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Publisher: Elsevier   (Total: 3159 journals)

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Showing 1 - 200 of 3159 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: 32, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 90, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 34, 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: 407, 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: 8, 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: 245, 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: 10, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, 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: 6)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 16, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 140, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, 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: 12, 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: 22, 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: 30, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, 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: 3)
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: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, 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: 11)
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: 24)
Advances in Ecological Research     Full-text available via subscription   (Followers: 43, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 44, 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: 54, 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: 21, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
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: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, 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: 6, 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: 21)
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: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 16, 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: 10)
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: 8)
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: 18)
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: 62)
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: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 396, 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: 10, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 31, 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: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 336, 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: 442, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 16, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 32, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
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: 11, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
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: 9, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 50, 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: 50, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 54, 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: 28, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 45)
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: 203, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, 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: 27, 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: 37, 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: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 62, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 16, 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: 40, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 171, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
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: 189, 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  [3159 journals]
  • Aims and Scope/Editorial Board
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s):
       
  • Adjuvant treatment patterns and outcomes in Patients with Stage IB-IIIA
           Non-Small Cell Lung Cancer in France, Germany, and the United Kingdom
           based on the LuCaBIS burden of illness study
    • Abstract: Publication date: Available online 10 August 2018Source: Lung CancerAuthor(s): Christos Chouaid, Sarah Danson, Stefan Andreas, Obukohwo Siakpere, Laure Benjamin, Rainer Ehness, Marie-Hélène Dramard-Goasdoue, Janina Barth, Hans Hoffmann, Vanessa Potter, Fabrice Barlesi, Mark Price, Costel Chirila, Kelly Hollis, Carolyn Sweeney, Sorrel Wolowacz, James A. Kaye, Ilias Kontoudis ObjectivesTo inform health-technology assessments of new adjuvant treatments, we describe treatment patterns in patients with complete resection of stage IB-IIIA non-small cell lung cancer (NSCLC) in France, Germany, and the United Kingdom (UK).Materials and MethodsData were collected via medical record abstraction. Patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC, diagnosed between 01 January 2009 and 31 December 2011. Median follow-up was 26 months. Adjuvant treatment patterns and clinical outcomes were summarized descriptively.ResultsAmong the 831 patients studied, 239 (29%) had stage IB disease, 179 (22%) had stage IIA disease, 165 (20%) had stage IIB disease, and 248 (30%) had stage IIIA disease. Adjuvant systemic therapy was received by 402 patients (48.4%), (France, 61.8%; Germany, 51.9%; UK, 33.4%). Use of adjuvant therapy increased with increasing stage of disease. Cisplatin/vinorelbine and carboplatin/vinorelbine were the most frequently prescribed adjuvant regimens. Median disease-free survival was 48.0 months (95% confidence interval [CI] 42.3–not estimable); the 25th percentile was 13.2 months (95% CI, 11.0–15.3). 204 patients (24%) died during the follow-up period. The median overall survival was not reached, the 25th percentile was 31.2 months (95% CI 26.8–36.0 months). 272 patients (33%) had disease recurrence during the follow-up period. For 86 of those patients, the first recurrence was local or regional with no distant metastasis and 14 had further progression to metastatic disease during the follow-up time. For the other 186 patients, the first recurrence involved distant metastases. A total of 200 patients had metastatic disease at any time during study follow-up.ConclusionsLess than half the patients with stage IB-IIIA NSCLC in this observational study received adjuvant systemic therapy. A high rate of first recurrence with distant metastatic disease was observed, emphasising the need for more effective systemic adjuvant therapies in this population.
       
