Detection Of Early-stage Lung Cancer Research Articles

Detection of Cancer in Lung with K-NN Classification Using Genetic Algorithm

This paper focuses on early stage lung cancer detection. Genetic K-Nearest Neighbour (GKNN) Algorithm is proposed for the detection which is a non parametric method. This optimization algorithm allows physicians to identify the nodules present in the CT lung images in the early stage hence the lung cancer. Since the manual interpretation of the lung cancer CT images are time consuming and very critical, to overcome this difficulty the Genetic Algorithm method is combined with K-Nearest Neighbour (K-NN) algorithm which would classify the cancer images quickly and effectively. The MATLAB image processing toolbox based implementation is done on the CT lung images and the classifications of these images are carried out. The performance measures like the classification rate and the false positive rates are analyzed. In traditional K-NN algorithm, initially the distance between all the test and training samples are calculated and K-neighbours with greater distances are taken for classification. In this proposed method, by using Genetic Algorithm, K (50-100) numbers of samples are chosen for each iteration and the classification accuracy of 90% is achieved as fitness. The highest accuracy is recorded each time.

Abstract 1866: Detection of early-stage lung cancer using a novel ELISA for thymidine kinase 1

Abstract Lung cancer is the number one cause of cancer mortality and early detection will increase the survival of this disease. Thymidine kinase 1 (TK1) is a biomarker indicative of cell proliferation that is elevated in numerous malignancies including lung cancer. TK1 has been found to be elevated early in the development of lung cancer and therefore is an ideal target as an early detection biomarker. We have developed an enzyme-linked immunosorbent assay (ELISA) to detect TK1 in serum. Forty patients with pulmonary nodules and 18 healthy control individuals had serum collected under standard conditions, prior to operative removal of any lesions. All serum samples were analyzed using TK1 radioassay to measure TK1 activity, and TK1 ELISA to measure TK1 concentration. TK1 was significantly elevated in all patients with confirmed lung cancer. This was true even in stage IA, where patients (n=16) had significantly higher TK1 levels than controls. The clearest cut-off was 4.9 nM with an area under the curve of 0.792 for early stage lung cancer. The corresponding sensitivity and specificity was 82.4 and 83.3, respectively. TK1 concentration was a more sensitive and accurate indicator of lung cancer than TK1 activity. Overall, TK1 is significantly elevated in serum of lung cancer patients. This TK1 ELISA is sensitive and specific for detection of lung cancer and further trials with a larger patient base can confirm the potential of this method of detection. Citation Format: Madison K. Ramsden, Melissa M. Alegre, Michael J. Weyant, Daine T. Bennett, Jessica A. Yu, Atif Elnaggar, Richard A. Robison, Kim L. O'Neill. Detection of early-stage lung cancer using a novel ELISA for thymidine kinase 1. [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 1866. doi:10.1158/1538-7445.AM2014-1866

Diagnostic utility of VEGF mRNA and SP1 mRNA expression in bronchial cells of patients with lung cancer

Bronchial brushing is important for cytological diagnosis of lung carcinoma; however, cytological evaluation alone remains relatively insensitive. The aim of this study was to assess the diagnostic utility of vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) and specificity protein 1 (SP1) mRNA in bronchial brushings in patients with or without lung cancer. VEGF mRNA and SP1 mRNA were measured in liquid-based cells from bronchial brushings in patients with verified lung cancer (n = 93) and with benign lung disease that included tuberculosis (n = 51). This was done using the reverse-transcription polymerase chain reaction. Both VEGF mRNA and SP1 mRNA were significantly more likely to be expressed in the cancer group than in the control (benign) group, whatever their cell type. It was also more often found in the tuberculosis group than in the inflammation group (P < 0.01). In the cancer group, VEGF mRNA was significantly correlated with SP1 mRNA (P < 0.01). Of the 36 false negative cytology results, 30 gave positive results for VEGF mRNA and 34 for SP1 mRNA. The four false positive VEGF results were all diagnosed as tuberculosis. VEGF mRNA gave the highest diagnostic performance with serial use: sensitivity 89.2% and accuracy 90.3%. This was significantly better than cytology (P < 0.01). Detection of VEGF mRNA and SP1 mRNA in bronchial brushing cells may be used as an ancillary tool to cytological diagnosis for detection of early-stage lung cancer. It may also help distinguish tuberculosis from other causes of lung inflammation.

