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1.
Anticancer Res ; 39(10): 5683-5688, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570467

RESUMO

BACKGROUND/AIM: This study aimed to compare the efficacies of cryobiopsy and forceps biopsy for peripheral lung cancer detection. PATIENTS AND METHODS: A retrospective review of peripheral lung cancer cases between December 2017 and April 2019 was conducted. Forceps biopsy was performed followed by cryobiopsy using a guide sheath (GS). Diagnostic yields were compared between cryobiopsy and forceps biopsy. RESULTS: A total of 53 lung cancer lesions were evaluated. The diagnostic yields of forceps biopsy and cryobiopsy were 86.8% and 81.1%, respectively. Univariate and multivariate analyses indicated that cryobiopsy with a GS was significantly associated with increased diagnostic yield (odds ratio(OR)=11.6; p=0.044). Among the four patients who tested positive on cryobiopsy and negative on forceps biopsy, one had diffused pulmonary metastases and the others showed intratumoural air bronchograms. CONCLUSION: Cryobiopsy using a GS can significantly increase diagnostic yield and help identify lesions with intratumoural air bronchograms and external wall lesions.


Assuntos
Biópsia/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia/métodos , Criocirurgia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Instrumentos Cirúrgicos
2.
Pol J Pathol ; 70(2): 63-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556556

RESUMO

The aim of this research was to investigate the clinical role and prognostic value of CD117 expression assessed immunohistochemically in lung carcinoma through a comprehensive meta-analysis in which 27 publications were acquired and 2645 patients were ultimately analysed. Statistical analysis and corresponding plots were performed using STATA version 12.0. Publication bias was assessed by Begg's funnel plots and Egger's test. Pooled HR and its 95% CI (HR = 1.53, 95% CI: 1.13-2.07, p = 0.007) for overall survival of patients indicated a poor prognostic value for CD117 expression in lung carcinoma, which was accompanied by heterogeneity and publication bias. In the subgroup analysis, there was strong evidence that could support an association between CD117 expression and poor prognosis in NSCLC patients (HR = 2.03, 95% CI: 1.41-2.90, p < 0.001; heterogeneity: I2 = 41.9%, c2 = 15.49, p = 0.078). Multivariate analysis also revealed consistent results in high-quality studies with reported HRs (HR = 2.16, 95% CI: 1.67-2.79, p < 0.001), and Asian patients (HR = 2.12, 95% CI: 1.45-3.10, p < 0.001). The correlations between CD117 expression and age, clinical stage, TNM stage, lymph node metastasis, or histology were not statistically significant. In conclusion, CD117 expression might be a potential marker for predicting poor prognosis, faster tumour growth, and early lymph node metastasis in NSCLC.


Assuntos
Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-kit/genética , Biomarcadores Tumorais/genética , Progressão da Doença , Humanos , Neoplasias Pulmonares/diagnóstico , Metástase Linfática , Prognóstico
3.
Anticancer Res ; 39(9): 4603-4612, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519557

RESUMO

BACKGROUND/AIM: Sarcopenia describes the loss of skeletal muscle mass. While this condition is associated with a high mortality in cancer patients, its influence on survival is still underestimated. PATIENTS AND METHODS: A systematic review for articles was performed using the PubMed database, Cochrane Library, Biomed Central, Science Direct and by manual search. We used data of overall survival in sarcopenic patients for assessing the death risk. We extracted hazard ratio estimates from univariate and multivariate Cox proportional hazards models for meta-analysis. RESULTS: A total of 15 studies were eligible for meta-analysis including a total of 2,521 lung cancer patients. Univariate meta-analysis revealed a two-fold increased death risk in sarcopenic patients; multivariate meta-analysis yielded a significant, three-fold elevated risk of death. This higher mortality is independent of tumour stage. CONCLUSION: Muscle loss is an independent risk factor for increased death risk in lung cancer patients independent of cancer stage. This argues for implementing screening for sarcopenia into cancer care.


