Lung Cancer
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Lung cancer is one of the most common types of cancer. The lungs are a pair of cone-shaped organs situated inside the chest, they bring oxygen into the body and take out waste carbon dioxide. There is a strong link between smoking and lung cancer. There are two main categories of lung cancer; Small Cell Lung Cancer (SCLC) , and Non-Small Cell Lung Cancer (NSCLC). World-wide over 1 million people are diagnosed with lung cancer each year.

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Latest Research Publications
Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Risk Factors and Prevention of Lung Cancer
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Information Patients and the Public (19 links)


Information for Health Professionals / Researchers (17 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Zhang X, Yang L, Liu W, et al.
Mining histopathological images via composite hashing and online learning.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 2):479-86 [PubMed] Related Publications
With a continuous growing amount of annotated histopathological images, large-scale and data-driven methods potentially provide the promise of bridging the semantic gap between these images and their diagnoses. The purpose of this paper is to increase the scale at which automated systems can entail scalable analysis of histopathological images in massive databases. Specifically, we propose a principled framework to unify hashing-based image retrieval and supervised learning. Concretely, composite hashing is designed to simultaneously fuse and compress multiple high-dimensional image features into tens of binary hash bits, enabling scalable image retrieval with a very low computational cost. Upon a local data subset that retains the retrieved images, supervised learning methods are applied on-the-fly to model image structures for accurate classification. Our framework is validated thoroughly on 1120 lung microscopic tissue images by differentiating adenocarcinoma and squamous carcinoma. The average accuracy as 87.5% with only 17ms running time, which compares favorably with other commonly used methods.


He T, Xue Z, Yu N, et al.
Estimating dynamic lung images from high-dimension chest surface motion using 4D statistical model.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 2):138-45 [PubMed] Related Publications
Computed Tomography (CT) has been widely used in image-guided procedures such as intervention and radiotherapy of lung cancer. However, due to poor reproducibility of breath holding or respiratory cycles, discrepancies between static images and patient's current lung shape and tumor location could potentially reduce the accuracy for image guidance. Current methods are either using multiple intra-procedural scans or monitoring respiratory motion with tracking sensors. Although intra-procedural scanning provides more accurate information, it increases the radiation dose and still only provides snapshots of patient's chest. Tracking-based breath monitoring techniques can effectively detect respiratory phases but have not yet provided accurate tumor shape and location due to low dimensional signals. Therefore, estimating the lung motion and generating dynamic CT images from real-time captured high-dimensional sensor signals acts as a key component for image-guided procedures. This paper applies a principal component analysis (PCA)-based statistical model to establish the relationship between lung motion and chest surface motion from training samples, on a template space, and then uses this model to estimate dynamic images for a new patient from the chest surface motion. Qualitative and quantitative results showed that the proposed high-dimensional estimation algorithm yielded more accurate 4D-CT compared to fiducial marker-based estimation.


Solomon BJ, Mok T, Kim DW, et al.
First-line crizotinib versus chemotherapy in ALK-positive lung cancer.
N Engl J Med. 2014; 371(23):2167-77 [PubMed] Related Publications
BACKGROUND: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown.
METHODS: We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review.
RESULTS: Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life.
CONCLUSIONS: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.).

Related: Carboplatin Non-Small Cell Lung Cancer Cisplatin Pemetrexed Crizotinib (Xalkori) ALK


Tan YN, Li XF, Li JJ, et al.
The accuracy of computed tomography in the pretreatment staging of colorectal cancer.
Hepatogastroenterology. 2014 Jul-Aug; 61(133):1207-12 [PubMed] Related Publications
Colorectal cancer (CRC) is one of the most frequent cancers around the world. Multimodality therapies are used for CRC including surgery, chemotherapy, radiotherapy and targeted therapy. Correct treatment plan depends greatly on the accurate pretreatment staging. Computed tomography (CT) is a widely used detection and staging modality for CRC patients in clinical practice. The role of CT in assessing the patients with CRC has been well established, but the accuracy of pretreatment staging by CT varies in different reports. With the development of CT techniques, some reformations such as multi-detector CT (MDCT), CT with water enema or air insufflations, multiple planner reconstruction (MPR) help to give us higher resolution images in shorter time. The accuracy of CT for N staging was still not so ideal, but CT played an important role in chest and liver staging. Magnetic resonance imaging (MRI) and endorectal ultrasound (ERUS) may provide more precise images and evaluation of local T and N staging for rectal cancer. And positron emission tomography (PET) or PET/CT is recommended as a complement of CT, only for cases suspected of residual or recurrent colorectal carcinoma or before metastasectomy, not for routine use.


