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Publisher: Elsevier   (Total: 3157 journals)

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Showing 1 - 200 of 3157 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 35, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 24, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 96, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 27, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 37, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 416, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 10, SJR: 0.18, CiteScore: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, CiteScore: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 262, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 7)
Acute Pain     Full-text available via subscription   (Followers: 14, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 17, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 10, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 23)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 160, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 33, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 4)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 9, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 12)
Advances in Digestive Medicine     Open Access   (Followers: 9)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 25)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 28, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 46, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 59, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 16, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 23, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 12, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 18, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 7, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 23)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 17, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 12)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 10)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 64)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 6)
Advances in Space Research     Full-text available via subscription   (Followers: 403, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 11, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 34, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 18)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 14)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 47, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 349, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 11, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 456, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 17, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 42, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 57, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 11)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 10, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 10, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 51, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 52, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 55, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 34, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 29, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 35, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 47)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 221, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 66, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 28, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 38, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 63, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 18, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 42, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 182, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 12, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 12)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 205, SJR: 1.58, CiteScore: 3)

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Journal Cover
Lung Cancer
Journal Prestige (SJR): 1.75
Citation Impact (citeScore): 4
Number of Followers: 14  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0169-5002
Published by Elsevier Homepage  [3157 journals]
  • Mutation patterns in a population-based non-small cell lung cancer cohort
           and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
    • Abstract: Publication date: Available online 9 January 2019Source: Lung CancerAuthor(s): Linnéa La Fleur, Elin Falk-Sörqvist, Patrik Smeds, Anders Berglund, Magnus Sundström, Johanna SM Mattsson, Eva Brandén, Hirsh Koyi, Johan Isaksson, Hans Brunnström, Mats Nilsson, Patrick Micke, Lotte Moens, Johan Botling ObjectivesNon-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.Materials and MethodsUsing targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.ResultsWe obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resemble the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.ConclusionHere we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.
       
  • Tumor autophagy is associated with survival outcomes in patients with
           resected non-small cell lung cancer
    • Abstract: Publication date: Available online 8 January 2019Source: Lung CancerAuthor(s): Ivo Uberall, Mariam Gachechiladze, Markus Joerger, Josef Andel, Petra Smickova, Vitezslav Kolek, Ivona Grygarkova, Josef Skarda ObjectivesLC3A protein is associated with autophagosomes, and LC3 A immunohistochemistry (IHC) is used for the detection of autophagy activity. The aim of this study was to assess the prognostic value of LC3 A expression in patients with resected non-small cell lung cancer (NSCLC).Materials and methodsWe used tissue microarrays (TMAs) constructed from 116 resected stage IB-III NSCLC patients. Standard immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue sections using antibody against LC3 A autophagic potein. Stained slides were scanned by Olympus dotSlide Digital Virtual Microscopy System (Japan) and the number of SLSs was evaluated digitally. Groups were compared using the Mann Whitney U test, and correlations were assessed using Spearman‘s rank test. Survival was calculated using Kaplan Meier analysis. Primary study endpoint was overall survival (OS), secondardy study endpoint disease-free survival (DFS). Cut-off optimization for LC3 A prognostic value was performed using the ‘‘cut-off finder‘ ‘software (Charite, Berlin, Germany). In addition, the Kaplan Meier plotter‚ KmPlot ‘was used to assess the relationship between LC3 A mRNA expression and clinical outcome (OS and DFS) in patients with NSCLC.ResultsFrom 116 patients, 88 tissue samples were available for final examination. No significant association was found between LC3 A staining and other clinicopathological variables, including tumor grade, stage and histological subtype. A higher number of LC3 A SLSs (>20), was significanly associated with poor OS (HR = 2.27, p = 0.011) and DFS (HR = 2.27, p = 0.003). A significant association between high LC3 A mRNA and both a worse OS and worse DFS was found by KMPlot analysis in patients with stage I-III NSCLC.ConslusionThis retrospective study suggests that SLSs as assessed by LC3 A IHC has a clinically relevant negative prognostic value in patients with resected NSCLC, and should be further investigated.
       
  • Osimertinib-induced Stevens-Johnson syndrome in a patient with EGFR T790M
           mutation-positive non-small cell lung cancer
    • Abstract: Publication date: Available online 31 December 2018Source: Lung CancerAuthor(s): Yi-Tsz Lin, Chia-Yu Chu
       
  • The impact of high PD-L1 expression on the surrogate endpoints and
           clinical outcomes of anti-PD-1/PD-L1 antibodies in non-small cell lung
           cancer
    • Abstract: Publication date: February 2019Source: Lung Cancer, Volume 128Author(s): Kentaro Ito, Satoru Miura, Tadashi Sakaguchi, Kenta Murotani, Nobuyuki Horita, Hiroaki Akamatsu, Kohei Uemura, Satoshi Morita, Nobuyuki Yamamoto BackgroundRecent reports have indicated that the objective response rate (ORR) and progression-free survival (PFS) cannot serve as surrogates for predicting overall survival (OS) in immune checkpoint inhibitor (ICI) trials. We performed a trial-based correlative analysis to evaluate conventional endpoints as surrogates for predicting OS in ICI-treated non-small cell lung cancer (NSCLC) patients.MethodsA systematic electronic literature search for randomized clinical trials using ICI monotherapies for NSCLC revealed 7 trials. The correlative analysis to clarify the correlations among clinical outcomes used a weighted Spearman rank correlation coefficient (wS), weighted Pearson correlation coefficient (wP), and weighted linear regression model (wL) in all patients and patients with high PD-L1 expression.ResultsThe correlative analysis of the total population revealed that the odds ratio of the ORR (OR-ORR) and the hazard ratio of OS (HR-OS) were strongly correlated with the hazard ratio of PFS (HR-PFS) (R for wP and wS, R2 for wL; −0.869, −0.968, 0.756 between OR-ORR and HR-PFS; 0.923, 0.959, 0.851 between HR-PFS and HR-OS). The strongest correlation was observed between one-year overall survival (1y-OS) and the HR-OS (R for wP and wS, R2 for wL; 0.985, 1.000, R2: 0.968). In those with high PD-L1 expression, the ORR and PFS were strongly associated with OS (R2: 0.842 between ORR and OS; 0.771 between PFS and OS).ConclusionsThe OR-ORR and HR-PFS could serve as surrogate endpoints for predicting the HR-OS in randomized trials using ICIs for NSCLC, while the ORR and PFS could be useful endpoints for predicting OS in trials with patient selection based on high PD-L1 expression.
       
