Diagnostic Tool For Lung Cancer Research Articles

Automatic Detection and Staging of Lung Tumors using Locational Features and Double-Staged Classifications

Lung cancer is a life-threatening disease with the highest morbidity and mortality rates of any cancer worldwide. Clinical staging of lung cancer can significantly reduce the mortality rate, because effective treatment options strongly depend on the specific stage of cancer. Unfortunately, manual staging remains a challenge due to the intensive effort required. This paper presents a computer-aided diagnosis (CAD) method for detecting and staging lung cancer from computed tomography (CT) images. This CAD works in three fundamental phases: segmentation, detection, and staging. In the first phase, lung anatomical structures from the input tomography scans are segmented using gray-level thresholding. In the second, the tumor nodules inside the lungs are detected using some extracted features from the segmented tumor candidates. In the last phase, the clinical stages of the detected tumors are defined by extracting locational features. For accurate and robust predictions, our CAD applies a double-staged classification: the first is for the detection of tumors and the second is for staging. In both classification stages, five alternative classifiers, namely the Decision Tree (DT), K-nearest neighbor (KNN), Support Vector Machine (SVM), Ensemble Tree (ET), and Back Propagation Neural Network (BPNN), are applied and compared to ensure high classification performance. The average accuracy levels of 92.8% for detection and 90.6% for staging are achieved using BPNN. Experimental findings reveal that the proposed CAD method provides preferable results compared to previous methods; thus, it is applicable as a clinical diagnostic tool for lung cancer.

Tumor specific DNA in bronchial lavage as a new diagnostic tool in lung cancer.

3047 Background: A considerable fraction of lung cancer patients raise diagnostic challenges requiring invasive procedures with a certain risk of complications. Therefore, new diagnostic tools are of major interest. Aberrant methylation of the HOXA9 gene occurs in almost all malignant lung tumors and HOXA9 methylated DNA (meth-ctDNA) is shed into the circulation. The present study aimed at a prospective investigation of the possible diagnostic value of HOXA9 meth-ctDNA in bronchial lavage (BL). Methods: Patients enrolled were referred from the general practitioner suspecting lung cancer. The diagnostic package according to national guidelines includes chest and abdominal CT scan, bronchoscopy, relevant blood tests, and histopathological or cytological verification. Twelve ml liquid was collected at bronchoscopy for analysis of meth-ctDNA based on ddPCR technology according to our published method. The analysis was performed blinded to the clinical data and compared to the final diagnosis. Results: Eighty-nine patients were consecutively included from the 1 November 2018 to 31 January 2019. Fifty-six patients (62.9%) were diagnosed with lung cancer and 33 (37.1%) with a variety of benign diseases. Meth-ctDNA was found in 42/56 of the patients with a malignant tumor, sensitivity = 75.0% (95%CI=61.6-85.6%), whereas 31/33 of the patients without cancer were negative, specificity = 93.9% (95%CI= 79.8-99.3%). Table summarizes the results. The false negative samples were mainly from patients with peripheral tumors. The two false positive patients included one patient with Cryptogenic Organizing Pneumonia and one with unspecific nodule. Conclusions: The presence of meth-ctDNA in BL has a high sensitivity and specificity. If validated, the analysis represents a valuable adjunct in the diagnosis of lung cancer. Potentially, it could save the patients from numerous examinations with potential harmful risks and ensure a fast diagnosis. The relation between meth-ctDNA and final lung cancer diagnosis (N= 89). [Table: see text]

CfDNA in exhaled breath condensate (EBC) and contamination by ambient air: toward volatile biopsies

Exhaled breath is a source of volatile and nonvolatile biomarkers in the body that can be accessed non-invasively and used for monitoring. The collection of lung secretions by conventional methods such as bronchoalveolar lavage, induced sputum collection, and core biopsies is limited by the invasive nature of these methods. Non-invasive collection of exhaled breath condensate (EBC) provides fluid samples that are representative of airway lining fluids. Various volatile and nonvolatile biomarkers can be detected in volatile condensates, such as H2O2, nitric oxide, lipid mediators, cytokines, chemokines, DNA, and microRNAs. Studies have examined cell-free DNA (cfDNA) in plasma samples from non-small-cell lung cancer patients, offering to new insights and fostering development of the liquid biopsy. However, few studies have examined cfDNA in EBC samples. This study examined whether EBC is an appropriate source of cfDNA using housekeeping-gene-specific primer probes and quantitative real-time polymerase chain reaction in healthy subjects. Ambient (room) air is contaminated with DNA, so caution is needed. Preliminary studies indicated that volatile biopsies are becoming an important diagnostic tool in lung cancer.