Assuntos
Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Sarcopenia/etiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Músculo Esquelético/patologia , Estadiamento de Neoplasias , Tamanho do Órgão , Prognóstico , Modelos de Riscos Proporcionais , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia
4.
Anticancer Res ; 39(9): 4987-4993, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519605

RESUMO

BACKGROUND/AIM: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. PATIENTS AND METHODS: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. RESULTS: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. CONCLUSION: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Docetaxel/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
5.
Anticancer Res ; 39(9): 5077-5081, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519618

RESUMO

BACKGROUND/AIM: Patient performance scores are used widely in clinical practice to assess a patient's general condition. The aim of this study was to evaluate the prognostic role of Eastern Cooperative Oncology Group performance score (ECOG PS) before, after and its changes during chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Records of 99 patients with stage III NSCLC were evaluated. ECOG PS before, during and after chemoradiotherapy was analyzed for prognostic impact on overall (OS) and event-free (EFS) survival. RESULTS: Median OS considering the entire cohort was 20.8 months (range=15.3-26.2 months). Median OS, and 1- and 2-year survival rates were 26.4 months, 85% and 53% in patients with ECOG PS 0 versus 18.9 months, 69% and 37% in patients with ECOG PS 1 (p=0.1, log-rank test), respectively. After the first follow-up, 35% of patients presented worsening ECOG PS, while in 65% it was stable or improved. Median EFS according to ECOG PS 0, 1, 2 and 3 was 9.6, 9.0, 7.9 and 3.5 months, respectively, at the first follow-up (p=0.018, log-rank test). Deterioration of ECOG PS after chemoradiotherapy resulted in reduced OS in the subgroups with initial ECOG PS 0 and 1 (p=0.005 and p=0.001, log-rank test). CONCLUSION: ECOG PS and its changes have a strong impact on patient outcome. Deterioration of performance status was a strong negative prognostic factor for EFS and OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Terapia Combinada , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Tomografia Computadorizada por Raios X
6.
Anticancer Res ; 39(9): 5219-5223, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519636

RESUMO

AIM: This study evaluated the prognostic value of soluble mesothelin-related protein (SMRP) levels in pleural effusions (PE) from patients with pleural mesothelioma (MPM). PATIENTS AND METHODS: SMRP level in PE was tested using an enzyme-linked immunosorbent assay (ELISA) in 109 patients with MPM at diagnosis before any treatment. The Kaplan-Meier method and the Cox regression were applied to compare overall survival probabilities across tertile categories of SMRP level. RESULTS: No significant differences in Kaplan-Meier overall survival probabilities among the SMRP categories were found. A statistically non-significant trend for increased death rate ratio (RR) was computed (p=0.327) when the higher (>46.5 nM, RR=1.38) and intermediate (8.5-46.5 nM, RR=1.18) SMRP categories were compared to the lower category (<8.5 nM, RR=1.00). Cox regression modelling including a restricted cubic spline showed a moderately rising non-linear trend in death rate. CONCLUSION: The SMRP level in PE does not appear to have prognostic significance and its detection is not recommended in routine clinical management of patients with MPM.


Assuntos
Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Mesotelioma/complicações , Mesotelioma/mortalidade , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/metabolismo , Neoplasias Pleurais/complicações , Neoplasias Pleurais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/diagnóstico , Mesotelioma/terapia , Pessoa de Meia-Idade , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Prognóstico , Curva ROC , Resultado do Tratamento
7.
J Cancer Res Clin Oncol ; 145(9): 2285-2292, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31372722

RESUMO

BACKGROUND: The cell adhesion molecule close homologue of L1 (CHL1) is a potential tumour suppressor and was recently detected in non-small cell lung cancer (NSCLC) specimens. The expression pattern, prognostic, and functional role of CHL1 in NSCLCs is unknown. METHODS: We evaluated the protein expression of CHL1 by immunohistochemistry in 2161 NSCLC patients based on a tissue microarray. The results were correlated with clinical, histopathological, and patient survival data (Chi square test, t test, and log-rank test, respectively). A multivariate analysis (Cox regression) was performed to validate its impact on patients' survival. RESULTS: CHL1 was expressed in NSCLC patients and was significantly overexpressed in lung adenocarcinomas and squamous cell carcinomas compared to neuroendocrine and large cell carcinomas of the lung (p < 0.001). CHL1 expression was associated with the T stage in adenocarcinomas (p = 0.011) and with metastatic lymph node status and UICC stage in squamous cell carcinomas (p = 0.034 and p = 0.035, respectively). Increased CHL1 expression was associated with improved survival in univariate (p = 0.031) and multivariate analyses (odds ratio 0.797, 95% confidence interval 0.677-0.939, p = 0.007). CONCLUSION: The prognostic significance of CHL1 makes it a potential prognostic and therapeutic target and underlines its role as a tumour suppressor. Further validation studies and functional analyses are needed to investigate its potential role in tumourigenesis and dissemination.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Moléculas de Adesão Celular/metabolismo , Neoplasias Pulmonares/mortalidade , Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos
8.
J Cancer Res Clin Oncol ; 145(9): 2273-2283, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31428934

