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The Value of CT and MRI for Determining Thymoma in Patients With Myasthenia Gravis. Tuan Phung Anh,Vien Mai Van,Dong Hoang Van,Sibell David,Giang Bui Van Cancer control : journal of the Moffitt Cancer Center The aim of the study was to evaluate the usefulness of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiating thymoma from nonthymoma abnormalities in patients with myasthenia gravis (MG). A cross-sectional study of 53 patients with MG, who had undergone surgical thymectomy, was conducted at 103 Hospital (Hanoi, Vietnam) and Cho Ray Hospital (Ho Chi Minh City, Vietnam) during August 2014 and January 2017. The CT and MRI images of patients with MG were qualitatively and quantitatively (radiodensity and chemical shift ratio [CSR]) analyzed to determine and compare their ability to distinguish thymoma from nonthymoma abnormalities. Logistic regression was used to identify the association between imaging parameters (eg, CSR) and the thymoma status. The receiver operating curve (ROC) analysis was used to determine the differentiating ability of CSR and radiodensity. As results, of the 53 patients with MG, 33 were with thymoma and 20 were with nonthymoma abnormalities. At qualitative assessment, MRI had significantly higher accuracy than did CT in differentiating thymoma from nonthymoma abnormalities (94.3% vs 83%). At quantitative assessment, both the radiodensity and CSR were significantly higher for thymoma compared with nonthymoma groups ( < .001). The ROC analysis showed that CSR had significantly higher sensitivity (Se) and specificity (Sp) than radiodensity in discriminating between the 2 groups (CSR: Se 100%, Sp 95% vs radiodensity: Se 90.9%, Sp 70%). When combining both qualitative and quantitative parameters, MRI had even higher accuracy than did CT in thymoma diagnosis ( = .031). In conclusion, chemical shift MRI was more accurate than CT for differentiating thymoma from nonthymoma in patients with MG. 10.1177/1073274819865281
Lung cancer screening with MRI: Evaluation of MRI for lung cancer screening by comparison of LDCT- and MRI-derived Lung-RADS categories in the first two screening rounds. Meier-Schroers Michael,Homsi Rami,Gieseke Jürgen,Schild Hans Heinz,Thomas Daniel European radiology PURPOSE:To evaluate MRI for lung cancer screening comparing LDCT- and MRI-derived Lung-RADS categories in the first two screening rounds. MATERIALS AND METHODS:224 participants in a lung cancer screening study were examined with MRI and low-dose CT (LDCT). Acquired MRI sequences were T2, balanced, T1 and DWI. MRI was prospectively analysed regarding nodules. Minimum nodule size was 4 mm. Nodules were assigned a Lung-RADS score based on appearance and size at baseline and after 3, 6 and 12 months. MRI findings were correlated with LDCT. RESULTS:The early recall rate dropped from 13.8% at baseline to 1.9% in the second screening round with biopsy rates of 3.6% in the first round and 0.5% in the second round. Histology revealed lung cancer in 8/9 participants undergoing biopsy/surgery. All eight cancers were accurately depicted by MRI. The following categories were assigned on MRI (results of LDCT in parentheses): 4B/4X in 10 (10) cases, 4A in 16 (15) cases, 3 in 13 (12) cases, 2 in 77 (92) cases and 1 in 140 (126) cases. Lung-RADS scoring correlated significantly between MRI and CT. The score was overestimated by MRI in one case for category 4A, in two cases for category 3 and in five cases for category 2. MRI-based Lung-RADS score was underestimated for category 1 in 20 cases. CONCLUSION:Lung-RADS might be applied for lung cancer screening with MRI, since findings correlated with LDCT. Relevant findings with a Lung-RADS score of 3 and higher were never missed or underestimated by MRI KEY POINTS: • MRI performed comparably to low-dose CT in a lung cancer-screening programme. • Lung-RADS might be applied for lung cancer screening with MRI. • Lung-RADS findings score of 3 and higher were never missed by MRI. 10.1007/s00330-018-5607-8