Yang ZY, Liu L, Mao C, et al.
Chemotherapy with cetuximab versus chemotherapy alone for chemotherapy-naive advanced non-small cell lung cancer.
Cochrane Database Syst Rev. 2014; 11:CD009948 [PubMed] Related Publications
BACKGROUND: In advanced non-small cell lung cancer (NSCLC), the effectiveness of standard cytotoxic chemotherapy seems to have reached a 'plateau', and there is a continuous need for new treatments to further improve the prognosis. Cetuximab is a monoclonal antibody targeted at the epidermal growth factor receptor (EGFR) signalling pathway. Basically, it is designed to inhibit the growth and metastasis among other biological processes of cancer. In combination with chemotherapy, it has been evaluated as a first-line treatment for advanced NSCLC in some randomised controlled trials (RCTs), with inconsistent results.
OBJECTIVES: To evaluate the efficacy and toxicity of chemotherapy plus cetuximab, compared with chemotherapy alone, for advanced non-small cell lung cancer (NSCLC) previously untreated with chemotherapy or epidermal growth factor receptor (EGFR)-targeted drugs.
SEARCH METHODS: We systematically searched the Cochrane Lung Cancer Review Group's Specialized Register (from inception to 17 December 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 12), MEDLINE (accessed through PubMed, 1966 to 17 December 2013), EMBASE (1980 to 17 December 2013), ClinicalTrials.gov (from inception to 17 December 2013), and the World Health Organization (WHO) International Clinical Trials Registry Platform (from inception to 17 December 2013). We also handsearched the proceedings related to lung cancer from the American Society of Clinical Oncology and European Society of Medical Oncology (2000 to 17 December 2013). We checked the reference lists of all eligible primary studies and review articles for additional potentially eligible studies.
SELECTION CRITERIA: Eligible studies were RCTs that compared chemotherapy plus cetuximab with the same chemotherapy alone, in advanced NSCLC, previously untreated with chemotherapy or EGFR-targeted drugs, and measured at least one of the following: overall survival, progression-free survival, one-year survival rate, objective response rate, quality of life, or serious adverse events.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. We extracted the following data from each study: publication details, participant characteristics, regimens for intervention and control arms, outcome measures and effect size, and information related to the methodological quality of the study. We measured the treatment effects on dichotomous and time-to-event outcomes by risk ratio (RR) and hazard ratio (HR), with 95% confidence intervals (CIs), respectively. We conducted meta-analyses with Review Manager 5 using the random-effects model. We employed the Mantel-Haenszel method to combine RRs and the inverse-variance method to combine HRs.
MAIN RESULTS: We included four trials, containing 2018 patients. The subjects were mostly white people (female: 26% to 56%), with a median age of 58 to 66 years. About half of them had histologically proven adenocarcinoma. Of the 2018 patients, 83% to 99% had their status measured using the Eastern Cooperative Oncology Group performance status, and had a score of 0 to 1 (which is usually considered as physically "fit").All four studies provided data on overall survival, progression-free survival, one-year survival rate, objective response rate, and serious adverse events, with two studies (1901 patients) investigating the effect of cetuximab on quality of life as well. The risk of bias was low for the data on overall survival and one-year survival rate, and high for the data on all other outcomes, mainly due to lack of blinding. Compared with chemotherapy alone, chemotherapy plus cetuximab improved overall survival (10.5 months versus 8.9 months; HR 0.87, 95% CI 0.79 to 0.96), one-year survival rate (45% versus 40%; RR 1.13, 95% CI 1.02 to 1.25), and objective response rate (30% versus 23%; RR 1.31, 95% CI 1.14 to 1.51). The difference in progression-free survival was at the limit of the statistical significance (4.9 months versus 4.4 months; HR 0.91, 95% CI 0.83 to 1.00). No significant difference in quality of life between the two treatment arms was reported by the two relevant studies. Patients in the cetuximab group experienced more acneiform rash (11.2% versus 0.3%; RR 37.36, 95% CI 10.66 to 130.95), hypomagnesemia (5.3% versus 0.8%; RR 6.57, 95% CI 1.13 to 38.12), infusion reaction (3.9% versus 1.1%; RR 3.50, 95% CI 1.76 to 6.94), diarrhoea (4.8% versus 2.3%; RR 2.10, 95% CI 1.26 to 3.48), hypokalaemia (6.3% versus 3.6%; RR 1.74, 95% CI 1.02 to 2.99), febrile neutropenia (10.6% versus 7.6%; RR 1.40, 95% CI 1.10 to 1.77), and leukopenia (58.1% versus 42.7%; RR 1.36, 95% CI 1.17 to 1.58) than did those in the control group. The difference in other adverse events did not reach statistical significance. According to the reports of original studies, the adverse events were generally manageable. There were no cetuximab-related deaths.The quality of the evidence is high for overall survival and one-year survival rate, but low for most secondary outcomes.
AUTHORS' CONCLUSIONS: The combination of chemotherapy plus cetuximab is better than chemotherapy alone as the first-line treatment of advanced NSCLC in improving overall survival, while inducing higher rates of some reportedly manageable adverse events.

Related: Non-Small Cell Lung Cancer Cetuximab (Erbitux)


