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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).

Lin LY, Chang MH, Lee WJ
Paraneoplastic Limbic Encephalitis Associated with Adenocarcinoma of Lung.
Acta Neurol Taiwan. 2014; 23(3):108-12 [PubMed] Related Publications
PURPOSE: Paraneoplastic limbic encephalitis (PLE) is a rare, immune-mediated entity. We present an unusual case of a patient who has double cancers and two different paraneoplastic neurological syndromes.
CASE REPORT: A 58-year-old gentleman has histories of adenocarcinoma of lung and malignant thymoma associated with myasthenia gravis, which underwent surgery and chemotherapy 3 years ago. This time, he presented to our ward with rapidly progressive memory decline and myoclonic jerks in his limbs for two weeks. Magnetic resonance imaging (MRI) of brain showed increased signal intensity over bilateral mesial temporal regions on T2 Fluid Attenuated Inversion Recover (FLAIR) series. Chest computed tomography showed cancer recurrence. He received steroid pulse therapy firstly and right lung lower lobe lobectomy later. Pathology report of the tumor was recurrent adenocarcinoma. After the immunotherapy and tumor resection, his mentality improved gradually. Six months later, brain MRI showed resolution of bilateral temporal hyperintensity with residual mesial temporal atrophy.
CONCLUSION: From our case, we would like to emphasize that paraneoplastic limbic encephalitis should be considered among the differential diagnosis of rapidly progressive dementia associated with myoclonus, along with other neurodegenerative diseases. Depending on its underlying malignancy, the cognitive impairment may be substantially reversible, despite atrophy of mesial temporal lobes.

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.

Brahmer J, Reckamp KL, Baas P, et al.
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.
N Engl J Med. 2015; 373(2):123-35 [PubMed] Related Publications
BACKGROUND: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population.
METHODS: We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.
RESULTS: The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P=0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group.
CONCLUSIONS: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.).

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.

Arslan D, Tural D, Koca T, et al.
Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer.
J BUON. 2015 Mar-Apr; 20(2):573-9 [PubMed] Related Publications
PURPOSE: Relatively few studies have focused on T4N2 (stage IIIB) locally advanced non-small cell lung cancer (NSCLC). In this study, we tried to identify prognostic factors for patients with clinical stage T4N2 NSCLC.
METHODS: We retrospectively identified 223 patients, of which 168 met the inclusion criteria. Patients treated with curative intent using concurrent chemoradiotherapy (CRT) with or without adjuvant chemotherapy, or concurrent CRT after induction chemotherapy, were included in this study. Relevant patient, treatment, and disease factors were evaluated for their prognostic significance in both univariate and multivariate analyses using the Cox proportional hazards model.
RESULTS: The median progression-free survival (PFS) was 13 months (95% confidence interval [CI], 10.6-15.4). The median overall survival (OS) was 20 months (95% CI, 16.8-23.1), and 71, 40.3 and 28.2% of the patients survived for 1, 2 and 3 years after diagnosis, respectively. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance status (PS) was independent predictor of PFS (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; p=0.001), and OS [HR, 0.48; 95% CI, 0.26-0.87; p=0.015). Absence of multifocal T4 tumors was also associated with a significantly longer OS (HR, 046; 95% CI, 0.31-0.7; p=0.001). There was no statistically significant difference in OS and PFS between treatment modalities.
CONCLUSION: PFS and OS were significantly shorter in patients with poor ECOG PS. OS was also significantly shorter in patients with multifocal T4 tumors. There were no differences between the two therapeutic approaches with respect to outcome.

Hountis P, Chounti M, Matthaios D, et al.
Surgical treatment for malignant pleural mesothelioma: extrapleural pneumonectomy, pleurectomy/decortication or extended pleurectomy?
J BUON. 2015 Mar-Apr; 20(2):376-80 [PubMed] Related Publications
Malignant pleural mesothelioma (MPM) is an asbestos-related disease with a dismal prognosis. Ethic, social, legal and economic parameters are implicated in its management. It is quite clear that multimodality therapy is necessary to improve long-term results but precise treatment schemes have not yet been equivocally accepted. The extent of surgery is questioned and radical operations are highly debatable. On the other hand, debulking or cyto-reductive surgery have been also proposed within a multimodality approach. However, the role and order of adjuvant or neoadjuvant use of chemotherapy, radiotherapy and surgery has not been established. The aim of this study was to analyze contemporary studies on the impact of different surgical approaches on outcome of patients with MPM.