Clinical relevance of PD-L1 expression and CD8+ T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer. Liu Si-Yang,Dong Zhong-Yi,Wu Si-Pei,Xie Zhi,Yan Li-Xu,Li Yu-Fa,Yan Hong-Hong,Su Jian,Yang Jin-Ji,Zhou Qing,Zhong Wen-Zhao,Tu Hai-Yan,Yang Xue-Ning,Zhang Xu-Chao,Wu Yi-Long Lung cancer (Amsterdam, Netherlands) OBJECTIVES:EGFR-mutated or ALK-rearranged non-small cell lung cancer (NSCLC) often showed unfavorable clinical benefit to checkpoint inhibitors (CPIs). However, few reports exist with integrated analysis, to interpret the underlying mechanism of poor response to PD-1/PD-L1 inhibitors. We have retrospectively analyzed the tumor microenvironment (TME) based on tumor PD-L1 expression and CD8+ T cells infiltration in patients with EGFR mutations and ALK rearrangements, and the prognostic value of TME subtypes on overall survival (OS). MATERIALS AND METHODS:Tumor samples from 715 patients with lung cancer were retrospectively collected at Guangdong Lung Cancer Institute. Tumoral PD-L1 expression (N = 715) and CD8+ T cells infiltration (N = 658) was determined by immunohistochemistry (IHC), based on which TME was categorized into four different subtypes: PD-L1+/CD8+, PD-L1-/CD8+, PD-L1+/CD8-, PD-L1-/CD8-. Proportion of four TME subtypes was determined, and overall survival with PD-L1 expression and TME was analyzed. RESULTS:In patients with EGFR mutations or ALK rearrangements, proportion of PD-L1+/CD8+ tumors was the lowest (5.0%, 17/342), and that of PD-L1-/CD8- tumors was the highest (63.5%, 217/342). In patients with wild-type EGFR and ALK, 14.2% (45/316) tumors were PD-L1+/CD8+ and 50.3% (159/316) tumors were PD-L1-/CD8- (P < 0.001). Median OS of EGFR-mutated or ALK-rearranged lung cancer was 78.6 months in PD-L1 positive group and 93.4 months in PD-L1 negative group (HR 0.47, 95%CI 0.23-0.76, P = 0.005). PD-L1+/CD8+ group exhibited the shortest OS, with 44.3 months, but is likely to respond to CPIs. The PD-L1-/CD8+ group exhibited the longest OS but is unlikely to respond to CPIs. CONCLUSION:Patients with EGFR mutations or ALK rearrangements exhibited lower PD-L1 and CD8 co-expression level in TME, which could be responsible for poor response to CPIs. PD-L1 and CD8 co-expression in EGFR-mutated or ALK-rearranged lung cancer is a biomarker for poor prognosis with shorter OS. 10.1016/j.lungcan.2018.09.010
Report of the Korean Association of Lung Cancer Registry (KALC-R), 2014. Cancer research and treatment PURPOSE:The aim of this study was to investigate epidemiology, clinical characteristics and sex differences of patients with lung cancer using nationwide registry in Korea. MATERIALS AND METHODS:The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry, and surveyed about 10% of lung cancer cases. For this first survey of cases diagnosed in 2014, cases were selected through a systematic sampling method. RESULTS:Total 2,621 lung cancer patients were surveyed, and the median patient age was 70 years. During the study period, adenocarcinoma was the most frequent histologic type, the proportion of female patients was 28.4%, and women had a better prognosis (median survival, not reached vs. 13 months; p<0.001) than did men for non-small cell lung cancer. The proportion of never-smokers was 36.4%, and never-smoking was more prevalent in women than in men (87.5 vs. 16.0%, p<0.001). Epidermal growth factor receptor (EGFR) mutations were found in 36.8% of stage IV adenocarcinoma patients, and higher in female compared to male patients (51.2 vs. 26.6%, p<0.001). In addition, patients with EGFR mutation showed better survival (median survival, 18 vs. 8 months; p<0.001) than patients without EGFR mutation in these patients. CONCLUSION:This is the first survey to gather unbiased nationwide lung cancer statistics in Korea. More than one-third of lung cancer patients had no smoking history. Female had a high proportion of non-smoker, more adenocarcinoma with EGFR mutation and generally better prognosis than male. 10.4143/crt.2018.704