  • Non-invasive detection of actionable mutations in advanced non-small-cell
           lung cancer using targeted sequencing of circulating tumor DNA
    • Abstract: Publication date: Available online 8 August 2018Source: Lung CancerAuthor(s): Wey Cheng Sim, Chet Hong Loh, Xian Toh Li, Chia Wei Lim, Akhil Chopra, Alex Yuan Chi Chang, Liuh Ling Goh ObjectiveTo evaluate the feasibility of detecting actionable gene mutations in circulating tumor DNA (ctDNA) in patients with advanced non-small-cell lung cancer (NSCLC) using targeted next-generation sequencing (NGS).Materials and methodsIn total 50 plasma samples from patients newly diagnosed with advanced NSCLC or resistant to first-line tyrosine kinase inhibitors (TKIs) were subjected to deep sequencing on a seven-gene panel (BRAF, EGFR, ERBB2, KRAS, NRAS, PIK3CA, PTEN) incorporated with molecular barcodes to improve accuracy in variant detection. When possible, results were compared with those from matched tissue samples.ResultsAt least one alteration in the ctDNA was detected in 44 out of 50 patients (88%); EGFR was the most frequently mutated gene. Half the total number of patients (50%, 25 of 50) had at least one actionable genetic alteration with targeted therapies available for treatment. Our results showed a high concordance rate of 81% in detection of EGFR mutation between 26 matched tissue and plasma samples. For progressive patients, from whom tissue is mostly unavailable, the resistant EGFR T790 M mutation was validated using the droplet digital polymerase chain reaction (ddPCR), yielding a concordance of 92% between alternative platforms.ConclusionOur study demonstrated that therapeutically actionable mutations can be detected with high accuracy in ctDNA using NGS. This promising approach offers alternative and non-invasive diagnostic methods for treatment guidance and clinical monitoring.
       
  • Targeted lung cancer screening selects individuals at high risk of
           cardiovascular disease
    • Abstract: Publication date: Available online 8 August 2018Source: Lung CancerAuthor(s): H Balata, S Blandin Knight, P Barber, D Colligan, EJ Crosbie, R Duerdan, P Elton, M Evison, M Greavesd, J Howells, K Irion, D Karunaratne, M Kirwan, A Macnab, S Mellor, C Miller, T Newton, J Novasio, R Sawyer, A Sharman BackgroundCardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention.MethodsThe Manchester Lung Screening Pilot consisted of annual low dose CT (LDCT) over 2 screening rounds, targeted at individuals in deprived areas at high risk of lung cancer (age 55-74 and 6-year risk ≥1.51%, using PLCOM2012 risk model). All participants of the second screening round were eligible to take part in the study. Ten-year CV risk was estimated using QRISK2 in participants without CVD and compared to age (±5 years) and sex matched Health Survey for England (HSE) controls; high risk was defined as QRISK2 score ≥10%. Coronary artery calcification (CAC) was assessed on LDCT scans and compared to QRISK2 score.ResultsSeventy-seven percent (n=920/1,194) of screening attendees were included in the analysis; mean age 65.6 ± 5.4 and 50.4% female. QRISK2 and lung cancer risk (PLCOM2012) scores were correlated (r = 0.26, p 
       
  • Multisite stereotactic body radiotherapy for metastatic non-small-cell
           lung cancer: delaying the need to start or change systemic therapy'
    • Abstract: Publication date: Available online 7 August 2018Source: Lung CancerAuthor(s): Tomas Merino Lara, Joelle Helou, Ian Poon, Arjun Sahgal, Hans T. Chung, William Chu, Hany Soliman, Yee Ung, Sunil Verma, Parneet Cheema, Susanna Cheng, Suneil Khanna, Darby Erler, Liying Zhang, Patrick Cheung ObjectivesThe purpose of this study was to review the clinical outcomes following the use of stereotactic body radiotherapy (SBRT) in patients with metastatic non-small-cell lung cancer (NSCLC) from a large academic institution.Materials and methods: Metastatic NSCLC patients treated with extracranial SBRT were identified from an institutional database. Treatment indications were: (1) oligometastases, (2) oligoprogression, and (3) local control of dominant tumors. Endpoints included overall survival (OS), progression-free survival (PFS), time to starting/changing systemic therapy (SCST), and local failure (LF). Univariate and multivariable analyses were performed to look for predictive factors.Results108 patients with 165 tumors were treated. SBRT was delivered for oligometastases in 66 patents, for oligoprogression in 20 patients, and for local control in 22 patients. Median OS and PFS for all patients were 27.3 months and 4.4 months, respectively, with treatment indication being the only predictive factor on multivariable analysis (patients with oligometastases having the highest median OS and PFS of 39.3 months and 7.6 months respectively). Cumulative incidence of SCST was only 21.5% at 1 year after SBRT, with larger tumor size and positivity for EGFR/ALK mutation being predictive of higher rates of SCST on multivariable analysis. LF was 15.6% at 1 year, with larger tumor size and exposure to previous systemic therapy being predictive of higher rates of LF on multivariable analysis.ConclusionPatients treated with SBRT for oligometastases have better OS and PFS than those treated for oligoprogression or for local control of dominant tumors. Use of SBRT may delay the need for SCST. Larger tumors and previous exposure to systemic therapy were predictive of higher rates of LF.
       
