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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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Risk Factors and Prevention of Lung Cancer

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).

Tsutani Y, Miyata Y, Nakayama H, et al.
Appropriate sublobar resection choice for ground glass opacity-dominant clinical stage IA lung adenocarcinoma: wedge resection or segmentectomy.
Chest. 2014; 145(1):66-71 [PubMed] Related Publications
BACKGROUND: The purpose of this multicenter study was to characterize ground glass opacity (GGO)-dominant clinical stage IA lung adenocarcinomas and evaluate prognosis of these tumors after sublobar resection, such as segmentectomy and wedge resection.
METHODS: We evaluated 610 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection after preoperative high-resolution CT scanning and 18 F-fl uorodeoxyglucose PET/CT scanning and revealed 239 (39.2%) that had a . 50% GGO component.
RESULTS: GGO-dominant tumors rarely exhibited pathologic invasiveness, including lymphatic, vascular, or pleural invasion and lymph node metastasis. There was no significant difference in 3-year recurrence-free survival (RFS) among patients who underwent lobectomy (96.4%), segmentectomy (96.1%), and wedge resection (98.7%) of GGO-dominant tumors ( P = .44). Furthermore, for GGO-dominant T1b tumors, 3-year RFS was similar in patients who underwent lobectomy (93.7%), segmentectomy (92.9%), and wedge resection (100%, P = .66). Two of 84 patients (2.4%) with GGO-dominant T1b tumors had lymph node metastasis. Multivariate Cox analysis showed that tumor size, maximum standardized uptake value on 18 F-fl uorodeoxyglucose PET/CT scan, and surgical procedure did not affect RFS in GGO-dominant tumors.
CONCLUSIONS: GGO-dominant clinical stage IA lung adenocarcinomas are a uniform group of tumors that exhibit low-grade malignancy and have an extremely favorable prognosis. Patients with GGOdominant clinical stage IA adenocarcinomas can be successfully treated with wedge resection of a T1a tumor and segmentectomy of a T1b tumor.

Walker K
International Association for the Study of Lung Cancer - 15th World Conference on Lung Cancer (October 27-31, 2013 - Sydney, Australia).
Drugs Today (Barc). 2013; 49(12):803-8 [PubMed] Related Publications
The 15th World Conference on Lung Cancer, organized by the International Association for the Study of Lung Cancer (IASLC), launched the association's celebration of its 40th year promoting research into lung cancer. This year's congress saw highlights from groundbreaking research in several areas, including surgery, radiation oncology, chemo-therapy, immunotherapy, imaging and screening, prevention and epidemiology, and supportive care, with a record number of delegates in attendance. This report focuses on highlights from a poster, oral and mini oral sessions covering from several tracks.

Related: Non-Small Cell Lung Cancer Small Cell Lung Cancer

Xing F, Yang L
Robust selection-based sparse shape model for lung cancer image segmentation.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):404-12 [PubMed] Related Publications
Accurate cellular level segmentation of lung cancer is the prerequisite to extract objective morphological features in digitized pathology specimens. It is of great importance for image-guided diagnosis and prognosis. However, it is challenging to correctly and robustly segment cells in lung cancer images due to cell occlusion or touching, intracellular inhomogeneity, background clutter, etc. In this paper, we present a novel segmentation algorithm combining a robust selection-based sparse shape model (top-down) and an efficient local repulsive balloon snake deformable model (bottom-up) to tackle these challenges. The algorithm has been extensively tested on 62 cases with over 6000 tumor cells. We experimentally demonstrate that the proposed algorithm can produce better performance than other state-of-the-art methods.

Related: Non-Small Cell Lung Cancer

Grimm R, Fürst S, Dregely I, et al.
Self-gated radial MRI for respiratory motion compensation on hybrid PET/MR systems.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):17-24 [PubMed] Related Publications
Accurate localization and uptake quantification of lesions in the chest and abdomen using PET imaging is challenging due to the respiratory motion during the exam. The advent of hybrid PET/MR systems offers new ways to compensate for respiratory motion without exposing the patient to additional radiation. The use of self-gated reconstructions of a 3D radial stack-of-stars GRE acquisition is proposed to derive a high-resolution MRI motion model. The self-gating signal is used to perform respiratory binning of the simultaneously acquired PET raw data. Matching mu-maps are generated for every bin, and post-reconstruction registration is performed in order to obtain a motion-compensated PET volume from the individual gates. The proposed method is demonstrated in-vivo for three clinical patients. Motion-corrected reconstructions are compared against ungated and gated PET reconstructions. In all cases, motion-induced blurring of lesions in the liver and lung was substantially reduced, without compromising SNR as it is the case for gated reconstructions.