Schmidt-Hansen M, Baldwin DR, Hasler E, et al.
PET-CT for assessing mediastinal lymph node involvement in patients with suspected resectable non-small cell lung cancer.
Cochrane Database Syst Rev. 2014; 11:CD009519 [PubMed] Related Publications
BACKGROUND: A major determinant of treatment offered to patients with non-small cell lung cancer (NSCLC) is their intrathoracic (mediastinal) nodal status. If the disease has not spread to the ipsilateral mediastinal nodes, subcarinal (N2) nodes, or both, and the patient is otherwise considered fit for surgery, resection is often the treatment of choice. Planning the optimal treatment is therefore critically dependent on accurate staging of the disease. PET-CT (positron emission tomography-computed tomography) is a non-invasive staging method of the mediastinum, which is increasingly available and used by lung cancer multidisciplinary teams. Although the non-invasive nature of PET-CT constitutes one of its major advantages, PET-CT may be suboptimal in detecting malignancy in normal-sized lymph nodes and in ruling out malignancy in patients with coexisting inflammatory or infectious diseases.
OBJECTIVES: To determine the diagnostic accuracy of integrated PET-CT for mediastinal staging of patients with suspected or confirmed NSCLC that is potentially suitable for treatment with curative intent.
SEARCH METHODS: We searched the following databases up to 30 April 2013: The Cochrane Library, MEDLINE via OvidSP (from 1946), Embase via OvidSP (from 1974), PreMEDLINE via OvidSP, OpenGrey, ProQuest Dissertations & Theses, and the trials register www.clinicaltrials.gov. There were no language or publication status restrictions on the search. We also contacted researchers in the field, checked reference lists, and conducted citation searches (with an end-date of 9 July 2013) of relevant studies.
SELECTION CRITERIA: Prospective or retrospective cross-sectional studies that assessed the diagnostic accuracy of integrated PET-CT for diagnosing N2 disease in patients with suspected resectable NSCLC. The studies must have used pathology as the reference standard and reported participants as the unit of analysis.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data pertaining to the study characteristics and the number of true and false positives and true and false negatives for the index test, and they independently assessed the quality of the included studies using QUADAS-2. We calculated sensitivity and specificity with 95% confidence intervals (CI) for each study and performed two main analyses based on the criteria for test positivity employed: Activity > background or SUVmax ≥ 2.5 (SUVmax = maximum standardised uptake value), where we fitted a summary receiver operating characteristic (ROC) curve using a hierarchical summary ROC (HSROC) model for each subset of studies. We identified the average operating point on the SROC curve and computed the average sensitivities and specificities. We checked for heterogeneity and examined the robustness of the meta-analyses through sensitivity analyses.
MAIN RESULTS: We included 45 studies, and based on the criteria for PET-CT positivity, we categorised the included studies into three groups: Activity > background (18 studies, N = 2823, prevalence of N2 and N3 nodes = 679/2328), SUVmax ≥ 2.5 (12 studies, N = 1656, prevalence of N2 and N3 nodes = 465/1656), and Other/mixed (15 studies, N = 1616, prevalence of N2 to N3 nodes = 400/1616). None of the studies reported (any) adverse events. Under-reporting generally hampered the quality assessment of the studies, and in 30/45 studies, the applicability of the study populations was of high or unclear concern.The summary sensitivity and specificity estimates for the 'Activity > background PET-CT positivity criterion were 77.4% (95% CI 65.3 to 86.1) and 90.1% (95% CI 85.3 to 93.5), respectively, but the accuracy estimates of these studies in ROC space showed a wide prediction region. This indicated high between-study heterogeneity and a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a lack of precision. Sensitivity analyses suggested that the overall estimate of sensitivity was especially susceptible to selection bias; reference standard bias; clear definition of test positivity; and to a lesser extent, index test bias and commercial funding bias, with lower combined estimates of sensitivity observed for all the low 'Risk of bias' studies compared with the full analysis.The summary sensitivity and specificity estimates for the SUVmax ≥ 2.5 PET-CT positivity criterion were 81.3% (95% CI 70.2 to 88.9) and 79.4% (95% CI 70 to 86.5), respectively.In this group, the accuracy estimates of these studies in ROC space also showed a very wide prediction region. This indicated very high between-study heterogeneity, and there was a relatively large 95% confidence region around the summary value of sensitivity and specificity, denoting a clear lack of precision. Sensitivity analyses suggested that both overall accuracy estimates were marginally sensitive to flow and timing bias and commercial funding bias, which both lead to slightly lower estimates of sensitivity and specificity.Heterogeneity analyses showed that the accuracy estimates were significantly influenced by country of study origin, percentage of participants with adenocarcinoma, (¹⁸F)-2-fluoro-deoxy-D-glucose (FDG) dose, type of PET-CT scanner, and study size, but not by study design, consecutive recruitment, attenuation correction, year of publication, or tuberculosis incidence rate per 100,000 population.
AUTHORS' CONCLUSIONS: This review has shown that accuracy of PET-CT is insufficient to allow management based on PET-CT alone. The findings therefore support National Institute for Health and Care (formally 'clinical') Excellence (NICE) guidance on this topic, where PET-CT is used to guide clinicians in the next step: either a biopsy or where negative and nodes are small, directly to surgery. The apparent difference between the two main makes of PET-CT scanner is important and may influence the treatment decision in some circumstances. The differences in PET-CT accuracy estimates between scanner makes, NSCLC subtypes, FDG dose, and country of study origin, along with the general variability of results, suggest that all large centres should actively monitor their accuracy. This is so that they can make reliable decisions based on their own results and identify the populations in which PET-CT is of most use or potentially little value.

Related: Non-Small Cell Lung Cancer


Black WC, Gareen IF, Soneji SS, et al.
Cost-effectiveness of CT screening in the National Lung Screening Trial.
N Engl J Med. 2014; 371(19):1793-802 [PubMed] Related Publications
BACKGROUND: The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST.
METHODS: We estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions.
RESULTS: As compared with no screening, screening with low-dose CT cost an additional $1,631 per person (95% confidence interval [CI], 1,557 to 1,709) and provided an additional 0.0316 life-years per person (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to 0.0314). The corresponding ICERs were $52,000 per life-year gained (95% CI, 34,000 to 106,000) and $81,000 per QALY gained (95% CI, 52,000 to 186,000). However, the ICERs varied widely in subgroup and sensitivity analyses.
CONCLUSIONS: We estimated that screening for lung cancer with low-dose CT would cost $81,000 per QALY gained, but we also determined that modest changes in our assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Related: Cancer Screening and Early Detection USA


Nieder C, Angelo K, Haukland E, Pawinski A
Survival after palliative radiotherapy in geriatric cancer patients.
Anticancer Res. 2014; 34(11):6641-5 [PubMed] Related Publications
BACKGROUND/AIM: Older cancer patients might experience inferior survival outcomes. However, no standard age cut-off is currently being used for commonly administered treatments such as radiotherapy. We evaluated survival outcomes and prognostic factors for survival after palliative radiotherapy (PRT) in our oldest patients (age≥80 years).
PATIENTS AND METHODS: This retrospective study covered the time period between 2007 and 2012, and included 94 patients in this age group who were treated with PRT. Comparisons to a group of younger patients (31-79 years of age, N=445) treated during the same time period were made. Uni- and multivariate analyses were also performed. Most patients received PRT for bone and brain metastases or in order to improve thoracic symptoms from lung cancer.
RESULTS: Median age was 83 years. Survival outcomes and rates of PRT completion were not significantly different. Short median survival of less than 2 months was observed in two sub-groups of geriatric patients; those with brain metastases and those with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 4. Multivariate analysis confirmed the prognostic impact of PS, adrenal gland metastases, progressive disease outside PRT target volume(s), need for opioid analgetics and steroids (all p<0.05). Brain metastasis was associated with a borderline increase in risk of mortality (p=0.051).
CONCLUSION: Our data support utilization of PRT irrespective of age for most patients with PS 0-3 but care should be taken in selecting the right fractionation regimen in order to avoid lengthy PRT courses when survival is limited.