[Investigation and Analysis of Primary Lung Cancer with Endotracheal and Endobronchial Metastases]. Lu Ming,Zhu Xiang,Cao Baoshan,Shen Ning Zhongguo fei ai za zhi = Chinese journal of lung cancer BACKGROUND:Endotracheal and endobronchial metastases (EEM) is a rare manifestation in primary lung cancer. It has not yet been reported in Chinese literatures. The aim of this study was to summarize and analyze the clinical feature of lung cancer with EEM. METHODS:We retrospectively reviewed 6 patients who presented with EEM of lung cancer from Peking University Third Hospital from January 2015 to December 2018. With "endotracheal metastases, endobronchial metastases, lung cancer" as the keywords, 13 cases were retrieved from PubMed database until February 2020. The clinical, radiologic and bronchoscopic data were collected. RESULTS:Six patients were selected from 967 patients with lung cancer, and all were diagnosed with lung cancer and EEM simultaneously. There were 4 cases of squamous cell carcinoma, 1 case of adenocarcinoma, and 1 case of small cell lung cancer. One patient had stage IIIb and 5 patients had stage IV. There were 5 cases of central lung cancer and 1 case of peripheral lung cancer. EEM on bronchoscope examination presented as endoluminal nodular or polypoid lesion in 5 patients, and abnormal white bulge in 1 patient. 5 cases metastasized to the contralateral bronchus, 1 case to the ipsilateral bronchus and 1 case to the trachea. The median overall survival was 7.5 months. Totally 13 cases of lung cancer with EEM were retrieved from PubMed database. 12 cases were diagnosed during the follow up after lung cancer resection. There were 8 cases of squamous cell carcinoma and 9 cases of central type. Endotracheal or endobronchial nodules showed in 10 cases and eccentric wall thickening in 2 cases were seen on chest computed tomography (CT), which corresponding to the nodular or polypoid lesion bronchoscopically. 5 cases metastasized to the contralateral bronchus, 10 cases to the trachea and 1 case to the ipsilateral bronchus. CONCLUSIONS:EEM is a rare metastasis of lung cancer, which can occur at the initial diagnosis of lung cancer or after surgical resection. It is often seen in the patients of squamous cell carcinoma with central type in advanced stage. The prognosis is poor. 10.3779/j.issn.1009-3419.2020.101.15
Elongation factor-2 kinase (eEF-2K) expression is associated with poor patient survival and promotes proliferation, invasion and tumor growth of lung cancer. Bircan Haci Ahmet,Gurbuz Nilgun,Pataer Apar,Caner Ayse,Kahraman Nermin,Bayraktar Emine,Bayraktar Recep,Erdogan Mumin Alper,Kabil Nashwa,Ozpolat Bulent Lung cancer (Amsterdam, Netherlands) OBJECTIVES:Lung cancer is the leading cause of cancer related deaths in worldwide. Despite recent advances in treatment options, patient survival has not improved substantially due to lack of commonly expressed molecular targets and effective targeted therapeutics. Thus, better understanding of the biology of lung cancer and identification of novel therapeutic targets are urgently needed for development of highly effective molecularly targeted therapies. MATERIALS AND METHODS:Viability, proliferation and metastatic ability of lung cancer cells were evaluated using methylthiazoltetrazolium (MTT), colony formation and matrigel invasion assays, respectively. Western blotting, RT-PCR, and gene knockdown by siRNA transfections were carried out to investigate the effects of eEF-2K on lung cancer cells. Athymic Nu/Nu mice were treated with liposomal eEF-2KeEF-2K or control siRNA and tumor growth was evaluated in tumor xenograft models of lung cancer. RESULTS AND DISCUSSION:Here, we report that Eukaryotic Elongation Factor-2 kinase (eEF-2K), a member of an atypical alpha kinases family, is significantly upregulated in lung cancer cell lines and its expression is associated with shorter overall patient survival in lung cancer. Inhibition eEF-2K expression by siRNA or a chemical inhibitorsignificantly suppressed lung cancer cell proliferation, colony formation, survival, migration/invasion and tumorigenesis by inhibiting cyclin D1, Src and Mitogen-Activated Protein Kinases/Extracellular Signal-Regulated Kinase (MAPK/ERK) signaling. In vivo targeting of eEF-2K by systemically injected nanoliposomal eEF-2K siRNA resulted in a significant inhibition of lung cancer tumor xenografts in nude mice. Our results suggest, for the first time, that expression of eEF-2K is associated with poor patient prognosis and involved in regulation of critical pathways, including Src and MAPK/ERK and cyclin D1, promoting tumor growth and progression, and thus may be a novel potential therapeutic target in lung cancer. 10.1016/j.lungcan.2018.07.027