Mlika M, Ayadi-Kaddour A, Boudaya S, et al.
About the necessity of improving the current nodal classification of non-small cell lung carcinoma.
Pathologica. 2013; 105(4):117-21 [PubMed] Related Publications
BACKGROUND: The current classification of lymph node status in non-small cell lung carcinoma has not been revised since 1997. This fact has prompted many authors to point out the limits of this classification.
METHODS: We tried to explore the prognostic relevance of the current TNM classification in comparison with the nodal classification based on the ratio of metastatic lymph nodes (LNR) and the nodal classification based on the number of metastatic LNs (nLN). Additionally, we tried to explore the recommended number of resected LNs. This was done through a retrospective study of 39 cases. We compared the survival curves of patients using the current, RLN and nLN classifications. In the nLN classification, we grouped patients into three categories: nNO (no metastatic LNs), nN1 (1 to 2 metastatic LNs) and nN2 (> 2 metastatic LN). In the LNR classification, we grouped patients into three categories: rNO (0%), rN1 (< or = 12) and rN2 (> 12). Concerning the total number of the resected LNs, patients were categorized into two groups according to the number of LNs: < 10 versus > or = 10 and < 15 versus > or = 15.
RESULTS: Our results showed that the LNR classification highlighted a difference in prognosis between the rN1 and rN2 groups. Moreover, survival of patients seemed to be better when the number of the resected LNs was higher.
CONCLUSION: The ratio of metastatic LNs seems to be an important prognostic factor, but further studies are necessary to standardize this classification.

Related: Non-Small Cell Lung Cancer

Moreira AL, Joubert P, Downey RJ, Rekhtman N
Cribriform and fused glands are patterns of high-grade pulmonary adenocarcinoma.
Hum Pathol. 2014; 45(2):213-20 [PubMed] Related Publications
The 2011 International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification of pulmonary adenocarcinoma recognizes the prognostic significance of different histologic patterns but does not address the issue of tumor grade. We previously developed an objective and prognostic grading system for pulmonary adenocarcinomas that is based on associating patterns with their metastatic potential. The best prognostic stratification was achieved by summing the grades of the 2 most predominant patterns (histologic score). Here, we extend this work by evaluating the prognostic importance of variant patterns of adenocarcinoma, which are not recognized by the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Pathologic specimens from 249 resected stage I adenocarcinomas were reviewed. The proportions of standard and nonstandard patterns (cribriform and fused glands) were recorded for each case. The associations between the presence of standard and nonstandard patterns, tumor histologic score, and disease-free survival were evaluated. Cribriform and fused gland patterns were observed in 15% and 29% of tumors, respectively. These nonstandard patterns each composed 10% to 100% of the entire tumors but were the predominant pattern in only 5% and 7% of tumors, respectively. The presence of complex glandular patterns was associated with solid pattern (P < .001) and high histologic score (P < .0001). Disease-free survival for tumors with predominant complex glandular patterns was similar to that for high-grade tumors (P = .932) and was significantly worse than that for low- and intermediate-grade tumors (P = .0025). Complex glandular patterns have a significant prognostic value and should be considered patterns of high-grade adenocarcinoma.

Related: KRAS gene

Qian Z, Qingshan C, Chun J, et al.
High expression of TNFSF13 in tumor cells and fibroblasts is associated with poor prognosis in non-small cell lung cancer.
Am J Clin Pathol. 2014; 141(2):226-33 [PubMed] Related Publications
OBJECTIVES: To examine high expression of tumor necrosis factor ligand superfamily member 13 (TNFSF13), which is correlated with several malignancies.
METHODS: TNFSF13 messenger RNA expression in tumor cells and fibroblasts in a cohort of patients with non-small cell lung cancer (NSCLC) was analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry using a tissue microarray.
RESULTS: TNFSF13 expression was significantly higher in lung adenocarcinomas compared with squamous cell carcinomas (P = .022). High TNFSF13 expression in NSCLC stroma was related with low differentiation (P = .045) and sex (male > female, P = .005). Cox proportional hazards regression univariate and multivariable analysis revealed TNFSF13 expression in NSCLC tumor cells (P = .007) or fibroblasts (P = .027) as an independent prognostic factor in the 5-year overall survival rate.
CONCLUSIONS: Our findings indicate TNFSF13 is a prognostic factor in NSCLC and suggest TNFSF13 may be a novel therapeutic target for NSCLC.

Related: Non-Small Cell Lung Cancer

Stella GM, Luisetti M, Pozzi E, Comoglio PM
Oncogenes in non-small-cell lung cancer: emerging connections and novel therapeutic dynamics.
Lancet Respir Med. 2013; 1(3):251-61 [PubMed] Related Publications
Non-small-cell lung cancer is a heterogeneous disease that is difficult to treat. Through efforts to define the molecular mechanisms involved in lung oncogenesis, molecularly targeted approaches for patients with lung cancer have now reached the clinical arena. Despite elucidation of some molecular mechanisms of lung carcinogenesis, prognosis for patients remains poor. This Review aims to highlight the functional associations between key oncogenes that drive lung tumorigenesis and are distinct targetable molecules. Oncogenes are defined by acquisition of mutations, which results in a dominant gain-of-function of the targeted protein. In this situation, a single mutated allele is sufficient to induce malignant transformation. Importantly, tumours become addicted to particular genetic alterations that cause oncogene activation and the continued expression of the signalling. An increasing amount of evidence sustains the rationale for targeting of oncogenic pathways rather than a single oncogene. A clear priority for both researchers and clinicians is to better understand the complexity of biological networks underlying lung cancer pathogenesis. This paradigmatic shift in tailoring therapies should effectively improve outcomes for patients.