Screening for lung cancer: time for large-scale screening by chest computed tomography

Lung cancer is the leading cause of cancer death worldwide. Age and smoking are the primary risk factors for lung cancer. Treatment based on surgical removal in the early stages of the disease results in better survival. Screening programmes for early detection that used chest radiography and sputum cytology failed to attain reduction of lung cancer mortality. Screening by low-dose computed tomography (CT) demonstrated high rates of early-stage lung cancer detection in a high-risk population. Nevertheless, no mortality advantage was manifested in small randomised control trials. A large randomised control trial in the U.S.A., the National Lung Screening Trial (NLST), showed a significant relative reduction of 20% in lung cancer mortality and 6.7% reduction in total mortality, yet no reduction was evidenced in the late-stage prevalence. Screening for lung cancer by low-dose CT reveals a high level of false-positive lesions, which necessitates further noninvasive and invasive evaluations. Based primarily on the NLST eligible criteria, new guidelines have recently been developed by major relevant organisations. The overall recommendation coming out of this collective work calls for lung cancer screening by low-dose CT to be performed in medical centres manned by specialised multidisciplinary teams, as well as for a mandatory, pre-screening, comprehensive discussion with the patient about the risks and advantages involved in the process. Lung cancer screening is on the threshold of a new era, with ever more questions still left open to challenge future studies.

Lung cancer screening: current status

Lung cancer remains the leading cause of death from malignancy with approximately 1.3 million deaths occurring world wide per year [1]. Approximately 70 % of cases have incurable disease at presentation which is either widely metastatic or locally advanced [1]. The overall 5-year survival still remains very low at only 14 % [1]. Lung cancer, however, which is detected early in its course, demonstrates much better survival data. Survival in non-small-cell lung cancer Stage I is greater than 70 % and small peripheral less than 1 cm lung cancers have survival rates of greater than 80 % [2]. The rationale for screening is, therefore, obvious. Diagnosis of lung cancer early in preclinical stages has a higher cure rate and, therefore, high-risk asymptomatic individuals are likely to benefit from screening. The introduction of helical and subsequently multidetector CT in the 1990s led to a number of feasibility studies in which CT was used as a screening tool for the detection of early asymptomatic lung cancer. Observational single arm trials were conducted for several years in many countries including the United States, Japan, and Europe [3–8]. These studies established the sensitivity of low-dose CT for early lung cancer detection. These trials also tested algorithms for diagnostic workup and demonstrated a reduction in the incidence of advanced non-small-cell lung cancer with screening. A high percentage (84–93 %) was Stage I lung cancers [3–5]. They also produced somewhat similar results. They demonstrated that detection of earlystage lung cancer was higher than that reported previously with standard chest radiography [9] but that the false positive rate was at least three times that of standard radiographs. In regard to diagnostic algorithms, these studies provided evidence that peripheral nodules greater than 8–10 mm in size required further investigation because of the high likelihood of lung cancer. Such investigations included further imaging with PET–CT, percutaneous biopsy or resection and often led to invasive procedures. Smaller nodules (\8 mm diameter) could be managed with CT follow-up to determine interval growth indicating the likelihood of malignancy. These single arm feasibility and observational studies provided compelling evidence of the effectiveness of helical and MDCT as a screening tool for early detection of lung cancer. However, they were not sufficient to determine screening effectiveness because they were not able to assess the influence of CT screening on lung cancer mortality. Only randomized controlled trials can determine effectiveness of screening where the end point must be a decrease in mortality in the screened group as compared to a non-screened control. Subsequently, several prospective randomized controlled trials were undertaken both in the United States and Europe. These included the National Lung Cancer Screening Trial (NLST) in the United States [10] and the Nelson Trial and others in Europe [11–15]. The results of the NLST trial were published in 2011 [16]. The trial was a cooperative effort between the National Cancer Institute of the NIH and ACRIN, the American College of Radiology Imaging Network. 53,454 individuals were enrolled in the trial. It was a randomized national study and the population group included individuals between the ages of 55 and 74 with history of C30-pack years of current or prior smoking. The enrollees underwent three annual screens. The study group received low-dose CT and the control group underwent standard chest radiography. CT was conducted with T. C. McLoud (&) Thoracic Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA e-mail: tmcloud@partners.org

Exhaled breath analysis for lung cancer.