A feature extraction method for lung nodules based on a multichannel principal component analysis network (PCANet)

Feature extraction of lung nodules is very important in the diagnosis of lung cancer and is the premise of feature description, target matching, recognition and benign and malignant diagnosis. The main contribution of this work is the development of a new end-to-end feature extraction method that learns effective feature representation from images to effectively establish the direct relationship between multiple features and tissue features (that is, benign or malignant). The architecture consists of three seamlessly connected functional layers. RGB multichannel can automatically extract ROI sequence images involving lung parenchyma from the lung imaging sequence. The feature extraction layers, using Principal Component Analysis Network - random binary hash (PCANet-RBH), a) extract high-level semantic features of the R/G/B channel by cascading PCA and fuse the extracted normal color patterns, and b) generate multiple binary patterns via RBH to produce richer features with color information. The connected spatial pyramid pooling (SPP) layer can extract the location features of the lung nodules and map the feature matrix to the low-dimensional space and then establish a correspondence between the image features and the organizational identity. We validate the performance of the proposed method using the public dataset LIDC. The experimental results show that the fusion features extracted by our method have high and stable classification accuracy (accuracy:93.25 ± 0.53, sensitivity:93.12 ± 0.62 specificity:91.37 ± 0.62), which is significantly better than the traditional algorithm for lung nodule feature extraction. Moreover, RGB-PCANet has a short training time, which can meet the requirements of real-time diagnosis of lung cancer. In general, the advantage of our framework is that it provides a better and more comprehensive method to establish a direct relationship between image high-level semantic features, color features, location features and tissue features, making it an attractive clinical diagnostic tool for lung cancer.

Urine Lunx mRNA as a Potential Molecular Diagnostic Tool for Lung Cancer

Urine Lunx mRNA as a Potential Molecular Diagnostic Tool for Lung Cancer

Bronchoscopic Myths and Legends: Is Age a Contraindication to Bronchoscopy?

Given the aging of the US population and the prevalence of lung disease, which warrants diagnostic services in this population, we undertook a survey of pulmonary physicians in order to evaluate their attitudes toward bronchoscopy in the elderly. Specific areas of interest included concerns with regard to comorbidities, preprocedural testing, and perception of procedural complication rates. From November 2013 to January 2014, we surveyed 1896 pulmonary physicians via e-mail about their opinions with regard to bronchoscopy in the elderly. The Survey Monkey service was used to administer the survey. Almost 1900 physicians were contacted with a 12% response rate to the survey. Roughly half the respondents were in an academic setting (attendings or fellows), and the other half were in private practice. The majority of respondents felt that age was not a contraindication to bronchoscopy, that patients do not require routine preprocedural testing, and that good functional status plays a role in decision making with regard to procedural safety. Most respondents performed <25 bronchoscopies per year on the very elderly (patients 85 y of age or more). Overall, this study shows that, for the most part, the clinicians’ real life findings and experience reflect the available literature when it comes to bronchoscopy in the very elderly, and that our clinician respondents for the most part agreed that flexible bronchoscopy is generally a safe and well-tolerated procedure in the very elderly, and that this is a useful diagnostic tool for lung cancer, especially in the very elderly with good functional status.

P1.02-036 Fine Needle Aspiration as a Diagnostic Tool in Lung Cancer: Worth Pursuing?

P1.02-036 Fine Needle Aspiration as a Diagnostic Tool in Lung Cancer: Worth Pursuing?