  • Chest radiography surveillance for lung cancer: Results from a National
           Health Insurance database in South Korea
    • Abstract: Publication date: February 2019Source: Lung Cancer, Volume 128Author(s): Hyun Jung Koo, Chang-Min Choi, Sojung Park, Han Na Lee, Dong Kyu Oh, Won-Jun Ji, Seulgi Kim, Mi Young Kim BackgroundLung cancer screening with low-dose computed tomography reduced mortality in selected high risk patients. However, the use of chest radiography for lung cancer screening in Asian populations is still controversial. We investigated the effectiveness of chest radiographic surveillance using a nationwide health service data in South Korea.MethodsData from the Korean National Health Insurance Service examinee cohort of 2004 to 2013 were examined, and 63,228 patients with lung cancer were identified, 38,494 (57%) of whom underwent chest radiography screening. The others did not undergo lung cancer screening and were considered as a control group. Clinical data including age, smoking, screening intervals, lung cancer stages, treatments, and survival were collected. Survival gain from surveillance after adjustment for lead-time bias based on the sojourn time was calculated. Cox-proportional hazard analyses were performed to evaluate the effectiveness of screening and to determine the appropriate screening interval for chest radiography surveillance.ResultsEarly lung cancer was found in 38% of patients receiving chest radiography versus 26% of those without surveillance. A patient age of more than 65 years (hazard ratio [HR], 1.53; 95% confidence limits [CL], 1.50–1.56), male (HR, 1.66; 95% CL, 1.62–1.70), and high lung cancer stages at the time of diagnosis were independent factors associated with mortality (each, P 
       
  • Anti-tumoral activity of the human-specific duplicated form of
           
    • Abstract: Publication date: Available online 28 December 2018Source: Lung CancerAuthor(s): José Luis Cedillo, Anna Bordas, Francisco Arnalich, Isabel Esteban-Rodríguez, Carolina Martín-Sánchez, María Extremera, Gema Atienza, Juan J. Rios, Raquel L. Arribas, Carmen Montiel ObjectivesTobacco smoking is strongly correlated with the onset and progression of non-small cell lung cancer (NSCLC). By activating α7 nicotinic acetylcholine receptors (α7-nAChRs) in these tumors nicotine and its tobacco-derived nitrosamine, NNK, contribute to these oncogenic processes. Here, we investigated whether the human-specific duplicated form of the α7-nAChR subunit (dupα7) behaves as an endogenous negative regulator of α7-nAChR-mediated tumorigenic activity induced by tobacco in NSCLC cells, similarly to its influence on other α7-nAChR-controlled functions in non-tumor cells.MethodsTwo human NSCLC cell lines, lung adenocarcinoma (A549) and squamous cell carcinoma of the lung (SK-MES-1), both wild-type or with stable overexpression of dupα7 (A549dupα7 or SK-MES-1dupα7), were used to investigate in vitro anti-tumor activity of dupα7 on nicotine- or NNK-induced tumor progression. For this purpose, migration, proliferation or epithelial-mesenchymal transition (EMT) were examined. The anti-tumor effect of dupα7 on nicotine-promoted tumor growth, proliferation or angiogenesis was also assessed in vivo in an athymic mouse model implanted with A549dupα7 or A549 xenografts.ResultsOverexpression of dupα7 in both cell lines almost completely suppresses the in vitro tumor-promoting effects induced by nicotine (1 µM) or NNK (100 nM) in wild-type cells. Furthermore, in mice receiving nicotine, A549dupα7 xenografts show: (i) a significant reduction of tumor growth, and (ii) decreased expression of cell markers for proliferation (Ki67) or angiogenesis (VEGF) compared to A549 xenografts.ConclusionOur study demonstrates, for the first time, the in vitro and in vivo anti-tumor capacity of dupα7 to block the α7-nAChR-mediated tumorigenic effects of tobacco in NSCLC, suggesting that up-regulation of dupα7 expression in these tumors could offer a potential new therapeutic target in smoking-related cancers.
       
  • Factors Influencing Recurrence Following Anatomic Lung Resection for
           Clinical Stage I Non-Small Cell Lung Cancer
    • Abstract: Publication date: Available online 26 December 2018Source: Lung CancerAuthor(s): Matthew J. Schuchert, Daniel P. Normolle, Omar Awais, Arjun Pennathur, David O. Wilson, James D. Luketich, Rodney J. Landreneau ObjectivesAnatomic lung resection provides the best opportunity for long-term survival in the setting of early-stage non-small cell lung cancer (NSCLC). However, 20-30% of patients develop recurrent disease following complete (R0) resection for Stage I disease. In the current study, we analyze the impact of patient, surgical and pathologic variables upon recurrence patterns following anatomic lung resection for clinical stage I NSCLC.Patients and MethodsA total of 1,132 patients (384 segmentectomies, 748 lobectomies) with clinical stage I NSCLC were evaluated. Predictors of recurrence were identified by proportional hazards regression. Differences in recurrence patterns between groups are illustrated by log rank tests applied to Kaplan-Maier estimates.ResultsA total of 227 recurrences (20.0%) were recorded at a median follow-up of 36.8 months (65 locoregional, 155 distant). There was no significant difference in recurrence patterns when comparing segmentectomy and lobectomy. Multivariate analysis demonstrated that angiolymphatic invasion, tumor size, tumor grade and the presence of only mild-moderate tumor inflammation were independent predictors of recurrence risk.ConclusionsRecurrence following anatomic lung resection is influenced predominantly by pathological variables (tumor size, tumor grade, angiolymphatic invasion, tumor inflammation). Optimization of surgical margin in relation to tumor size may improve outcomes. Extent of resection (segmentectomy vs. lobectomy) does not appear to have an impact on recurrence-free survival when adequate margins are obtained.
       
