratified into tertiles according to their homocysteine levels. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA. Logistic regression analysis was used to determine the association between homocysteine levels and subclinical coronary atherosclerosis. RESULTS: The prevalence of significant coronary artery stenosis, any atherosclerotic, calcified, mixed, and non-calcified plaques increased with homocysteine tertiles (all p < 0.05). However, after adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios (ORs) for any atherosclerotic plaque (OR 1.06; 95% CI [confidence interval] 0.85-1.32; p = 0.610), calcified plaques (OR 1.17; 95% CI 0.92-1.48; p = 0.199), non-calcified plaques (OR 0.80; 95% CI 0.61-1.04; p = 0.089), and mixed plaques (OR 1.42; 95% CI 0.96-2.11; p = 0.077) between the third and first homocysteine tertiles. In addition, the adjusted OR for significant coronary artery stenosis (OR 0.92; 95% CI 0.63-1.36; p = 0.687) did not differ between the first and third tertiles. CONCLUSIONS: In asymptomatic individuals, homocysteine is not associated with an increased risk of subclinical coronary atherosclerosis.

7.
JMIR Med Inform ; 8(3): e16349, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186517

RESUMO

BACKGROUND: Cardiac arrest is the most serious death-related event in intensive care units (ICUs), but it is not easily predicted because of the complex and time-dependent data characteristics of intensive care patients. Given the complexity and time dependence of ICU data, deep learning-based methods are expected to provide a good foundation for developing risk prediction models based on large clinical records. OBJECTIVE: This study aimed to implement a deep learning model that estimates the distribution of cardiac arrest risk probability over time based on clinical data and assesses its potential. METHODS: A retrospective study of 759 ICU patients was conducted between January 2013 and July 2015. A character-level gated recurrent unit with a Weibull distribution algorithm was used to develop a real-time prediction model. Fivefold cross-validation testing (training set: 80% and validation set: 20%) determined the consistency of model accuracy. The time-dependent area under the curve (TAUC) was analyzed based on the aggregation of 5 validation sets. RESULTS: The TAUCs of the implemented model were 0.963, 0.942, 0.917, 0.875, 0.850, 0.842, and 0.761 before cardiac arrest at 1, 8, 16, 24, 32, 40, and 48 hours, respectively. The sensitivity was between 0.846 and 0.909, and specificity was between 0.923 and 0.946. The distribution of risk between the cardiac arrest group and the non-cardiac arrest group was generally different, and the difference rapidly increased as the time left until cardiac arrest reduced. CONCLUSIONS: A deep learning model for forecasting cardiac arrest was implemented and tested by considering the cumulative and fluctuating effects of time-dependent clinical data gathered from a large medical center. This real-time prediction model is expected to improve patient's care by allowing early intervention in patients at high risk of unexpected cardiac arrests.

8.
Cell Death Dis ; 11(3): 177, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152266

RESUMO

There have been few advances in the treatment of small-cell lung cancer (SCLC) because of the lack of targets. MCL1, a member of the anti-apoptotic BCL-2 family, may be a treatment target in several cancers, including SCLC. However, whether the expression profile of the anti-apoptotic BCL-2 family affects MCL1 inhibition strategy is unknown. A tissue microarray (TMA) was created from consecutive patients who were diagnosed with SCLC and had previously undergone surgery at Kyoto University Hospital (Kyoto, Japan) between 2001 and 2017. We used S63845, a MCL1 inhibitor, to assess the cytotoxic capacity in SCLC cell lines including a patient-derived cell line in vitro and in vivo. The combination of S63845 with navitoclax, a double BCL-XL/BCL-2 inhibitor, was also employed to examine the comprehensive inhibition of the anti-apoptotic BCL-2 family. Immunohistochemistry of a TMA from patients with surgically resected SCLC demonstrated high MCL1 expression with low BCL-XL and BCL-2 to be the most common expression profile. S63845 was effective in high MCL1- and low BCL-XL-expressing SCLC cell lines. S63845 induced BAK-dependent apoptosis in vitro, and the anti-tumor efficacy was confirmed in an in vivo model. Although knockdown of BCL-XL and BCL-2 improved the cytotoxic activity of S63845 and its combination with navitoclax increased the anti-tumor cytotoxicity, the therapeutic range of S63845 with navitoclax was narrow in in vivo studies. Our study suggests MCL1 inhibition therapy be applied for high MCL1- and low BCL-XL-expressing SCLC patients.