P3.02c-052 Electronic Nose: An Early Response Biomarker for Anti-PD1 Therapy in Patients with NSCLC: Topic: IT

Multiple studies have shown the activity of the anti-PD(L)-1 agents in patients with advanced non-small-cell lung cancer (NSCLC). There is an urgent need to explore biomarkers that predict outcome to anti-PD-1 therapy. The electronic (e) Nose is used to analyze the exhaled gasses and is under development as a diagnostic tool for lung cancer. We aimed to determine the diagnostic accuracy of exhaled breath analysis for responders vs. non-responders to anti-PD-1 treatment in NSCLC patients. Patients with NSCLC who were about to receive Nivolumab, were asked to participate. At baseline and after 6 weeks of treatment exhaled breath analysis took place. Breathprints were collected in duplicate by an e-Nose positioned at the rear end of a pneumotachograph (SpiroNose) (de Vries J Breath Res 2015). RECIST 1.1 criteria were used for response evaluation at three months and six months and reported accordingly: Complete response (CR), Partial response (PR), stable disease (SD), and progressive disease (PD). Data-analysis involved signal processing, environment correction and statistics based on principal component analysis (PCA), followed by discriminant analysis (Matlab2014/SPSS20). From August 2015 until April 2016, 56 patients participated in this trial. Forty-two patients had a response evaluation. Principal component 3 and 4 showed a significant difference (p=0.005 and p=0.001) between responders (PR and SD) and non-responders (PD) [Figure A]. Twenty-five patients had a second exhaled breath analysis after 6 weeks. Analysis showed significant differences in PC3 and PC4 between both SD vs. PR (p<0.001) and PD vs. PR (p=0.002) [Figure B]. E-Nose is able to discriminate between responders and non-responders to anti-PD-1 treatment at baseline and 6 weeks follow-up and may therefore be of great value to predict outcome.

Exosomal Proteins as Diagnostic Biomarkers in Lung Cancer

IntroductionExosomes have been suggested as promising biomarkers in NSCLC because they contain proteins from their originating cells and are readily available in plasma. In this study, we explored the potential of exosome protein profiling in diagnosing lung cancers of all stages and various histological subtypes in patients. MethodsPlasma was isolated from 581 patients (431 with lung cancer and 150 controls). The extracellular vesicle array was used to phenotype exosomes. The extracellular vesicle array contained 49 antibodies for capturing exosomes. Subsequently, a cocktail of biotin-conjugated CD9, CD81, and CD63 antibodies was used to detect and visualize captured exosomes. Multimarker models were made by combining two or more markers. The optimal multimarker model was evaluated by area under the curve (AUC) and random forests analysis. ResultsThe markers CD151, CD171, and tetraspanin 8 were the strongest separators of patients with cancer of all histological subtypes versus patients without cancer (CD151: AUC = 0.68, p = 0.0002; CD171: AUC = 0.60, p = 0.0002; and TSPAN8: AUC = 0.60, p = 0.0002). The multimarker models with the largest AUC in the cohort of patients with all lung cancer histological subtypes and in the cohort of patients with adenocarcinoma only covered 10 markers (all cancer: AUC = 0.74 [95% confidence interval: 0.70–0.80]; adenocarcinoma only: AUC = 0.76 [95% confidence interval: 0.70–0.83]). In squamous cell cancer and SCLC, multimarker models did not exceed CD151 as an individual marker in separating patients with cancer from controls. ConclusionWe have demonstrated exosome protein profiling to be a promising diagnostic tool in lung cancer independently of stage and histological subtype. Multimarker models could make a fair separation of patients, demonstrating the perspectives of exosome protein profiling as a biomarker.

Negative Predictive Value of Granulomas on EBUS-TBNA in Suspected Extrathoracic Malignancy

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic tool for lung cancer, sarcoidosis, and suspected metastatic extrathoracic malignancy. EBUS-TBNA carries a high diagnostic yield, but its negative predictive value (NPV) requires further clarification. We reviewed EBUS-TBNA at our cancer center from 2008 to 2015. We identified negative diagnostic samples for adenopathy suspected to represent metastatic disease from extrathoracic malignancy. We reviewed 529 EBUS-TBNAs. Ninety patients underwent EBUS-TBNA sampling of the hilum and/or mediastinum (121 nodes, 14 masses) for suspected extrathoracic malignancy. Thirty-seven patients had negative samples (lymph node, granulomas or non-diagnostic specimens). The overall NPV was 98%. Granulomas (11 patients, 25 nodes) seen on histology had a 100% NPV, including those that were FDG-PET (fluorodeoxyglucose positron emission tomography) avid (n=14 nodes). Negative EBUS-TBNA in patients with extrathoracic malignancy and suspected secondary hilar or mediastinal metastases can infer a high NPV especially if granulomas are seen on histology. Larger prospective investigations are needed to confirm the high NPV of EBUS-TBNA with granulomas in extrathoracic malignancies.