  • Cost-effectiveness of a low-dose computed tomography screening programme
           for lung cancer in New Zealand
    • Abstract: Publication date: Available online 6 August 2018Source: Lung CancerAuthor(s): Richard Jaine, Giorgi Kvizhinadze, Nisha Nair, Tony Blakely ObjectivesThe cost-effectiveness of low-dose computed tomography (LDCT) screening for lung cancer is uncertain. This study estimated the health gains, costs (net health system, and including ‘unrelated’) and cost-effectiveness of biennial LDCT screening among 55-74 years olds with a smoking history of at least 30 pack years, and (if a former smoker) having quit within last 15 years, in New Zealand.MethodsWe used a macrosimulation stage shift model with New Zealand-specific lung cancer incidence rates and intervention parameters from the National Lung Screening Trial, a health system perspective, and a lifetime horizon for quality-adjusted life-years (QALYs) and costs discounted at 3% per annum. We also examined heterogeneity by gender, ethnicity (Māori (indigenous population) versus non-Māori), age and current versus ex-smoking status.Results and ConclusionWe estimated 0.037 QALYs gained (95% uncertainty interval (UI) 0.024 to 0.053) per eligible participant, at a cost of US$3606 ($2689-4681). The overall incremental cost effectiveness ratio (ICER) was US$104,000 per QALY gained (95% UI US$59,000 to US$175,000).The cost-effectiveness varied moderately by socio-demographics, with the ‘best’ ICER being US$52,000 for 70-74 year old Māori females and the ‘worst’ ICER being US$142,000 for 55-59 year old non-Māori females. The ICER varied little by current smoking status, due to higher competing mortality risk limiting QALY gains for current smokers.The two scenarios that lowered the ICER the most were increasing the screening uptake to 100% (ICER = US$50,000 per QALY), and improving the sensitivity (from 93.8% to 98%) and specificity (from 73.4% to 95%) of the screening test (ICER = US$42,000 per QALY).Based on a threshold of GDP per capita per QALY gained (i.e. US$30,000), LDCT screening for lung cancer is unlikely to be cost-effective in New Zealand for any sociodemographic group.
       
  • Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC):
           outcomes with immune check-point inhibitors (ICPi)
    • Abstract: Publication date: Available online 3 August 2018Source: Lung CancerAuthor(s): Elizabeth Dudnik, Elias Bshara, Ahuva Grubstein, Ludmila Fridel, Tzippy Shochat, Laila C. Roisman, Maya Ilouze, Anna Belilovski Rosenblum, Smadar Geva, Alona Zer, Ofer Rotem, Aaron M. Allen, Nir Peled ObjectivesEfficacy of immune check-point inhibitors (ICPi) in NSCLC with rare targetable drivers (RTDs) is largely unknown.Materials and MethodsConsecutive patients with NSCLC and RTDs (non-EGFR/ALK, n-82) were selected from the Davidoff Cancer Center database. ORR, PFS, OS with ICPi, OS since advanced disease diagnosis, TMB, MSI, and PD-L1 expression were analyzed; uni- and multivariate PFS and OS analyses were done. OS with ICPi was compared between the RTD cohort and the non-selected NSCLC cohort (n-278).ResultsOf 50 tumors tested, 32%, 38%, and 30% were associated with ≥50%, 1-49% and  0.4), TMB (p > 0.8), or RTD type (p > 0.3). In the multivariate analysis, ECOG PS (p-0.005), targeted agents exposure (p-0.005), and ICPi exposure (p-0.04) were the only variables which correlated with OS since advanced disease diagnosis. Median OS since advanced disease diagnosis comprised 32 months (95% CI, 19.9-44.9) and 13 months (95% CI, 6.6-15.9) for patients who were and were not exposed to ICPi, respectively (log-rank test-6.3; p-0.01). In the inter-cohort comparison, for patients matched for ECOG PS (0/1), median OS with ICPi comprised 17.5 months (95% CI, 8.1-NR) and 8.6 months (95% CI, 6.7-NR) for RTD and non-selected patients, respectively (log-rank test-2.4, p-0.1).ConclusionIn NSCLC with RTD, ICPi have favorable efficacy and independent impact on OS. NSCLC with RTD is associated with MSI stable status and variable levels of PD-L1 expression and TMB; their predictive value remains to be determined.
       