RESUMO

OBJECTIVES: Recent research has classified lung adenocarcinoma patients with KRAS mutation into three subtypes by co-occurring genetic events in TP53 (KP subgroup), STK11/LKB1 (KL subgroup) and CDKN2A/B inactivation plus TTF-1 low expression (KC subgroup). The aim of this study was to identify valuable biomarkers by searching the candidate molecules that contribute to lung adenocarcinoma pathogenesis, especially KC subtype. MATERIALS AND METHODS: We analyzed the publicly available database and identified the candidate REG4 using the E-GEOD-31210 dataset, and then confirmed by TCGA dataset. In addition, an independent cohort of 55 clinical samples was analyzed by quantitative real-time PCR analysis. Functional studies and RNA sequencing were performed after silencing the REG4 expression. RESULTS: REG4, an important regulator of gastro-intestinal carcinogenesis, was highly expressed in KRAS mutant lung adenocarcinoma with low expression of TTF-1 (KC subtype). The results were validated both by gene expression analysis and immunohistochemistry study in an independent 55 clinical samples from Fudan University Shanghai Cancer Center. Further in vitro and in vivo functional assays revealed silencing REG4 expression significantly reduces cancer cell proliferation and tumorigenesis. Moreover, RNA sequencing and GSEA analysis displayed that REG4 knockdown might induce cell cycle arrest by regulating G2/M checkpoint and E2F targets. CONCLUSION: Our results indicate that REG4 plays an important role in KRAS-driven lung cancer pathogenesis and is a novel biomarker of lung adenocarcinoma subtype. Future studies are required to clarify the underlying mechanisms of REG4 in the division and proliferation of KC tumors and its potential therapeutic value.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/genética , Transformação Celular Neoplásica/genética , Proteínas de Ligação a DNA/genética , Neoplasias Pulmonares/diagnóstico , Proteínas Associadas a Pancreatite/genética , Proteínas Proto-Oncogênicas p21(ras)/fisiologia , Fatores de Transcrição/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Estudos de Coortes , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Mutantes/genética , Proteínas Mutantes/fisiologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Transcrição/metabolismo
9.
Medicine (Baltimore) ; 98(33): e16834, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415404

RESUMO

RATIONALE: Pembrolizumab, an immune-checkpoint inhibitor (ICI), has been shown to be effective for treatment-naive patients with non-small cell lung cancer (NSCLC) and high expression of programmed death-ligand 1 (PD-L1). Therefore, treatment regimens containing pembrolizumab have become a standard therapy for these patients. However, the use of pembrolizumab is limited owing to the side effects of ICIs. PATIENT CONCERNS AND DIAGNOSES: The patient was a 65-year-old man with a left lung mass surrounded by interstitial shadow. The tumor was diagnosed as adenocarcinoma, cT4N3M0, stage IIIC, and the tumor cells showed high PD-L1 expression. It was unclear whether the interstitial shadow was interstitial lung disease (ILD) or lymphangitis carcinomatosa. INTERVENTIONS AND OUTCOMES: The patient received carboplatin and nab-paclitaxel, a less risky regimen for ILD, as the first-line therapy. Administration of 2 cycles of this regimen markedly improved both the tumor diameter and interstitial shadow. The interstitial shadow was clinically diagnosed as lymphangitis carcinomatosa and not ILD. Subsequently, the patient was treated with pembrolizumab, and the tumor showed much further shrinkage with no deterioration of the interstitial shadow. To date, the patient is alive with no complaints and no disease progression, and has continued pembrolizumab treatment for a total of 12 months. LESSONS: In patients at a high risk of ICI-related side effects, platinum-doublet chemotherapy may be permitted as the first-line therapy for NSCLC with high PD-L1 expression. However, if the risk associated with ICIs is resolved, early switching from chemotherapy to pembrolizumab might be desirable, even if the chemotherapy is effective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfangite/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfangite/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos de Platina/uso terapêutico
10.
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
12.
J Cancer Res Clin Oncol ; 145(9): 2375-2382, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31292713