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection.

Molecular sputum analysis for the diagnosis of lung cancer

Lung cancer is the leading cause of cancer mortality rate worldwide, mainly because of the presence of metastatic disease at the time of diagnosis. Early detection of lung cancer improves prognosis, and towards this end, large screening trials in high-risk individuals have been conducted since the past century. Despite all efforts, the need for novel (complementary) lung cancer diagnostic and screening methods still exists. In this review, we focus on the assessment of lung cancer-related biomarkers in sputum in the past decennium. Besides cytology, mutation and microRNA analysis, special attention has been paid to DNA promoter hypermethylation, of which all available literature is summarised without time restriction. A model is proposed to aid in the distinction between diagnostic and risk markers. Research on the use of sputum for non-invasive detection of early-stage lung cancer has brought new insights and advanced molecular techniques. The sputum shows a promising potential for routine diagnostic and possibly screening purposes.

Computer-aided detection for pulmonary nodule identification: improving the radiologist‘s performance?

Computer-aided detection (CAD) systems for pulmonary nodule identification in CT images can represent valuable tools in assisting radiologists with a second opinion in the detection of early-stage lung cancers. This task becomes more and more challenging when low-dose CT protocols are implemented, which are the optimal choice for screening the asymptomatic population. The absolute performance of the CAD systems, as well as the reliability and reproducibility of the results across different data samples, is a fundamental requirement for these tools to be integrated in the diagnostic algorithm for lung cancer. An overview of the methods recently implemented to build CAD systems and a comparison of the performance achieved are provided. A fair comparison can be carried out only on common data samples, thus the validation of CAD systems on publicly available data sets, such as the Lung Image Database Consortium database, is highly recommended. The necessary steps to evaluate whether these systems can be valua...

Early Detection of Lung Cancer Using CT Scan and Bronchoscopy in a High Risk Population

Background: Computed tomography (CT) and bronchoscopy have been shown to improve the detection rates of peripheral and central lung cancers (LC), respectively. However, the performance of the combination of CT and bronchoscopy in detecting LC, in high-risk patients, is not clear. Patients & Methods: This prospective study included 205 high-risk patients with a history of at least 2 of the following risk factors: 1) heavy smoking; 2) aero-digestive cancer; 3) pulmonary asbestosis or; 4) chronic obstructive pulmonary disease. Patients were offered chest X-ray, sputum cytology, conventional white-light followed by autofluorescence bronchoscopy (WL/AFB) and low-dose spiral CT both at baseline and follow-up visits. Results: Seven patients (3.4%) were diagnosed with LC or carcinoma in-situ (CIS) at baseline: CT evaluation detected 5 LC/CIS, while WL/AFB evaluation also identified 5 LC/CIS, 2 of which were not detected on CT. Six (85%) of these baseline lesions were early stage (0/IA). The relative-sensitivity of CT with WL/ AFB was 40% better than CT alone. By four year follow-up, 20 patients (9.8%) were diagnosed with LC/CIS. CT with WL/AFB detected 19 cases (95%), whereas CT alone detected 15 cases (75%). Conclusion: Bimodality surveillance with spiral CT and WL/AFB can improve the detection of early stage LCs among high-risk patients.

Place for Biochemical Markers in Early-Stage Lung Cancer Detection?

Place for Biochemical Markers in Early-Stage Lung Cancer Detection?