  • Impact of estrogen monotherapy on survival in women with stage III-IV
           non-small cell lung cancer
    • Abstract: Publication date: Available online 24 December 2018Source: Lung CancerAuthor(s): Samuel P Heilbroner, Eric P Xanthopoulos, Donna Buono, Yongmei Huang, Daniel Carrier, Anand Shah, Jerry Kim, Michael Corradetti, Jason D Wright, Alfred I Neugut, Dawn L Hershman, Simon Cheng ObjectivesWomen with lung cancer have better survival than men. The reasons are unknown, but estrogen is hypothesized to improve survival. Our objective was to examine the association between estrogen monotherapy and cancer-specific and overall survival in elderly women with non-small cell lung cancer (NSCLC).Materials and MethodsWe used the SEER-Medicare database to identify women ≥65 years old who were diagnosed with stage III or IV NSCLC. Estrogen monotherapy (EM) was defined as at least one estrogen claim without any progesterone claims 6 months prior to diagnosis. To assess cancer-specific survival and overall survival, we used Kaplan-Meier and multivariate Cox modeling with propensity score adjustments. As an exploratory analysis, we also examined the effect of combined estrogen and progesterone hormonal therapy on survival using Cox modeling.ResultsWe identified 6,958 women in our initial cohort: 283 used EM (4%) and 6,675 (96%) did not. The median follow-up time was 46.5 months in the EM patients and 49.5 months in the non-EM patients. In a Kaplan-Meier analysis, median overall survival was 8.2 months in patients who receive EM and 6.2 months in those who did not (p = 0.004).In our 1:4 propensity-matched cohort, median follow-up was 46.5 in the EM group and 50.6 in the non-EM group; median overall survival was 8.0 months in the EM group and 6.4 months in the non-EM group (p = 0.02). In a multivariate Cox regression of the matched cohort, EM was significantly associated with overall survival (HR 0.84; 95% CI 0.73 – 0.97). All results were similar for cancer-specific survival. In our exploratory analysis, combined Estrogen-Progesterone did significantly impact overall survival (HR 0.84; 95% CI 0.71 - 0.99, p = 0.04) but did not appear to effect cancer-specific survival (HR 0.91; 95% CI 0.77 - 1.09, p = 0.30).ConclusionEM was associated with a significant improvement in cancer-specific survival and overall survival in women with late stage NSCLC.
       
  • Stereotactic Ablative Radiotherapy (SABR) in Early Stage Non-Small Cell
           Lung Cancer: Comparing Survival Outcomes in Adenocarcinoma and Squamous
           Cell Carcinoma
    • Abstract: Publication date: Available online 24 December 2018Source: Lung CancerAuthor(s): Stephen Abel, Shaakir Hasan, Richard White, Lana Schumacher, Gene Finley, Athanasios Colonias, Rodney E. Wegner PurposeRecent retrospective studies have demonstrated mixed results regarding the histologic association of squamous cell carcinoma (SCC) with reduced overall survival in patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiotherapy (SABR).MethodsWe queried the National Cancer Database (NCDB) for ES-NSCLC (T1-2N0, Stage I-IIA) patients with SCC or adenocarcinoma (ADC) treated with SABR. Univariable and multivariable analyses identified characteristics predictive of overall survival. Cox proportional hazard ratios with propensity adjustment were used to mitigate indication bias between the two histologic arms.ResultsUltimately 15,110 ES-NSCLC patients with either ADC (n = 8,924) or SCC (n = 6,186) were eligible for analysis. Univariable analysis demonstrated a median overall survival of 44 months and 33 months (p 
       
  • Identification of a novel WNK1–ROS1 fusion in a lung adenocarcinoma
           sensitive to crizotinib
    • Abstract: Publication date: Available online 19 December 2018Source: Lung CancerAuthor(s): Yutao Liu, Tianfeng Liu, Nan Li, Tao Wang, Pu Yue, Rui Lin ObjectivesNon-small-cell lung cancer (NSCLC) has various driver mechanisms, including ROS1 rearrangement with different fusion patterns. There is a need to identify and evaluate new ROS1 fusions and the response to targeted therapy.Materials and methodsA targeted next-generation sequencing (NGS) panel was used to analyze DNA extracted from tumor tissue and blood samples from an NSCLC patient. Results were validated using Sanger sequencing.ResultsWe found a novel ROS1 rearrangement form, namely a WNK1–ROS1 fusion. The transmembrane and kinase domains of ROS1 remained intact in this fusion. No EGFR, MET, KRAS, ALK, ROS1 or other NSCLC driver mutations were detected in the patient. The patient achieved a partial response after treatment with crizotinib. When disease progressed, ROS1 G2032R mutation—a classical mechanism of crizotinib resistance—was detected in the DNA sample extracted from the patient’s plasma sample.ConclusionWe identified a novelWNK1–ROS1 fusion that was sensitive to crizotinib and developed an ROS1 G2032R mutation when the disease progressed. The WNK1–ROS1 rearrangement appeared to be a novel driver of the lung cancer.
       
  • Atezolizumab in patients with advanced non-small cell lung cancer and
           history of asymptomatic, treated brain metastases: exploratory analyses of
           the phase III OAK study
    • Abstract: Publication date: Available online 19 December 2018Source: Lung CancerAuthor(s): Shirish M. Gadgeel, Rimas V. Lukas, Jerome Goldschmidt, Paul Conkling, Keunchil Park, Diego Cortinovis, Filippo de Marinis, Achim Rittmeyer, Jyoti D. Patel, Joachim von Pawel, Carol O’Hear, Catherine Lai, Sylvia Hu, Marcus Ballinger, Alan Sandler, Mayank Gandhi, Lou Fehrenbacher ObjectivesTo assess the safety and efficacy of atezolizumab and docetaxel in patients with and without a history of asymptomatic, treated brain metastases in the phase III OAK trial.Materials and methodsPatients received 1200 mg atezolizumab or 75 mg/m2 docetaxel every 3 weeks until unacceptable toxicity, disease progression, or loss of clinical atezolizumab benefit. Patients with asymptomatic, treated supratentorial metastases were eligible. Patients had brain scans before enrollment; follow-up brain scans and treatment were required when clinically indicated.ResultsApproximately 14% of patients in each arm had a history of asymptomatic, treated brain metastases (61/425 in the atezolizumab arm and 62/425 in the docetaxel arm).Fewer treatment-related adverse events (AEs), serious AEs, and treatment-related neurologic AEs were reported with atezolizumab than with docetaxel, regardless of history of asymptomatic, treated brain metastases. In patients with a history of asymptomatic, treated brain metastases, median overall survival (OS) was longer with atezolizumab than with docetaxel (16.0 vs 11.9 months; hazard ratio = 0.74; 95% CI: 0.49–1.13). Median OS was also longer with atezolizumab in patients without a history of asymptomatic, treated brain metastases (13.2 vs 9.3 months; hazard ratio = 0.74; 95% CI: 0.63–0.88). Landmark analyses showed that patients with a history of asymptomatic, treated brain metastases had a lower probability of developing new symptomatic brain lesions with atezolizumab vs docetaxel at 6 to 24 months. Patients without a history had a lower probability with atezolizumab at 18 to 24+ months.ConclusionAtezolizumab had an acceptable neurologic safety profile, showed a trend toward an OS benefit, and led to a prolonged time to radiographic identification of new symptomatic brain lesions compared with docetaxel in patients who had a history of asymptomatic, treated brain metastases.Clinicaltrials.gov registration number: NCT02008227.
       