Related: Cancer Prevention and Risk Reduction


Tanagornmeatar K, Chaotham C, Sritularak B, et al.
Cytotoxic and anti-metastatic activities of phenolic compounds from Dendrobium ellipsophyllum.
Anticancer Res. 2014; 34(11):6573-9 [PubMed] Related Publications
BACKGROUND/AIM: Phenolic compounds isolated from Dendrobium ellipsophyllum Tang & Wang (Orchidaceae) have been shown to possess potential pharmacological activity; however, their anticancer as well as anti-metastasis activities are largely unknown. The aim of the present study was to isolate active compounds from D. ellipsophyllum and to explore the possible effects of phenolic compounds isolated from the plant for cytotoxic as well as anti-metastatic properties.
MATERIALS AND METHODS: The compounds were isolated by using chromatographic techniques including silica gel and Sephadex LH20. Each of the isolates was evaluated for their cytotoxicity on H292 human lung cancer cell lines by 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. The cytotoxic compounds were further evaluated for apoptosis-inducing and anoikis-sensitizing effects.
RESULTS: Ten phenolic compounds were isolated, 5,7-dihydroxy-chromen-4-one (1:); 4,5-dihydroxy-2,3-dimethoxy-9,10-dihydrophenanthrene (2:); moscatilin (3:), 4,4'-dihydroxy-3,5-dimethoxybibenzyl (4:); 4,5,4'-trihydroxy-3,3'-dimethoxybibenzyl (5:); (2S)-homoeriodictyol (6:); (2S)-eriodictyol (7:); chrysoeriol (8:); phloretic acid (9:); and luteolin (10:). Compounds 4:, 5:, 8: and 10: exhibited appreciable cytotoxic activity with 50% inhibitory concentration values less than 250 μM. These compounds also showed potential apoptosis induction and anoikis-sensitizing effect at non-toxic concentrations.
CONCLUSION: Compounds 4:, 5:, 8: and 10: are responsible for cytotoxic and anti-metastatic activities of D. ellipsophyllum.

Related: Apoptosis


Gavrilov V, Lavrenkov K, Ariad S, Shany S
Sodium valproate, a histone deacetylase inhibitor, enhances the efficacy of vinorelbine-cisplatin-based chemoradiation in non-small cell lung cancer cells.
Anticancer Res. 2014; 34(11):6565-72 [PubMed] Related Publications
AIM: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co-administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to elucidate molecular events underpinning treatment efficacy.
MATERIALS AND METHODS: The NSCLC A549 cell line was treated with cisplatin (0.2 μg/ml), vinorelbine (2 nM), VPA (1 mM) and IR (2.5 Gy) alone, or in combination. Cell proliferation, cell-cycle distribution, apoptosis, and levels of DNA double-strand breaks, activated DNA damage checkpoint kinases pCHK1, pCHK2, cell-cycle inhibitors p21CIP1/WAF1 and p27KIP1 were assessed.
RESULTS: VPA markedly enhanced the DNA-damaging effect of the cisplatin-vinorelbine-IR combination and induced increased DSBs, and expression of pCHK2, pCHK1, p21CIP1/WAF1 and p27KIP1. These molecular changes led to cell-cycle arrest and increased apoptosis and consequently markedly curtailed cancer cell growth.
CONCLUSION: VPA markedly enhances the anticancer activity of cisplatin-vinorelbine-IR combination. This finding has translational implications for enhancing the efficacy of anticancer treatment and for reducing side-effects by reducing doses of radiation and drugs.

Related: Apoptosis Non-Small Cell Lung Cancer Cisplatin Vinblastine Vinorelbine


Lee CJ, Yue CH, Lin YJ, et al.
Antitumor activity of acriflavine in lung adenocarcinoma cell line A549.
Anticancer Res. 2014; 34(11):6467-72 [PubMed] Related Publications
UNLABELLED: Aim/Materials and Methods: In order to develop better drugs against non-small cell lung cancer (NSCLC), we screened a variety of compounds and treated the human lung adenocarcinoma cell line A549 with different drug concentrations. We then examined the cell viability using the MTT assay.
RESULTS: Data show that a new candidate drug, acriflavine (ACF), suppresses the viability of A549 cells in a concentration- and time-dependent manner. Flow cytometry analysis revealed that ACF significantly caused cell growth arrest in the G2/M phase on A549 cells. Moreover, ACF decreased Bcl-2 expression and increased Bax expression. The content of cleaved poly(ADP-ribose)polymerase-1 (PARP-1) and caspase-3 are significantly increased. These findings suggest that ACF is cytotoxic against A549 cells and suppresses A549 cells growth through the caspase-3 activation pathway. In the in vivo test, nude mice bearing A549 cells xenografts by intravenous injection were randomly assigned into two groups: control and experimental group. Treatment was initiated 10 days after implantation and intraperitoneal injection of 0.9% normal saline or 2 mg/kg of ACF was continued daily for five weeks. ACF treatment significantly decreased tumor size and tumor spots on lung surface of tumor-bearing mice.
CONCLUSION: ACF can inhibit cell growth in A549 cells. Our results may assist on the delineation of the mechanism(s) leading to NSCLC cell growth inhibition and provide a new antitumor strategy against NSCLC.

Related: Apoptosis Non-Small Cell Lung Cancer


Wu CF, Wu CY, Fu JY, et al.
Prognostic value of metastatic N1 lymph node ratio and angiolymphatic invasion in patients with pathologic stage IIA non-small cell lung cancer.
Medicine (Baltimore). 2014; 93(20):e102 [PubMed] Related Publications
With regard to pathologic stage IIA (pIIA) non-small cell lung cancer (NSCLC), there is a paucity of literature evaluating the risk factors for disease-free survival (DFS) and overall survival (OS). The aim of this study was to identify the prognostic factors of DFS and OS in patients with NSCLC pIIA.We performed a retrospective review of 98 stage II patients (7th edition of the American Joint Committee on Cancer) who underwent lung resection from January 2005 to February 2011. Of these, 23 patients were excluded for this study because of loss of follow-up or different substage, and 75 patients with pIIA were included for further univariate and multivariate analysis. Risk factors for DFS and OS were analyzed, including age, gender, smoking history, operation method, histology, differential grade, visceral pleural invasion, angiolymphatic invasion, and metastatic N1 lymph node ratio (LNR).Of the 75 patients with pIIA NSCLC who were examined, 29 were female and 46 were male, with a mean age of 61.8 years (range: 34-83 years). The average tumor size was 3.188 cm (range: 1.10-6.0 cm). Under univariate analysis, angiolymphatic invasion and metastatic N1 LNR were risk factors for DFS (P = 0.011, P = 0.007). Under multivariate analysis, angiolymphatic invasion and metastatic N1 LNR were all independent risk factors for DFS, while adjuvant chemotherapy and higher metastatic N1 LNR were independent prognostic factors for OS.For patients with pIIA, higher metastatic N1 LNR and angiolymphatic invasion were related to poor DFS. In addition to DFS, higher metastatic N1 LNR was also a poor prognostic factor for OS rates and adjuvant therapy effectiveness. Clinical physicians should devise different postsurgical follow-up programs depending on these factors, especially for patients with high risk.