RESUMO

OBJECTIVES: Spread through air spaces (STAS) as a pattern of invasion in lung adenocarcinomas had been recognized by WHO in 2015. Moreover, STAS was associated significantly with aggressive micropapillary or solid components when presented predominant pattern in lung adenocarcinomas, which had a poor prognostic significance. Small amounts of micropapillary or solid with components could also reduce overall survival and recurrence-free survival but its impact on STAS is unknown now. Some studies have demonstrated manipulations of surgeons and pathologists could affect STAS but the degree of these impacts is not clear. MATERIALS AND METHODS: We reviewed resected small (≤ 2 cm) stage I invasive lung adenocarcinomas by thoracoscopic surgery at our institution from January 2017 to October 2018 (n = 277). Micropapillary or solid pattern was considered to be present when the subtype occupied at least 1% of the entire tumor. Lobectomy and segmentectomy were performed using three portals thoracoscopic surgery. Statistical analysis was performed to analyze the correlations of STAS and clinicopathological characteristics. Moreover, we also analyzed the correlated factors of STAS in solid nodules. RESULTS: STAS was found in 59 of 163 (36.2%) lobectomy cases and 27 of 114 (23.7%) limited resection cases. Lobectomy group showed a higher incidence of STAS compared with limited resection group (p = 0.027), but the difference was disappeared in multivariate analysis, which showed that STAS was significantly correlated to solid nodules and presence of high grade histologic subtype (mircopapillary or solid). However, both lobectomy and presence of high grade histologic subtype were significantly correlated with STAS in solid nodules. CONCLUSIONS: The small amounts of high grade histologic subtypes were also associated with STAS. Thoracoscopic surgery could affect STAS to some degree.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Sistema Respiratório/patologia , Sistema Respiratório/cirurgia , Cirurgia Torácica Vídeoassistida , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Sistema Respiratório/diagnóstico por imagem , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Adulto Jovem
13.
J Cancer Res Clin Oncol ; 145(9): 2325-2333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317326

RESUMO

PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/metabolismo , Linfonodos/metabolismo , Mutação , Transcriptoma/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
14.
Medicine (Baltimore) ; 98(27): e16298, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277165

RESUMO

BACKGROUND: The optimal treatment strategy for stage N2-3A/3B non-small cell lung cancer (NSCLC) remains controversial owing to its heterogeneity. Although multimodal therapy is considered the standard therapeutic approach for stage N2-3A/3B resectable NSCLC patients, the optimal combination strategy still needs to be clarified. PATIENTS AND METHODS: In total, 25 male and female patients aged between 20 and 75 years with stage N2-3A/3B resectable NSCLC will be included. Eligible patients will undergo tri-modality therapy comprising induction chemotherapy (3 cycles of combination therapy with carboplatin and nab-paclitaxel), followed by surgery and postoperative radiotherapy. Recruitment was commenced in April 2017, with a planned last follow-up in March 2024. As of May 2019, 1 subject has been enrolled. The primary endpoint is the treatment completion rate. The secondary endpoints are objective response rate (ORR) of induction chemotherapy, treatment-related adverse event, recurrence-free survival (RFS) time, and overall survival (OS) time. RFS and OS time will be calculated as the time from this study registration to first recurrence and all-cause death, respectively. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating hospitals. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. The study results will be disseminated via publication in peer-reviewed journals. TRIAL REGISTRATION: Trial registration number UMIN000025010 and jRCT1051180028.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimioterapia de Indução/métodos , Neoplasias Pulmonares/terapia , Estadiamento de Neoplasias , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Pneumonectomia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Radioterapia Adjuvante , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
15.
Pan Afr Med J ; 32: 170, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31303939

RESUMO

Tuberculosis is a disease caused by tubercle bacillus infection. It can affect all of the body's organs. Pulmonary tuberculosis accounts for a little more than 50% of its occurrences. It is a public health problem worldwide, and developing countries in particular. Pseudotumoral bronchopulmonary tuberculosis is a particular form of tuberculosis in immunocompetent subject. It can manifests as a bronchial or pulmonary lesion, suggesting a neoplasia visible on chest CT scan or bronchoscopy. This similarity can confuse clinicians, making diagnosis challenging and requiring the use of invasive diagnostic techniques, since traditional means are often lacking. This increases burden of care and causes delayed treatment. This study aims to educate clinicians about this particular and uncommon form of tuberculosis, which should be suspected in patient with radiological findings compatible with the disease, especially since they live in a highly endemic country. Therapy and treatment duration are the same as for common forms of tuberculosis.