  • Primary pulmonary collision tumor comprising squamous cell carcinoma and
           mucosa-associated lymphoid tissue lymphoma
    • Abstract: Publication date: Available online 18 December 2018Source: Lung CancerAuthor(s): Masahiro Yamasaki, Tomoyoshi Takenaka, Naoko Matsumoto, Hideki Asaoku, Masaya Taniwaki, Noboru Hattori
       
  • Nut and peanut butter consumption and the risk of lung cancer and its
           subtypes: a prospective cohort study
    • Abstract: Publication date: Available online 18 December 2018Source: Lung CancerAuthor(s): Lisette Nieuwenhuis, Piet A. van den Brandt ObjectivesNut consumption has been associated with reduced cancer-related mortality, but evidence for a relation between nut intake and lung cancer risk is limited. We investigated the association between total nut, tree nut, peanut, and peanut butter intake and the risk of lung cancer and its subtypes in the Netherlands Cohort Study.Materials and MethodsIn 1986, dietary and lifestyle habits of 120,852 participants, aged 55-69 years, were measured with a questionnaire. After 20.3 years of follow-up, 3,720 subcohort members and 2,861 lung cancer cases were included in multivariable case-cohort analyses.ResultsTotal nut intake was not significantly associated with total lung cancer risk in men or women. For small cell carcinoma, a significant inverse association with total nut intake was observed in men after controlling for detailed smoking habits (HR (95%CI) for 10+ g/day vs. nonconsumers: 0.62 (0.43-0.89), p-trend: 0.024). Inverse relations with small cell carcinoma were also found for tree nut and peanut intake in men in continuous analyses (HR (95%CI) per 5 g/day increment: 0.70 (0.53-0.93) and 0.93 (0.88-0.98), respectively). For the other lung cancer subtypes, no significant associations were seen in men. Nut intake was not related to the risk of lung cancer subtypes in women, and no associations were found for peanut butter in both sexes.ConclusionIncreased nut intake might contribute to the prevention of small cell carcinoma in men. No significant associations were found in men for the other subtypes or total lung cancer, in women, or for peanut butter intake.
       
  • Case Report: Crizotinib is Effective in a Patient with ROS1-rearranged
           Pulmonary Inflammatory Myofibroblastic Tumor
    • Abstract: Publication date: Available online 17 December 2018Source: Lung CancerAuthor(s): Shijie Mai, Gang Xiong, Dingwei Diao, Wenjing Wang, Yujie Zhou, Ruijun Cai ObjectivesInflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor and is prevalent among children and adolescents. In recent years, following the emergence of high-throughput sequencing techniques, rearrangements in genes, such asALK, ROS1, NTRK, RET, and PDGFRβ, have been detected in a considerable proportion of IMT patients. However, the practice of targeted therapy for those patients remains extremely limited. In this study, we report about a 14-year-old boy diagnosed with pulmonary IMT with a mass measuring 12 × 8 cm in the right lower lobe.Materials and methodsImmunohistochemistry (IHC) assay and comprehensive next-generation sequencing (NGS) were performed on the biopsied tumor tissue.ResultsThe IHC assay revealed an ALK-negative tumor, while NGS detected aTFG-ROS1 rearrangement. The patient achieved continuous remission after treatment with crizotinib (250 mg, bid).ConclusionThis case broadens the experience regarding targeted therapy forROS1-rearranged IMT and supports the use of broad molecular profiling testing for optimizing therapeutic options.
       
  • Pembrolizumab in Combination with Ipilimumab as Second-Line or Later
           Therapy for Advanced Non–Small-Cell Lung Cancer: KEYNOTE-021 Cohorts D
           and H
    • Abstract: Publication date: Available online 17 December 2018Source: Lung CancerAuthor(s): M.A. Gubens, L.V. Sequist, J.P. Stevenson, S.F. Powell, L.C. Villaruz, S.M. Gadgeel, C.J. Langer, A. Patnaik, H. Borghaei, S.I. Jalal, J. Fiore, S. Saraf, H. Raftopoulos, L. Gandhi ObjectivesCombination immunotherapy may result in improved antitumor activity compared with single-agent treatment. We report results from dose-finding and dose-expansion cohorts of the phase 1/2 KEYNOTE-021 study that evaluated combination therapy with anti‒programmed death 1 (PD-1) antibody pembrolizumab plus anti‒cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in patients with previously treated advanced non–small-cell lung cancer (NSCLC).Materials and MethodsEligibility criteria stipulated histologically/cytologically confirmed advanced NSCLC and treatment failure on ≥1 prior systemic therapy (platinum-based chemotherapy or targeted therapy for patients with EGFR/ALK aberrations). In the dose-finding cohort, patients initially received pembrolizumab 10 mg/kg plus ipilimumab 1 or 3 mg/kg once every 3 weeks for 4 cycles followed by pembrolizumab 10 mg/kg monotherapy for up to 2 years. Based on emerging published data, subsequent patients received pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg. Objective response rate (ORR; primary efficacy endpoint) was assessed per RECIST version 1.1 by blinded, independent central review. Phase 2 hypothesis that ORR would be greater than the 20% rate for historical controls was evaluated using the exact binomial test.ResultsFifty-one patients were enrolled; 71% received ≥2 prior lines of therapy. No dose-limiting toxicities occurred at any dose level. Among patients who received pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg (n = 44), ORR was 30% (95% CI, 17%–45%), but not statistically significantly>20% (P = 0.0858). Median progression-free survival in this group was 4.1 (95% CI, 1.4–5.8) months; median overall survival was 10.9 (95% CI, 6.1–23.7) months. With pembrolizumab 2 mg/kg plus ipilimumab 1 mg/kg, incidences of treatment-related adverse events, grade 3–5 treatment-related adverse events, and immune-mediated adverse events and infusion reactions were 64%, 29% and 42%, respectively.ConclusionsIn patients with heavily pretreated advanced NSCLC, pembrolizumab plus ipilimumab showed evidence of antitumor activity, but was associated with meaningful toxicity.
       