De Meis E, Brandão BC, Capella FC, et al.
Catastrophic antiphospholipid syndrome in cancer patients: an Interaction of clotting, autoimmunity and tumor growth?
Isr Med Assoc J. 2014; 16(9):544-7 [PubMed] Related Publications
Thrombosis is a common phenomenon in patients with malignancies. It is believed that thrombosis is multifactorial and that in addition to mechanisms directly associated with cancer and its treatment, it may also be related to the interaction between the immune system and clotting. The present work describes four cancer patients (three adults and one child) whose clinical course was characteristic of catastrophic antiphospholipid syndrome (CAPS) in intensive care units of the National Cancer Institute of Rio de Janeiro. The presence of findings similar to those in CAPS can be attributed to an unbalanced interaction between the immune system and coagulation.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma) Bone Cancers Ewing's Sarcoma


Kim BG, Kwon HY, Sohn EJ, et al.
Activation of caspases and inhibition of ribosome biogenesis mediate antitumor activity of Chijongdan in A549 non-small lung cancer cells.
BMC Complement Altern Med. 2014; 14:420 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Though herbal medicines have been used for cancer prevention and treatment, their scientific evidences still remain unclear so far. Thus, complementary and alternative medicine (CAM) project has been actively executed to reveal the scientific evidences in the USA and other countries. In the present study, we elucidated antitumor mechanism of Chijongdan, an oriental prescription of Rhus verniciflua, processed Panax ginseng, Persicaria tinctoria and Realgar, that has been traditionally applied for cancer treatment in Korea.
METHODS: Chijongdan was prepared with extracts of Rhus verniciflua, processed Panax ginseng, Persicaria tinctoria and processed Realgar. The cytotoxicity of Chijongdan was measured by MTT colorimetric assay. Cell cycle analysis was performed by FACS. Western blot was performed to see the apoptosis related proteins.
RESULTS: Chijongdan significantly exerted cytotoxicity in A549, H460 and H1299 non-small cell lung carcinoma (NSCLC) cells by MTT assay and also increased the number of ethidium homodimer positively stained cells in A549 NSCLC cells. Also, cell cycle analysis showed that Chijongdan increased sub-G1 population in a concentration dependent manner in A549 cells. In addition, Western blotting revealed that Chijongdan activated cleaved PARP, and caspase 9/3, while attenuated the expression of survival genes such as Bcl-2, Bcl-XL and survivin in A549 cells. Furthermore, Chijongdan suppressed the expression of ribosomal biogenesis related proteins such as upstream binding factor (UBF), Fibrillarin, NPM (B23) and Importin-7 (IPO7) and conversely pan-caspase inhibitor Z--VAD-FMK reversed the apoptotic ability of Chijongdan to cleave PARP and caspase 3 and attenuate the expression of UBF and Fibrillarin in A549 cells.
CONCLUSIONS: These findings suggest that Chijongdan induces apoptosis and inhibits ribosomal biogenesis proteins via caspase activation.

Related: Apoptosis Non-Small Cell Lung Cancer CASP3


Kwak TK, Sohn EJ, Kim S, et al.
Inhibitory effect of ethanol extract of Ocimum sanctum on osteopontin mediated metastasis of NCI-H460 non-small cell lung cancer cells.
BMC Complement Altern Med. 2014; 14:419 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Osteopontin (OPN) is one of important molecular targets in cancer progression, metastasis as a calcium-binding, extracellular-matrix-associated protein of the small integrin-binding ligand and, N-linked glycoprotein. In the present study, anti-metastatic mechanism of ethanol extracts of Ocimum sanctum (EEOS) was elucidated on OPN enhanced metastasis in NCI-H460 non- small cell lung cancer cells.
METHODS: Cell viability was measured by MTT assay. Adhesion and invasion assays were carried out to see that EEOS inhibited cell adhesion and invasion in OPN treated and non-treated NCI-H 460 cells. RT-PCR was used to determine the mRNA levels of uPA, uPAR, and EGFR.
RESULTS: EEOS significantly inhibited cell adhesion and invasion in OPN treated and non treated NCI-H460 cells, though EEOS did not show any toxicity up to 200 μg/ml. EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated the expression of CD44 in NCI-H460 cells. In addition, EEOS effectively suppressed the expression of phosphatidylinositide 3-kinases (PI3K) and cyclooxygenase 2 (COX-2) and the phosphorylation of Akt at protein level in OPN treated NCI-H460 cells. Also, EEOS significantly attenuated the expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and epidermal growth factor receptor (EGFR) at mRNA level and reduced vascular endothelial growth factor (VEGF) production and MMP-9 activity in OPN treated NCI-H460 cells. Furthermore, PI3K/Akt inhibitor LY294002 enhanced anti-metastatic potential of EEOS to attenuate the expression of uPA and MMP-9 in OPN treated NCI-H 460 cells.
CONCLUSION: Overall, our findings suggest that anti-metastatic mechanism of EEOS is mediated by inhibition of PI3K/Akt in OPN treated NCI-H460 non-small cell lung cancer cells.

Related: Non-Small Cell Lung Cancer AKT1 VEGFA


Comin CE, Novelli L, Cavazza A, et al.
Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma.
Tumori. 2014 Sep-Oct; 100(5):559-67 [PubMed] Related Publications
AIMS AND BACKGROUND: A number of immunohistochemical markers have been suggested as useful in the positive diagnosis of epithelioid mesothelioma. The most widely used mesothelioma markers are thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1. Numerous investigations have demonstrated their variable sensitivity and specificity in differentiating epithelioid mesothelioma from lung adenocarcinoma. However, data on the expression of these markers in other types of lung carcinomas are very limited. We evaluated the expression of these markers in a series of 172 primary carcinomas of the lung and in 75 epithelioid pleural mesotheliomas.
RESULTS: Thrombomodulin expression was found in squamous cell carcinomas (71%), small cell lung carcinomas (11%), adenocarcinomas (4%), large cell carcinomas (50%), large cell neuroendocrine carcinomas (25%) and in sarcomatoid carcinomas (10%). Calretinin expression was common in small cell lung carcinomas (44%) and large cell neuroendocrine carcinomas (25%), less common in squamous cell carcinomas (20%), rare and focal in adenocarcinomas (4%) and sarcomatoid carcinomas (10%). Cytokeratin 5/6 was expressed in most of the squamous cell carcinomas (94.5%). Immunoreactivity was also found in large cell carcinomas (50%), sarcomatoid carcinomas (30%) and rarely in adenocarcinomas (4%). D2-40 was consistently expressed in squamous cell carcinomas (42%). Focal immunoreactivity was found in adenocarcinomas (3%). WT-1 was focally present in one (2%) squamous cell carcinoma.
CONCLUSIONS: These results indicate that some of the most commonly used mesothelioma markers may react with different types of primary lung carcinomas. These data should be taken into consideration especially when dealing with small biopsy fragments and poorly differentiated tumors.