9.
Oncology ; : 1-8, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32222702

RESUMO

BACKGROUND: Brain metastases (BM) are one of the strongest negative prognostic factors in patients with non-small cell lung cancer (NSCLC). Molecularly targeted agents are standard of care for NSCLC patients with a driver mutation; however, their efficacy in patients with BM is not fully understood because patients with BM are usually excluded from clinical studies. This study investigated the current management and outcomes of newly diagnosed NSCLC patients with BM in Japanese clinical practice, focusing on their driver mutation status. PATIENTS AND METHODS: We enrolled newly diagnosed, treatment-naïve NSCLC patients with BM between January 2012 and December 2015 from 4 institutions in Japan. The medical records of each patient were retrospectively reviewed, and the treatment details and outcomes were evaluated. RESULTS: In total, 203 patients with BM were enrolled in this study and 73 (36%) were neurologically symptomatic. Regarding initial treatment, 110 patients (54%) received local therapy, including radiotherapy and surgery, whereas 77 (38%) received systemic therapy. The median overall survival (OS) was 14.3 months for all patients, and it was significantly longer among patients with a driver mutation (28.9 months; 95% confidence interval [CI], 20.9-41.0) than among patients without a driver mutation (9.9 months; 95% CI, 7.0-13.4) (hazard ratio [HR] 0.39; 95% CI, 0.27-0.57; p < 0.001). Multivariate analysis identified performance status (HR 1.78; 95% CI, 1.16-2.72; p = 0.009) and driver mutation status (HR 0.27; 95% CI, 0.17-0.44; p < 0.001) as significant prognostic factors. No significant difference in OS was noted according to the type of initial treatment, i.e., local versus systemic. CONCLUSION: The median OS of patients with a driver mutation was longer than 2 years, even of patients with BM, and it was significantly longer than that of patients without a driver mutation. Driver mutation status, in addition to performance status, was a significant prognostic factor in NSCLC patients with BM.

10.
Mol Cancer Ther ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32217741

RESUMO

Alectinib is used as a first-line treatment for anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Whereas other ALK inhibitors have been reported to be involved in resistance to ATP binding cassette (ABC) transporters, no data are available regarding the association between resistance to alectinib and ABC transporters. To investigate whether ABC transporters contribute to alectinib resistance, ABC transporter expression in alectinib-resistant cell lines derived from a patient with ALK-rearranged NSCLC and from H2228 lung cancer cells was evaluated and compared with that in each parent cell type. ATP-binding cassette subfamily C member 11 (ABCC11) expression was significantly increased in alectinib-resistant cell lines compared to that in alectinib-sensitive lines. ABCC11 inhibition increased sensitivity to alectinib in vitro. ABCC11-overexpressing cells were established by transfection of an ABCC11 expression vector into H2228 cells, while control cells were established by transfecting H2228 cells with an empty vector. ABCC11-overexpressing cells exhibited decreased sensitivity to alectinib compared with that of control cells in vitro. Moreover, the tumor growth rate following alectinib treatment was higher in ABCC11-overexpressing cells than that in control cells in vivo. In addition, the intracellular alectinib concentration following exposure to 100 nM alectinib was significantly lower in the ABCC11-overexpressing cell line compared with that in control cells. This is the first preclinical evidence showing that ABCC11 expression may be involved in acquired resistance to alectinib.