  • Prognostic value of preoperative exercise capacity in patients undergoing
           thoracoscopic lobectomy for non-small cell lung cancer
    • Abstract: Publication date: Available online 16 December 2018Source: Lung CancerAuthor(s): Kazumi Hamada, Masataka Irie, Yoshihisa Fujino, Masahiro Hyodo, Takeshi Hanagiri ObjectivesWhether or not the preoperative exercise capacity, as assessed by 6-min walk test, influences the survival of patients undergoing thoracoscopic lobectomy for lung cancer is unclear. We therefore investigated the prognostic value of the 6-min walk distance in this population.Materials and MethodsThis prospective cohort study was conducted between 2005 and 2013. We studied 224 consecutive subjects with stage I-II non-small cell lung cancer who underwent thoracoscopic lobectomy. Survival was calculated by the Kaplan-Meier method. The log-rank test was used to assess the survival rate. Cox proportional hazards models were used to estimate the risk of 5-year all-cause mortality based on the preoperative 6-min walk distance with adjustment for other prognostic factors, including the age, performance status, postoperative cardiopulmonary complication, and pathological stage.ResultsThe median follow-up period was 60.8 months. During this period, 38 deaths were recorded. The 5-year overall survival rate of the subjects with a preoperative 6-min walk distance of
       
  • Static lung hyperinflation is an independent risk factor for lung cancer
           in patients with chronic obstructive pulmonary disease
    • Abstract: Publication date: Available online 14 December 2018Source: Lung CancerAuthor(s): Ester Zamarrón, Eva Prats, Elena Tejero, Paloma Pardo, Raúl Galera, Raquel Casitas, Elisabet Martínez-Cerón, Delia Romera, Ana Jaureguizar, Francisco García-Río IntroductionStatic hyperinflation, a hallmark characteristic of some patients with chronic obstructive pulmonary disease, is related to higher mortality and cardiovascular morbidity. However, information about its association with lung cancer is scarce. Our aim was to evaluate whether static hyperinflation is associated with future risk of lung cancer in COPD patients.MethodsA cohort of 848 COPD patients recruited outside the hospital setting was monitored for an average period of 4.3 years, totaling 2,858 person-years, regarding diagnosis of cancer of any origin or lung cancer. Static hyperinflation was defined by functional residual capacity measured by plethysmography greater than 120% of the predicted value.ResultsThe incidence rates for cancer of any origin and lung cancer were 16.0 (95%CI, 15.1-17.8) and 8.7 (95%CI, 7.7-9.8) per 1000 patient-years, respectively. Among the patients with lung cancer, non-small cell lung cancer predominated (88%). In a stepwise multivariate Cox regression model, body mass index (BMI), pack-years, Charlson index, and postbronchodilator FEV1/FVC ratio were retained as independent predictors of cancer of any origin. In contrast, features associated with a future risk of lung cancer included older age, low BMI, increased pack-years and presence of static hyperinflation (adjusted hazard ratio: 4.617, 95%CI: 1.007-21.172, p = 0.049).ConclusionIn a general COPD outpatient population, static hyperinflation is an independent risk factor for the development of lung cancer, which might contribute towards justifying the excess mortality identified in COPD patients with hyperinflation.
       
  • Loss of T790M mutation is associated with early progression to osimertinib
           in Chinese patients with advanced NSCLC who are harboring EGFR T790M
    • Abstract: Publication date: Available online 12 December 2018Source: Lung CancerAuthor(s): Sha Zhao, Xuefei Li, Chao Zhao, Tao Jiang, Yijun Jia, Jinpeng Shi, Yayi He, Jiayu Li, Fei Zhou, Guanghui Gao, Wei Li, Xiaoxia Chen, Chunxia Su, Shengxiang Ren, Caicun Zhou BackgroundOsimertinib demonstrates superior efficacy in patients with non-small cell lung cancer (NSCLC) who acquired EGFR T790M mutation as resistant mechanism to upfront EGFR tyrosine kinase inhibitors (TKIs). Not all the T790M-positive tumors are homogeneously sensitive to osimertinib, however, and the duration of response often varies. Previous studies suggest that loss of T790 M at osimertinib resistance is correlated with shortened survival benefit of osimertinib. The aim of this study is to investigate the prevalence of T790 M loss after progression to osimertinib in Chinese patients with NSCLC harboring EGFR T790 M mutation and to compare their clinical outcomes and characteristics when stratified by T790 M mutational status at osimertinib resistance.Patients and MethodsAll patients with a secondary T790 M mutation after progression to prior-line EGFR TKIs and received single-agent osimertinib were reviewed. The patients who were reassessed for T790 M mutation post-osimertinib resistance were included in final analysis. Detailed clinicopathologic characteristics and response data were collected.ResultsOf the patients with confirmed T790 M mutation as acquired resistance to early-generation EGFR TKIs and subsequently received single-agent osimertinib, 84 patients experienced clinical progression after osimertinib treatment and were eligible for analysis. Among them, 31 patients underwent repeated T790 M mutation testing on osimertinib resistance. Sixteen patients had maintained T790 M mutation, whereas 15 patients lost T790 M at resistance. Loss of T790 M at resistance was remarkably correlated with shorter duration of response to osimertinib (P = 0.0005). Furthermore, the overall survival after osimertinib treatment was also decreased in T790M-loss group (P=0.021). The objective response rates were comparable between T790M-maintain and T790M-loss group (31.3% and 26.7%, respectively). In multivariate analysis, loss of T790M remained statistically associated with early progression to osimertinib.ConclusionLoss of T790 M mutation at resistance was correlated with early progression and overall survival in response to osimertinib treatment in Chinese patients with NSCLC harboring acquired T790 M mutation.
       
