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).

Gu F, Wacholder S, Kovalchik S, et al.
Time to smoke first morning cigarette and lung cancer in a case-control study.
J Natl Cancer Inst. 2014; 106(6):dju118 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: Targeting smokers at higher lung cancer risk can improve efficiency and reduce false-positive detection in lung cancer screening. We evaluated whether time to first cigarette after waking (TTFC), a single-item measure of nicotine dependency, could improve stratification of lung cancer risk beyond standard smoking metrics (intensity, duration, and pack-years).
METHODS: In 3249 ever-smokers (n = 1812 case subjects; n = 1437 control subjects) from a population-based case-control study in Italy, we examined the association between TTFC and lung cancer using logistic regression and estimated lung cancer incidence by levels of TTFC, and intensity, duration, and pack-years using absolute risk regression. Significance tests were two-sided.
RESULTS: Compared with smokers with TTFC greater than 60 minutes, the lung cancer odds ratios for TTFC of 31 to 60 minutes, 6 to 30 minutes, and 5 or fewer minutes (by increasing dependency) were 2.57 (95% confidence interval [CI] = 2.03 to 3.26), 2.27 (95% CI = 1.79 to 2.88), and 3.50 (95% CI = 2.64 to 4.64), respectively (P trend < .0001). The average lung cancer incidence rates for smokers of 1 to 10, 11 to 20, 21 to 30 and more than 30 cigarettes per day were consistently higher among smokers with TTFC of 60 or fewer minutes vs more than 60 minutes (64.1 vs 11.7; 125.6 vs 28.6; 130.1 vs 40.7; and 260.8 vs 108.9 per 100000 person-years, respectively). The slopes of increase in lung cancer rates with smoking duration and pack-years were statistically significantly greater among smokers with higher dependency (P interaction < .001).
CONCLUSIONS: Lung cancer risk increases with shorter TTFC; this simple nicotine dependency measure increases lung cancer risk stratification beyond standard smoking measures. Assessing TTFC may improve lung cancer risk prediction and could be useful in lung cancer screening and smoking cessation programs.

Umihanic S, Umihanic S, Jamakosmanovic S, et al.
Glasgow prognostic score in patients receiving chemotherapy for non-small-cell lung cancer in stages IIIb and IV.
Med Arch. 2014; 68(2):83-5 [PubMed] Related Publications
INTRODUCTION: Lung cancer is most common cause of cancer-related mortality worldwide. Non-small-cell lung carcinoma (NSCLC) is disease with very low 5-year relative survival rate. For patients with non-small cell lung cancer, roles of current treatments are to prolong survival time and to improve quality of life.
AIM: The aim of the work was to compare values of Glasgow Prognostic Score (GPS) before application of the chemotherapy medication with response to chemotherapy and toxic side effects associated with chemotherapy in patients treated with cisplatin-etopozid (PE) and cisplatin-gemcitabin (PG) in stages IIIb and IV of NSCLC. Testing role of Glasgow Prognostic Score as a possible predictor of response to therapy and toxic side effects of chemotherapeutic protocol was another aim of this work.
PATIENTS AND METHODS: This prospective study included 60 patients in stages IIIb or IV of NSCLC, with ECOG < or = 2. The patients were divided in two groups. First group contained 30 patients treated with chemotherapeutic protocol using cisplatin-etopozid (PE), and the same number of patients in the second group were treated with cisplatin-gemcitabin (PG).
RESULTS: Glasgow Prognostic Score (GPS) evaluation before the chemotherapy inclusion showed values of 1 (43.30:53.30), then 2 (40.00:36.70) and the lowest 0 (16.70:10.00) which supports the pathological values of GPS in developed lung cancer, i.e. most patients had pathological GPS value in both protocols (83.30:90.00). Monitoring of toxic side effects and response to chemotherapy was done after each cycle of treatment.
DISCUSSION: Results of this study revealed importance of GPS in selection of patients for treatment with chemotherapy. Patients with lower values of GPS treated using PE chemotherapeutic protocol had weaker response to therapy.
CONCLUSION: Coefficient of correlation for therapy response in both chemotherapeutic protocol, compared with values of GPS before treatment, were not statistically significant, therefore GPS cannot be considered as a predictor of therapeutic on chemotherapy.

Related: Non-Small Cell Lung Cancer Cisplatin Etoposide Gemcitabine

Sato T, Arai E, Kohno T, et al.
Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease.
Int J Cancer. 2014; 135(2):319-34 [PubMed] Related Publications
The aim of this study was to clarify the significance of DNA methylation alterations during lung carcinogenesis. Infinium assay was performed using 139 paired samples of non-cancerous lung tissue (N) and tumorous tissue (T) from a learning cohort of patients with lung adenocarcinomas (LADCs). Fifty paired N and T samples from a validation cohort were also analyzed. DNA methylation alterations on 1,928 probes occurred in N samples relative to normal lung tissue from patients without primary lung tumors, and were inherited by, or strengthened in, T samples. Unsupervised hierarchical clustering using DNA methylation levels in N samples on all 26,447 probes subclustered patients into Cluster I (n = 32), Cluster II (n = 35) and Cluster III (n = 72). LADCs in Cluster I developed from the inflammatory background in chronic obstructive pulmonary disease (COPD) in heavy smokers and were locally invasive. Most patients in Cluster II were non-smokers and had a favorable outcome. LADCs in Cluster III developed in light smokers were most aggressive (frequently showing lymphatic and blood vessel invasion, lymph node metastasis and an advanced pathological stage), and had a poor outcome. DNA methylation levels of hallmark genes for each cluster, such as IRX2, HOXD8, SPARCL1, RGS5 and EI24, were again correlated with clinicopathological characteristics in the validation cohort. DNA methylation profiles reflecting carcinogenetic factors such as smoking and COPD appear to be established in non-cancerous lung tissue from patients with LADCs and may determine the aggressiveness of tumors developing in individual patients, and thus patient outcome.

Tammemägi MC, Berg CD, Riley TL, et al.
Impact of lung cancer screening results on smoking cessation.
J Natl Cancer Inst. 2014; 106(6):dju084 [PubMed] Related Publications
BACKGROUND: Lung cancer screening programs may provide opportunities to reduce smoking rates among participants. This study evaluates the impact of lung cancer screening results on smoking cessation.
METHODS: Data from Lung Screening Study participants in the National Lung Screening Trial (NLST; 2002-2009) were used to prepare multivariable longitudinal regression models predicting annual smoking cessation in those who were current smokers at study entry (n = 15489, excluding those developing lung cancer in follow-up). The associations of lung cancer screening results on smoking cessation over the trial period were analyzed. All hypothesis testing used two sided P values.
RESULTS: In adjusted analyses, smoking cessation was strongly associated with the amount of abnormality observed in the previous year's screening (P < .0001). Compared with those with a normal screen, individuals were less likely to be smokers if their previous year's screen had a major abnormality that was not suspicious for lung cancer (odds ratio [OR] = 0.811; 95% confidence interval [CI] = 0.722 to 0.912; P < .001), was suspicious for lung cancer but stable from previous screens (OR = 0.785; 95% CI = 0.706 to 0.872; P < .001), or was suspicious for lung cancer and was new or changed from the previous screen (OR = 0.663; 95% CI = 0.607 to 0.724; P < .001). Differences in smoking prevalence were present up to 5 years after the last screen.
CONCLUSIONS: Smoking cessation is statistically significantly associated with screen-detected abnormality. Integration of effective smoking cessation programs within screening programs should lead to further reduction in smoking-related morbidity and mortality.

Related: Cancer Screening and Early Detection Smoking and Smoking Cessation USA

Backhus LM, Wood DE
Management of centrally located non-small-cell carcinoma.
Oncology (Williston Park). 2014; 28(3):215-21 [PubMed] Related Publications
Treatment optimization for centrally located lung cancers requires special considerations for determining resectability and patient selection. Evaluation involves an experienced multidisciplinary team performing careful clinical and invasive-disease staging to identify the best management approach and ascertain the need for multimodality therapy. Preoperative imaging alone is often inaccurate in its ability to determine whether the patient is at an advanced clinical T stage that might preclude curative surgical resection. Therefore, other modalities are often necessary to complete the clinical staging. In the absence of irrefutable evidence of unresectability, however, surgical exploration should be undertaken with curative intent. Long-term outcomes can be favorable in select patients, and most of the procedures, including complex reconstructions, can be performed with acceptable morbidity and mortality.

Related: Non-Small Cell Lung Cancer

Li L, Wang M, Yu G, et al.
Overactivated neddylation pathway as a therapeutic target in lung cancer.
J Natl Cancer Inst. 2014; 106(6):dju083 [PubMed] Related Publications
BACKGROUND: A number of oncoproteins and tumor suppressors are known to be neddylated, but whether the neddylation pathway is entirely activated in human cancer remains unexplored.
METHODS: NEDD8-activating enzyme (NAE) (E1) and NEDD8-conjugating enzyme (E2) expression and global-protein neddylation were examined by immunohistochemistry, immunoblotting, and real-time polymerase chain reaction analysis. Cell proliferation, clonogenic survival, migration, and motility in vitro, as well as tumor formation and metastasis in vivo, were determined upon neddylation inhibition by MLN4924, an investigational NEDD8-activating enzyme inhibitor. Survival was analyzed with Kaplan-Meier methods and compared by the log-rank test. All statistical tests were two-sided.
RESULTS: The entire neddylation pathway, including NEDD8-activating enzyme E1, NEDD8-conjugating enzyme E2, and global-protein neddylation, is overactivated in both lung adenocarcinoma and squamous-cell carcinoma. Compared with lung adenocarcinoma patients with low expression, those with high expression had worse overall survival (NEDD8-activating enzyme E1 subunit 1 [NAE1]: hazard ratio [HR] = 2.07, 95% confidence interval [CI] = 0.95 to 4.52, P = .07; ubiquitin-conjugating enzyme E2M (UBC12): HR = 13.26, 95% CI = 1.77 to 99.35, P = .01; global protein neddylation: HR = 3.74, 95% CI = 1.65 to 8.47, P = .002). Moreover, inhibition of neddylation by the NAE inhibitor MLN4924 statistically significantly suppressed proliferation, survival, migration, and motility of lung cancer cells in vitro and tumor formation and metastasis in vivo. At the molecular level, MLN4924 inactivated Cullin-RING E3 ligases, led to accumulation of tumor-suppressive Cullin-RING E3 ligase substrates and induced phorbol-12-myristate-13-acetate-induced protein 1 (NOXA)-dependent apoptosis or cellular senescence.
CONCLUSIONS: Our study highlights the overactivated neddylation pathway in lung cancer development and as a promising therapeutic target.

Related: Signal Transduction

Kris MG, Johnson BE, Berry LD, et al.
Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.
JAMA. 2014; 311(19):1998-2006 [PubMed] Related Publications
IMPORTANCE: Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials.
OBJECTIVES: To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival.
DESIGN, SETTING, AND PARTICIPANTS: From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival.
INTERVENTIONS: Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies.
MAIN OUTCOMES AND MEASURES: Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival.
RESULTS: From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006).
CONCLUSIONS AND RELEVANCE: Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival.
TRIAL REGISTRATION: Identifier: NCT01014286.

Grando SA
Connections of nicotine to cancer.
Nat Rev Cancer. 2014; 14(6):419-29 [PubMed] Related Publications
This Opinion article discusses emerging evidence of direct contributions of nicotine to cancer onset and growth. The list of cancers reportedly connected to nicotine is expanding and presently includes small-cell and non-small-cell lung carcinomas, as well as head and neck, gastric, pancreatic, gallbladder, liver, colon, breast, cervical, urinary bladder and kidney cancers. The mutagenic and tumour-promoting activities of nicotine may result from its ability to damage the genome, disrupt cellular metabolic processes, and facilitate growth and spreading of transformed cells. The nicotinic acetylcholine receptors (nAChRs), which are activated by nicotine, can activate several signalling pathways that can have tumorigenic effects, and these receptors might be able to be targeted for cancer therapy or prevention. There is also growing evidence that the unique genetic makeup of an individual, such as polymorphisms in genes encoding nAChR subunits, might influence the susceptibility of that individual to the pathobiological effects of nicotine. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the evaluation of regulations on nicotine product manufacturing, distribution and marketing.

Related: Signal Transduction

Zhao GY, Ding JY, Lu CL, et al.
The overexpression of 14-3-3ζ and Hsp27 promotes non–small cell lung cancer progression.
Cancer. 2014; 120(5):652-63 [PubMed] Related Publications
BACKGROUND: The 14-3-3ζ protein has been identified as a putative oncoprotein in several cancers, including non–small cell lung cancer (NSCLC). However, the mechanisms underlying its functions have not been well defined.
METHODS: Proteins that interact with 14-3-3ζ were identified through coimmunoprecipitation and mass spectrometry in NSCLC cells. The interaction of 14-3-3ζ with these molecular partners and their roles in the invasiveness and metastasis of NSCLC cells were assayed through specific disruptions in the 14-3-3ζ signaling network. In addition, the clinical implications of this 14-3-3ζ complex were examined in samples from patients with NSCLC.
RESULTS: Among the identified proteins that interacted with 14-3-3ζ, there were 230 proteins in 95-D cells, 181 proteins in 95-C cells, and 203 proteins in A549 cells; and 16 interacting proteins were identified that overlapped between all cell lines. Further studies revealed 14-3-3ζ complexes within the heat shock protein 27 (Hsp27) protein and demonstrated that the interference of Hsp27 or 14-3-3ζ inhibited the invasion and metastasis of NSCLC cells. The invasive and metastatic capabilities of cells with both Hsp27 and 14-3-3ζ interference could be completely restored only by Hsp27 and 14-3-3ζ complementary DNA transfection and not by either agent alone. Clinically, the postoperative 5-year overall survival (OS) in patients who had high expression of both 14-3-3ζ and Hsp27 was significantly lower than the 5-year OS in patients who had low expression of both 14-3-3ζ and Hsp27 (26.5% vs 59.7%, respectively). Multivariate analysis revealed that the combined expression of 14-3-3ζ and Hsp27 was an independent prognostic indicator of OS(P = .036).
CONCLUSIONS: The current data suggest that the combined expression of 14-3-3ζ and Hsp27 may be a biomarker for predicting survival in patients with NSCLC, and this combination may have potential as a therapeutic target for NSCLC.

Related: Non-Small Cell Lung Cancer Signal Transduction

Sun CT, Xu X, Sheng W, et al.
A meta-analysis of pemetrexed-based doublet compared with pemetrexed alone for the second-line treatment of advanced non-small-cell lung cancer.
Bratisl Lek Listy. 2014; 115(4):233-7 [PubMed] Related Publications
PURPOSE: This meta-analysis investigated pemetrexed-based doublet compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer.
METHODS: Randomized controlled trials which compared pemetrexed-based doublet with single-agent pemetrexed in patients as second-line treatment of advanced non-small cell lung cancer were searched. Overall survival (OS) was the primary end point, while secondary end points included progression-free survival, overall response rate, 1-year survival rate, and grade 3 or 4 toxicity.
RESULTS: Four eligible randomized clinical trials including 1,084 patients were selected. Meta-analysis demonstrated that pemetrexed-based doublet arm significantly improved the overall response rate (OR=2.70, 95% CI: 1.76-4.15, p=0.000), compared with docetaxel alone group, while there were no significant differences in overall survival (HR=0.88, 95% CI: 0.74-1.04, p=0.132), progression-free survival (HR=0.91, 95% CI: 0.73-1.15, p=0.443), and 1-year survival rate (OR=1.43, 95% CI: 0.85-2.40, p=0.178) between the two arms. However, there were more frequencies of grade 3-4 leucopenia (OR=2.86, 95% CI: 1.32-6.20, p=0.008), neutropenia (OR=2.69, 95% CI: 1.55-4.68, p=0.000) and thrombocytopenia (OR=6.92, 95% CI: 2.51-19.07, p=0.000) in pemetrexed-based doublet group. Grade 3-4 anemia (OR=0.62, 95% CI: 0.33-1.18, p=0.144) and fatigue (OR=1.15, 95% CI: 0.73-1.79, p=0.550) had equivalent incidences in the two groups.
CONCLUSIONS: This is the first meta-analysis to compare pemetrexed-based doublet with single-agent pemetrexed in second-line therapy of non-small cell lung cancer. Our meta-analysis suggested that pemetrexed combination chemotherapy was not superior to single-agent arm and was not recommended as the second-line chemotherapy for patients with non-small cell lung cancer (Tab. 2, Fig. 6, Ref. 20).

Related: Non-Small Cell Lung Cancer Pemetrexed

Yasuda M, Nagashima A, Haro A, Saitoh G
How should synchronous multiple primary adenocarcinomas of the lung be resected?
Ann Thorac Surg. 2014; 97(5):e151-3 [PubMed] Related Publications
We often encounter patients with multiple primary lung cancers with ground-glass opacity. However, there are no established guidelines regarding the optimal extent of resection for multifocal lung adenocarcinoma, so it is necessary to determine the most suitable strategy for each case. A 62-year-old man visited our hospital with 7 lesions in the lung field. We evaluated the structural information using high-resolution computed tomography (HRCT) and the aggressiveness of the tumors using fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) and then developed a surgical strategy. Using FDG-PET/CT in addition to HRCT might improve the selection of appropriate surgical strategies for patients with multifocal lung adenocarcinoma.

Lerner AD, Riker DR
Use of endobronchial ultrasonography in the diagnosis of a pulmonary artery aneurysm.
Ann Thorac Surg. 2014; 97(5):e139-41 [PubMed] Related Publications
We present the case of an 84-year-old man with nonmassive hemoptysis and an obstructing endobronchial mass who was referred for rigid bronchoscopy and biopsy of the lesion. We illustrate how the pulsatile movement of his endobronchial lesion could be differentiated by convex probe endobronchial ultrasound bronchoscopy to be a vascular lesion rather than an endobronchial mass or tumor. Although convex probe endobronchial ultrasonography has many mediastinal applications, it has yet to be used to characterize endobronchial masses. We describe the first case of using convex probe endobronchial ultrasonography in the diagnosis of a left upper lobe pulmonary artery aneurysm presenting as an endobronchial mass.

Zhang Z, Mao Y, Chen H, et al.
Endotracheal and endobronchial metastases in a patient with stage I lung adenocarcinoma.
Ann Thorac Surg. 2014; 97(5):e135-7 [PubMed] Related Publications
Endotracheal or endobronchial metastasis from primary lung cancer is extremely rare. We report a case of endotracheal and endobronchial metastases from peripheral early lung adenocarcinoma 7 months after complete resection. The patient harbored the same gene mutation in both primary and metastatic lesions. This report highlights that enough attention on endotracheal metastases should be paid no matter what the pathologic TNM stage of primary lung cancer is.

Plojoux J, Buffard-Morel M, Ducamp D, et al.
Guillain-Barre syndrome after lung lobectomy: is there any relationship?
Ann Thorac Surg. 2014; 97(5):e133-4 [PubMed] Related Publications
Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculopathy frequently triggered by infection. It has also been reported in some cases after surgical procedures. We describe the first case of GBS occurring 9 days after lung lobectomy for localized lung cancer and efficiently treated with intravenous immunoglobulins. The exact physiopathology of GBS after surgical procedures is unknown. An immune-mediated process and perioperative infection are the most accepted etiologic hypotheses.

Sato W, Watanabe H, Sato T, et al.
Contralateral pulmonary embolism caused by pulmonary artery stump thrombosis after pneumonectomy.
Ann Thorac Surg. 2014; 97(5):1797-8 [PubMed] Related Publications
A 73-year-old man with atrial fibrillation and previous left pneumonectomy was admitted with pleural effusion. Anticoagulant therapy was discontinued because of chest tube drainage. Six days later, the patient experienced chest discomfort. Echocardiography showed a pedunculated thrombus with swaying motion in the left pulmonary artery (PA) stump. Contrast-enhanced computed tomography of the chest revealed filling defects in not only the left PA stump but also the right PA, implying contralateral pulmonary embolism. Anticoagulants were resumed, and thrombolysis was successful 3 days later. Patients undergoing pneumonectomy in whom anticoagulant therapy is discontinued should be recognized as being at high risk for PA stump thrombosis and subsequent contralateral pulmonary embolism.

Moreira BL, Guimaraes MD, de Oliveira AD, et al.
Value of ultrasound in the imaging-guided transthoracic biopsy of lung lesions.
Ann Thorac Surg. 2014; 97(5):1795-7 [PubMed] Related Publications
Transthoracic needle biopsy with fluoroscopic or computed tomographic guidance is a well-established and safe method for diagnosing malignant and benign thoracic lesions. Nonetheless, ultrasound is as effective as computed tomography for the guidance of transthoracic biopsies of peripheral pulmonary lesions and mediastinal tumors, and it offers some advantages. In this case report, we exemplify the proper use of ultrasound for the percutaneous biopsy of a lung lesion, aiming to show that it can be a safe, inexpensive, rapid, and effective alternative to computed tomography in appropriate cases.

Related: Cancer of the Larynx Laryngeal Cancer - Molecular Biology Prostate Cancer

Nakajima T, Anayama T, Matsuda Y, et al.
Orthotopic lung cancer murine model by nonoperative transbronchial approach.
Ann Thorac Surg. 2014; 97(5):1771-5 [PubMed] Related Publications
PURPOSE: The aim of this work was to establish a novel orthotopic human non-small cell lung cancer (NSCLC) murine xenograft model by a nonsurgical, transbronchial approach.
DESCRIPTION: Male athymic nude mice and human NSCLC cell lines, including A549, H460, and H520 were used. Under direct visualization of the vocal cords, a 23-gauge blunt-tip slightly curved metal catheter was introduced into the trachea to the bronchus, and 2.5×10(5) tumor cells mixed with Matrigel (BD Biosciences, Mississauga, Ontario, Canada) were administered into the lung. Mice were monitored using weekly microcomputed tomography scans for tumor formation.
EVALUATION: When the tumor size reached more than 4 mm in diameter, the animals were euthanized, and the tumor tissue was evaluated histopathologically. Of 37 mice studied, 34 were confirmed to have tumor formation: 29 developed solitary tumors and 5 had multifocal lesions. There was no evidence of extrapleural dissemination or effusion.
CONCLUSIONS: Transbronchial delivery of tumor cells enabled the establishment of a novel orthotopic human NSCLC murine xenograft model. This clinically relevant preclinical model bearing a solitary nodule is of value for a variety of in vivo research studies.

Related: Apoptosis Non-Small Cell Lung Cancer

Medbery RL, Perez SD, Force SD, et al.
Video-assisted thoracic surgery lobectomy cost variability: implications for a bundled payment era.
Ann Thorac Surg. 2014; 97(5):1686-92; discussion 1692-3 [PubMed] Related Publications
BACKGROUND: In 2013, the Centers for Medicare and Medicaid Services began its Bundled Payments for Care Improvement Initiative. If payments are to be bundled, surgeons must be able to predict which patients are at risk for more costly care. We aim to identify factors driving variability in hospital costs after video-assisted thoracic surgery (VATS) lobectomy for lung cancer.
METHODS: Our institutional Society of Thoracic Surgeons data were queried for patients undergoing VATS lobectomy for lung cancer during fiscal years 2010 to 2011. Clinical outcomes data were linked with hospital financial data to determine operative and postoperative costs. Linear regression models were created to identify the impact of preoperative risk factors and perioperative outcomes on cost.
RESULTS: One hundred forty-nine VATS lobectomies for lung cancer were reviewed. The majority of patients had clinical stage IA lung cancer (67.8%). Median length of stay was 4 days, with 30-day mortality and morbidity rates of 0.7% and 37.6%, respectively. Mean operative and postoperative costs per case were $8,492.31 (±$2,238.76) and $10,145.50 (±$7,004.71), respectively, resulting in an average overall hospital cost of $18,637.81 (±$8,244.12) per patient. Patients with chronic obstructive pulmonary disease and coronary artery disease, as well as postoperative urinary tract infections and blood transfusions, were associated with statistically significant variability in cost.
CONCLUSIONS: Variability in cost associated with VATS lobectomy is driven by assorted patient and clinical variables. Awareness of such factors can help surgeons implement quality improvement initiatives and focus resource utilization. Understanding risk-adjusted clinical-financial data is critical to designing payment arrangements that include financial and performance accountability, and thus ultimately increasing the value of health care.

Related: USA

Sarioglu N, Susur A, Goksel T, et al.
An unexpected cause of hemoptysis: endobronchial lipomatous hamartoma.
Med Arch. 2014; 68(1):65-6 [PubMed] Related Publications
Hamartomas are the most common benign tumors of the lung. Endobnronchial hamartomas are even rarer and infrequently causes hemoptysis. We report a case of endobronchial hamartoma that was originating from a segment bronchus and invisible in chest X-ray. A 63-year-old man was admitted to hospital with hemoptysis. A CT scan revealed endobronchial mass obstructing anterior bronchus of the right lower lob of the right lung. It wasn't radiographically presented. Flexible bronchoscopy detected a polypoid mass (1.5 x 1.0 cm) that arising from the posterior wall of the anterior segment of right lower lob. Histopathologic examination revealed lipoumatous hamartoma. It was resected with an electro-surgical snare. Cryotherapy was applied to residual lesion on surface of the bronchus. The patient was successfully recovered. In conclusion, lipoumatous hamartoma may presented as rare cause of hemoptysis. Endoscopic treatment is safe and currently modality used for select cases.

Louie BE
Robotic pneumonectomy.
Thorac Surg Clin. 2014; 24(2):169-75, vi [PubMed] Related Publications
Pneumonectomy is indicated for centrally placed tumors when a lung-preserving operation cannot be performed for oncologic reasons. The technique of robotic pneumonectomy is still undergoing development and modification. Several pioneering surgeons have determined it to be feasible but more data are required to determine the benefits and disadvantages of robotic pneumonectomy.

Pardolesi A, Veronesi G
Robot-assisted lung anatomic segmentectomy: technical aspects.
Thorac Surg Clin. 2014; 24(2):163-8, vi [PubMed] Related Publications
Anatomic lung segmentectomy is a possible alternative to lobectomy for small (<2 cm) primary lung cancers. Interest in anatomic lung segmentectomy has increased further after the adoption of high-resolution computed tomography and the implementation of lung cancer screening studies, which are increasing the detection rate of small lung cancers. Robotic surgery seems well suited to the precise dissection required for anatomic segmentectomy. Initial experience of robotic anatomic segmentectomy in patients with a single primary or metastatic lung lesion is highly encouraging. The introduction of robotic staplers, aspirators, and 5-mm lung forceps will further increase precision.

Related: Non-Small Cell Lung Cancer

Park BJ
Robotic lobectomy for non-small cell lung cancer: long-term oncologic results.
Thorac Surg Clin. 2014; 24(2):157-62, vi [PubMed] Related Publications
Robotic lobectomy is a feasible, safe, and oncologically sound surgical treatment of early-stage lung cancer. The technique is reproducible across multiple centers and in the long-term yields results consistent with the best seen with conventional video-assisted thoracic surgery (VATS) and thoracotomy. Lymphadenectomy may reduce inadequate staging of the hilar and mediastinal nodes during curative, anatomic resection. Differences between robotic versus VATS versus thoracotomy approaches to thoracic diseases should be evaluated to define the appropriate role of each approach.

Related: Non-Small Cell Lung Cancer

Cerfolio RJ
Total port approach for robotic lobectomy.
Thorac Surg Clin. 2014; 24(2):151-6, v [PubMed] Related Publications
Robotic surgery is safe and efficient, with similar survival rates to the open and video-assisted thoracoscopic surgery (VATS) approaches. The surgeon can provide an R0 resection in patients with cancer. Technical modifications lead to decreased operative times and may improve the ability to teach. The capital cost, service contract costs, and equipment costs have to be carefully considered and studied, and patient selection is critical. There are few achievable benefits of using a robotic system compared with VATS when performing a sympathotomy for patients with hyperhidrosis or a pulmonary wedge resection for tissue diagnosis for patients with interstitial lung disease.

Melfi FM, Fanucchi O, Davini F, Mussi A
VATS-based approach for robotic lobectomy.
Thorac Surg Clin. 2014; 24(2):143-9, v [PubMed] Related Publications
Lobectomy with systematic lymph node sampling or dissection remains the mainstay of treatment of early stage non-small cell lung cancer. The use of video-assisted thoracic surgery (VATS) to perform lobectomy was first reported in 1992. Advantages of VATS include less trauma and pain, shorter chest drainage duration, decreased hospital stay, and preservation of short-term pulmonary function. However, VATS is characterized by loss of binocular vision and a limited maneuverability of thoracoscopic instruments, an unstable camera platform, and poor ergonomics for the surgeon. To overcome these limitations, robotic systems were developed during the last decades. This article reviews the technical aspects of robotic lobectomy using a VATS-based approach.

Related: Non-Small Cell Lung Cancer

Veronesi G
Robotic thoracic surgery: technical considerations and learning curve for pulmonary resection.
Thorac Surg Clin. 2014; 24(2):135-41, v [PubMed] Related Publications
Retrospective series indicate that robot-assisted approaches to lung cancer resection offer comparable radicality and safety to video-assisted thoracic surgery or open surgery. More intuitive movements, greater flexibility, and high-definition three-dimensional vision overcome limitations of video-assisted thoracic surgery and may encourage wider adoption of robotic surgery for lung cancer, particularly as more early stage cases are diagnosed by screening. High capital and running costs, limited instrument availability, and long operating times are important disadvantages. Entry of competitor companies should drive down costs. Studies are required to assess quality of life, morbidity, oncologic radicality, and cost effectiveness.

Korkmaz GG, Inal BB, Ortakoylu GM, et al.
Changes in oxidative stress parameters and antioxidant status in lung cancer: Western blot analysis of nitrotyrosine and protein carbonyls content.
Clin Lab. 2014; 60(4):599-607 [PubMed] Related Publications
INTRODUCTION: The source of many diseases, including tumors, lies in an increased generation of reactive oxygen species resulting in oxidative stress. We investigated the relationships between advanced oxidation protein products (AOPPs), nitrotyrosine (NT), protein carbonyls (PCO) content, and the prooxidant-antioxidant balance (PAB) in patients with lung cancer.
METHODS: A total of 14 age-matched healthy controls, 14 subjects with non-lung cancer pulmonary disease, and 41 patients with lung cancer were included in this study. Spectrophotometry was used to examine plasma AOPP, serum FRAP, and PAB, while serum PCO and NT were assessed with western blot analysis.
RESULTS: A significant difference in AOPP levels were found between patients and controls (p < 0.01). Also, there was a highly significant difference in NT levels between patients and controls (p < 0.001). PAB showed negative correlation with albumin (r = -0.340, p = 0.011) and positive correlation with CRP (r = 0.342, p = 0.011). AOPP, albumin, gender, and smoking were the significant independent variables found by backward stepwise multiple logistic regression (MLR) analysis method. MLR analysis revealed that AOPP was the variable that had a significant effect on lung cancer [(p = 0.006, OR = 1.074, (95% CI) (1.020-1.131)].
CONCLUSIONS: The use of non-invasive diagnostic biochemical parameters would represent a very important contribution to our diagnostic armamentarium in lung cancer, considering the high incidence of this deadly disease. In this regard, AOPP and NT levels have appeared to play a prominent role, although further studies are certainly warranted.

Varesano S, Leo C, Boccardo S, et al.
Status of Anaplastic Lymphoma Kinase (ALK) in malignant mesothelioma.
Anticancer Res. 2014; 34(5):2589-92 [PubMed] Related Publications
BACKGROUND: Malignant mesothelioma (MM) is a particularly aggressive type of primary tumor, associated with exposure to asbestos, and characterized by high mortality. To date, there is no curative therapy for MM. The receptor anaplastic lymphoma kinase (ALK) was found to be mutated in many cases of cancer and used as a target in biological therapies. We investigated whether this pharmacological treatment could also be applicable to MM.
MATERIALS AND METHODS: The state of ALK was analyzed by immunohistochemistry and fluorescent in situ hybridization in 63 MM tissue specimens.
RESULTS: None of the 63 MM samples showed overexpression or translocation of ALK.
CONCLUSION: Our preliminary data exclude the utility of analysis of the ALK gene in MM and suggest that ALK inhibitor therapy is not applicable to MM.

Related: FISH Mesothelioma

Bobek V, Kacprzak G, Rzechonek A, Kolostova K
Detection and cultivation of circulating tumor cells in malignant pleural mesothelioma.
Anticancer Res. 2014; 34(5):2565-9 [PubMed] Related Publications
UNLABELLED: Malignant pleural mesothelioma (MPM) is an aggressive disease with very poor prognosis which tends to affect older patients. Progress in the management of this group of patients has been limited by the rarity of the disease and hence, difficulty in conducting randomized trials. The vast majority of cancer deaths occur due to metastasis of the primary tumor to distant sites via circulating tumor cells (CTCs) in the circulation. CTCs are extremely rare and limits in technology used to capture these cells hamper our complete understanding over the metastatic process. In the present study we present a new method for detection and cultivation of CTCs isolated from peripheral blood of MPM patients.
PATIENTS AND METHODS: Patients with diagnosed MPM were enrolled into this study.
RESULTS: A size-based separation method for viable CTC enrichment from unclothed peripheral blood has been introduced; MetaCell. The size-based enrichment process was based on filtration of peripheral blood (PB) through porous polycarbonate membrane. The separated CTCs are cultured on the membrane in vitro under standard cancer cell culture conditions and observed by an inverted microscope.
CONCLUSION: The reported methodology allows for quick and easy enrichment of CTCs and their cultivation. The cultivated cells can be used for next specification of gene expression and histological/biological specificity of concrete mesothelioma.

Related: Mesothelioma

Jeong JU, Chung WK, Nam TK, et al.
Early metabolic response on 18F-fluorodeoxyglucose-positron-emission tomography/computed tomography after concurrent chemoradiotherapy for advanced stage III non-small cell lung cancer is correlated with local tumor control and survival.
Anticancer Res. 2014; 34(5):2517-23 [PubMed] Related Publications
AIM: We evaluated the relationship of early metabolic responses on (18)F-fluorodeoxyglucose-positron-emission tomography/computed tomography (PET/CT) performed within one month after concurrent chemoradiotherapy (CCRT) with local tumor control and survival in patients with advanced stage III non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS: One hundred and nineteen patients with unresectable stage III NSCLC who completed definitive CCRT were included. PET/CT was performed 2-4 weeks after completion of radiotherapy.
RESULTS: The maximum standardized uptake value (SUVmax) reduction ratio of the primary lesion (primary SRR, 80%, p<0.001), gross tumor volume (150 cm(3), p=0.036), and pre-radiotherapy ratio of SUVmax of the metastatic lymph node to that of the primary lesion (60%, p=0.05) were significantly associated with OS in multivariate analysis. The primary SRR was the only statistically significant parameter for local control.
CONCLUSION: Early metabolic response of the primary lesion after CCRT correlated with local control and overall survival in patients with unresectable stage III NSCLC.

Related: Non-Small Cell Lung Cancer

Rades D, Weber A, Karstens JH, et al.
Number of extraspinal organs with metastases: a prognostic factor of survival in patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC).
Anticancer Res. 2014; 34(5):2503-7 [PubMed] Related Publications
BACKGROUND/AIM: In patients irradiated for MSCC from NSCLC, the number of extraspinal organs involved by metastases was investigated for associations with survival.
PATIENTS AND METHODS: The data of 131 patients irradiated with 10×3 Gy in two weeks for MSCC were evaluated. The number of involved extraspinal organs plus eight other factors were retrospectively analyzed.
RESULTS: The 6-month survival rates were 72%, 57%, 20%, and 11% for the involvement of 0, 1, 2, and ≥3 extraspinal organs, respectively (p<0.001). On multivariate analysis, the number of involved extraspinal organs remained significant (risk ratio 1.60; 95% CI 1.28-2.00; p<0.001). Gender (p=0.028), ECOG performance score (p=0.001), histology (p=0.014), ambulatory status (p=0.002), and time to developing motor deficits (p=0.041) were also independent prognostic factors for survival.
CONCLUSION: The number of extraspinal organs with metastases is an independent prognostic factor for the survival of NSCLC patients presenting with MSCC and should be considered in future studies.

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