Siegelman JW, Supanich MP, Gavrielides MA
Pulmonary nodules with ground-glass opacity can be reliably measured with low-dose techniques regardless of iterative reconstruction: results of a phantom study.
AJR Am J Roentgenol. 2015; 204(6):1242-7 [PubMed] Related Publications
OBJECTIVE: Pulmonary nodules of ground-glass opacity represent one imaging manifestation of a slow-growing variant of lung cancer. The objective of this phantom study was to quantify the effect of the radiation dose used for the examination (volume CT dose index [CTDI(vol)]), type of reconstruction algorithm, and choice of postreconstruction enhancement algorithms on the measurement error when assessing the volume of simulated lung nodules with CT, focusing on two radiodensity levels.
MATERIALS AND METHODS: Twelve synthetic nodules of two radiodensities (-630 and -10 HU), three shapes (spherical, lobulated, and spiculated), and two sizes (nominal diameters of 5 and 10 mm) were inserted into an anthropomorphic chest phantom and scanned with techniques varying in CTDI(vol) (from subscreening dose [0.8 mGy] to diagnostic levels [6.5 mGy]), reconstruction algorithms (iterative reconstruction and filtered back projection), and different postreconstruction enhancement algorithms. Nodule volume was measured from the resulting reconstructed CT images with a matched filter estimator.
RESULTS: No significant over- or underestimation of nodule volume was observed across individual variables, with low percentage error overall (-1.4%) and for individual variables (range, -3.4% to 0.4%). The magnitude of percentage error was also low (overall average percentage error < 6% and SD values < 4.5%) and for individual variables (absolute percentage error range 3.3-5.6%). No clinically significant differences were observed between different levels of CTDI(vol), use of iterative reconstruction algorithms, or use of different postreconstruction enhancement algorithms.
CONCLUSION: These results indicate that, if validated for other measurement tools and scanners, lung nodule volume measurements from scans acquired and reconstructed with significantly different acquisition and reconstruction techniques can be reliably compared.

Oh SY, Kim MY, Kim JE, et al.
Evolving Early Lung Cancers Detected During Follow-Up of Idiopathic Interstitial Pneumonia: Serial CT Features.
AJR Am J Roentgenol. 2015; 204(6):1190-6 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the CT characteristics of newly developed lung cancer on CT studies obtained during follow-up of idiopathic interstitial pneumonia (IIP) before the appearance of identifiable tumors to the time of detectable lung cancer and thereafter.
MATERIALS AND METHODS: The study sample included 66 cancers diagnosed in 63 patients with IIP and lung cancer (59 men, four women; median age, 64 years; range, 40-85 years) between October 1998 and July 2012. Two radiologists independently reviewed 193 CT scans, determined the earliest presence of cancer and IIP, and evaluated tumor size, lobar and axial location, shape, and tumor density. Delay in clinical diagnosis and doubling time were measured with first and second follow-up CT examinations.
RESULTS: Interobserver agreement was good (κ > 0.77). The median tumor size was 17 mm (range, 5-30 mm) for the 46 T1a and 20 T1b cancers. Most of the tumors (42 [63.6%]) were located in the lower lobes. Thirty-five tumors (53.0%) were at the interface between fibrotic cyst and normal lung, and 21 (31.8%) were in the midst of fibrotic lung cysts. Most of the tumors had a round or oval shape (52 [78.8%]) and were solid (62 [93.9%]). The median delay in diagnosis was 46 days (range, 8-760 days). The first median doubling time was 77 days (range, 15-525 days), and the second was 53 days (27-248).
CONCLUSION: New lung cancers during CT follow-up of IIP usually appear as small solid nodules with a round or oval shape. Most cancers are located at the interface between fibrotic cyst and normal lung or in the midst of fibrotic cysts of the lower lobes of subpleural lung.

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.

Silvestri GA, Vachani A, Whitney D, et al.
A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.
N Engl J Med. 2015; 373(3):243-51 [PubMed] Related Publications
BACKGROUND: Bronchoscopy is frequently nondiagnostic in patients with pulmonary lesions suspected to be lung cancer. This often results in additional invasive testing, although many lesions are benign. We sought to validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy.
METHODS: Current or former smokers undergoing bronchoscopy for suspected lung cancer were enrolled at 28 centers in two multicenter prospective studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in epithelial cells collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer.
RESULTS: A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A total of 43% of bronchoscopic examinations were nondiagnostic for lung cancer, and invasive procedures were performed after bronchoscopy in 35% of patients with benign lesions. In AEGIS-1, the classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78 (95% confidence interval [CI], 0.73 to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95% CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to 0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI, 36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2, independent of lesion size and location. In 101 patients with an intermediate pretest probability of cancer, the negative predictive value of the classifier was 91% (95% CI, 75 to 98) among patients with a nondiagnostic bronchoscopic examination.
CONCLUSIONS: The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of lung cancer. In intermediate-risk patients with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic approach. (Funded by Allegro Diagnostics and others; AEGIS-1 and AEGIS-2 ClinicalTrials.gov numbers, NCT01309087 and NCT00746759.).

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.

Marquez-Medina D, Martin-Marco A, Caldero SG, Montero-Fernandez A
Little things make big things happen: angiolymphatic invasion and tumor necrosis prognosticate the outcome of locally advanced non-small cell lung cancer treated with a prior induction therapy.
Am J Clin Pathol. 2015; 143(6):889-94 [PubMed] Related Publications
OBJECTIVES: Size, invasion of thoracic structures, and ipsilateral mediastinal lymph node involvement (pN2) are well-known prognostic factors that configure the staging of resectable, locally advanced non-small cell lung cancer (LA-NSCLC). The prognostic impact of angiolymphatic invasion (ALI) and tumor necrosis (TN) has been barely explored in LA-NSCLC treated with prior induction therapies.
METHODS: We retrospectively reviewed 47 resected LA-NSCLCs treated with a prior platin-based chemotherapy or chemoradiation. The impact of ALI, TN, and other pathologic features on survival was analyzed.
RESULTS: ALI was presented in 23.4% of cases and TN in 29.8%. Disease-free and overall survival decreased when ALI, TN, or pN2 was present. The incidence of ALI was lower in LA-NSCLC with a good response to induction.
CONCLUSION: Our series is the first to report the prognostic impact of ALI and TN in induction-treated LA-NSCLC. The presence of ALI and TN should be included in the pathologic reports.

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.

Komaki R, Allen PK, Wei X, et al.
Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer.
Int J Radiat Oncol Biol Phys. 2015; 92(2):317-24 [PubMed] Article available free on PMC after 01/06/2016 Related Publications
PURPOSE: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity.
METHODS AND MATERIALS: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel-carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status.
RESULTS: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown).
CONCLUSIONS: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of distant failures underscores the need for effective systemic therapy.

Calabrò L, Maio M
Immune checkpoint blockade in malignant mesothelioma.
Semin Oncol. 2015; 42(3):418-22 [PubMed] Related Publications
Malignant mesothelioma (MM) is a highly aggressive malignancy with a very dismal prognosis. Current treatment for unresectable MM is largely unsatisfactory; therefore, new therapeutic approaches are eagerly awaited. A better understanding of the complex mechanisms of immune escape operated by neoplastic cells and the ability to unleash an efficient anti-tumor immune response by targeting regulatory immune checkpoint(s) with immunomodulatory monoclonal antibodies (mAbs), is leading to very promising clinical results in different tumor types. Herein, we highlight the clinical impact so far identified for these new immunomodulatory agents in MM patients and discuss their prospective use to design novel clinical trials.

Reck M, Paz-Ares L
Immunologic checkpoint blockade in lung cancer.
Semin Oncol. 2015; 42(3):402-17 [PubMed] Related Publications
Despite the availability of radiotherapy, cytotoxic agents, and targeted agents, a high unmet medical need remains for novel therapies that improve treatment outcomes in patients with lung cancer who are ineligible for surgical resection. Building upon the early promise shown with general immunostimulatory agents, immuno-oncology is at the forefront of research in this field, with several novel agents currently under investigation. In particular, agents targeting immune checkpoints, such as the cytotoxic T-lymphocyte antigen-4 (CTLA-4) receptor and programmed death-1 (PD-1) receptor, have shown in early clinical trials potential for improving tumor responses and survival in patients with non-small cell lung cancer (NSCLC). Here, we examine the rationale for targeting immune checkpoints in lung cancer and review the clinical data from studies with immune checkpoint inhibitors currently in development. The challenges associated with optimizing treatment with these agents in lung cancer also are discussed.

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.

Pricopi C, Rivera C, Varnous S, et al.
Pre- and post- transplantation lung cancer in heart transplant recipients.
Ann Thorac Surg. 2015; 99(5):1793-4 [PubMed] Related Publications
Heart transplantation after lung cancer surgery can be questionable because of the high risk of cancer recurrence. We report the results of two patients. The first underwent right lobectomy in 2008 for pT1N0 adenocarcinoma, heart-transplantation in 2010, and surgery for synchronous adenocarcinoma and squamous-cell carcinoma in 2012. The second underwent left segmentectomy for pT1aN0 adenosquamous carcinoma and transplantation in 1995 and then surgery for pT1aN1 adenocarcinoma in 2013. Posttransplantation lung cancer histologic analysis results were different in both cases, demonstrating the absence of metastatic recurrence. Thus, early stage lung cancer might not be a contraindication to heart transplantation, nor are long delays be necessary before registering on a waiting list.

Quaife SL, McEwen A, Janes SM, Wardle J
Smoking is associated with pessimistic and avoidant beliefs about cancer: results from the International Cancer Benchmarking Partnership.
Br J Cancer. 2015; 112(11):1799-804 [PubMed] Related Publications
BACKGROUND: Smoking cessation is the key cancer prevention behaviour for smokers; nonetheless, smokers can still benefit from earlier diagnosis of cancer. However, fewer smokers participate in screening despite their increased risk, which may reflect different beliefs about cancer.
METHODS: A UK population-representative sample of ⩾50 year-olds (n=6965) was surveyed using the Awareness and Beliefs about Cancer measure. These analyses examine six items on cancer beliefs (e.g., 'cancer can often be cured'), and four on help-seeking barriers (e.g., 'I would be too embarrassed').
RESULTS: Smokers were more likely to hold pessimistic cancer beliefs than never-smokers or former-smokers on four of six items. For example, 34% agreed 'a cancer diagnosis is a death sentence', compared with 24% of non/former-smokers (P<0.001). More smokers (18%) than non/former-smokers (11%) would not want to know if they had cancer (P<0.01). The only barrier to symptomatic help-seeking differing by smoking status was 'worry about what the doctor might find' (36% vs 28%, P<0.01). Associations were independent of demographics, self-rated health and cancer experience.
CONCLUSIONS: Smokers held more pessimistic and avoidant beliefs about cancer, which could deter early-detection behaviour. A better understanding of these beliefs is needed to increase engagement in early diagnosis by this high-risk group.

Chang LC, Yu YL, Liu CY, et al.
The newly synthesized 2-arylnaphthyridin-4-one, CSC-3436, induces apoptosis of non-small cell lung cancer cells by inhibiting tubulin dynamics and activating CDK1.
Cancer Chemother Pharmacol. 2015; 75(6):1303-15 [PubMed] Related Publications
PURPOSE: To investigate the anticancer therapeutic potential of a new synthetic compound, 2-(3-hydroxyphenyl)-5-methylnaphthyridin-4-one (CSC-3436), on non-small cell lung cancer (NSCLC) cells.
METHODS: Cell viability was determined by MTT assay. Cell cycle distribution was assessed by propidium iodide staining and subjected to flow cytometry analysis. Protein expression was detected by western blot analysis. Pharmacological inhibitors and shRNAs were applied to examine the possible pathways involved CSC-3436-inhibited viability of NSCLC cells.
RESULTS: CSC-3436 decreased NSCLC cell viability by inducing apoptosis. In vivo and in vitro tubulin polymerization assays revealed that CSC-3463 caused tubulin depolymerization by directly binding to the colchicine-binding site. Furthermore, CSC-3436 caused the mitotic arrest with a marked activation of cyclin-dependent kinase 1 (CDK1) and increased the expression of phospho-Ser/Thr-Pro mitotic protein monoclonal 2. The CDK1 inhibitor, roscovitine, reversed the CSC-3436-induced upregulation of CDK1 activity as well as the mitotic arrest. DNA damage response kinases, including ataxia telangiectasia mutated (ATM), ATM and Rad3-related, DNA-dependent protein kinase, checkpoint kinase 1, and checkpoint kinase 2, were phosphorylated and activated by CSC-3436. c-Jun N-terminal kinase was activated by CSC-3436 and involved in the regulation of mitotic arrest and apoptosis. CSC-3436-induced apoptosis was accompanied by the activation of pro-apoptotic factors FADD, TRADD, and RIP and the inactivation of anti-apoptotic proteins Bcl-2 and Bcl-xL, resulting in the cleavage and subsequent activation of caspases.
CONCLUSIONS: Our results reveal the cellular events in which CSC-3436 induces tumor cell death and demonstrate that CSC-3436 is a potential tubulin-disrupting agent for antitumor therapy against NSCLC.

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.

Murgu SD
Diagnosing and staging lung cancer involving the mediastinum.
Chest. 2015; 147(5):1401-12 [PubMed] Related Publications
The purpose of this article is to provide an update on evidence-based methods for mediastinal staging in patients with lung cancer. This is a review of the recently published studies and a summary of relevant guidelines addressing the role of CT scan, PET scan, endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA), and mediastinoscopy as pertinent to lung cancer staging and restaging. The focus is on how these diagnostic methods fit into the best algorithm for patients with chest imaging abnormalities suspected of malignant disease. Several studies, meta-analyses, and systematic reviews specifically targeted the role of PET scan, EBUS-TBNA, and mediastinoscopy for detecting mediastinal lymph node involvement in patients suffering from lung cancer. Based on the recommendations from the currently published guidelines, algorithms of care are proposed for staging and restaging of the mediastinum.

Jin G, Zhu M, Yin R, et al.
Low-frequency coding variants at 6p21.33 and 20q11.21 are associated with lung cancer risk in Chinese populations.
Am J Hum Genet. 2015; 96(5):832-40 [PubMed] Related Publications
Genome-wide association studies have successfully identified a subset of common variants associated with lung cancer risk. However, these variants explain only a fraction of lung cancer heritability. It has been proposed that low-frequency or rare variants might have strong effects and contribute to the missing heritability. To assess the role of low-frequency or rare variants in lung cancer development, we analyzed exome chips representing 1,348 lung cancer subjects and 1,998 control subjects during the discovery stage and subsequently evaluated promising associations in an additional 4,699 affected subjects and 4,915 control subjects during the replication stages. Single-variant and gene-based analyses were carried out for coding variants with a minor allele frequency less than 0.05. We identified three low-frequency missense variants in BAT2 (rs9469031, c.1544C>T [p.Pro515Leu]; odds ratio [OR] = 0.55, p = 1.28 × 10(-10)), FKBPL (rs200847762, c.410C>T [p.Pro137Leu]; OR = 0.25, p = 9.79 × 10(-12)), and BPIFB1 (rs6141383, c.850G>A [p.Val284Met]; OR = 1.72, p = 1.79 × 10(-7)); these variants were associated with lung cancer risk. rs9469031 in BAT2 and rs6141383 in BPIFB1 were also associated with the age of onset of lung cancer (p = 0.001 and 0.006, respectively). BAT2 and FKBPL at 6p21.33 and BPIFB1 at 20q11.21 were differentially expressed in lung tumors and paired normal tissues. Gene-based analysis revealed that FKBPL, in which two independent variants were identified, might account for the association with lung cancer risk at 6p21.33. Our results highlight the important role low-frequency variants play in lung cancer susceptibility and indicate that candidate genes at 6p21.33 and 20q11.21 are potentially biologically relevant to lung carcinogenesis.

Li F, Han X, Li F, et al.
LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response.
Cancer Cell. 2015; 27(5):698-711 [PubMed] Related Publications
LKB1 regulates both cell growth and energy metabolism. It remains unclear how LKB1 inactivation coordinates tumor progression with metabolic adaptation in non-small cell lung cancer (NSCLC). Here in Kras(G12D);Lkb1(lox/lox) (KL) mouse model, we reveal differential reactive oxygen species (ROS) levels in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). ROS can modulate ADC-to-SCC transdifferentiation (AST). Further, pentose phosphate pathway deregulation and impaired fatty acid oxidation collectively contribute to the redox imbalance and functionally affect AST. Similar tumor and redox heterogeneity also exist in human NSCLC with LKB1 inactivation. In preclinical trials toward metabolic stress, certain KL ADC can develop drug resistance through squamous transdifferentiation. This study uncovers critical redox control of tumor plasticity that may affect therapeutic response in NSCLC.

Lee YC, Park YJ, Gang SJ, et al.
Repeated occurrence of second primary lung cancer at different sites in trachea: a case report.
Medicine (Baltimore). 2015; 94(17):e770 [PubMed] Related Publications
Multiple or second primary lung cancers can develop at any sites in the lung with same or different histologic types, synchronously and/or metachronously. In case of metachronous occurrence of the second primary lung cancer, it is easy to confuse with the primary lung cancer as a recurrence of precedent lung malignancy treated successfully or metastasis. Previous reports have demonstrated that majority of the second primary lung malignancies have same histologic types regardless of their developing time and location. However, the repeated occurrence of the second primary lung malignancy, in particular with the different histologic features, is a very rare condition.A 62-year-old male who had past history of squamous cell carcinoma treated with surgery and adjuvant chemotherapy and the recurrence of lung malignancy on the trachea, which was also resected successfully visited our hospital due to blood tinged sputum. Evaluation using bronchoscopy and chest computed tomography revealed the tracheal mass looked similar grossly to the previous recurred tracheal mass that was resected surgically. Unexpectedly, the newly developed tracheal mass was confirmed as small cell lung cancer, the different histologic type from previous ones.In this report, we describe an interesting case of subsequent occurrence of second primary lung cancers showing histologic shifting at different sites in trachea, suggesting that it is important for physician to make an effort to identify the histologic characteristics of second primary lung cancers for the correct and adequate treatment no matter what they exhibit similar gross morphology.

Liu J, Li C, Hu M, et al.
Exploring spatial overlap of high-uptake regions derived from dual tracer positron emission tomography-computer tomography imaging using 18F-fluorodeoxyglucose and 18F-fluorodeoxythymidine in nonsmall cell lung cancer patients: a prospective pilot study.
Medicine (Baltimore). 2015; 94(17):e678 [PubMed] Related Publications
Interest is growing in radiotherapy to nonuniformly boost radioresistant regions within nonsmall cell lung cancer (NSCLC) using molecular imaging techniques. The complexity of tumor behavior is beyond the ability of any single radiotracer to reveal. We hold dual tracer positron emission tomography-computer tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) and fluorodeoxythymidine (FLT) for NSCLC patients to offer an integrated overlook of tumor biological behaviors quantitatively and localizationally, which may help biological target volume delineation and subvolume boost.Pathological confirmed that NSCLC patients were eligible. FDG and FLT PET/CT were performed for each patient before anticancer treatment and coregistrated for analysis. Maximum and mean standardized uptake values (SUVmax and SUVmean) were calculated automatically. Metabolic volumes (MVs) were delineated by a fixed 50% of SUVmax in FDG PET/CT and proliferative volumes (PVs) were delineated by 50% to 90% of SUVmax with 10% interval in FLT PET/CT. Overlap ratio (OR) were determined as overlapped volume between MV and PV divided PV. Conventional contrast-enhanced CT-based intensity-modulated radiotherapy (IMRT) plans with and without additional PET/CT-guided subtarget boost were made for each of the 5 typical NSCLC patients. Dosimetric parameters derived from dose-volume histogram, tumor control probability (TCP), and normal tissue complication probability (NTCP) of lung, esophagus, heart, and spinal cord were calculated and compared.Thirty-one patients were prospectively included and 23 were selected for analysis. Totally, 23 primary diseases, 41 metastatic lymph nodes, and 15 metastatic lesions were positive in dual PET/CTs and included for analysis. Median ORs increased from 58.61% to 93.12% under thresholds of 50% of SUVmax in FDG PET/CT and increased thresholds from 50% to 90% of SUVmax in FLT PET/CT. Based on conventional IMRT, additional boost to union of high FDG (determined by 50% SUVmax) and FLT (determined by 80% SUVmax) uptake subtargets exhibited higher TCP without significant elevated NTCP of lung, esophagus, spinal cord, and heart.Dual tracer PET/CT of FDG and FLT is suggested for NSCLC patients to guide tumor target delineation in clinical practice. FDG PET/CT is necessary whereas FLT PET/CT may be optional when guiding tumor target delineation clinically. Additional information from randomized trials is required to validate.

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