  • Optimal management of brain metastases in oncogenic-driven non-small cell
           lung cancer (NSCLC)
    • Abstract: Publication date: Available online 10 December 2018Source: Lung CancerAuthor(s): Nicolaus Andratschke, Johannes Kraft, Carsten Nieder, Rebecca Tay, Raffaele Califano, Riccardo Soffietti, Matthias Guckenberger Brain metastases are common events in the natural course of many advanced solid cancers like breast, lung and renal cancer or melanoma with a cumulative risk of 10-30% in adults [[1], [2], [3]]. Non-small cell lung cancer (NSCLC) is associated with an increased risk for the development of brain metastases and the prognosis until recently has been poor except for some patients’ subgroups and depending on the disease-specific GPA prognostic factors [4].For patients receiving only best supportive care, average survival is about 3 months and it is assumed that through additional whole brain radiotherapy average survival may be improved up to 6-9 months in selected patients [5].In recent years, complex treatment strategies for different solid tumors have been developed and this has impacted on the general management of brain metastases. Most of the studies on brain metastases have included different histological subtypes and therefore have made tumor- specific recommendations difficult. In this review, we discuss the current evidence on management of brain metastases and incorporate specific recent data on oncogenic-driven NSCLC in order to suggest recommendations on the optimal management of brain metastases in this subgroup of NSCLC where formal level I evidence is lacking.
       
  • Co-expression of IDO1 and PD-L1 in lung squamous cell carcinoma: Potential
           targets of novel combination therapy
    • Abstract: Publication date: Available online 10 December 2018Source: Lung CancerAuthor(s): Kazuki Takada, Kenichi Kohashi, Mototsugu Shimokawa, Akira Haro, Atsushi Osoegawa, Tetsuzo Tagawa, Takashi Seto, Yoshinao Oda, Yoshihiko Maehara Objectives Combination therapy with an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1) and an agent targeting programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) is expected to be a novel and effective treatment option for various solid tumors including non-small cell lung cancer (NSCLC). Therefore, it is important to elucidate the clinical and pathological features of tumors with IDO1/PD-L1 co-expression and the association between IDO1/PD-L1 co-expression and efficacy of combination therapy in NSCLC patients. In this study, we examined the prognostic impact of IDO1/PD-L1 co-expression and its relationship with tumor-infiltrating lymphocytes (TILs) in primary lung squamous cell carcinoma (SCC).Materials and methods The expression levels of IDO1, PD-L1, Ki-67, cluster of differentiation 3 (CD3), CD4, and CD8 in 202 patients with surgically resected primary lung SCC were evaluated by immunohistochemistry.Results Among 202 patients, 176 (87.1%) were positive for IDO1 expression, 106 (52.5%) were positive for PD-L1 expression, and 99 (49.0%) showed co-expression of IDO1/PD-L1 proteins. Fisher’s exact test showed a significant association between IDO1 and PD-L1 tumor proportion scores (P =  0.0011). Kaplan–Meier curve showed that PD-L1 alone and co-expression of IDO1 and PD-L1 were significantly associated with shorter overall survival, but IDO1 alone was not (log rank test: P =  0.0122, P =  0.0303 and P =  0.5168, respectively). The Ki-67 labeling index was significantly higher in patients with co-expression of IDO1 and PD-L1 than in patients without co-expression (Student’s t-test: P =  0.0005). Moreover, IDO1/PD-L1 co-expression was significantly associated with high CD3, CD4, and CD8 expression (Fisher’s exact test: P =  0.0033, P =  0.0003, and P 
       
  • Efficacy of first-line treatment with epidermal growth factor
           receptor-tyrosine kinase inhibitor (EGFR-TKI) alone or in combination with
           chemotherapy for advanced non-small cell lung cancer (NSCLC) with
           low-abundance mutation
    • Abstract: Publication date: Available online 6 December 2018Source: Lung CancerAuthor(s): Xiangtao Yan, Huijuan Wang, Peng Li, Guowei Zhang, Mina Zhang, Jinpo Yang, Xiaojuan Zhang, Xuanxuan Zheng, Zhiyong Ma ObjectiveThe objective of this study was to investigate whether first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy improves the prognosis of patients with advanced non-small cell lung cancer (NSCLC) who harbour low-abundance EGFR mutations.Patients and methodsWe retrospectively analysed the clinical data of 76 patients with advanced NSCLC who harboured low-abundance EGFR mutations. The patients were divided into the combination group and the monotherapy group. The combination group received EGFR-TKI combined with a platinum-based regimen. After the end of chemotherapy, EGFR-TKI was administered daily. The monotherapy group was administered EGFR-TKI therapy daily.ResultsNo significant difference was observed in response rate between the different groups. The median PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.9 months [95% CI,5.73-10.07] vs 5.9 months [95% CI, 4.99-6.81], p = 0.015; OS: 25.8 months[95% CI,16.27-35.33] vs 19.8 months [95% CI, 18.60-21.00], p = 0.047). Subgroup analysis showed that, for patients with the exon 21 L858R mutation, the PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.2 months vs 5.8 months, p = 0.013; OS: 22.0 months vs 18.7 months, p = 0.024). The incidence of adverse events was significantly higher in the combination group.ConclusionFor patients with advanced NSCLC and low-abundance EGFR mutations, first-line treatment with EGFR-TKI plus chemotherapy significantly improved PFS and OS. The combination therapy increased the incidence of adverse reactions, but all adverse reactions were expected and tolerated.
       
  • Prognostic impact of microscopic vessel invasion and visceral pleural
           invasion and their correlations with epithelial–mesenchymal transition,
           cancer stemness, and treatment failure in lung adenocarcinoma
    • Abstract: Publication date: Available online 6 December 2018Source: Lung CancerAuthor(s): Shinya Neri, Toshi Menju, Terumasa Sowa, Yojiro Yutaka, Daisuke Nakajima, Masatsugu Hamaji, Akihiro Ohsumi, Toyofumi F. Chen-Yoshikawa, Toshihiko Sato, Makoto Sonobe, Akihiko Yoshizawa, Hironori Haga, Hiroshi Date ObjectivesMicroscopic vessel invasion (MVI) and visceral pleural invasion (VPI) have been recently reported as poor prognostic factors of non-small cell lung cancer. Epithelial–mesenchymal transition (EMT) and cancer stemness (CS) are known malignant phenotypes that induce resistance to cancer therapy. We aimed to assess the prognostic significance of MVI and the correlations among VPI/MVI, EMT, CS, and treatment failure for recurrent tumor.Materials and methodsFrom 2002 to 2013, 1034 consecutive patients with pathological T1-4N0-2M0 lung adenocarcinoma underwent complete resection. Moreover, we established 206 tissue microarray (TMA) samples from 2002 to 2007. We then evaluated the prognostic impact of MVI, including conventional clinicopathological factors, and analyzed the VPI/MVI, EMT, CS, and treatment failure by TMA immunohistochemical staining.ResultsAmong the 1034 cases, the proportion of patients with a 5-year overall survival (OS) period was 63.9% and 88.2% (MVI: +/−; p < .001). Multivariate analysis revealed that both MVI and VPI were independent predictors of OS (HR 1.57 and 1.47, respectively). Significant separation of the OS rate curves was observed among the 3 groups [VPI/MVI: both positive (2), either positive (1), and both negative (0)]. Among the 206 TMA cases, these 3 groups of VPI/MVI were significantly correlated with EMT and CS. The median time to progression after recurrence were 3.8, 8.9, and 15.9 months, respectively (VPI/MVI: 2/1/0; p =  0.016).ConclusionMVI and VPI are significant prognostic factors of lung cancer, and they are correlated with EMT, CS, and treatment failure for recurrent tumor.Graphical abstractGraphical abstract for this article
       