11.
In Vivo ; 34(2): 897-902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32111801

RESUMO

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the gold standard for limited-stage small-cell lung cancer (LS-SCLC); however, most patients inevitably experience relapse. We hypothesized consolidation amrubicin following CCRT to be a potential treatment for LS-SCLC. PATIENTS AND METHODS: All enrolled patients were treated using induction CCRT consisting of four cycles of etoposide and cisplatin plus concurrent thoracic radiotherapy. Eligible patients then received three cycles of amrubicin as consolidation therapy (consolidation population). The primary endpoint was the 2-year progression-free survival rate in the consolidation population. RESULTS: Of the 36 intention-to-treat patients, 28 (78%) received amrubicin and 24 (67%) completed all planned treatments. The 2-year progression-free survival rate and overall response rate were 35.7% and 86%, respectively. The median progression-free and overall survival were 14.3 and 60.9 months, respectively. There were no treatment-related deaths in the intention-to-treat population. CONCLUSION: This study was terminated due to slow patient accrual; however, this treatment strategy was feasible and demonstrated promising efficacy.

12.
Lipids Health Dis ; 19(1): 7, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937313

RESUMO

BACKGROUND: Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs). METHODS: This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles. RESULTS: The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026-2.166); especially non-calcified (OR 1.581, 95% CI 1.002-2.493) and mixed plaques (OR 2.419, 95% CI 1.051-5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex. CONCLUSIONS: TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.

13.
Nat Commun ; 11(1): 74, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900393

RESUMO

Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Quinase do Linfoma Anaplásico/genética , Apoptose/efeitos dos fármacos , Carbazóis/administração & dosagem , Rearranjo Gênico/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Piperidinas/administração & dosagem , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Quinase do Linfoma Anaplásico/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Fatores de Transcrição/genética
14.
Atherosclerosis ; 292: 171-177, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809986

RESUMO

BACKGROUND AND AIMS: Intravascular ultrasound (IVUS)-derived morphological criteria are poor predictors of the functional significance of intermediate coronary stenosis. IVUS-based supervised machine learning (ML) algorithms were developed to identify lesions with a fractional flow reserve (FFR) ≤0.80 (vs. >0.80). METHODS: A total of 1328 patients with 1328 non-left main coronary lesions were randomized into training and test sets in a 4:1 ratio. Masked IVUS images were generated by an automatic segmentation model, and 99 computed IVUS features and six clinical variables (age, gender, body surface area, vessel type, involved segment, and involvement of the proximal left anterior descending artery) were used for ML training with 5-fold cross-validation. Diagnostic performances of the binary classifiers (L2 penalized logistic regression, artificial neural network, random forest, AdaBoost, CatBoost, and support vector machine) for detecting ischemia-producing lesions were evaluated using the non-overlapping test samples. RESULTS: In the classification of test set lesions into those with an FFR ≤0.80 vs. >0.80, the overall diagnostic accuracies for predicting an FFR ≤0.80 were 82% with L2 penalized logistic regression, 80% with artificial neural network, 83% with random forest, 83% with AdaBoost, 81% with CatBoost, and 81% with support vector machine (AUCs: 0.84-0.87). With exclusion of the 28 lesions with borderline FFR of 0.75-0.80, the overall accuracies for the test set were 86% with L2 penalized logistic regression, 85% with an artificial neural network, 87% with random forest, 87% with AdaBoost, 85% with CatBoost, and 85% with support vector machine. CONCLUSIONS: The IVUS-based ML algorithms showed good diagnostic performance for identifying ischemia-producing lesions, and may reduce the need for pressure wires.