Reliable EGFR mutation testing in ultrasound-guided supraclavicular lymph node fine-needle aspirates: a cohort study with diagnostic performance analysis

Introduction15–30% of patients with lung cancer will have supraclavicular and cervical lymphadenopathy (SCLN). Ultrasound (US)-guided fine-needle aspiration (FNA) cytology is regarded as an effective diagnostic tool in small size lymph...

Detection biomarkers of lung cancer using mini-GC-PID system integrated with micro GC column and micro pre-concentrator.

The survival rate of lung cancer can be significantly improved by monitoring biomarkers in exhaled air that indicate diseases in early stage, so it is very important to develop micro analytical systems which can offer a fast, on-site, real-time detecting biomarkers in exhaled air. In this paper, a mini-gas chromatography (GC)-photo-ionization detector (PID) system integrated with a micro GC column and a micro pre-concentrator was developed for forming an inexpensive, fast, and non-invasive diagnostic tool for lung cancer. This system has very strong concentrate ability owing to its integrated micro pre-concentrator, which make the detection of trace components in exhaled air very easy. In addition, the integrated micro GC column can separate complex mixtures, which overcome low resolution and poor anti-interference ability of other instruments. The results indicated that the mini-GC-PID system can effectively separate and detect the biomarkers at parts-per-billion (ppb) level.

Abstract 5599: Serum biomarkers reflecting specific tumor tissue remodeling is a valuable diagnostic tool for lung cancer

Abstract Background: The extracellular matrix (ECM) that integrates and surrounds malignant tumors consists of several proteins, amongst other type I collagen and elastin. These structural proteins, as well as intermediate filament (IMF) proteins like vimentin, are remodeled and dysregulated as part of malignant changes. We investigated whether serum biomarkers reflecting ECM and IMF remodeling/dysregulation could be used to differentiate lung cancer patients from healthy controls, other lung pathologies, and other cancer types. Methods: Levels of matrix metalloproteinase (MMP) generated fragments of type I collagen (C1M), of elastin (ELM) and of citrullinated vimentin (VICM) were measured in serum from patients with lung cancer (n=40), gastrointestinal cancer (n=25), prostate cancer (n=14), malignant melanoma (n=7), chronic obstructive pulmonary disease (COPD) (n=13), and idiopathic pulmonary fibrosis (IPF) (n=10), as well as in age-matched controls (n=33). The area under the receiver operating characteristics (AUROC) was calculated for the biomarkers and a diagnostic decision tree was generated from specific cut-off values. Results: Circulating levels of C1M and VICM were significantly elevated in lung cancer patients as compared to healthy controls (AUROC=0.98, p&amp;lt;0.0001) and other cancers (AUROC=0.83 p&amp;lt;0.0001). A trend was detected when comparing lung cancer with COPD+IPF. No difference could be seen for ELM. Interestingly, C1M and VICM were able to identify patients with lung cancer with a positive predictive value of 0.9 and an odds ratio of 40 (95% CI=8.7-186, p&amp;lt;0.0001). Conclusion: This study indentifies biomarkers specifically reflecting ECM and IMF remodeling as applicable for lung cancer patients. We speculate that these markers may aid in diagnosing and characterizing patients with lung cancer. Citation Format: Nicholas Willumsen, Cecilie L. Bager, Diana J. Leeming, Victoria Smith, Claus Christiansen, Morten A. Karsdal, David Dornan, Anne-Christine Bay-Jensen. Serum biomarkers reflecting specific tumor tissue remodeling is a valuable diagnostic tool for lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5599. doi:10.1158/1538-7445.AM2014-5599

Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer.

Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a great potential for cancer. Levels of matrix metalloproteinase (MMP) generated fragments of type I collagen (C1M), of elastin (ELM), and of citrullinated vimentin (VICM) were measured in serum from patients with lung cancer (n = 40), gastrointestinal cancer (n = 25), prostate cancer (n = 14), malignant melanoma (n = 7), chronic obstructive pulmonary disease (COPD) (n = 13), and idiopathic pulmonary fibrosis (IPF) (n = 10), as well as in age-matched controls (n = 33). The area under the receiver operating characteristics (AUROC) was calculated and a diagnostic decision tree generated from specific cutoff values. C1M and VICM were significantly elevated in lung cancer patients as compared with healthy controls (AUROC = 0.98, P < 0.0001) and other cancers (AUROC = 0.83 P < 0.0001). A trend was detected when comparing lung cancer with COPD+IPF. No difference could be seen for ELM. Interestingly, C1M and VICM were able to identify patients with lung cancer with a positive predictive value of 0.9 and an odds ratio of 40 (95% CI = 8.7–186, P < 0.0001). Biomarkers specifically reflecting degradation of collagen type I and citrullinated vimentin are applicable for lung cancer patients. Our data indicate that biomarkers reflecting ECM and IMF protein dysregulation are highly applicable in the lung cancer setting. We speculate that these markers may aid in diagnosing and characterizing patients with lung cancer.

Detection of circulating antibodies to linear peptide antigens derived from ANXA1 and DDX53 in lung cancer

The EarlyCDT®-Lung test was the first autoantibody-based diagnostic tool for lung cancer, which was developed with a panel of recombinant protein antigens. To confirm whether the antibody test developed with linear peptide antigens has a similar power to that developed with the whole protein molecules, the present work was then undertaken to develop an in-house enzyme-linked immunosorbent assay with linear peptide antigens derived from annexin A1 (ANXA1) and DEAD box protein 53 (DDX53), which have been used to develop the EarlyCDT®-Lung test. A total of 272 patients with non-small cell lung cancer (NSCLC) and 227 control subjects matched in age and smoking history were recruited. Student's t test showed that the levels of circulating IgG to ANXA1-derived peptide antigens were significantly higher in patients with NSCLC than control subjects (t = 5.66, P < 0.0001), in which the increased anti-ANXA1 IgG levels were observed only in patients at stages I, II, or III, but not in those at stage IV. However, the levels of circulating IgG to DDX53-derived peptide antigens were not significantly altered in NSCLC (t = 1.78, P = 0.076). Receiver operating characteristic analysis showed that the sensitivity against specificity of >90% was 23.7% for ANXA1 IgG assay and 13.8% for DDX53 IgG assay. This work suggests that the linear peptide antigen derived from ANXA1 may be suitable for the development of diagnostic tool for lung cancer although further screening is needed to identify more such peptide antigens derived from tumor-associated antigens.

DNA copy number changes as diagnostic tools for lung cancer

Lung cancer usually presents as advanced stage disease and there is a need for early diagnosis so that appropriate treatments can be provided prior to tumour progression. Copy number variation...

Abstract A199: Using Fiber Array Scanning Technology (FAST) Platform for sensitive detection and analysis of circulating tumor cells with a hybrid epithelial/mesenchymal phenotype from non-small cell lung cancer.