  • Complete tumor response of a locally advanced lung large-cell
           neuroendocrine carcinoma after palliative thoracic radiotherapy and
           immunotherapy with nivolumab
    • Abstract: Publication date: Available online 5 December 2018Source: Lung CancerAuthor(s): Charlotte Mauclet, Fabrice Duplaquet, Lionel Pirard, Benoît Rondelet, Michael Dupont, Claudia Pop-Stanciu, Thierry Vander Borght, Myriam Remmelink, Nicky D’Haene, Suzan Lambin, Marie Wanet, Vincent Remouchamps, Sebahat Ocak Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.
       
  • Exploration of germline variants responsible for adverse events of
           crizotinib in anaplastic lymphoma kinase-positive non-small cell lung
           cancer by target-gene panel sequencing
    • Abstract: Publication date: Available online 4 December 2018Source: Lung CancerAuthor(s): Hidenori Mizugaki, Akinobu Hamada, Tatsuhiro Shibata, Fumie Hosoda, Hiromi Nakamura, Yusuke Okuma, Takehito Shukuya, Shigeki Umemura, Atsushi Horiike, Tomoya Fukui, Yoshihito Kogure, Haruko Daga, Yoshiko Urata, Kazuhiko Yamada, Sho Saeki, Yasuhito Fujisaka, Yukiko Nakamura, Mitsuo Sato, Tatsuya Yoshida, Takamasa Hotta ObjectivesCrizotinib is a standard treatment for advanced anaplastic lymphoma kinase (ALK)- or ROS1-fusion-gene-positive non-small cell lung cancer; however, serious adverse events (AEs), including elevated alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and interstitial lung disease (ILD), develop occasionally. Here, we evaluated relationships between clinically significant crizotinib-associated AEs and germline variations.Materials and MethodsDNA obtained from 75 patients allowed selection of 147 genes according to function, exon identification and sequencing, and determination of germline single nucleotide variants (SNVs). Correlations between clinically significant AEs and presence of germline variants were estimated by Fisher’s exact test.ResultsWe defined clinically significant AEs as grade 4 hematological toxicity, grade ≥3 non-hematological toxicity, and any grade of ILD. These AEs were observed in 26 patients (35%), with elevated AST/ALT (15%) the most common, followed by neutropenia (5%), ILD (4%), and thromboembolic events (4%). Nonsynonymous SNVs in epoxide hydrolase 1 (EPHX1) [odds ratio (OR): 3.86; p = 0.0009) and transcription factor 7-like 2 (TCF7L2) (OR: 2.51; p = 0.025) were associated with the presence of clinically significant AEs.ConclusionNonsynonymous EPHX1 and TCF7L2 SNVs might be associated with clinically significant crizotinib-associated AEs. These data indicated that target-gene sequencing could be feasible for predicting anticancer-agent toxicity, and that germline multi-gene information might be useful for predicting patient-specific AEs to promote precision medicine.
       
  • Oral vinorelbine versus etoposide with cisplatin and chemo-radiation as
           treatment in patients with stage III non-small cell lung cancer: a
           randomized phase II (RENO study)
    • Abstract: Publication date: Available online 1 December 2018Source: Lung CancerAuthor(s): Dolores Isla, Ramón De Las Peñas, Amelia Insa, Raquel Marsé, Natividad Martínez-Banaclocha, Pilar Mut, Teresa Morán, María Ángeles Sala, Bartomeu Massuti, Ana Laura Ortega, José Miguel Jurado, José Gómez-Codina, Pilar Diz, Ángel Artal, Vanesa Gutiérrez, María Francisca Vázquez, Nuria Viñolas, Inmaculada Maestu, Carlos Camps, Rosa Álvarez ObjectivesConcomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC). The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting.Material and MethodsAn open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomized1:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on days 1 and 8 in 4-week cycles; 2 cycles in concomitance). Both groups received concomitant radiotherapy 2 Gy/day (66 Gy). The primary endpoint was progression free survival (PFS).ResultsOne hundred and forty patients were enrolled. Sixty-nine patients received OVP and 71 received EP. Globally adverse events grade 3/4 per cycle were fewer in the vinorelbine arm (19.4%) than in the etoposide arm (62.6%) (p < 0.001). One patient (1.5%) in the OVP arm and 12 pts (17.6%) in the EP arm presented esophagitis grade 3/4 (p = 0.002). Median PFS was similar in both groups (10.8 [95% CI 7.7-13.8] and 9.6 months [95% CI 4.4-14.8]; p = 0.457, respectively). Preliminary median overall survival was 30 months in the OVP arm and 31.9 months in the EP arm (p = 0.688).ConclusionsOur findings show that OVP could be considered a standard combination with similar efficacy and better safety profile for the treatment of LA-NSCLC patients.
       