Related: Mesothelioma WT1


Lin J, He B, Cao L, et al.
CYP1A1 Ile462Val polymorphism and the risk of non-small cell lung cancer in a Chinese population.
Tumori. 2014 Sep-Oct; 100(5):547-52 [PubMed] Related Publications
AIMS AND BACKGROUND: Cytochrome P450 (CYP) 1A1 enzyme plays an important role in the metabolism of carcinogens, such as polycyclic aromatic hydrocarbons, nitroaromatics and arylamines.
METHODS: The study examined the association of CYP1A1 Ile462Val polymorphism with the risk of developing non-small cell lung cancer in a Chinese population. We conducted a case-control study including 526 non-small cell lung cancer cases and 526 cancer-free controls. The odds ratios and 95% confidence intervals were calculated by logistic regression models.
RESULTS: Compared with 462Ile/Ile genotype carriers, subjects with CYP1A1 462Ile/Val or Val/Val genotype had a decreased risk of developing non-small cell lung cancer with odds ratios of 0.57 (95% CI, 0.44-0.75) and 0.54 (95% CI, 0.36-0.81), respectively. When stratified by smoking status, the decreased risk of non-small cell lung cancer associated with CYP1A1 462Ile/Val or Val/Val genotype was observed among non-smokers (OR = 0.62, 95% CI, 0.45-0.87) and among smokers (OR = 0.54, 95% CI, 0.37-0.78). When stratified by smoking-dose, the correlation between CYP1A1 genotypes and the risk of non-small cell lung cancer was detected among light smokers (OR = 0.30, 95% CI, 0.19-0.48) but not among heavy smokers (OR = 0.93, 95% CI, 0.61-1.43).
CONCLUSIONS: The CYP1A1 Ile462Val variant was associated with a low risk of developing non-small cell lung cancer in a Chinese population.

Related: Non-Small Cell Lung Cancer Polymorphisms


Inomata M, Hayashi R, Tokui K, et al.
Outcome and prognostic factors in patients with small cell lung cancer who receive third-line chemotherapy.
Tumori. 2014 Sep-Oct; 100(5):507-11 [PubMed] Related Publications
AIMS AND BACKGROUND: It is reported that about 20% of patients with small cell lung cancer (SCLC) receive third-line chemotherapy. We conducted a retrospective study to investigate the outcome and prognostic factors of patients with SCLC who receive third-line chemotherapy.
METHODS AND STUDY DESIGN: The medical records of patients with SCLC who received third-line chemotherapy at our institution were reviewed. Overall survival (OS) from the initiation of third-line chemotherapy was evaluated, and the association between OS and patient characteristics was assessed by the log-rank test.
RESULTS: A total of 73 patients with SCLC were treated with cytotoxic drugs between 2004 and 2012, and 19 patients received third-line chemotherapy. Median OS from initiation of third-line chemotherapy was 8.5 months. Patients with higher body mass index (BMI) (P = 0.0071), lower levels of lactate dehydrogenase (LDH) (P = 0.0036), higher levels of hemoglobin (P = 0.048), longer time to progression (TTP) from the initiation of second-line treatment (P = 0.0036), and better response to second-line treatment (P = 0.029) had longer duration of OS.
CONCLUSIONS: It is suggested that TTP and tumor response in second-line chemotherapy, serum levels of LDH and hemoglobin, and BMI at initiation of third-line chemotherapy could be possible prognostic factors.

Related: Small Cell Lung Cancer


Hansakul P, Aree K, Tanuchit S, Itharat A
Growth arrest and apoptosis via caspase activation of dioscoreanone in human non-small-cell lung cancer A549 cells.
BMC Complement Altern Med. 2014; 14:413 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Dioscoreanone (DN) isolated from Dioscorea membranacea Pierre has been reported to exert potent cytotoxic effects against particular types of cancer. The present study was carried out to investigate the cytotoxicity of DN against a panel of different human lung cancer cell lines. The study further examined the underlying mechanisms of its anticancer activity in the human lung adenocarcinoma cell line A549.
METHODS: Antiproliferative effects of DN were determined by SRB and CFSE assays. The effect of DN on cell cycle distribution was assessed by flow cytometric analysis. Apoptotic effects of DN were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses, as well as by changes in caspase-3 activity and relative levels of Bax and Bcl-2 mRNA.
RESULTS: DN exerted antiproliferative and cytotoxic effects on all three subtypes of non-small cell lung cancer (NSCLC) cells, but not on small cell lung cancer (SCLC) cells and normal lung fibroblasts. DN slowed down the cell division and arrested the cell cycle at the G2/M phase in treated A549 cells, leading to a dose- and time- dependent increase of the sub-G1 population (apoptotic cells). Consistently, early apoptotic cells (AnnexinV +/PI-) were detected in those cells that were treated for 24 h and increased progressively over time. Moreover, the highest activity of caspase-3 in DN-treated A549 cells was detected within the first 24 h, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity and also DN-induced apoptosis in a dose-dependent manner. Additionally, DN increased the Bax/Bcl-2 ratio in treated A549 cells with time, indicating its induction of apoptosis via the mitochondrial pathway.
CONCLUSIONS: This study reveals for the first time that the anticancer activity of DN was induced through regulation of the Bcl-2 family protein-mediated mitochondrial pathway and the subsequent caspase-3 activation in A549 cancer cells, thus supporting its potential role as a natural apoptosis-inducing agent for NSCLC.