Assuntos
Neoplasias Brônquicas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adulto , Broncoscopia/métodos , Diagnóstico Diferencial , Humanos , Imunocompetência , Masculino , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/patologia
16.
Cancer Immunol Immunother ; 68(8): 1351-1358, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31327024

RESUMO

Monoclonal antibodies targeting PD-1 are used for treating NSCLC. To date, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been poorly investigated in the oncologic field. Here, we aimed at evaluating whether serum PCSK9 might represent a predictive factor for OS in older patients with advanced NSCLC under nivolumab treatment. Among 78 patients with advanced, pre-treated NSCLC previously enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 44 patients have been included in this sub-analysis due to the availability of serum samples for the measurement of PCSK9. Before each nivolumab administration, clinical information and blood samples were collected. Median age was 71, with a prevalence of the male sex. The most represented histological type of lung cancer was adenocarcinoma. The majority of patients were former smokers (72.1%). Median PCSK9 levels were 123.59 (86.32-169.89) ng/mL and 117.17 (80.46-147.79) ng/mL at cycle 1 and 2, respectively. Based on a receiver operating characteristic curve analysis, a PCSK9 value at cycle 2 of 95 ng/mL was found as the best cutoff point for OS. Kaplan-Meier analysis demonstrated that patients below the PCSK9 cutoff (< 95 ng/mL) experienced a better OS, as confirmed by Cox proportional hazard regression analysis. In this pilot study, circulating levels of PCSK9 < 95 ng/mL at the time of the second cycle of nivolumab treatment could independently predict a better OS in elderly patients with advanced, pre-treated NSCLC. However, further studies are warranted to validate these preliminary results.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Imunoterapia/métodos , Neoplasias Pulmonares/diagnóstico , Nivolumabe/uso terapêutico , Pró-Proteína Convertase 9/sangue , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Itália , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
17.
Medicina (B Aires) ; 79(3): 208-211, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31284257

RESUMO

The lymphomas of mucosa-associated lymphoid tissue (MALT), are uncommon entities, of low grade of malignancy with very infrequent or no lymph node involvement. They represent about 80% of the primary pulmonary lymphomas. The synchronous appearance with lung adenocarcinoma is an extremely rare finding. We present the case of an ex-smoker 68-year-old man, in whom, in the follow-up of a pulmonary nodule, a second pulmonary nodule was found. The surgical biopsy confirmed the diagnosis of both neoplasms.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Tomografia Computadorizada por Raios X
18.
Cancer Treat Rev ; 78: 31-41, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326635

RESUMO

Current classification and treatment of lung cancer rely increasingly on molecular and genetic testing. Obtaining tumor tissue is not always feasible and multiple biopsies are undesirable. In response to the demand for non-invasive molecular and genetic testing in cancer care, several liquid biopsy technologies, including circulating DNA (ctDNA), have been developed. ctDNA analysis is now technically feasible to be carried out in large scales and integrated into clinical practice owing to the advances in technology. Despite the challenges in improving test accuracy and cost-effectiveness, there are huge potentials for ctDNA analysis in lung cancer management. This review focuses on the clinical utility of ctDNA analysis in lung cancer, including early detection, monitoring treatment response and detecting residual disease, identification of genetic determinants for targeted therapy, and predicting efficacy of immune checkpoint blockade.


Assuntos
Biomarcadores Tumorais/sangue , DNA Tumoral Circulante/sangue , DNA de Neoplasias/sangue , Neoplasias Pulmonares/diagnóstico , Humanos , Biópsia Líquida , Neoplasias Pulmonares/sangue
19.
Chem Commun (Camb) ; 55(68): 10060-10063, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31328750
20.
Drugs ; 79(12): 1277-1286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313100

RESUMO

ROS1 gene rearrangements exist in 1-2% of non-small cell lung cancers, typically occurring in younger, never or light smokers with adenocarcinoma. ROS1 gene fusions are potent oncogenic drivers, the presence of which results in the susceptibility of tumours to ROS1-targeted therapy. Crizotinib was the first tyrosine kinase inhibitor to demonstrate activity in ROS1-rearranged lung cancer, and remains the recommended first-line therapy for patients with advanced ROS1-rearranged non-small cell lung cancer. Despite excellent initial responses to crizotinib, the majority of patients develop disease progression, which may be intracranial or extracranial. Identification of resistance mechanisms to crizotinib, and newer generation tyrosine kinase inhibitors with increased potency against ROS1 and ROS1-resistance mutations, and improved intracranial activity are under evaluation in clinical trials. In this review, we discuss ROS1 rearrangements in non-small cell lung cancer, and provide an update on targeting ROS1-rearranged non-small cell lung cancer with crizotinib and newer generation tyrosine kinase inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/uso terapêutico , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Barreira Hematoencefálica/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Terapia de Alvo Molecular , Mutação , Permeabilidade , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética
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