Related: Non-Small Cell Lung Cancer

Brown Johnson CG, Brodsky JL, Cataldo JK
Lung cancer stigma, anxiety, depression, and quality of life.
J Psychosoc Oncol. 2014; 32(1):59-73 [PubMed] Related Publications
This study investigated lung cancer stigma, anxiety, depression, and quality of life (QOL) and validated variable similarities between ever and never smokers. Patients took online self-report surveys. Variable contributions to QOL were investigated using hierarchical multiple regression. Patients were primarily White females with smoking experience. Strong negative relationships emerged between QOL and anxiety, depression and lung cancer stigma. Lung cancer stigma provided significant explanation of the variance in QOL beyond covariates. No difference emerged between smoker groups for study variables. Stigma may play a role in predicting QOL. Interventions promoting social and psychological QOL may enhance stigma resistance skills.

Javed MA, Sheel AR, Sheikh AA, et al.
Size of metastatic deposits affects prognosis in patients undergoing pulmonary metastectomy for colorectal cancer.
Ann R Coll Surg Engl. 2014; 96(1):32-6 [PubMed] Related Publications
INTRODUCTION: Pulmonary metastectomy for colorectal cancer (CRC) is a well accepted procedure although data regarding indications and prognostic outcomes are inconsistent. This study aimed to analyse our experience with resection of pulmonary CRC metastases to evaluate clinically relevant prognostic factors affecting survival.
METHODS: A retrospective analysis was undertaken of the records of all patients with pulmonary metastases from CRC who underwent a thoracotomy between 2004 and 2010 at a single surgical centre.
RESULTS: Sixty-six patients with pulmonary metastases from the colon (n=34) and the rectum (n=32) were identified. The 30-day hospital mortality rate was 0%, with 63 patients undergoing a R0 resection and 3 having a R1 resection. The median survival was 45 months and the cumulative 3-year survival rate was 61%. Size of pulmonary metastasis and ASA (American Society of Anesthesiologists) grade were statistically significant prognostic factors (p=0.047 and p=0.009 respectively) with lesions over 20mm associated with a worse prognosis. Sex, age, site, disease free interval (cut-off 36 months), primary tumour stage, hepatic metastases, number of metastases (solitary vs multiple), type of operation (wedge vs lobe resection), hilar lymph node involvement and administration of adjuvant chemotherapy were not found to be statistically significant prognostic factors.
CONCLUSIONS: Pulmonary metastectomy has a potential survival benefit for patients with metastatic CRC. Improved survival even in the presence of hepatic metastases or multiple pulmonary lesions justifies aggressive surgical management in carefully selected patients. In our cohort, size of metastatic deposit was a statistically significant poor prognostic factor.

Milner J, Shrubsole C, Das P, et al.
Home energy efficiency and radon related risk of lung cancer: modelling study.
BMJ. 2014; 348:f7493 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To investigate the effect of reducing home ventilation as part of household energy efficiency measures on deaths from radon related lung cancer.
DESIGN: Modelling study.
SETTING: England.
INTERVENTION: Home energy efficiency interventions, motivated in part by targets for reducing greenhouse gases, which entail reduction in uncontrolled ventilation in keeping with good practice guidance.
MAIN OUTCOME MEASURES: Modelled current and future distributions of indoor radon levels for the English housing stock and associated changes in life years due to lung cancer mortality, estimated using life tables.
RESULTS: Increasing the air tightness of dwellings (without compensatory purpose-provided ventilation) increased mean indoor radon concentrations by an estimated 56.6%, from 21.2 becquerels per cubic metre (Bq/m(3)) to 33.2 Bq/m(3). After the lag in lung cancer onset, this would result in an additional annual burden of 4700 life years lost and (at peak) 278 deaths. The increases in radon levels for the millions of homes that would contribute most of the additional burden are below the threshold at which radon remediation measures are cost effective. Fitting extraction fans and trickle ventilators to restore ventilation will help offset the additional burden but only if the ventilation related energy efficiency gains are lost. Mechanical ventilation systems with heat recovery may lower radon levels and the risk of cancer while maintaining the advantage of energy efficiency for the most airtight dwellings but there is potential for a major adverse impact on health if such systems fail.
CONCLUSION: Unless specific remediation is used, reducing the ventilation of dwellings will improve energy efficiency only at the expense of population wide adverse impact on indoor exposure to radon and risk of lung cancer. The implications of this and other consequences of changes to ventilation need to be carefully evaluated to ensure that the desirable health and environmental benefits of home energy efficiency are not compromised by avoidable negative impacts on indoor air quality.

Kaabachi S, Kaabachi W, Rafrafi A, et al.
Tumor necrosis factor gene polymorphisms in Tunisian patients with non-small cell lung cancer.
Clin Lab. 2013; 59(11-12):1389-95 [PubMed] Related Publications
BACKGROUND: Lung cancer (LC) is one of the most lethal malignant disorders; it is generally divided into two groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In our present study we have been interested to NSCLC. Several approaches were adopted to study the etiology or pathophysiology of this disease. As recent reports have focused on the genetic susceptibility to this disease, with many candidate genes studied, we chose TNF in view of the major role it plays in the immune pro inflammatory system and its association with increased risk of a variety of human cancers. We have investigated three polymorphisms in the promoter region of the TNFalpha gene (-308 G/A and -238 G/A) and TNFbeta + 252A > G for their susceptibility to non-small cell lung cancer (NSCLC) in Tunisian population.
METHODS: We compared the distribution of these polymorphisms between 133 NSCLC patients and 174 healthy controls using a polymerase chain reaction restriction fragment length-polymorphism (PCR-RFLP) analysis. The frequencies of the two TNFalpha (-238 and -308) "A" alleles were significantly higher in NSCLC patients than in healthy controls respectively (p = 0.01; OR = 1.92; 95% CI 1.14 - 3.23 and p = 0.0000008; OR = 3.65; 95% CI 2.12 - 6.30), whereas the frequency of the TNFbeta + 252 G allele was approximately similar in the two compared groups.
RESULTS: This study supports a relationship between TNFalpha -238G/A and TNFalpha -308G/A polymorphisms and the susceptibility to lung cancer. Contrary to other studies, the -308 A and -238A alleles have an inductive action on lung cancer development and progression in our Tunisian population.
CONCLUSIONS: This study indicates that the TNFalpha -308G > A and TNFalpha -238G > A would be associated with increased susceptibility to lung cancer but no significant association was found in TNFbeta + 252A > G polymorphism.

Related: Non-Small Cell Lung Cancer Polymorphisms TNF

Boldo E, Linares C, Aragonés N, et al.
Air quality modeling and mortality impact of fine particles reduction policies in Spain.
Environ Res. 2014; 128:15-26 [PubMed] Related Publications
BACKGROUND: In recent years, Spain has implemented a number of air quality control measures that are expected to lead to a future reduction in fine particle concentrations and an ensuing positive impact on public health.
OBJECTIVES: We aimed to assess the impact on mortality attributable to a reduction in fine particle levels in Spain in 2014 in relation to the estimated level for 2007.
METHODS: To estimate exposure, we constructed fine particle distribution models for Spain for 2007 (reference scenario) and 2014 (projected scenario) with a spatial resolution of 16×16km(2). In a second step, we used the concentration-response functions proposed by cohort studies carried out in Europe (European Study of Cohorts for Air Pollution Effects and Rome longitudinal cohort) and North America (American Cancer Society cohort, Harvard Six Cities study and Canadian national cohort) to calculate the number of attributable annual deaths corresponding to all causes, all non-accidental causes, ischemic heart disease and lung cancer among persons aged over 25 years (2005-2007 mortality rate data). We examined the effect of the Spanish demographic shift in our analysis using 2007 and 2012 population figures.
RESULTS: Our model suggested that there would be a mean overall reduction in fine particle levels of 1µg/m(3) by 2014. Taking into account 2007 population data, between 8 and 15 all-cause deaths per 100,000 population could be postponed annually by the expected reduction in fine particle levels. For specific subgroups, estimates varied from 10 to 30 deaths for all non-accidental causes, from 1 to 5 for lung cancer, and from 2 to 6 for ischemic heart disease. The expected burden of preventable mortality would be even higher in the future due to the Spanish population growth. Taking into account the population older than 30 years in 2012, the absolute mortality impact estimate would increase approximately by 18%.
CONCLUSIONS: Effective implementation of air quality measures in Spain, in a scenario with a short-term projection, would amount to an appreciable decline in fine particle concentrations, and this, in turn, would lead to notable health-related benefits. Recent European cohort studies strengthen the evidence of an association between long-term exposure to fine particles and health effects, and could enhance the health impact quantification in Europe. Air quality models can contribute to improved assessment of air pollution health impact estimates, particularly in study areas without air pollution monitoring data.

Yu H, Jiang L, Sun C, et al.
Decreased circulating miR-375: a potential biomarker for patients with non-small-cell lung cancer.
Gene. 2014; 534(1):60-5 [PubMed] Related Publications
MicroRNAs (miRNAs) are directly involved in cancer initiation, progression and metastasis. Alterations of miRNAs expression in cancer tissue may be reflected in circulation.We attempted to investigate the expression and clinical significance of plasma miR-20a, miR-31 and miR-375 in patients with non-small cell lung cancer (NSCLC). The plasma levels of miR-20a, miR-31 and miR-375 in 164 NSCLC patients and 164 healthy controls (discovery cohort)were evaluated and compared among various clinicopathological characteristics. The relationship between miRNA expression and clinical outcome of NSCLC patients was examined in an independent cohort (53 cases and 53 controls). The expression level of miR-375 in tissue was also examined. Plasma miR-375 levels in NSCLC patients were significantly decreased in both patient cohorts (P b 0.05). In addition, patients with metastatic NSCLC had lower plasma miR-375 expression than those with non-metastatic NSCLC (P b 0.05). Survival analysis showed that patients with low miR-375 expression had worse overall survival rates than those with high miR-375 expression (hazard ratios (HR)=1.537 (1.046–2.258), P=0.029). This association was independently validated in a separate cohort of 53 NSCLC patients (HR=2.406, 95% CI 1.170–4.945, P=0.017). The expression level of miR-375 was also found to be significantly down-regulated in NSCLC tissues compared with paracancerous tissues (P b 0.001). These findings indicate that miR-375 has an important role in NSCLC initiation and progression, and may be an independent poor prognostic factor in NSCLC patients.

Related: Non-Small Cell Lung Cancer

Henley SJ, Richards TB, Underwood JM, et al.
Lung cancer incidence trends among men and women--United States, 2005-2009.
MMWR Morb Mortal Wkly Rep. 2014; 63(1):1-5 [PubMed] Related Publications
Lung cancer is the leading cause of cancer death and the second most commonly diagnosed cancer (excluding skin cancer) among men and women in the United States. Although lung cancer can be caused by environmental exposures, most efforts to prevent lung cancer emphasize tobacco control because 80%-90% of lung cancers are attributed to cigarette smoking and secondhand smoke. One sentinel health consequence of tobacco use is lung cancer, and one way to measure the impact of tobacco control is by examining trends in lung cancer incidence rates, particularly among younger adults. Changes in lung cancer rates among younger adults likely reflect recent changes in risk exposure. To assess lung cancer incidence and trends among men and women by age group, CDC used data from the National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for the period 2005-2009, the most recent data available. During the study period, lung cancer incidence decreased among men in all age groups except <35 years and decreased among women aged 35-44 years and 54-64 years. Lung cancer incidence decreased more rapidly among men than among women and more rapidly among adults aged 35-44 years than among other age groups. To further reduce lung cancer incidence in the United States, proven population-based tobacco prevention and control strategies should receive sustained attention and support.

Related: USA

Yamashita T, Kamada H, Kanasaki S, et al.
Epidermal growth factor receptor localized to exosome membranes as a possible biomarker for lung cancer diagnosis.
Pharmazie. 2013; 68(12):969-73 [PubMed] Related Publications
Detection of drug-target proteins and biomarkers that are expressed in cancer tissue has significant potential for both diagnosis and treatment of cancer. However, current immuno-histochemical and cytogenetic analyses of biopsy specimens for pre-operational diagnosis are highly invasive and often difficult to apply to lung cancer patients. The purpose of this study was to evaluate the possible utility of determining epidermal growth factor receptor (EGFR) expression on exosomal membranes using a targeted ELISA with an anti-CD81 antibody as a capture antibody for lung cancer diagnosis. While soluble EGFR (sEGFR) levels in plasma were not remarkably different between lung cancer patients and normal controls, significantly higher exosomal EGFR expression levels were observed in 5/9 cancer cases compared to normal controls. These results suggest that measurement of exosomal protein levels could be useful for in vitro diagnosis, and that exosomal EGFR is a possible biomarker for characterization of lung cancer.

Malefyt AP, Wu M, Vocelle DB, et al.
Improved asymmetry prediction for short interfering RNAs.
FEBS J. 2014; 281(1):320-30 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
In the development of RNA interference therapeutics, merely selecting short interfering RNA (siRNA) sequences that are complementary to the mRNA target does not guarantee target silencing. Current algorithms for selecting siRNAs rely on many parameters, one of which is asymmetry, often predicted through calculation of the relative thermodynamic stabilities of the two ends of the siRNA. However, we have previously shown that highly active siRNA sequences are likely to have particular nucleotides at each 5'-end, independently of their thermodynamic asymmetry. Here, we describe an algorithm for predicting highly active siRNA sequences based only on these two asymmetry parameters. The algorithm uses end-sequence nucleotide preferences and predicted thermodynamic stabilities, each weighted on the basis of training data from the literature, to rank the probability that an siRNA sequence will have high or low activity. The algorithm successfully predicts weakly and highly active sequences for enhanced green fluorescent protein and protein kinase R. Use of these two parameters in combination improves the prediction of siRNA activity over current approaches for predicting asymmetry. Going forward, we anticipate that this approach to siRNA asymmetry prediction will be incorporated into the next generation of siRNA selection algorithms.

Related: Non-Small Cell Lung Cancer

Hellmann MD, Chaft JE, William WN, et al.
Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint.
Lancet Oncol. 2014; 15(1):e42-50 [PubMed] Related Publications
Improvements in outcomes for patients with resectable lung cancers have plateaued. Clinical trials of resectable non-small-cell lung cancers with overall survival as the primary endpoint require a decade or longer to complete, are expensive, and limit innovation. A surrogate for survival, such as pathological response to neoadjuvant chemotherapy, has the potential to improve the efficiency of trials and expedite advances. 10% or less residual viable tumour after neoadjuvant chemotherapy, termed here major pathological response, meets criteria for a surrogate; major pathological response strongly associates with improved survival, is reflective of treatment effect, and captures the magnitude of the treatment benefit on survival. We support the incorporation of major pathological response as a surrogate endpoint for survival in future neoadjuvant trials of resectable lung cancers. Additional prospective studies are needed to confirm the validity and reproducibility of major pathological response within individual histological and molecular subgroups and with new drugs.

Related: Non-Small Cell Lung Cancer

Menna C, De Falco E, Pacini L, et al.
Axitinib affects cell viability and migration of a primary foetal lung adenocarcinoma culture.
Cancer Invest. 2014; 32(1):13-21 [PubMed] Related Publications
Fetal lung adenocarcinoma (FLAC) is a rare variant of lung adenocarcinoma. Studies regarding FLAC have been based only on histopathological observations, thus representative in vitro models of FLAC cultures are unavailable. We have established and characterized a human primary FLAC cell culture, exploring its biology, chemosensitivity, and migration. FLAC cells and specimen showed significant upregulation of VEGF165 and HIF-1α mRNA levels. This observation was confirmed by in vitro chemosensitivity and migration assay, showing that only Axitinib was comparable to Cisplatin treatment. We provide a suitable in vitro model to further investigate the nature of this rare type of cancer.

Related: Cisplatin VEGFA

Sachdeva R, Gupta KB, Mathur SK, Sachdeva S
Solitary fibrous tumour of lung.
Indian J Chest Dis Allied Sci. 2013 Jul-Sep; 55(3):171-3 [PubMed] Related Publications
Fibrous tumours arising entirely within the substance of the lung are rare. We report one such rare case in whom the diagnosis was established after surgical removal.

Murugan P, Stevenson ME, Hassell LA
Performance validation in anatomic pathology: successful integration of a new classification system into the practice setting using the updated lung non-small cell carcinoma recommendations.
Arch Pathol Lab Med. 2014; 138(1):105-9 [PubMed] Related Publications
CONTEXT: The new, international, multidisciplinary classification of lung adenocarcinoma, from the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society, presents a paradigm shift for diagnostic pathologists.
OBJECTIVE: To validate our ability to apply the recommendations in reporting on non-small cell lung cancer cases.
DESIGN: A test based on the new non-small cell lung cancer classification was administered to 16 pathology faculty members, senior residents, and fellows before and after major educational interventions, which included circulation of articles, electronic presentations, and live presentations by a well-known lung pathologist. Surgical and cytologic (including cell-block material) reports of lung malignancies for representative periods before and after the educational interventions were reviewed for compliance with the new guidelines. Cases were scored on a 3-point scale, with 1 indicating incorrect terminology and/or highly inappropriate stain use, 2 indicating correct diagnostic terminology with suboptimal stain use, and 3 indicating appropriate diagnosis and stain use. The actual error type was also evaluated.
RESULTS: The average score on initial testing was 55%, increasing to 88% following the educational interventions (60% improvement). Of the 54 reports evaluated before intervention, participants scored 3 out of 3 points on 15 cases (28%), 2 of 3 on 31 cases (57%), and 1 of 3 on 8 cases (15%). Incorrect use of stains was noted in 23 of 54 cases (43%), incorrect terminology in 15 of 54 cases (28%), and inappropriate use of tissue, precluding possible molecular testing, in 4 out of 54 cases (7%). Of the 55 cases after intervention, participants scored 3 out of 3 points on 46 cases (84%), 2 of 3 on 8 cases (15%), and 1 of 3 on 1 case (2%). Incorrect use of stains was identified in 9 of 55 cases (16% of total reports), and inappropriate use of tissue, precluding possible molecular testing, was found in 1 of the 55 cases (2%).
CONCLUSIONS: The study results demonstrated marked improvement in the pathologists' understanding and application of the new non-small cell lung cancer classification recommendations, which was sufficient to validate our use of the system in routine practice. The results also affirm the value of intensive education on, and validation of, pathologists' use of a classification or diagnostic algorithm.

Related: Non-Small Cell Lung Cancer

Mattei J, Achcar RD, Cano CH, et al.
Gastrin-releasing peptide receptor expression in lung cancer.
Arch Pathol Lab Med. 2014; 138(1):98-104 [PubMed] Related Publications
CONTEXT: Gastrin-releasing peptide receptors (GRPRs) activate mitogen-activated protein kinase signaling pathway primarily through epidermal growth factor receptor activation and are under investigation as a molecular target because they are overexpressed in several solid tumors.
OBJECTIVE: To determine GRPR expression in both non-small cell lung carcinoma and small cell lung carcinoma, comparing results with clinical stages and demographic data.
DESIGN: We analyzed the immunohistochemical expression of GRPR in 200 non-small cell lung carcinoma and 38 small cell lung carcinoma archival cases from 2004 to 2008.
RESULTS: Non-small cell lung carcinoma cases tended to be higher GRPR expressers at a rate of 62.5% (weak, moderate, and strong expression in 41.5%, 13.5%, and 7.5%, respectively), compared with 52.62% in small cell lung carcinoma cases (weak, moderate, and strong expression in 34.21%, 15.78%, and 2.63%, respectively; P = .30). In non-small cell lung carcinoma there was a trend for higher percentages of strong expression in adenocarcinoma cases (10%; P = .67), and in patients with advanced stages (III and IV; 9.43% and 6.9%; P = .01).
CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate GRPR tissue expression in a large population of patients with lung cancer. Although GRPR expression was similar in small cell and non-small cell carcinoma, the expression was more pronounced in an advanced-stage lung cancer, particularly in adenocarcinoma cases, and may represent a potential target for the development of new treatment approaches in this population.

Related: Non-Small Cell Lung Cancer

Yildiz-Aktas IZ, Sturgis CD, Barkan GA, et al.
Primary pulmonary non-small cell carcinomas: the College of American Pathologists Interlaboratory Comparison Program confirms a significant trend toward subcategorization based upon fine-needle aspiration cytomorphology alone.
Arch Pathol Lab Med. 2014; 138(1):65-70 [PubMed] Related Publications
Context.-Subtyping of non-small cell lung carcinomas (NSCLCs) is necessary for optimal patient management with specific diagnoses triggering specific molecular tests and affecting therapy. Objective.-To assess the accuracy of the participants of the College of American Pathologists Interlaboratory Comparison Program in diagnosing and subtyping NSCLC fine-needle aspiration (FNA) slides, based on morphology alone, considering preparation and participant type and trends over time. Design.-The performance of program participants was reviewed for the 5-year period spanning 2007-2011. Lung FNA challenges with reference diagnoses of adenocarcinoma and squamous cell carcinoma (SCC) were evaluated for diagnostic concordance by using a nonlinear mixed model analysis. Results.-There were 10 493 pathologist and 6378 cytotechnologist responses with concordance rates of 97.4% and 97.9% for malignancy, respectively. Overall concordance rates for subcategorization were 54.6% for adenocarcinoma and 74.9% for SCC. For the exact reference diagnoses, pathologists performed better for adenocarcinoma and cytotechnologists performed better for SCC. Accurate subcategorization of adenocarcinomas significantly increased over time with 31.5% of adenocarcinomas classified as NSCLC in 2007 and 25.5% of adenocarcinomas classified as NSCLC in 2011 (P < .001). In comparing preparation types, modified Giemsa-stained smears showed the lowest overall concordance (46.8%). Modified Giemsa-stained smears with SCCs were the least likely to be accurately subcategorized (36.4%). Conclusions.-Participants are proficient at interpreting NSCLCs as malignant by FNA but are less successful at subcategorization with cytomorphology alone. During the study period, a statistically significant trend was confirmed toward greater accuracy of subcategorization of adenocarcinomas, suggesting that participants are cognizant of the impact that more specific cytomorphologic interpretations have in directing molecular triage and therapy.

Related: Non-Small Cell Lung Cancer

Lu TP, Chuang EY, Chen JJ
Identification of reproducible gene expression signatures in lung adenocarcinoma.
BMC Bioinformatics. 2013; 14:371 [PubMed] Article available free on PMC after 01/01/2015 Related Publications
BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Tremendous research efforts have been devoted to improving treatment procedures, but the average five-year overall survival rates are still less than 20%. Many biomarkers have been identified for predicting survival; challenges arise, however, in translating the findings into clinical practice due to their inconsistency and irreproducibility. In this study, we proposed an approach by identifying predictive genes through pathways.
RESULTS: The microarrays from Shedden et al. were used as the training set, and the log-rank test was performed to select potential signature genes. We focused on 24 cancer-related pathways from 4 biological databases. A scoring scheme was developed by the Cox hazard regression model, and patients were divided into two groups based on the medians. Subsequently, their predictability and generalizability were evaluated by the 2-fold cross-validation and a resampling test in 4 independent datasets, respectively. A set of 16 genes related to apoptosis execution was demonstrated to have good predictability as well as generalizability in more than 700 lung adenocarcinoma patients and was reproducible in 4 independent datasets. This signature set was shown to have superior performances compared to 6 other published signatures. Furthermore, the corresponding risk scores derived from the set were found to associate with the efficacy of the anti-cancer drug ZD-6474 targeting EGFR.
CONCLUSIONS: In summary, we presented a new approach to identify reproducible survival predictors for lung adenocarcinoma, and the identified genes may serve as both prognostic and predictive biomarkers in the future.

Marech I, Vacca A, Gnoni A, et al.
Surgical resection of locally advanced epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma after gefitinib and review of the literature.
Tumori. 2013 Sep-Oct; 99(5):e241-4 [PubMed] Related Publications
Gefitinib is the current first-line treatment for advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutations. The possibility of using gefitinib as neoadjuvant therapy is interesting because of the low toxicity profile of tyrosine kinase inhibitors. Here we report the case of a 67-year-old nonsmoking woman affected by locally advanced lung adenocarcinoma, in whom one-year treatment with gefitinib rendered the tumor amenable to surgical removal. The results of ongoing clinical trials exploring the ability of preoperative gefitinib to achieve better results than can be obtained with chemotherapy in patients selected on the basis of EGFR mutations are urgently awaited.

Related: Gefitinib (Iressa)

Bavieri M, Tiseo M, Lantuejoul S, et al.
Fishing for ALK with immunohistochemistry may predict response to crizotinib.
Tumori. 2013 Sep-Oct; 99(5):e229-32 [PubMed] Related Publications
BACKGROUND: ALK (anaplastic lymphoma kinase) gene rearrangement is a novel oncogenic driver in non-small cell lung cancer (NSCLC) against which a selective inhibitor, namely crizotinib, is effective. Fluorescence in situ hybridization (FISH) is considered the reference method in selecting patients with ALK-positive tumors for treatment with crizotinib.
CASE REPORT: We report the case of a 42-year-old non-smoking woman with an advanced pulmonary ALK FISH-negative adenocarcinoma characterized by strong immunohistochemical expression of ALK fusion protein. The patient received targeted therapy with crizotinib in compassionate use and experienced a long-lasting clinical response.
CONCLUSION: FISH testing should not be considered the only method to select patients for therapy with ALK inhibitors and the use of multiple ALK-detecting techniques could be helpful in screening ALK-positive patients more appropriately.

Related: Non-Small Cell Lung Cancer FISH Crizotinib (Xalkori)

Thomas DC
Invited commentary: is it time to retire the "pack-years" variable? Maybe not!
Am J Epidemiol. 2014; 179(3):299-302 [PubMed] Article available free on PMC after 01/02/2015 Related Publications
Cumulative exposure--the product of intensity and duration for a constant exposure rate or its integral over time if variable--has been widely used in epidemiologic analyses of extended exposures, for example, the "pack-years" variable for tobacco smoking. Although the effects of intensity and duration are known to differ for exposures like smoking and ionizing radiation and simple cumulative exposure does not explicitly allow for modification by other time-related variables, such as age at exposure or time since exposure, the cumulative exposure variable has the merit of simplicity and has been shown to be one of the best predictors for many exposure-response relationships. This commentary discusses recent refinements of the pack-years variable, as discussed in this issue of the Journal by Vlaanderen et al. (Am J Epidemiol. 2014;179(3):290-298), in the broader context of general exposure-time-response relationships.

Related: Smoking and Smoking Cessation

Vlaanderen J, Portengen L, Schüz J, et al.
Effect modification of the association of cumulative exposure and cancer risk by intensity of exposure and time since exposure cessation: a flexible method applied to cigarette smoking and lung cancer in the SYNERGY Study.
Am J Epidemiol. 2014; 179(3):290-8 [PubMed] Article available free on PMC after 01/02/2015 Related Publications
The indiscriminate use of the cumulative exposure metric (the product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and cancer risk. To assess the independent effects of duration and intensity of exposure on cancer risk, we explored effect modification of the association of cumulative exposure and cancer risk by intensity of exposure. We applied a flexible excess odds ratio model that is linear in cumulative exposure but potentially nonlinear in intensity of exposure to 15 case-control studies of cigarette smoking and lung cancer (1985-2009). Our model accommodated modification of the excess odds ratio per pack-year of cigarette smoking by time since smoking cessation among former smokers. We observed negative effect modification of the association of pack-years of cigarette smoking and lung cancer by intensity of cigarette smoke for persons who smoked more than 20-30 cigarettes per day. Patterns of effect modification were similar across individual studies and across major lung cancer subtypes. We observed strong negative effect modification by time since smoking cessation. Application of our method in this example of cigarette smoking and lung cancer demonstrated that reducing a complex exposure history to a metric such as cumulative exposure is too restrictive.

Related: Canada Smoking and Smoking Cessation

Voulgaridis A, Apollonatou V, Lykouras D, et al.
Pleural mesothelioma in a young male patient.
Monaldi Arch Chest Dis. 2013; 79(2):96-9 [PubMed] Related Publications
We present the case of a 33-year-old male patient suffering from lymphocytic pleural effusion, as a result of pleural mesothelioma. Mesothelioma is a malignant tumor of the pleura that is mainly caused by chronic exposure to asbestos fibers and more than 40 years of exposure are needed to develop the disease. Early studies on the relationship of asbestos and mesothelioma were issued in the 1960s. Fibers migrate from the parenchyma of the lung to the visceral pleura. It is widely known that asbestos is an oncogenic factor which can cause damage to DNA. A chest x-ray may reveal pleural effusion with or without pleural thickening, whereas a chest CT may also reveal pleural thickening, uniform and/or lobular. Specific tests, such as immunohistochemical staining, are used in order to help differential diagnosis. Extrapleural pneumonectomy is used as a therapeutic option which involves removal of the lung as well as both the visceral and parietal pleura, the affected part of the pericardium and diaphragm. Surgery should be followed up by radiotherapy and chemotherapy. The surgery may lead to a mean survival rate of approximately 9-21 months. The case presented underlines that in the event of pleural effusion with a lymphocyte type physicians should consider the possibility of a pleural mesothelioma during differential diagnosis, even in relatively young patients.

Related: Mesothelioma

Pasqua F, Geraneo K, Nardi I, et al.
Pulmonary rehabilitation in lung cancer.
Monaldi Arch Chest Dis. 2013; 79(2):73-80 [PubMed] Related Publications
Non-small-cell lung cancer (NSCLC) represents a very severe disease, being its incidence increasingly reported and, nowadays, successfully treatable only when surgery is deemed to be feasible. Furthermore, the disease and the clinical effects related to the complementary therapies (radio and/or chemotherapy) may strongly affect, frequently with dramatic clinical side effects, the patient's ability to endure physical exercise. In such context, the PR(PR), which has already been proved to be useful and effective in other diseases such as COPD, could play a pivotal role. The aim of this review article is, therefore, to analyze the pertinent data recently reported in English literature in order to highlight the role of rehabilitation as complementary therapy in the management of patients with NSCLC. The evidence currently available suggests that, when surgery is indicated, PR is a safe and feasible option, both during pre-operative and post-operative timing.The safety and feasibility of rehabilitation are proven even in inoperable patients, although to date, little evidence has been reported on its role in the overall management of such complex diseases.

Related: Non-Small Cell Lung Cancer Complementary Therapies

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