Related: Apoptosis Non-Small Cell Lung Cancer CASP3


Sánchez-Rivera FJ, Papagiannakopoulos T, Romero R, et al.
Rapid modelling of cooperating genetic events in cancer through somatic genome editing.
Nature. 2014; 516(7531):428-31 [PubMed] Related Publications
Cancer is a multistep process that involves mutations and other alterations in oncogenes and tumour suppressor genes. Genome sequencing studies have identified a large collection of genetic alterations that occur in human cancers. However, the determination of which mutations are causally related to tumorigenesis remains a major challenge. Here we describe a novel CRISPR/Cas9-based approach for rapid functional investigation of candidate genes in well-established autochthonous mouse models of cancer. Using a Kras(G12D)-driven lung cancer model, we performed functional characterization of a panel of tumour suppressor genes with known loss-of-function alterations in human lung cancer. Cre-dependent somatic activation of oncogenic Kras(G12D) combined with CRISPR/Cas9-mediated genome editing of tumour suppressor genes resulted in lung adenocarcinomas with distinct histopathological and molecular features. This rapid somatic genome engineering approach enables functional characterization of putative cancer genes in the lung and other tissues using autochthonous mouse models. We anticipate that this approach can be used to systematically dissect the complex catalogue of mutations identified in cancer genome sequencing studies.


Colin T, Cornelis F, Jouganous J, et al.
Patient specific image driven evaluation of the aggressiveness of metastases to the lung.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 1):553-60 [PubMed] Related Publications
Metastases to the lung are a therapeutic challenge because some are fast-evolving while others evolve slowly. Any insight that can be provided for which nodule has to be treated first would help clinicians. In this work, we evaluate the aggressiveness but also the response to treatment of these nodules using a calibrated mathematical model. This model is a macroscopic model describing tumoral growth through a set of nonlinear partial differential equations. It has to be calibrated to a specific patient and a specific nodule using a temporal sequence of CT scans. To this end, a new optimization technique based on a reduced order method is developed. Finally, results on two clinical cases are presented that give satisfactory numerical prognosis of the evolution of a nodule during different phases: growth, treatment and post-treatment relapse.


Hytych V, Pohnan R, Taskova A, et al.
Importance of histological verification of mediastinal lymphadenopathy in exact staging of non-small cell bronchogenic carcinoma.
Bratisl Lek Listy. 2014; 115(9):585-7 [PubMed] Related Publications
BACKGROUND: Diagnostics and treatment of bronchogenic non-small cell lung carcinoma is a severe clinical problem. Radical surgery is the major treatment modality with the highest chance for a long-time survival. The aim of the study was to map metastasizing of bronchogenic non-small cell lung carcinoma into homolateral mediastinal lymph nodes and to assess the importance of histological verification of mediastinal lymphadenectomy for exact staging and treatment.
METHODS: Study of 29 patients with non-small cell lung carcinoma in stage IIIa, IIIb and IV (TNM classification) diagnosed from September 2006 to March 2007, with mediastinal lymph nodes invasion according to CT, and with subsequent mediastinal lymph node dissection during autopsy.
RESULTS: 50% of the right upper lobe tumors metastasized into group 1 nodes (N1-N4) and 50% into group 3 (N7). 66% of the right lower lobe tumors metastasized into group 3 nodes (N7) and 33.3% into group 1 (N1-4). 20.0% of the left upper lobe tumors metastasized into group 1 nodes (N1-4), 33.0% into group 2 (N5-6), 25.0% into group 3 (N7) and 16.7% into group 4 (N8-9). 23.5% of the left lower lobe tumors metastasized into group 1 nodes (N1-4), 23.5% into group 2 (N5-6), 23.5 % into group 4 (N8-9) and 29.5% into group 3 (N7). 27.6% of examined patients had false positivity of lymph node metastasis according to CT.
CONCLUSION: Histological verification of suspect mediastinal lymph nodes via Endobronchial Ultrasound Biopsy (EBUS) or mediastinoscopy or thoracoscopy is crucial for determining the stage of the disease according to the TNM classification. False positivity of imaging methods in diagnostics of non-small cell brochogenic carcinoma can contraindicate up to quarter of potentially operable patients (Tab. 3, Ref. 11).


Zhang J, Fujimoto J, Zhang J, et al.
Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing.
Science. 2014; 346(6206):256-9 [PubMed] Related Publications
Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.


de Bruin EC, McGranahan N, Mitter R, et al.
Spatial and temporal diversity in genomic instability processes defines lung cancer evolution.
Science. 2014; 346(6206):251-6 [PubMed] Related Publications
Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.

Related: Non-Small Cell Lung Cancer


Billè A, Giovannetti R, Calarco G, Pastorino U
Tailored stent for bronchial stump fistula closure and omentoplasty for infection control: a combined approach with low morbidity.
Tumori. 2014 Jul-Aug; 100(4):157e-9e [PubMed] Related Publications
Bronchopleural fistula (BPF) after pneumonectomy remains a dangerous complication with high mortality and morbidity. Primary closure of the fistula with muscle flaps and a thoracic window is generally used to treat BPF. New techniques for secondary stump closure including glues, stents and coils have been introduced recently. We report the use of a J-shaped tracheal stent device placed during bronchoscopy combined with omentoplasty to control the symptoms related to BPF and pleural space infection, respectively.


Xu C, Yu LK, Zhang X
Serum receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a diagnostic and prognostic marker for non-small cell lung cancer.
Tumori. 2014 Jul-Aug; 100(4):107e-11e [PubMed] Related Publications
BACKGROUND: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a human tumor-associated antigen that induces cell-cycle arrest and apoptosis in cells bearing the RCAS1 receptor. The aim of the study was to elucidate the diagnostic and prognostic value of RCAS1 levels in patients with non-small cell lung cancer.
METHODS: Sera collected from 30 healthy volunteers, 40 patients with benign lung diseases and 97 non-small cell lung cancer cases were subjected to RCAS1 ELISA, and relationships between serum RCAS1 and clinical characteristics were evaluated.
RESULTS: Serum RCAS1 levels were higher in the non-small cell lung cancer group than in the healthy volunteers and benign lung disease groups (P <0.001). With a cutoff level 19.8 U/ml, RCAS1 had a sensitivity of 87.6%, a specificity of 82.5% and an accuracy of 86.1% for non-small cell lung cancer. Univariate analysis revealed that non-small cell lung cancer patients with elevated RCAS1 levels had significantly shorter overall survival (P = 0.042) than the other two groups. By multivariate analysis, serum RCAS1 was identified as an independent prognostic factor (P = 0.003).
CONCLUSIONS: Assessment of serum RCAS1 levels could be considered as a diagnostic and prognostic marker in non-small cell lung cancer.