Abstract Circulating tumor cell (CTC) analysis uses a “liquid biopsy” to provide critical information regarding diagnosis, prognosis, response to therapy and risk of relapse. To date, CTC analysis in non-small cell lung cancer (NSCLC) patients using epithelial cell adhesion molecule (EpCAM) immunomagnetic enrichment techniques has met with limited success. This is thought to be because the majority of CTCs detected in NSCLC patients demonstrate the mesenchymal phenotype to various extents, and epithelial markers on CTCs are lost during the epithelial-mesenchymal transition (EMT). We report here that the non-enrichment, FAST platform can be used for rapid detection and characterization of CTCs with a hybrid EMT phenotype. We developed a model using whole blood from healthy donors spiked with human NSCLC cell lines that have been classified as having varying levels of EMT. These included “more epithelial, high EpCAM type” (A549 and EKVX), and “more mesenchymal, low EpCAM type” (H2228 and Calu-1) cell lines. A multiplexed assay was developed to simultaneously evaluate cellular and molecular markers of the hybrid phenotypes. FAST was used to develop an optimized assay with high yields (more than 75% retention, detection performance as high as 1 CTC/5 ml blood) of CTCs with hybrid phenotype. 100% of NSCLC cells detected by the FAST platform co-expressed mesenchymal/stem cell markers such as Vimentin, N-Cadherin and ALDH1. FACS analysis of NSCLC cells confirmed levels of EpCAM expression ranging from negative to high. CTCs harboring anaplastic lymphoma kinase (ALK) translocations also demonstrated mesenchymal-like phenotypes. Finally, a high incidence of CTC clusters (circulating tumor microemboli; CTM) that have been previously reported with the hybrid phenotype, was detected from Stage IV NSCLC patients. These data illustrate that the FAST platform is suitable for high-sensitivity detection and comprehensive analyses of the full spectrum of EMT phenotypes in NSCLC CTCs. We have also developed assays to multiplex cellular and molecular biomarkers on single CTCs to guide personalized therapy, including the detection of ALK to select patients appropriate for Crizotinib therapy. Further work is planned to analyze the dynamic change of EMT components in CTCs during disease progression to correlate EMT biomarkers in CTCs with patient outcomes and provide new diagnostic tools for lung cancer. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A199. Citation Format: Xiaohe Liu, Janey C. Ly, Laurie Kara, Heather Wakelee, Nathan Collins, Keith Laderoute, Lidia C. Sambucetti. Using Fiber Array Scanning Technology (FAST) Platform for sensitive detection and analysis of circulating tumor cells with a hybrid epithelial/mesenchymal phenotype from non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A199.

Telomerase as a potential marker for inflammation and cancer detection in bronchial washing: A prospective study

ObjectivesThe diagnosis of lung cancer remains difficult especially in peripheral tumors, given the absence of relevant markers and of sensitive imaging techniques. Telomerase is a ribonucleotide enzyme responsible for the immortalization of cancerous cells and seems to increase in bronchial aspirates of lung cancer patients. The purpose of our study is to further investigate the value of telomerase measurement in bronchial aspirates as a diagnostic tool for lung cancer. Design and methodsRandom 82 bronchial aspirates were obtained from patients undergoing bronchoscopy to diagnose any lung illness including inflammation and cancer. Cytology examination, quantification of proteins by Bradford method, and telomerase activity measurement by quantitative Real-time PCR were performed. Out of 82 specimens, 11 were excluded because of hemolysis, absence of elements or lack of final diagnosis. ROC curve analysis was done. ResultsA significant difference in telomerase activity average was noted between normal patients and those with inflammation and cancer. Discriminatory capacity of telomerase activity was: for cancer vs. non cancer, AUC =0.74 (95% CI: 0.62–0.84), sensitivity=78%, specificity=72%, Negative Predictive Value=87%, at cut-off >0.46 atmol/mg protein/20min; for cancer vs. normal, AUC=0.87 (95% CI: 0.72–0.96), se=78%, sp=92%, NPV=71%, at cut-off >0.46; for cancer vs. inflammation, AUC=0.69 (95% CI: 0.55–0.80), se=74%, sp=70%, NPV=79%, at cut-off >1.03, and for inflammation vs. normal, AUC=0.76 (95% CI: 0.62–0.88), se=79%, sp=77%, NPV=59%, at cut-off >0. ConclusionTelomerase activity in bronchial aspirates is a promising diagnostic marker for lung cancer and inflammation detection.

Abstract 4703: Telomerase activity in bronchial aspiration is a potential marker for inflammation and cancer detection: A prospective study.