  • Lung cancer CT screening: psychological responses in the presence and
           absence of pulmonary nodules
    • Abstract: Publication date: Available online 3 August 2018Source: Lung CancerAuthor(s): Marcia E Clark, Laura E Bedford, Ben Young, John FR Robertson, Roshan das Nair, Kavita Vedhara, Roberta Littleford, Francis M Sullivan, Frances S Mair, Stuart Schembri, Petra Rauchhaus, Denise Kendrick ObjectivesTo determine the psychological response (thoughts, perceptions and affect) to a diagnosis of pulmonary nodules following a novel antibody blood test and computed tomography (CT) scans within a UK population.Materials and methodsThis study was nested within a randomised controlled trial of a blood test (Early CDT®-Lung test), followed by a chest x-ray and serial CT-scanning of those with a positive blood test for early detection of lung cancer (ECLS Study). Trial participants with a positive Early CDT®-Lung test were invited to participate (n = 338) and those agreeing completed questionnaires assessing psychological outcomes at 1, 3 and 6 months following trial recruitment. Responses of individuals with pulmonary nodules on their first CT scan were compared to those without (classified as normal CT) at 3 and 6 months follow-up using random effects regression models to account for multiple observations per participant, with loge transformation of data where modelling assumptions were not met.ResultsThere were no statistically significant differences between the nodule and normal CT groups in affect, lung cancer worry, health anxiety, illness perceptions, lung cancer risk perception or intrusive thoughts at 3 or 6 months post-recruitment. The nodule group had statistically significantly fewer avoidance symptoms compared to the normal CT group at 3 months (impact of events scale avoidance (IES-A) difference between means -1.99, 95%CI -4.18, 0.21) than at 6 months (IES-A difference between means 0.88, 95%CI -1.32, 3.08; p-value for change over time = 0.003) with similar findings using loge transformed data.ConclusionA diagnosis of pulmonary nodules following an Early CDT®-Lung test and CT scan did not appear to result in adverse psychological responses compared to those with a normal CT scan.
       
  • Carving Out Another Slice of the Pie: Exceptional Response to Single Agent
           Imatinib in an Asian Female Never-smoker with Advanced NSCLC and a De-novo
           PDGFR-α N848 K Mutation
    • Abstract: Publication date: Available online 31 July 2018Source: Lung CancerAuthor(s): Samuel J. Klempner, Kyle Gowen, Thomas K. Lee, Viola W. Zhu, Alexa B. Schrock, Vincent A. Miller, Siraj M. Ali, Sai-Hong Ignatius Ou Non-small cell lung cancer (NSCLC) has emerged as a paradigm for clinical application of precision medicine as optimal therapy is commonly chosen based on genomic biomarkers identified in a patient’s tumor sample. Recurrent driver alterations are well described, however, a need to continually identify rare variants remains clinically relevant. We identified an incident case of advanced NSCLC with a PDGFR-α N848 K activation loop mutation with no other concurrent oncogenic drivers. Amino acid sequence alignment confirmed homology to the imatinib-sensitive KIT N822 K activation loop mutation observed in GIST. The patient achieved a 2-year response to single agent imatinib that is ongoing. While PDGFRA N848 K is rare among public sequencing databases our cases strongly suggests functional relevance and highlights the importance of studying rare variants in NSCLC.
       
  • Automated chromogenic multiplexed immunohistochemistry assay for diagnosis
           and predictive biomarker testing in non-small cell lung cancer
    • Abstract: Publication date: Available online 31 July 2018Source: Lung CancerAuthor(s): Marius Ilie, Mélanie Beaulande, Marame Hamila, Gilles Erb, Véronique Hofman, Paul HofmanABSTRACTObjectivesThe current challenge in the management of non-small cell lung cancer (NSCLC) in pathology laboratories is to combine immunohistochemistry (IHC) and molecular approaches on increasingly smaller biopsies and the need to reserve a fair amount of tumor material for molecular analyses with increasingly larger panels. The latest lung cancer classification, especially in the setting of poorly differentiated tumors, requires an IHC workup to allow for accurate diagnosis and also to preserve as much tissue as possible for molecular testing. Thus, it is recommended to reduce use of the term NSCLC not otherwise specified as much as possible and classify tumors according to their specific histologic subtype. This implies limiting the number of tissue slides despite the existence of specific and sensitive biomarkers (ALK, ROS1, BRAF V600E, PD-L1) and the obligation to distinguish lung adenocarcinoma (TTF-1 positive) from squamous cell carcinoma (p40 positive).Materials and MethodsSamples from 18 patients with NSCLC, previously characterized for histologic and genomic/immune features, were included. Two multiplexed IHC assays were developed, for diagnosis and immunophenotyping including TTF1, p40, PD-L1, and pan-Keratin antibodies, and for molecular profiling panel including ALK, ROS1 and BRAF V600E antibodies.ResultsWe developed two sensitive multiplexed IHC assays to comprehensively characterize major NSCLC histotypes and FDA-cleared predictive biomarkers, without antigenicity loss, steric interference or increased cross-reactivity. The assays rely on standard antigen retrieval and automated staining protocols, limiting the need for validation strategies.ConclusionOur multiplexed IHC approach provides a unique sample-sparing tool to characterize limited tissue samples in lung oncology and making it an alternative method in the clinical setting for therapeutic decision making of advanced NSCLC, provided that validation in a larger population is performed.
       