15.
Lung Cancer ; 139: 195-199, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31812890

RESUMO

OBJECTIVES: The J-ALEX study compared the efficacy and safety of alectinib with crizotinib in Japanese patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). Superiority in independent review facility (IRF)-assessed progression-free survival (PFS) was demonstrated for alectinib at the second pre-planned interim PFS analysis (data cutoff: December 3, 2015; hazard ratio [HR] 0.34, 99.7 % confidence interval [CI]: 0.17-0.71, P < 0.0001). We report final PFS data and the second pre-planned interim analysis of overall survival (OS) and safety (data cutoff: June 30, 2018). METHODS: Patients aged ≥20 years who were ALK inhibitor-naïve and chemotherapy-naïve, or had received one prior chemotherapy regimen, were randomized to receive alectinib 300 mg (n = 103) or crizotinib 250 mg (n = 104) twice daily. The primary end point was IRF-assessed PFS. Secondary end points included OS and safety. All patients entered survival follow-up in July 2018. RESULTS: Median follow-up was 42.4 months for alectinib and 42.2 months for crizotinib. Sustained improvement in IRF-assessed PFS with alectinib was shown (HR 0.37, 95 % CI: 0.26-0.52; median PFS 34.1 months vs 10.2 months crizotinib). At the second interim OS analysis, superiority of alectinib to crizotinib could not be concluded (stratified HR 0.80, 99.8799 % CI: 0.35-1.82, stratified log-rank P = 0.3860; median OS not reached alectinib vs 43.7 months crizotinib). Fewer alectinib-treated patients experienced grade ≥3 adverse events (36.9 % vs 60.6 % crizotinib). CONCLUSIONS: At the final PFS analysis, alectinib continued to demonstrate superiority in IRF-assessed PFS versus crizotinib in ALK-inhibitor-naïve ALK-positive NSCLC, with a favorable safety profile. OS follow-up continues.

16.
Lung Cancer ; 140: 8-18, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838169

RESUMO

OBJECTIVES: To describe the treatment patterns and determine the effectiveness and safety of nivolumab treatment for non-small cell lung cancer (NSCLC) in real-world setting in Japan. MATERIALS AND METHODS: Japanese patients with NSCLC who received nivolumab were analyzed retrospectively. Patients who had started nivolumab treatment between April 2016 and December 2016 were enrolled. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness and safety of nivolumab treatment and that of treatments just before and after nivolumab treatment, and programmed death-ligand 1 (PD-L1) expression status, if available, were collected. Factors associated with nivolumab effectiveness identified by univariate and multivariate analyses were further investigated for plotting Kaplan-Meier curves of epidermal growth factor receptor (EGFR) gene mutation status, PD-L1 expression status, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: In this study, 901 NSCLC patients were enrolled. Nivolumab was used the most as a second line treatment with a median number of nivolumab doses of five. The median overall survival (OS) was 14.6 months, one-year survival rate was 54.3 %, and median progression-free survival (PFS) was 2.1 months. The objective response rate was 20.5 % and disease control rate was 57.4 %. According to multivariate analyses, better OS and PFS were associated with favorable ECOG PS and absence of liver metastasis. Better PFS was observed in patients without EGFR mutation and patients with smoking history. PFS and best overall response in PD-L1 expression subgroups were expression level-dependent. The overall incidence of irAEs was 45.8 %, and the incidence of adverse events of grade 3 or higher was 14.0 %. CONCLUSION: The real-world effectiveness and safety of nivolumab is consistent with that reported by previous clinical trials and other real-world data. Subgroup analysis showed that ECOG PS, EGFR mutation status, smoking status, and PD-L1 were associated with the effectiveness of nivolumab.