Cost-effectiveness of lung MRI in lung cancer screening. Allen Bradley D,Schiebler Mark L,Sommer Gregor,Kauczor Hans-Ulrich,Biederer Juergen,Kruser Timothy J,Carr James C,Hazen Gordon European radiology OBJECTIVES:Recent studies with lung MRI (MRI) have shown high sensitivity (Sn) and specificity (Sp) for lung nodule detection and characterization relative to low-dose CT (LDCT). Using this background data, we sought to compare the potential screening performance of MRI vs. LDCT using a Markov model of lung cancer screening. METHODS:We created a Markov cohort model of lung cancer screening which incorporated lung cancer incidence, progression, and mortality based on gender, age, and smoking burden. Sensitivity (Sn) and Sp for LDCT were taken from the MISCAN Lung Microsimulation and Sn/Sp for MRI was estimated from a published substudy of the German Lung Cancer Screening and Intervention Trial. Screening, work-up, and treatment costs were estimated from published data. Screening with MRI and LDCT was simulated for a cohort of male and female smokers (2 packs per day; 36 pack/years of smoking history) starting at age 60. We calculated the screening performance and cost-effectiveness of MRI screening and performed a sensitivity analysis on MRI Sn/Sp and cost. RESULTS:There was no difference in life expectancy between MRI and LDCT screening (males 13.28 vs. 13.29 life-years; females 14.22 vs. 14.22 life-years). MRI had a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women driven by fewer false-positive screens. On sensitivity analysis, MRI remained cost effective at screening costs < $396 dollars and Sp > 81%. CONCLUSIONS:In this Markov model of lung cancer screening, MRI has a near-equivalent life expectancy benefit and has superior cost-effectiveness relative to LDCT. KEY POINTS:• In this Markov model of lung cancer screening, there is no difference in mortality between yearly screening with MRI and low-dose CT. • Compared to low-dose CT, screening with MRI led to a reduction in false-positive studies from 26 to 2.8% in men and 26 to 2.6% in women. • Due to similar life-expectancy and reduced false-positive rate, we found a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women of MRI relative to low-dose CT. 10.1007/s00330-019-06453-9
Association of Variants in IL6-Related Genes with Lung Cancer Risk in Moroccan Population. Kaanane Houda,Senhaji Nezha,Berradi Hind,Benchakroun Nadia,Benider Abdellatif,Karkouri Mehdi,El Attar Hicham,Igot Casa ,Khyatti Meriem,Nadifi Sellama Lung PURPOSE:Lung cancer is known to be a complex multifactorial disease, involving both genetic and environmental factors. The study of the different signaling pathways and the identification of the genes involved, will contribute to further understanding the pathogenesis of the disease, thus allowing the development of appropriate targeted treatments. Recently, the link between cancer and inflammation has become more evident and inflammation has been proposed as the seventh hallmark of cancer. Previous studies have suggested that key cytokines involved in inflammation may have an important role in the etiology of lung cancer. The aim of this study was to investigate whether common variants in inflammation-related genes: IL-6, IL6-R, and IL6-ST, influence lung cancer risk in Moroccan population. MATERIALS AND METHODS:Single nucleotide polymorphisms (SNPs) in IL-6, IL6-R, and IL6-ST genes were assessed in 120 controls and 120 patients with confirmed lung cancer diagnosis. Genotyping analysis was performed with the TaqMan® allelic discrimination technology. The results were analyzed using SPSS 24.0 software. RESULTS:Among the studied SNPs, we found a significant association for the IL-6 (rs2069840) (OR = 1.63; 95% confidence interval 1.08-2.47; p = 0.01). No significant association was observed for the remaining SNPs of IL-6R (rs2228145) and IL-6ST (rs2228044) genes. CONCLUSION:Our results suggest the IL-6 (rs2069840) polymorphism may influence the occurrence of lung cancer in Moroccan patients. 10.1007/s00408-019-00261-0