Abstract Background: Lung cancer is the leading cause of cancer death in the United States for both men and women. Bronchoscopy is one of the major tools, along with bronchial aspirates, brushings, biopsies and bronchoalveolar lavage, used to obtain specimens revealing the diagnosis in more than 85% of cases. The diagnosis remains difficult especially in distal tumors, given the absence of a relevant marker and/or sensitive imaging technique. Telomerase is a ribonucleotide enzyme that elongates telomeres and is responsible for the immortalization of cancerous cells. This enzyme, that is expressed in more than 90% of cancers, seems to increase in bronchial aspirates of patients with lung cancer. Purpose: The objective of our study is to further investigate the value of telomerase measurement in the bronchial aspirates as a diagnostic tool for lung cancer. Methods: Random 82 bronchial aspirates were obtained from patients undergoing bronchoscopy to diagnose any lung illness type including inflammation and cancer. Patient consent form was filled. The bronchial aspirates were divided for cytology examination and telomerase activity measurement. The latter were washed twice with ice-child phosphate buffer, observed by microscope, treated with lysis buffer, incubated 30 minutes on ice and then centrifuged at 14 000 rpm at 4oC for 25 minutes. The supernatant was used to quantitate proteins using Bradford reagent and to measure telomerase activity by quantitative Real-time PCR technique. Out of 82 specimens, 11 were excluded because of high hemolysis that interfered with the technique and/or because of the complete absence of cells or elements. Results: A significant difference in telomerase activity average was noted between normal patients and those with inflammation and cancer (0.27, 3.83 and 19.96 atmol/mg protein/20min, p&amp;lt;0.05) respectively. Using the ROC (Receiver Operating Characteristic) curve, telomerase activity was predictive of cancer vs. non cancer conditions (including normal and inflammation), area under the curve (AUC) = 0.74 [(95% CI: 0.62-0.84); sensitivity (se) =78%, specificity (sp) =72%, Negative predictive value (NPV) = 87%, at cut-off &amp;gt;0.46]. Telomerase activity was also predictive of cancer vs. normal condition, AUC=0.87 [(95% CI: 0.72-0.96); se=78%, sp=92%, NPV = 71%, at cut-off &amp;gt;0.46]. Its predictive power of cancer vs. inflammation was AUC=0.69 [(95% CI: 0.55-0.80); se=74%, sp=70%, NPV = 79%, at cut-off &amp;gt;1.03], and of inflammation vs. normal condition was AUC=0.76 [(95% CI: 0.62-0.88); se=79%, sp=77%, NPV = 59%, at cut-off &amp;gt;0].Conclusion: The detection of telomerase activity in bronchial aspirates is a promising diagnostic marker for lung cancer and inflammation detection. Citation Format: George Hilal, Najib Nassani, Georges Khayat. Telomerase activity in bronchial aspiration is a potential marker for inflammation and cancer detection: A prospective study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4703. doi:10.1158/1538-7445.AM2013-4703

Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer

Lung cancer is sometimes difficult to differentiate from benign lung diseases expressing nodular shadow in imaging study. We assessed the diagnostic value of two commonly used tumor markers in distinguishing primary lung cancer from benign lung disease. The serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were retrospectively analyzed in 655 lung cancer patients and 237 patients with benign lung disease. The standard cut-off levels of 3.2ng/mL CEA and 3.5ng/mL CYFRA 21-1 and twice these respective levels (6.4ng/mL and 7.0ng/mL) were used. CEA and CYFRA 21-1 levels were elevated in 32% and 11% of benign lung disease patients, respectively. CEA sensitivity and specificity for lung cancer diagnosis was 69% and 68% respectively, while that for CYFRA 21-1 was 43% and 89%, respectively. Thus, the combined value for the specificity of the two tumor markers was greater than either alone. Patients were grouped depending on their hospital status, and prevalence rates were determined. The prevalence rate of lung cancer in admitted patients was 51%, the prevalence rate of lung cancer in outpatients was 12%, and the prevalence rate of lung cancer identified during health check-ups was 0.1%. Positive predictive values (PPVs) were calculated using Bayes’ theorem, and varied with the serum tumor marker and prevalence rate: PPVs of CEA [prevalence rate] were 69.2% [51%], 22.7% [12%], and 0.22% [0.1%], while PPVs of CYFRA 21-1 were 80.3% [51%], 34.8% [12%], and 0.39% [0.1%]. However, PPVs for lung cancer diagnosis at a prevalence rate of 51% were 87.3% or higher when the patient exhibited positive CEA and CYFRA 21-1, or CEA or CYFRA 21-1 levels twice the standard cut-off. Our results indicate that CEA and CYFRA 21-1 are reliable serum tumor markers for the diagnosis of lung cancer in addition to CT scans when combined or used individually at twice the standard cut-off level in high prevalence rate groups. The prevalence rate should therefore be taken into account when these serum tumor markers are used as diagnostic tools for lung cancer.