  • Imaging in Pleural Mesothelioma: A Review of the 14th International
           Conference of the International Mesothelioma Interest Group
    • Abstract: Publication date: Available online 28 November 2018Source: Lung CancerAuthor(s): Samuel G. Armato, Roslyn J. Francis, Sharyn Katz, Guntulu Ak, Isabelle Opitz, Eyjolfur Gudmundsson, Kevin G. Blyth, Ashish Gupta Mesothelioma patients rely on the information their clinical team obtains from medical imaging. Whether x-ray-based computed tomography (CT) or magnetic resonance imaging (MRI) based on local magnetic fields within a patient’s tissues, different modalities generate images with uniquely different appearances and information content due to the physical differences of the image-acquisition process. Researchers are developing sophisticated ways to extract a greater amount of the information contained within these images. This paper summarizes the imaging-based research presented orally at the 2018 International Conference of the International Mesothelioma Interest Group (iMig) in Ottawa, Ontario, Canada, held May 2-5, 2018. Presented topics included advances in the imaging of preclinical mesothelioma models to inform clinical therapeutic strategies, optimization of the time delay between contrast administration and image acquisition for maximized enhancement of mesothelioma tumor on CT, an investigation of image-based criteria for clinical tumor and nodal staging of mesothelioma by contrast-enhanced CT, an investigation of methods for the extraction of mesothelioma tumor volume from MRI and the association of volume with patient survival, the use of deep learning for mesothelioma tumor segmentation in CT, and an evaluation of CT-based radiomics for the prognosis of mesothelioma patient survival.
       
  • Interest in lifestyle advice at lung cancer screening: determinants and
           preferences
    • Abstract: Publication date: Available online 27 November 2018Source: Lung CancerAuthor(s): Claire Stevens, Samuel G. Smith, Samantha L Quaife, Charlotte Vrinten, Jo Waller, Rebecca J. Beeken BackgroundLung cancer screening could be a ‘teachable moment’ for behaviour change. Little is known about how advice about smoking cessation, or other behavioural cancer risk factors, would be received in this setting.MethodsUsing a population-based survey of 459 English adults (current smokers and recent quitters aged 50-75) we assessed willingness to receive lifestyle advice (about smoking, diet, weight, physical activity, alcohol consumption) at lung screening. Additional items assessed whether advice should be provided following abnormal screening results, the potential impact of advice on screening uptake, and preferred timing of advice.ResultsOverall, 64% (n = 292) of participants were willing to receive lifestyle advice at lung screening. A greater proportion of participants were willing to receive advice in a scenario where results required further investigation (83%; p 
       
  • Potential for afatinib as an optimal treatment for advanced non-small cell
           lung carcinoma in patients with uncommon EGFR mutations
    • Abstract: Publication date: Available online 14 November 2018Source: Lung CancerAuthor(s): Ichidai Tanaka, Masahiro Morise, Yuta Kodama, Akira Matsui, Naoya Ozawa, Sachiko Ozone, Daiki Goto, Ayako Miyazawa, Tetsunari Hase, Naozumi Hashimoto, Mitsuo Sato, Yoshinori Hasegawa
       
  • Letter in Reply to Xu
    • Abstract: Publication date: Available online 8 November 2018Source: Lung CancerAuthor(s): Chong Hyun Suh, Kyung Won Kim, Mizuki Nishino
       
  • The novel microRNA smR-164 regulates cell proliferation and apoptosis in
           human lung cancer by targeting XIAP
    • Abstract: Publication date: Available online 13 April 2018Source: Lung CancerAuthor(s): Jung Ki Yoo, Ji Min Lee, Seung Hee Kang, Seong Ho Jeon, Chang Min Kim, Seung-Hun Oh, Chang-Hyun Kim, Nam Keun Kim, Jin Kyeoung Kim ObjectivesMicroRNAs have critical roles in cancer development by regulating the expression of oncogenes or tumor suppressor genes. We identified and characterized a novel miRNA, smR-164, in human lung cancer cells. The aim of this study was to investigate its novel function in human lung cancer by targeting XIAPMaterial and methodsNovel miRNA cloning, Real-time qRT-PCR, western blotting, dual luciferase assay, miRNA transfection, proliferation and apoptosis assay were carried on human lung cancer cell line A549. Fifteen paired NSCLC tissues and noncancerous lung tissues were collected. In vivo xenograft assay was performed.ResultsExpression of smR-164 was downregulated in human lung cancer cell lines and tissues compared with normal cells and tissues. We identified a putative target gene, XIAP, whose expression was regulated by smR-164 overexpression. XIAP is an inhibitor of apoptosis that represses the activation of caspase 3 and 9. XIAP mRNA and protein levels were directly suppressed by smR-164. XIAP has an important role in carcinogenesis, and previous studies suggest that it may regulate cell survival and proliferation by its anti-apoptotic ability.ConclusionTaken together, smR-164 inhibited cell proliferation and induced apoptosis in vitro and in vivo by targeting XIAP. These data can be applied to identify novel therapeutic targets for lung cancer therapy.
       
  • Tumor autoantibodies (TAAs) panel can improve the accuracy of early
           diagnosis in lung cancer presenting with ground-glass nodules (GGNs) in
           Chinese population
    • Abstract: Publication date: Available online 9 February 2018Source: Lung CancerAuthor(s): Yayi He, Shengxiang Ren, Kenichi Suda, Christopher Rivard, Yan Wang, Xuefei Li, Caicun Zhou, Fred R. Hirsch BackgroundAutoantibody is an attractive diagnostic approach for early detection of malignant tumors. We performed this study to validate the performance of a panel of 7 tumor autoantibodies (TAAs) (p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1, CAGE) to aid early diagnosis of lung adenocarcinoma with ground-glass nodules (GGNs) in Chinese population and to find an effective simple blood test which can be used in further assessing the risk of lung cancer being present GGNs.MethodsA prospective audit was conducted on 592 individuals known to have lung GGNs. We detected TAAs quantitation by ELISA method.Results198 were positive detected by autoantibody panel test (186 pulmonary malignant or borderline lung diseases, 12 lung benign GGNs). The sensitivity and specificity of autoantibody assay were 39.6% and 90.2% respectively. In lung invasive adenocarcinoma, the sensitivity of autoantibody assay was 49.4%. When the TAAs were combined with miRNAs panel in patients with GGNs, the sensitive was increased to 50.0%. In GGNs>8 mm patients, the sensitive of the TAAs combined with miRNAs panel was more than 60%.ConclusionThe greatest impact of using the new TAAs was the highly significant improvement in the sensitivity and specificity of the test in the clinical setting. Our study suggested that the TAAs can be combined with CT imaging to aid diagnosis of lung cancer with GGNs.
       
  • Comment on: Pneumonitis in advanced non-small-cell lung cancer patients
           treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts
           with 15,713 patients: Meta-analysis of incidence and risk factors of
           EGFR-TKI pneumonitis in NSCLC
    • Abstract: Publication date: Available online 24 September 2018Source: Lung CancerAuthor(s): Ran Xu, Jing Zhu
       
 
 
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