An Approach to Studying Lung Cancer-related Proteins in Human Blood

Early stage lung cancer detection is the first step toward successful clinical therapy and increased patient survival. Clinicians monitor cancer progression by profiling tumor cell proteins in the blood plasma of afflicted patients. Blood plasma, however, is a difficult cancer protein assessment medium because it is rich in albumins and heterogeneous protein species. We report herein a method to detect the proteins released into the circulatory system by tumor cells. Initially we analyzed the protein components in the conditioned medium (CM) of lung cancer primary cell or organ cultures and in the adjacent normal bronchus using one-dimensional PAGE and nano-ESI-MS/MS. We identified 299 proteins involved in key cellular process such as cell growth, organogenesis, and signal transduction. We selected 13 interesting proteins from this list and analyzed them in 628 blood plasma samples using ELISA. We detected 11 of these 13 proteins in the plasma of lung cancer patients and non-patient controls. Our results showed that plasma matrix metalloproteinase 1 levels were elevated significantly in late stage lung cancer patients and that the plasma levels of 14-3-3 sigma, beta, and eta in the lung cancer patients were significantly lower than those in the control subjects. To our knowledge, this is the first time that fascin, ezrin, CD98, annexin A4, 14-3-3 sigma, 14-3-3 beta, and 14-3-3 eta proteins have been detected in human plasma by ELISA. The preliminary results showed that a combination of CD98, fascin, polymeric immunoglobulin receptor/secretory component and 14-3-3 eta had a higher sensitivity and specificity than any single marker. In conclusion, we report a method to detect proteins released into blood by lung cancer. This pilot approach may lead to the identification of novel protein markers in blood and provide a new method of identifying tumor biomarker profiles for guiding both early detection and therapy of human cancer.

CT Screening for Lung Cancer: Five-year Prospective Experience

To report results of a 5-year prospective low-dose helical chest computed tomographic (CT) study of a cohort at high risk for lung cancer. After informed written consent was obtained, 1520 individuals were enrolled. Protocol was approved by institutional review board and National Cancer Institute and was compliant with Health Insurance Portability and Accountability Act, or HIPAA. Participants were aged 50 years and older and had smoked for more than 20 pack-years. Participants underwent five annual (one initial and four subsequent) CT examinations. A significant downward shift was evaluated in non-small cell lung cancers detected initially from advanced stage down to stage I by using a one-sided binomial test of proportions. Poisson regression and Fisher exact tests were used for comparisons with Mayo Lung Project. In 788 (52%) men and 732 (48%) women, 61% (927 of 1520) were current smokers, and 39% were former smokers. After five annual CT examinations, 3356 uncalcified lung nodules were identified in 1118 (74%) participants. Sixty-eight lung cancers were diagnosed (31 initial, 34 subsequent, three interval cancers) in 66 participants. Twenty-eight subsequent cases of non-small cell cancers were detected, of which 17 (61%; 95% confidence interval: 41%, 79%) were stage I tumors. Diameter of cancers detected subsequently was 5-50 mm (mean, 14.4 mm; median, 10.0 mm). Analysis for a more than 50% shift in proportion of stage I non-small cell cancer detection did not show statistical significance. Forty-eight participants died of various causes since enrollment. Lung cancer mortality rate for incidence portion of trial was 1.6 per 1000 person-years. There was no significant difference in lung cancer mortality rates of cancers detected in subsequent examinations between this trial and Mayo Lung Project after separation of participants into subsets (2.8 vs 2.0 per 1000 person-years, P = .43). CT allows detection of early-stage lung cancers. Benign nodule detection rate is high. Results suggest no stage shift.

Diagnosis and Treatment of Early Lung Cancer: As It Stands Today

Treatment of "early" stage lung cancer should offer the patient the best chance for cure. Disease-free survival after surgical resection of lung carcinoma in situ has been reported as over 90%. For "microinvasive" lung cancer it may be similar. After resection of stage IA non-small cell lung cancer, survival at 5 years is approximately 60 to 70%. If endoscopic or bronchoscopic treatments of early stage lung cancer can offer similar disease-free survival with less perioperative mortality, morbidity, and cost, then they may be alternative front-line therapies. Regardless of therapeutic choice, the initial hurdle is developing a practical detection method for early stage disease. This article reviews early stage lung cancer detection by fluorescence bronchoscopy and potential treatment by the endoscopic techniques of photodynamic therapy, brachytherapy, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, electrocautery, and cryotherapy.