17.
JCI Insight ; 5(2)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31855576

RESUMO

BACKGROUNDCurrent clinical biomarkers for the programmed cell death 1 (PD-1) blockade therapy are insufficient because they rely only on the tumor properties, such as programmed cell death ligand 1 expression frequency and tumor mutation burden. Identifying reliable, responsive biomarkers based on the host immunity is necessary to improve the predictive values.METHODSWe investigated levels of plasma metabolites and T cell properties, including energy metabolism markers, in the blood of patients with non-small cell lung cancer before and after treatment with nivolumab (n = 55). Predictive values of combination markers statistically selected were evaluated by cross-validation and linear discriminant analysis on discovery and validation cohorts, respectively. Correlation between plasma metabolites and T cell markers was investigated.RESULTSThe 4 metabolites derived from the microbiome (hippuric acid), fatty acid oxidation (butyrylcarnitine), and redox (cystine and glutathione disulfide) provided high response probability (AUC = 0.91). Similarly, a combination of 4 T cell markers, those related to mitochondrial activation (PPARγ coactivator 1 expression and ROS), and the frequencies of CD8+PD-1hi and CD4+ T cells demonstrated even higher prediction value (AUC = 0.96). Among the pool of selected markers, the 4 T cell markers were exclusively selected as the highest predictive combination, probably because of their linkage to the abovementioned metabolite markers. In a prospective validation set (n = 24), these 4 cellular markers showed a high accuracy rate for clinical responses of patients (AUC = 0.92).CONCLUSIONCombination of biomarkers reflecting host immune activity is quite valuable for responder prediction.FUNDINGAMED under grant numbers 18cm0106302h0003, 18gm0710012h0105, and 18lk1403006h0002; the Tang Prize Foundation; and JSPS KAKENHI grant numbers JP16H06149, 17K19593, and 19K17673.

18.
EuroIntervention ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31793885

RESUMO

AIMS: To compare percutaneous coronary intervention (PCI) outcomes in relation to stent optimization profiles between in-stent chronic total occlusions (CTOs) and de novo CTOs. METHODS AND RESULTS: We evaluated 1,516 consecutive patients who underwent PCI for 147 in-stent CTOs (9.3%) and 1,439 de novo CTOs between 2007 and 2018. The primary endpoint was target vessel failure (TVF) consisting of a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. The final post-stenting intravascular ultrasound (IVUS) images were analysed. Target lesion complexity reflected by the Japanese-CTO score was similar, albeit calcification was more prevalent in de novo CTOs, whereas occlusion length >20 mm was more frequent in in-stent CTOs. The technical success (88.4% vs. 87.5%, P=0.84) and in-hospital adverse event (1.4% vs. 3.6%, P=0.26) rates were similar between CTO types. Among those who received drug-eluting stents, the 5-year TVF (11.0% vs. 10.7%, P=0.99) and target vessel revascularization (4.2% vs. 3.7%, P=0.81) rates were similar between groups. Total stent length, minimum stent area (5.4±1.8 vs. 5.5±1.8 mm2, P=0.77), and maximal plaque burden of the reference segments were largely comparable between groups. CONCLUSIONS: In-stent CTO-PCI with drug-eluting stent optimized by IVUS guidance offers acceptable long-term clinical results as that achieved in de novo CTOs.

20.
Sci Rep ; 9(1): 16897, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729445

RESUMO

X-ray coronary angiography is a primary imaging technique for diagnosing coronary diseases. Although quantitative coronary angiography (QCA) provides morphological information of coronary arteries with objective quantitative measures, considerable training is required to identify the target vessels and understand the tree structure of coronary arteries. Despite the use of computer-aided tools, such as the edge-detection method, manual correction is necessary for accurate segmentation of coronary vessels. In the present study, we proposed a robust method for major vessel segmentation using deep learning models with fully convolutional networks. When angiographic images of 3302 diseased major vessels from 2042 patients were tested, deep learning networks accurately identified and segmented the major vessels in X-ray coronary angiography. The average F1 score reached 0.917, and 93.7% of the images exhibited a high F1 score > 0.8. The most narrowed region at the stenosis was distinctly captured with high connectivity. Robust predictability was validated for the external dataset with different image characteristics. For major vessel segmentation, our approach demonstrated that prediction could be completed in real time with minimal image preprocessing. By applying deep learning segmentation, QCA analysis could be further automated, thereby facilitating the use of QCA-based diagnostic methods.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA