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Lung Cancer

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
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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).

Kumar A, Ramanathan K
Analyzing resistance pattern of non-small cell lung cancer to crizotinib using molecular dynamic approaches.
Indian J Biochem Biophys. 2015; 52(1):23-8 [PubMed] Related Publications
Crizotinib is the potential anticancer drug used for the treatment of non-small cell lung cancer (NSCLC) approved by FDA in 2011. The main target for the crizotinib is anaplastic lymphoma kinase (ALK). Evidences available indicate that double mutant ALK (L1196M and G1269A) confers resistance to crizotinib. However, how mutation confers drug resistance is not well-understood. Hence, in the present study, molecular dynamic (MD) simulation approach was employed to study the impact of crizotinib binding efficacy with ALK structures at a molecular level. Docking results indicated that ALK double mutant (L1196M and G1269A) significantly affected the binding affinity for crizotinib. Furthermore, MD studies revealed that mutant ALK-crizotinib complex showed higher deviation, higher fluctuation and decreased number of intermolecular H-bonds, when compared to the native ALK-crizotinib complex. These results may be immense importance for the molecular level understanding of the crizotinib resistance pattern and also for designing potential drug molecule for the treatment of lung cancer.

Macri A, Matache R, Leonte D, Stoica R
Nodular pulmonary amyloidosis--rare cause of calcified pulmonary nodules.
Pneumologia. 2015 Jan-Mar; 64(1):30-5 [PubMed] Related Publications
The article presents the case of a 60-year-old asymptomatic woman whose chest X-ray screening showed bilateral pulmonary nodules of uncertain etiology. Initially, the main suspicion concerned multiple pulmonary metastases, but the anatomical pathology examination of two of the surgically removed lung nodules revealed a benign pattern--foreign body granulomatous reaction to cholesterol crystals. Patient follow-up with a repeat computed tomography one year later showed that some pulmonary nodules had slightly increased in number and size, so the diagnosis required re-evaluation. Congo red staining revealed a positive reaction in the amorphous material, pointing to a nodular form of pulmonary amyloidosis. This case attests to the wide range of investigations needed to examine multiple pulmonary nodules and to the great variety of possible diagnoses. Surgical biopsy, alongside histopathological examination and immunohistochemical tests of the lung are critical in establishing a positive diagnosis. Pulmonary amyloidosis requires additional investigations and long-term follow-up of the patient, as this condition is frequently associated with MALT (mucosa-associated lymphoid tissue) lymphoma or multiple myeloma.

Szeszenia-Dąbrowska N, Świątkowska B, Sobala W, et al.
Asbestos related diseases among workers of asbestos processing plants in relation to type of production and asbestos use.
Med Pr. 2015; 66(1):1-9 [PubMed] Related Publications
BACKGROUND: Asbestos dust is one of the most dangerous pneumoconiotic and carcinogenic agents. The aim of this study was to assess the occurrence of asbestosis and pleural mesothelioma, depending on asbestos consumption and the type of manufactured products, among former asbestos workers in Poland.
MATERIAL AND METHODS: The study subjects included employees of 18 large state-owned asbestos processing enterprises operating in the Polish market in 1945-1998. The study is based on data obtained from asbestos company records and the Central Register of Occupational Diseases data on the cases of asbestosis and mesothelioma for the period from 1970 till 2012 as well as data from Amiantus Programme. The analysis was performed for 5 sectors comprising plants classified according to the products manufactured and applied production technology.
RESULTS: In the study period, 2160 cases of asbestosis and 138 cases of mesothelioma were reported. The plants processed a total of about 2 million tonnes of asbestos, including about 7.5% of crocidolite. Total asbestos consumption was a strong predictor of the rate ofasbestosis incidence (R2 = 0.68, p = 0.055). The highest risk occurrence of asbestosis was observed in the production of textiles and sealing products. Mesothelioma occurred only in plants where crocidolite had been ever processed.
CONCLUSIONS: Total asbestos consumption was a strong predictor of the rate of ashestosis incidence. The observation confirms the relationship between exposure to crocidolite and the occurrence of nesotheliona, regardless of the manufactured products, and suggests the absence of such a link for the total volume of asbestos consumption.

Gao XJ, Liu JW, Zhang QG, et al.
Nobiletin inhibited hypoxia-induced epithelial-mesenchymal transition of lung cancer cells by inactivating of Notch-1 signaling and switching on miR-200b.
Pharmazie. 2015; 70(4):256-62 [PubMed] Related Publications
Epithelial-mesenchymal transition (EMT) is an early step in the process of tumor metastasis. It is well known that tumor microenvironment affects malignancy in various carcinomas; in particular, that hypoxia induces EMT. Deregulated notch signaling also contributes a lot to the development of EMT in lung cancer. In this study, we investigated the use of Notch-1-inhibiting compound as novel therapeutic candidates to regulate hypoxia-induced EMT in lung cancer cells. According to previous screening, nobiletin was selected as a Notch-1 inhibitor. Hypoxia-induced EMT was characteristic of increased N-cadherin & vimentin expressions and decreased E-cadherin expressions. Treatment with nobiletin notably attenuated hypoxia-induced EMT, invasion and migration in H1299 cells, accompanied with reduced Notch-1, Jagged1/2 expressions and its downstream genes Hey-1 and Hes-1. Nobiletin treatment also promoted tumorsuppressive miR-200b level. Moreover, notch-1 siRNA prevented hypoxia-mediated cell migration and decreased Twist1, Snail1, and ZEB1/2 expressions, which are key EMT markers. Re-expression of miR-200b blocked hypoxia-induced EMT and cell invasion. Our findings suggest that downregulation of Notch-1 and reexpression of miR-200b by nobiletin might be a novel remedy for the therapy of lung cancer.

Shete HK, Vyas SS, Patravale VB, Disouza JI
Pulmonary multifunctional nano-oncological modules for lung cancer treatment and prevention.
J Biomed Nanotechnol. 2014; 10(9):1863-93 [PubMed] Related Publications
Mortality associated with lung cancer and its metastasis has outnumbered those related to other forms of cancer. Despite being a directly accessible organ, conventional oncological strategies exhibiting prolific outcome in treatment and prevention of lung cancer is far from reality. This is attributed to numerous challenges posed by lung environment. The extracellular aura of lung comprises immensely complicated structures, ciliary escalators, omnipresence of mucus and alveolar fluid, and macrophagial uptake which presents an array of impediments to the arrival of therapeutic moiety at the tumor site. Besides these, intracellular obstacles viz enzymatic degradation, cell membrane translocation, endosomal escape and/or nuclear entry also limit superior therapeutic efficacy. The current review elaborates wide-ranging challenges to lung cancer treatment and its circumvention by latest developments in multifunctional nano-oncological modules delivered via the pulmonary route-which smartly deal with the abovementioned issues and bestow positivity to this complication.

Chaouki W, Meddah B, Hmamouchi M
Antiproliferative and apoptotic potential of Daphne gnidium L. root extract on lung cancer and hepatoma cells.
Pharmazie. 2015; 70(3):205-10 [PubMed] Related Publications
Daphne gnidium L. (Thymeleacees) is a famous Moroccan plant with cancer-related ethnobotanical use. Previously, we demonstrated that ethyl acetate extract of D. gnidium had antiproliferative and pro-apoptotic potential on human breast tumor MCF-7 cells. The purpose of this study was to investigate if the antiproliferative effect of this extract was similar for different human cancer cell lines such as A549 lung cancer and SMMC-7721 hepatoma cells. Moreover, this work essentially focused on the intrinsic apoptotic signaling pathway. Antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide on A549 and SMMC-7721 cells. The characterization of the mechanisms involved in this effect was determined by lactate dehydrogenase test, apoptosis assays and western blot analyses. Our present study has shown that this extract strongly inhibited proliferation of A549 (IC50: 213 ± 15 μg/ml) and SMMC-7721 (IC50: 170 ± 13 μLg/ml) cells. The characterization of antiproliferative effect demonstrated that this extract was an apoptosis inducer in both cell lines tested. The results of western blot analyses have shown in SMMC-7721 cells that this extract activated caspase signaling triggered by the modulation of Bcl-2 family proteins. These findings suggest that this natural extract-induced effects may have novel therapeutic applications for the treatment of different cancer types.

Bosînceanu M, Sandu C, Roată CE, et al.
Epidemiological evaluation of the outcomes after video-assisted thoracoscopic talcage in neoplastic pleurisy.
Rev Med Chir Soc Med Nat Iasi. 2015 Jan-Mar; 119(1):112-8 [PubMed] Related Publications
AIM: Clinical-epidemiological investigations for further assessing the importance of video-assisted thoracoscopy in the treatment y of patients with neoplastic pleurisy.
MATERIALS AND METHODS: The researches included a group of 72 patients (31.9% men and 68.1% women aged 31-81 years, mean age ± 60 years) with neoplastic pleurisy who underwent pleural symphysis by video-assisted thoracoscopic talcage. For statistical-mathematical processing and interpretation the Pearson correlation index with the level of significance at p = 0.05 and highly significant at p < 0.005 was used.
RESULTS: Neoplastic pleurisy prevalently affected the age groups 51-80 years (84.9%). Dyspnea was present in all cases, and patient history at the time of admission revealed 14 conditions, of which 25% were lung cancers. Macroscopically nodular and vegetative tumors were found in 66.7% of cases. An amount of 1000-2000 ml of pleural fluid was found in 44.5% of the cases and a serocitrin appearance in 50%. In 23.6% of the cases cytology results were positive for malignancy and in 13.8% suspicious. In 65.2% of the cases the pleural fluid was exudative and anatomopathology was suggestive of adenocarcinoma in 34.7% of the cases and breast cancer in 18%. The prevalence of recurrences varied from 1 month to more than 7 months, with 36.4% for 1-2 months.
CONCLUSIONS: The obtained additional data support the important role of pleural symphysis by video-assisted thoracoscopic talcage in the patients with neoplastic pleurisy.

Rusu-Cordunean F, Cernomaz AT, Berlea ML, et al.
Implementing EBUS TBNA: first experience and review of literature.
Rev Med Chir Soc Med Nat Iasi. 2015 Jan-Mar; 119(1):31-7 [PubMed] Related Publications
Lung cancer has a very dismal prognosis and careful diagnosis and staging is of outmost importance. EBUS has become a cornerstone investigation for diagnosis and staging and current guidelines stress that there is a steep learning curve when introducing this tech- nique in practice (only 30 procedures are considered necessary). Over a period of 10 months a total of 21 patients have been addressed to our unit for an EBUS TBNA procedure. Only three were referred for staging purposes (for lung, digestive and cervix cancers) the others being primary diagnostic approaches where simpler procedures had previously failed. Procedures were initially performed under local anesthesia (3 cases) then under general anesthesia and jet ventilation using a laryngeal mask approach. Mediastinal lymph node group 7 was the most frequent target (9 cases) followed by group 4R (8 cases) and peribronchial tumoral processes (7 cases); one case did not required any needle-aspiration. On average each examination resulted in the sampling of 1.4 targets. There were no significant procedure related severe adverse events. Although 21 G cytology needles were used, adequate histological samples were obtained for 11 cases and cytology was the examination of choice for 9 cases. The pathology/cytology results were retrospectively assessed as satisfactory for 15 cases (confirmed neoplastic or other disease) and inconclusive for 5 cases. Non neoplastic disorders were represented by sarcoidosis, tuberculosis and bronchogenic cyst (3 cases). The procedure can be considered fast and safe; trained pathology personnel play an extremely important role: presently referrals are rare for staging purposes.

Babu KA, Supraja K, Singh RB
Pulmonary capillary haemangiomatosis: a rare cause of pulmonary hypertension.
Indian J Chest Dis Allied Sci. 2014 Oct-Dec; 56(4):259-62 [PubMed] Related Publications
Pulmonary capillary haemangiomatosis (PCH) is a rare disorder of unknown aetiology, characterised by proliferating capillaries that invade the pulmonary interstitium, alveolar septae and the pulmonary vasculature. It is often mis-diagnosed as primary pulmonary hypertension and pulmonary veno-occlusive disease. Pulmonary capillary haemangiomatosis is a locally aggressive benign vascular neoplasm of the lung. We report the case of a 19-year-old female who was referred to us in the early post-partum period with severe pulmonary artery hypertension, which was diagnosed as PCH by open lung biopsy.

Iliaz S, Iliaz R, Avsar N, et al.
Lung cancer presenting with choroidal metastasis in a pregnant woman.
Indian J Chest Dis Allied Sci. 2014 Oct-Dec; 56(4):249-51 [PubMed] Related Publications
A 28-year-old, non-smoker pregnant woman who was initially diagnosed to have deep vein thrombosis and pulmonary thromboembolism earlier in pregnancy, presented at 22 weeks of gestation with dyspnoea, visual loss initially in the right eye and then in the left eye. Fundoscopic examination revealed metastatic foci, suggestive of choroid metastases. Computed tomography of the chest revealed a right hilar mass. Fibreoptic bronchoscopy and bronchoscopic biopsy confirmed lung adenocarcinoma. As the patient and family wished to continue with the pregnancy, chemotherapy with cisplatin and was administered from the 31st week of pregnancy and she had undergone Caesarian section in the 32nd week and the baby was healthy. We report this case as it is probably the first reported case of lung cancer presenting with choroidal metastasis in a pregnant woman.

Ghosh S, Ansar W
Indoor air pollution: impact on health and stem cells.
J Stem Cells. 2014; 9(4):269-81 [PubMed] Related Publications
Nearly 2 million people annually die prematurely from various illness contributed by indoor air pollutants (IAP). Such pollutants affect the lungs leading to diseases ranging from bronchial diseases to malignant lung cancer. Stem cells (SC) with the property of self-renewal, pluripotency, and capability of homing into tumors and metastases, have been reported to be promising in treatment of lung cancer. In this review, we have tried to understand the role of components of IAP affect the SC. Although very few studies have been conducted in these lines, existing reports suggest that IAP causes damage to stem cells and their niches thereby reducing successful chances of autologous stem cell transplantation and therapy. The mechanism by which components of IAP affects the functioning of stem cells thus conferring toxicity remains unexplored. The future scope of this review lies in revealing answer to underlying questions of repair and modulation of stem cells in therapeutic treatment of lung diseases.

Ren Y, Yin Z, Li K, et al.
TGFβ-1 and TGFBR2 polymorphisms, cooking oil fume exposure and risk of lung adenocarcinoma in Chinese nonsmoking females: a case control study.
BMC Med Genet. 2015; 16:22 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Transforming growth factor-β (TGF-β) plays an important role in regulating cellular functions, and many studies have demonstrated important roles for TGF-β in various cancers. Single nucleotide polymorphisms (SNPs) of TGF-β may influence lung carcinogenesis. The aim of this study was to test whether TGF-β1 C509T and TGF-β receptor II (TGFBR2) G-875A polymorphisms were associated with lung adenocarcinoma in nonsmoking females.
METHODS: A hospital-based case-control study was performed in Chinese nonsmoking females. Genotyping was performed using TaqMan SNP genotyping assay, and demographic data and environmental exposure were collected by trained interviewers after informed consents were obtained.
RESULTS: A total of 272 (95.4%) cases and 313 (99.4%) controls were successfully genotyped, and the results showed that the polymorphic allele frequencies of C509T and G875A were similar among lung adenocarcinoma patients and controls (P=0.589 and 0.643, respectively). However, when the data were stratified for cooking oil fume exposure, the TT genotype of the TGFB1 C509T polymorphism showed a significantly decreased risk for lung adenocarcinoma compared with the CC genotype (adjusted OR=0.362, 95% CI=0.149-0.878, P=0.025).
CONCLUSIONS: TGF-β1 gene C509T polymorphism might be associated with decreased risk of lung adenocarcinoma in Chinese females exposed to cooking oil fumes, but no association was observed TGFBR2 gene G875A polymorphism.

Sequist LV, Soria JC, Goldman JW, et al.
Rociletinib in EGFR-mutated non-small-cell lung cancer.
N Engl J Med. 2015; 372(18):1700-9 [PubMed] Related Publications
BACKGROUND: Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by the T790M EGFR mutation in most cases. Rociletinib (CO-1686) is an EGFR inhibitor active in preclinical models of EGFR-mutated NSCLC with or without T790M.
METHODS: In this phase 1-2 study, we administered rociletinib to patients with EGFR-mutated NSCLC who had disease progression during previous treatment with an existing EGFR inhibitor. In the expansion (phase 2) part of the study, patients with T790M-positive disease received rociletinib at a dose of 500 mg twice daily, 625 mg twice daily, or 750 mg twice daily. Key objectives were assessment of safety, side-effect profile, pharmacokinetics, and preliminary antitumor activity of rociletinib. Tumor biopsies to identify T790M were performed during screening. Treatment was administered in continuous 21-day cycles.
RESULTS: A total of 130 patients were enrolled. The first 57 patients to be enrolled received the free-base form of rociletinib (150 mg once daily to 900 mg twice daily). The remaining patients received the hydrogen bromide salt (HBr) form (500 mg twice daily to 1000 mg twice daily). A maximum tolerated dose (the highest dose associated with a rate of dose-limiting toxic effects of less than 33%) was not identified. The only common dose-limiting adverse event was hyperglycemia. In an efficacy analysis that included patients who received free-base rociletinib at a dose of 900 mg twice daily or the HBr form at any dose, the objective response rate among the 46 patients with T790M-positive disease who could be evaluated was 59% (95% confidence interval [CI], 45 to 73), and the rate among the 17 patients with T790M-negative disease who could be evaluated was 29% (95% CI, 8 to 51).
CONCLUSIONS: Rociletinib was active in patients with EGFR-mutated NSCLC associated with the T790M resistance mutation. (Funded by Clovis Oncology; ClinicalTrials.gov number, NCT01526928.).

Jänne PA, Yang JC, Kim DW, et al.
AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.
N Engl J Med. 2015; 372(18):1689-99 [PubMed] Related Publications
BACKGROUND: The EGFR T790M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation (EGFR-mutated lung cancer). In preclinical models, the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790M resistance mutations.
METHODS: We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors. The study included dose-escalation cohorts and dose-expansion cohorts. In the expansion cohorts, prestudy tumor biopsies were required for central determination of EGFR T790M status. Patients were assessed for safety, pharmacokinetics, and efficacy.
RESULTS: A total of 253 patients were treated. Among 31 patients enrolled in the dose-escalation cohorts, no dose-limiting toxic effects occurred at the doses evaluated. An additional 222 patients were treated in five expansion cohorts. The most common all-cause adverse events were diarrhea, rash, nausea, and decreased appetite. The overall objective tumor response rate was 51% (95% confidence interval [CI], 45 to 58). Among 127 patients with centrally confirmed EGFR T790M who could be evaluated for response, the response rate was 61% (95% CI, 52 to 70). In contrast, among 61 patients without centrally detectable EGFR T790M who could be evaluated for response, the response rate was 21% (95% CI, 12 to 34). The median progression-free survival was 9.6 months (95% CI, 8.3 to not reached) in EGFR T790M-positive patients and 2.8 months (95% CI, 2.1 to 4.3) in EGFR T790M-negative patients.
CONCLUSIONS: AZD9291 was highly active in patients with lung cancer with the EGFR T790M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01802632.).

Smetana GW, Boiselle PM, Schwartzstein RM
Screening for lung cancer with low-dose computed tomography: grand rounds discussion from the Beth Israel Deaconess Medical Center.
Ann Intern Med. 2015; 162(8):577-82 [PubMed] Related Publications
In December 2013, the U.S. Preventive Services Task Force recommended screening for lung cancer with low-dose computed tomography (LDCT) for selected current and former smokers. The Task Force based the recommendation primarily on the results of the NLST (National Lung Screening Trial). In this trial, patients randomly assigned to LDCT screening for 3 years had lower rates of both lung cancer-specific mortality and all-cause mortality (relative risk reduction, 6.7% [95% CI, 1.2% to 13.6%]; absolute risk reduction, 0.46% [CI, 0% to 0.9%]). Clinicians and health systems confront questions and challenges as they begin to implement lung cancer screening. This paper summarizes a conference during which an internist and a radiologist discuss the application of the Task Force recommendation to an individual patient.

Garon EB, Rizvi NA, Hui R, et al.
Pembrolizumab for the treatment of non-small-cell lung cancer.
N Engl J Med. 2015; 372(21):2018-28 [PubMed] Related Publications
BACKGROUND: We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit.
METHODS: We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review.
RESULTS: Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached.
CONCLUSIONS: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab. (Funded by Merck; KEYNOTE-001 ClinicalTrials.gov number, NCT01295827.).

Svaton M, Pesek M, Chudacek Z, Vosmiková H
Current two EGFR mutations in lung adenocarcinoma -  case report.
Klin Onkol. 2015; 28(2):134-7 [PubMed] Related Publications
Nowadays, EGFR TKIs (epidermal growth factor receptor-tyrosine kinase inhibitors) targeted therapy is well established treatment for patients with the so-called EGFR common mutations with advanced or metastatic nonsmall cell lung cancer. The efficacy for the so-called rare and especially for the very rare complex EGFR mutations is not clear. We describe a case of a 63- year-old female with metastatic nonsmall cell lung cancer with complex EGFR mutation (G719X + S768I) who had been treated by gefitinib. She achieved progression free survival within eight months. Then, we discuss our case with other literature case reports. Together, it seems that described complex EGFR mutation has a relatively good sensitivity for EGFR TKIs treatment.Key words: nonsmall cell lung cancer -  EGFR gene -  EGFR protein -  complex mutations -  rare EGFR mutations -  EGFR TKIs.

Dabrowska M, Krenke R, Korczynski P, et al.
Diagnostic accuracy of contrast-enhanced computed tomography and positron emission tomography with 18-FDG in identifying malignant solitary pulmonary nodules.
Medicine (Baltimore). 2015; 94(15):e666 [PubMed] Related Publications
Contrast-enhanced computed tomography (CECT) and positron emission tomography with 18-FDG (FDG-PET/CT) are used to identify malignant solitary pulmonary nodules. The aim of the study was to evaluate the accuracy of CECT and FDG-PET/CT in diagnosing the etiology of solitary pulmonary nodule (SPN). Eighty patients with newly diagnosed SPN >8 mm were enrolled. The patients were scheduled for either or both, CECT and FDG-PET/CT. The nature of SPN (malignant or benign) was determined either by its pathological examination or radiological criteria. In 71 patients, the etiology of SPN was established and these patients were included in the final analysis. The median SPN diameter in these patients was 13 mm (range 8-30 mm). Twenty-two nodules (31%) were malignant, whereas 49 nodules were benign. FDG-PET/CT was performed in 40 patients, and CECT in 39 subjects. Diagnostic accuracy of CECT was 0.58 (95% confidence interval [CI] 0.41-0.74). The optimal cutoff level discriminating between malignant and benign SPN was an enhancement value of 19 Hounsfield units, for which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CECT were 100%, 37%, 32%, and 100%, respectively. Diagnostic accuracy of FDG-PET/CT reached 0.9 (95% CI 0.76-0.9). The optimal cutoff level for FDG-PET/CT was maximal standardized uptake value (SUV max) 2.1. At this point, the sensitivity, specificity, PPV, and NPV were 77%, 92%, 83%, and 89%, respectively. The diagnostic accuracy of FDG-PET/CT is higher than that of CECT. The advantage of CECT is its high sensitivity and negative predictive value.

Chen LS, Hung RJ, Baker T, et al.
CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.
J Natl Cancer Inst. 2015; 107(5) [PubMed] Related Publications
BACKGROUND: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.
METHODS: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided.
RESULTS: The rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P = .0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10(-5)).
CONCLUSION: These data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk.

Kim D, Ferraris VA, Davenport D, Saha S
Outcomes of lobar and sublobar resections for non-small-cell lung cancer: a single-center experience.
South Med J. 2015; 108(4):230-4 [PubMed] Related Publications
OBJECTIVES: Lung cancer is the leading cause of cancer-related mortality in the United States. Kentucky has the highest age-adjusted lung cancer rate and has one of the highest death rates from lung cancer in the country. Lobectomy is considered the standard therapy for non-small-cell lung cancer (NSCLC), whereas sublobar resection remains an option for selected patients. We investigated outcomes in patients having standard resections for lung cancer (lobectomy) compared with those having sublobar resections in a population with high prevalence of, and with a high death rate from, lung cancer.
METHODS: We studied patients having lung cancer resections at the University of Kentucky between 2002 and 2007. We reviewed the records of 222 patients who had either lobar or sublobar resections for NSCLC. This retrospective review identified key outcome variables, as well as short- and long-term survival. Propensity analysis allowed outcome comparison between patients having lobar and sublobar resections matched for preoperative variables.
RESULTS: Of the 222 study patients, 181 patients had lobectomies and 41 had sublobar resections. For all resections, lobectomy was associated with improved 1-, 3-, and 5-year survival rates compared with sublobar resections. Compared with patients having sublobar resections, lobectomy patients had significantly increased unadjusted perioperative morbidity (43.1% lobectomy vs 7.3% sublobar), but not mortality. After propensity analysis, sublobar resection predicted significantly reduced morbidity (6.3% vs 53.3%, P < 0.001), but not operative mortality (3.3% vs 3.3%, P = not significant), compared with lobectomy in patients matched for age, sex, cancer stage, and date of operation. Adjuvant chemotherapy combined with radiation therapy showed significantly improved long-term survival for either type of resection. Cox regression with adjustment for age, cancer stage, and postoperative complications suggested that neoadjuvant chemotherapy/radiotherapy increased long-term survival (P = 0.038, hazard ratio 0.49).
CONCLUSIONS: Sublobar resections for NSCLC have less morbidity compared with lobectomy, but at the cost of decreased long-term survival. These results imply that surgeons select patients for lobar or sublobar resections based on physiologic and functional parameters, and that differences in outcomes between these two groups reflect this selection bias. We suspect that these results are typical of surgical treatment of NSCLC in a heterogeneous high-risk population with a high penetration and prevalence of lung cancer.

Schmidt-Hansen M, Baldwin DR, Zamora J
FDG-PET/CT imaging for mediastinal staging in patients with potentially resectable non-small cell lung cancer.
JAMA. 2015; 313(14):1465-6 [PubMed] Related Publications
CLINICAL QUESTION: What is the sensitivity and specificity of 18F-fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging for detecting mediastinal lymph node involvement in patients with potentially resectable non-small cell lung cancer (NSCLC)?
BOTTOM LINE: Sensitivity and specificity of FDG-PET/CT imaging ranged from 0.77 to 0.81 for sensitivity and 0.79 to 0.90 for specificity, and were related to the brand of scanner, NSCLC subtype, FDG dose, and country of study origin. These sensitivities and specificities are not sufficiently accurate to warrant reliance on FDG-PET/CT scanning alone to make decisions about surgery as a single option for patients with potentially resectable NSCLC. Instead FDG-PET/CT imaging should be used to determine whether the next step should be biopsy (endobronchial ultrasound-guided biopsy or mediastinoscopy) or surgical resection.

Başyiğit I, Boyaci H, Uçar EK, et al.
Tongue carcinoma with endobronchial metastasis: a rare case.
Acta Clin Croat. 2014; 53(4):483-6 [PubMed] Related Publications
Endobronchial metastases of extrapulmonary malignant tumors are quite rare. We present a patient with endobronchial metastasis previously operated for tongue carcinoma. A 71-year-old female patient presented with the complaint of cough. She had a history of tongue carcinoma operation 2 years before. Chest x-ray revealed an air-fluid level in the lower zone of the right hemithorax. There was a big cavitary lesion in the right lower lobe and bilateral multiple nodular lesions, some of which had cavity formation on computed tomography. Bronchoscopy re- vealed a polypoid lesion with necrotic appearance and pathologic examination showed squamous cell carcinoma. The lesion was accepted as a metastasis of tongue carcinoma after evaluation of the materials taken from the tongue on previous operation. There was no finding suggestive of local recurrence; however, the patient died from hemoptysis and respiratory insufficiency. In conclusion, endobronchial metastasis should be considered in patients with extrapulmonary malignancies and bronchoscopic examination should be performed in such cases, even in the presence of atypical radiological findings.

Živković D
Effect of delays on survival in patients with lung carcinoma in Montenegro.
Acta Clin Croat. 2014; 53(4):390-8 [PubMed] Related Publications
Lung cancer is a global medical problem with a rising incidence and 5-year survival of 5%-10%. The aim of this study was to investigate whether waiting times and delays in diagnosis and treatment of patients with lung carcinoma have any bearing on prognosis and survi- val. The study was performed in the Brezovik Special Hospital for Lung Diseases and Tuberculosis. The study included all cases with the diagnosis of lung carcinoma in the Republic of Montenegro in 2009, a total of 206 patients, with follow up until the end of 2010. Median age was 66, median Karnofsky score 80, and male to female ratio 5:1. Diagnostic procedure was bronchoscopy in 89% of patients. Histologic type was small cell lung cancer in 25.7% and non small cell lung cancer in 74.3% of cases. Surgery was the main treatment for 24.4% of patients. Median delay from first symptoms to diagnosis of lung cancer was 10.35 weeks, mean 8 weeks (median patient's delay was 6.20 weeks, doctor's delay at primary health care 2.07 weeks and in pulmonology services 2.37 weeks). Median survival time for all patients was 39.27 weeks, mean 34. There was no statistically significant diffe- rence between patient's delay/doctor's delay/total delay and stage of lung carcinoma at the time of diagnosis, treatment choice and survival. Our results indicate that longer delay is not associated with poorer prognosis of lung carcinoma. The possible ways of reducing mortality of lung cancer include prevention by decreasing smoking prevalence and improved therapeutic options.

Zendah I, Habibech S, Kwas H, et al.
Primary sarcomatoid lung cancer: clinical and evolutive features: about five cases.
Tunis Med. 2014; 92(11):678-80 [PubMed] Related Publications
BACKGROUND: Primary sarcomatoid carcinoma of the lung are rare non small cell lung cancers (NSCLC) recently individualized by the World Health Organization. Their clinical, radiological and evolutive features are not well known but they seem to have bad prognosis with rapid progression and early metastases. Although they are felt to be chemo-refractory they must be treated as the other subtypes of NSCLC.
AIM: To evaluate clinical, radiological and evolutive features of primary sarcomatoid carcinoma of the lung.
METHODS: We report the cases of five patients presenting sarcomatoid carcinomas and assess their clinical and evolutive data.
RESULTS: One patient had stage IIB cancer underwent surgical resection and adjuvant chemotherapy, he is alive 18 months later; another had stage IIIB was treated by radio and chemotherapy and is alive 6 months later; and three other patients had stage IV in whom one had chemotherapy, the two others did not because of they had performance status. They died 1 to 3 months after the diagnosis.
CONCLUSION: Lung sarcomatoid carcinomas are of bad prognosis. Their treatment is nowadays not well established. Much more good studies are therefore needed.

Wang HQ, Wang J
Expression of pleiotrophin in small cell lung cancer.
J Biol Regul Homeost Agents. 2015 Jan-Mar; 29(1):175-9 [PubMed] Related Publications
Pleiotrophin (PTN) is a kind of heparin binding growth factor closely related to tumor progression. This study aimed to discuss the significance of the expression of PTN in benign and malignant lung cancer tissues, especially small cell lung cancer. Lung cancer samples were collected for study and lung tissue samples with benign lesions were taken as controls. The expression of PTN was detected using tissue chip combined with the immunohistochemical method, and the differences of small cell lung cancer with non-small cell lung cancer and benign lesion tissue were compared. It was found that PTN expression was mainly located in the cytoplasm and membrane of cells; PTN expression in the lung cancer group was higher than that in the control group (p < 0.01), and PTN expression in the small cell cancer group was higher than that in the squamous carcinoma group and glandular cancer group (p < 0.05). In addition, PTN expression quantity in patients with lung cancer were in close correlation with TNM staging, pathological type and tumor differentiation degree (p < 0.05). PTN was found to express abnormally high in lung cancer, especially small cell lung cancer tissue. PTN is most likely to be a new tumor marker for diagnosis and prognosis of lung cancer.

Fihel A, Muszyńska MM
The regional variation in tobacco smoking - attributable mortality in Poland, 2006-2010.
Przegl Epidemiol. 2015; 69(1):87-92, 181-4 [PubMed] Related Publications
STUDY OBJECTIVE: To explain the regional variation in smoking-attributable mortality in Poland by selected environmental characteristics.
MATERIAL AND METHODS: On the basis of the simplified Peto method, standardized smoking-attributable death rates were estimated by applying data on overall mortality and mortality due to malignant neoplasms of trachea, bronchus and lung for the years 2006-2010 obtained from the Central Statistical Office. The correlation between smoking-attributable mortality (SAM) and selected regional characteristics was estimated in two models of linear regression (for men and women). The characteristics of 379 NUTS-4 regions for the years 2006-2010 were derived from the CSO and other public data sources.
RESULTS: In both absolute and relative terms, the male and female SAM appeared to be higher in the northern and western regions of Poland. For both men and women, the linear regression confirmed the significant positive correlation between the level of SAM and poverty, hazardous working conditions, crime level, low level of settlement, low proportion of persons in agriculture and of University graduates. Additional variables correlating with the male SAM pointed to unemployment, proportion employed in services, mortality due to intentional self-harm and electoral turnout.
CONCLUSION: At the NUTS-4 level, the territorial variation in male and female SAM can be partially explained by the variation in regional characteristics indicating unfavourable economic and social conditions.

Oser MG, Niederst MJ, Sequist LV, Engelman JA
Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin.
Lancet Oncol. 2015; 16(4):e165-72 [PubMed] Article available free on PMC after 01/04/2016 Related Publications
Lung cancer is the most common cause of cancer deaths worldwide. The two broad histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. Although NSCLC and SCLC are commonly thought to be different diseases owing to their distinct biology and genomic abnormalities, the idea that these malignant disorders might share common cells of origin has been gaining support. This idea has been supported by the unexpected findings that a subset of NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase inhibitors develops. Additionally, other case reports have described the coexistence of NSCLC and SCLC, further challenging the commonly accepted view of their distinct lineages. Here, we summarise the published clinical observations and biology underlying tumours with combined SCLC and NSCLC histology and cancers that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies pointing to common potential cells of origin, and speculate how the distinct paths of differentiation are determined by the genomics of each disease.

Chen D, Guo W, Qiu Z, et al.
MicroRNA-30d-5p inhibits tumour cell proliferation and motility by directly targeting CCNE2 in non-small cell lung cancer.
Cancer Lett. 2015; 362(2):208-17 [PubMed] Related Publications
MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules that are dysregulated in many types of human cancers, although their precise functions in driving non-small cell lung cancer (NSCLC) are incompletely understood. In the present study, we found that miR-30d-5p, often downregulated in NSCLC tissues, significantly inhibited the growth, cell cycle distribution, and motility of NSCLC cells. Furthermore, we demonstrated that cyclin E2 (CCNE2), which was often upregulated in NSCLC tissues, was a direct target of miR-30d-5p. CCNE2 expression promoted the proliferation, invasion, and migration of NSCLC cells. In addition, the re-introduction of CCNE2 expression antagonised the inhibitory effects of miR-30d-5p on the capacity of NSCLC cells for proliferation and motility. Together, these results suggest that the miR-30d-5p/CCNE2 axis may contribute to NSCLC cell proliferation and motility, indicating miR-30d-5p as a potential therapeutic target for the treatment of NSCLC.

Baste JM, Haddad L, Melki J, Peillon C
Anterior subcarinal node dissection on the left side using video thoracoscopy: an easier technique.
Ann Thorac Surg. 2015; 99(4):e99-e101 [PubMed] Related Publications
Lobectomy for lung carcinoma is usually associated with complete node dissection, but it is often difficult to perform using video thoracoscopy, especially on the left side. In this case, our team uses an anterior technique for subcarinal lymphadenectomy. After left lobectomy, we lift the bronchial stump by its anterior face to open and dissect the subcarinal space. Exposure is difficult using the more usual technique of posterior subcarinal lymphadenectomy, and the different techniques (often requiring retractors) remain complex because some vessels might be injured. We recommend using anterior lymphadenectomy, which should facilitate video thoracoscopy for lymphadenectomy on the left side.

Chiarelli M, De Simone M, Gerosa M, et al.
An incidental pulmonary meningioma revealing an intracranial meningioma: primary or secondary lesion?
Ann Thorac Surg. 2015; 99(4):e83-4 [PubMed] Related Publications
A 68-year-old man underwent a resection of the right middle lobe for a solitary lesion detected at computed tomography. The histologic result was suggestive for a pulmonary meningioma. Although the result of a preoperative brain computed tomography scan was negative, magnetic resonance imaging showed a skull-base meningioma. On the basis of the absence of symptoms, we decided to observe the intracranial meningioma. At 3 years of follow-up, the patient was free of recurrence and the cerebral lesion was stable. Primary pulmonary meningioma and benign meningioma metastasis share identical microscopic findings, and only a central nervous system radiologic study allows their distinction. The pulmonary lesion in our patient was classified as a meningioma metastasis.

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