Related: Non-Small Cell Lung Cancer


Sun H, Gan ZC, Gao JJ, Zheng F
Non-invasive detection of EGFR deletion at exon 19 in non-small cell lung cancer by real time diagnostic.
Clin Lab. 2014; 60(9):1517-26 [PubMed] Related Publications
BACKGROUND: The non-invasive identification of epidermal growth factor receptor (EGFR) mutations is important for the institution of individualized therapy of non-small cell lung cancer (NSCLC). In this study, the feasibility of screening for EGFR exon 19 E746_A750del mutations in circulating DNA from plasma was assessed.
METHODS: Mutant-specific primers with a Taqman probe (MST-PCR) were designed. The ability of this method to accurately detect decreasing concentrations of E746_A750del mutant within a wild type DNA background that mimics the situation of a plasma sample from patients with acquired mutations is verified. To verify the clinical applicability of this method, 55 plasma samples from NSCLC patients were tested, and the sensitivity of MST-PCR was compared to that of direct sequencing.
RESULTS: The results showed that MST-PCR could detect 10 to 50 copies/microL of E746_A750del, representing 0.1% of the wild type EGFR allelic population. Among the 55 cases of NSCLC, 10 cases of E746_A750del were detected by MST-PCR, while only 1 case was revealed by direct sequencing.
CONCLUSIONS: These findings demonstrate that MST-PCR provides superior sensitivity for the detection of the E746_A750del mutation, suggesting its potential application in the noninvasive detection of E746_A750del mutations in plasma samples from NSCLC patients.

Related: Non-Small Cell Lung Cancer EGFR


Pan JB, Hou YH, Zhang GJ
Correlation between efficacy of the EGFR tyrosine kinase inhibitor and serum tumor markers in lung adenocarcinoma patients.
Clin Lab. 2014; 60(9):1439-47 [PubMed] Related Publications
BACKGROUND: The mutation at epidermal growth factor receptor (EGFR) is a clinical predictor of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer (NSCLC). The serum carcinoembryonic antigen (CEA) level was regarded as a predictive factor for the EGFR-TKI efficacy. Are there any other serum markers? This study analysed the correlation between the EGFR-TKI treatment effect and multiple serum tumor markers only in lung adenocarcinoma to find serum predictive markers for the EGFR-TKI efficacy.
METHODS: Clinical features, survival time, and serum tumor marker levels before EGFR-TKI treatment were analysed, retrospectively, in 48 advanced lung adenocarcinoma patients treated with EGFR-TKI.
RESULTS: With EGFR-TKI treatment, the response rate was 58.3% and disease control rate was 65.6% in lung adenocarcinoma; median survival time was 13.2 months. The efficiency of EGFR-TKI significantly correlated with smoking history and the serum level of CEA and CA199 (p < 0.05). Patients with a higher level of serum CEA and CA199 had a higher disease control rate and longer survival time (p < 0.05).
CONCLUSIONS: Serum CA199 and CEA levels can predict the response of EGFR-TKI in lung adenocarcinoma patients.

Related: EGFR


Karnatovskaia LV, Khoor A, Johnson MM, Kaplan J
A 60-year-old woman with PET scan-avid lung nodules and a history of a ruptured silicone breast implant.
Chest. 2014; 146(4):e138-42 [PubMed] Related Publications
A 60-year-old woman was referred to the pulmonary clinic for evaluation of lung nodules. Her medical history was notable for hypothyroidism, anxiety, and a ruptured breast implant for which incomplete surgical resection and evacuation had been performed 10 years previously. She was a lifelong nonsmoker and worked as a gym instructor. The patient denied occupational exposures and had not traveled recently. Medications included levothyroxine and alprazolam. Except for a 1-month history of occasional dry cough, the review of systems was negative. The patient's physician queried whether the previously ruptured silicone breast implant may have played a role in the genesis of the nodules and referred the patient to our institution for further management. The lack of systemic symptoms relative to the degree of lung involvement provided an early diagnostic clue.


Hogan J, O'Rourke C, Duff G, et al.
Preoperative staging CT thorax in patients with colorectal cancer: its clinical importance.
Dis Colon Rectum. 2014; 57(11):1260-6 [PubMed] Related Publications
BACKGROUND: Recent studies suggest that there is little benefit to routine preoperative staging CT of the thorax in colorectal cancer.
OBJECTIVE: The current study hypothesized that staging CT of the thorax is not mandated in all patients with colorectal cancer.
DESIGN: This study was a tertiary-care center retrospective observational study.
PATIENTS: Patients with a diagnosis of colon and rectal adenocarcinoma during 2006 to 2011 were included in a hospital database. Demographic, pathological, radiological, survival, and clinical factors were recorded. Three hundred eighty-two patients were included in the analysis (234 male, 148 female).
INTERVENTIONS: All patients underwent preoperative staging CT of the thorax to determine the presence of pulmonary metastasis and/or indeterminate lesions.
MAIN OUTCOME MEASURES: Patients demographics were reviewed, and the factors associated with pulmonary metastasis and indeterminate lesions were evaluated.
RESULTS: Distant metastases were evident in 61 patients (16%). CT scans revealed pulmonary metastasis in 23 patients (6%), and indeterminate lesions in 33 (8.6%). Only one-third of pulmonary lesions were evident on chest x-ray. On logistic regression analysis, nodal positivity was associated with an increased risk for pulmonary metastasis (p = 0.03). There was no difference in overall survival between patients with pulmonary metastasis and indeterminate lesions (p = 0.35, Kaplan-Meier estimate, log rank analysis). Pulmonary metastasis developed during postoperative surveillance in 7 patients with indeterminate lesions (21.2%).
LIMITATIONS: This is a retrospective, single-center study with a relatively small sample size.
CONCLUSIONS: Pulmonary metastasis is relatively rare in colorectal cancer, and staging CT of the thorax may not be mandated in low-risk patients.


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