Detección precoz del cáncer de pulmón por tomografía computarizada de baja dosis de radiación: resultados de una muestra de 150 individuos asintomáticos

Our aim is to present initial baseline data from a screening trial on low-dose spiral computed tomography (CT). We describe enrollment criteria and a diagnostic algorithm based on initial low-dose CT findings. From September 2000 to May 2001, 150 asymptomatic smokers (age range 40-78 years; mean 55 years) were studied using non-enhanced low-dose spiral CT of the chest. Repeated short-term high resolution CT follow-up was performed for non-calcified pulmonary nodules smaller than 10 mm in diameter. Non-calcified pulmonary nodules 10 mm or larger were considered as potentially malignant and a complementary positron emission tomography (PET) exam was recommended. 54 non-calcified pulmonary nodules were found in 34 out of 141 (24.15%) symptom-free subjects. The diameter was 5 mm or shorter in 24 participants (70.6%), 6-10 mm in 7 (20.6%) and longer than 10 mm in 3 (8.8%) individuals. One patient with a non-calcified pulmonary nodule of at least 10 mm underwent a complementary PET exam, which was positive. Biopsy of this nodule demonstrated lung cancer (squamous cell carcinoma). CT follow-up over one year was decided in the other two subjects having non-calcified pulmonary nodules longer than 10 mm, as no radiographic signs indicative of malignancy were observed in the baseline scan. Following this low-dose CT based screening programme, detection of early-stage lung cancer in asymptomatic subjects at high risk of developing the disease is feasible. Further studies are however necessary to pursue more definitive results.

Detection of early-stage lung cancer: Computed tomographic scan or chest radiograph?

Objective: Computed tomography has recently been proposed as a useful method for the early detection of lung cancer. In this study we compared the stage distribution of lung cancers detected by a computed tomographic scan with that of lung cancers detected by a routine chest x-ray film. Methods: Two groups of patients with biopsy-proven non–small cell lung cancer were reviewed. In the first group of 32 patients, the tumors were detected by a computed tomographic scan. In a second group (n = 101), the lung cancers were detected on routine chest x-ray films. Patients with pulmonary symptoms or a history of cancer were excluded. Results: There was no difference in age, sex, or cell-type distribution between the 2 groups. A significantly greater number of patients undergoing a computed tomographic scan had stage IA disease compared with those having an x-ray film. Of the 32 patients in the group having a scan, 10 had tumors 1 cm or less in size versus 6 of 101 in the group having a chest radiograph. Additionally, there was a significant reduction in advanced stage disease in the group having a scan. Conclusions: In this retrospective study, a higher incidence of stage IA lung cancers and significantly fewer cases of more advanced disease were observed in patients screened with computed tomography than in those having a chest radiograph. These data suggest that computed tomographic screening may be of value in improving the survival of patients with non–small cell lung cancer. (J Thorac Cardiovasc Surg 2001;121:1053-7)

Endoscopic Treatment of Early-Stage Lung Cancer

Disease-free survival after surgical resection of lung carcinoma in situ has been reported as over 90%. After resection of stage IA non-small cell lung cancer, survival at 5 years is approximately 60% to 70%. If endoscopic or bronchoscopic treatments of early-stage lung cancer can provide similar disease-free survival with less perioperative mortality, morbidity, and cost, then they may be alternative front-line therapies. The authors review early-stage lung cancer detection by fluorescence bronchoscopy and the potential treatment of this disease by endoscopic techniques (photodynamic therapy, brachytherapy, Nd:YAG laser, electrocautery, and cryotherapy). Several reports have noted improved outcomes using endoscopic therapies for early-stage lung cancer, but insufficient data preclude firm conclusions regarding the role of fluorescence bronchoscopy, endobronchial brachytherapy, or electrocautery in early-stage lung cancer. Other than resection, photodynamic therapy may represent the best approach at this time. The principal indication for laser bronchoscopy is palliation of central airway obstruction. The identification of early-stage lung cancer provides no advantage if we have little to offer the patient short of traditional therapy. The value of newer treatment techniques and methods requires verification.