  • Crizotinib treatment for patients with EGFR mutation positive NSCLC that
           acquire cMET amplification after EGFR TKI therapy results in short-lived
           and heterogeneous responses
    • Abstract: Publication date: Available online 30 July 2018Source: Lung CancerAuthor(s): Bianca van Veggel, Adrianus J. de Langen, Sayed Hashemi, Kim Monkhorst, Efraim H. Rosenberg, Daniëlle A.M. Heideman, Teodora Radonic, Egbert F. Smit PurposeNext to secondary epidermal growth factor receptor (EGFR) mutations, cMET amplification plays an important role in mediating acquired resistance to EGFR tyrosine kinase inhibitors (TKI) treatment. Crizotinib, a dual ALK and cMET inhibitor, can induce responses in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) that acquire cMET amplification after EGFR TKI treatment. However, little is known about the duration of response and post-progression resistance mechanisms. Here, we report on the clinical outcome of a series of patients with cMET-driven resistance to EGFR TKIs, treated with crizotinib.Materials and methodsEight patients with EGFR mutation positive NSCLC that acquired cMET amplification after EGFR TKI treatment were treated with crizotinib 250 mg twice daily, as monotherapy (n = 2) or in combination with an EGFR TKI (n = 6).ResultsFour out of eight patients (50%) showed a partial response (PR) according to RECIST 1.1. Median progression-free survival (PFS) was 1.4 (95% CI 1.2 – 5.0) months. Responses were short-lasting with a median PFS of 3.5 (95% CI 1.4 – 5.2) months in patients with a PR. Median overall survival was 5.9 (95% CI 1.3 – 6.0) months and not statistically different between responders and non-responders (p = 0.37). All but one patient tolerated crizotinib treatment well. Heterogeneous responses were seen in patients with progressive disease as best response with a marked size decrease of the biopsied (cMET amplification positive) lesion and progression of other lesions. cMET amplification was not always mutually exclusive with other EGFR TKI resistance mechanisms. Post-progression biopsies were negative for cMET amplification.ConclusionCrizotinib treatment for patients with EGFR mutation positive NSCLC that acquire cMET amplification after EGFR TKI treatment results in short-lived and often heterogeneous responses, possibly due to subclonality of cMET-driven resistance and co-occurrence of other EGFR TKI resistance mechanisms.
       
  • Highlights of the 14th International Mesothelioma Interest Group Meeting:
           Pathologic Separation of Benign from Malignant Mesothelial Proliferations
           and Histologic/Molecular Analysis of Malignant Mesothelioma Subtypes
    • Abstract: Publication date: Available online 30 July 2018Source: Lung CancerAuthor(s): Andrew Churg, Kazuki Nabeshima, Greta Ali, Rossella Bruno, Lynnette Fernandez-Cuesta, Francoise Galateau-Salle ObjectivesThe separation of benign from malignant mesothelial proliferations and exact subclassification of mesothelioma subtypes is crucial to determining patient care and prognosis but morphologically can be very difficult.MethodsThis session of the 2018 IMIG meeting addressed these problems.ResultsA new immunohistochemical marker, methylthioadenosine phosphorylase, was shown to correlate well with CDKN2 A FISH and is cheaper and faster to run. A 117 gene expression panel also provided good separation on both tissue biopsy and cytology samples. Review of a series of mesotheliomas thought to be biphasic produced only a moderate level of agreement among expert pathologists with some cases being classified as purely epithelioid or sarcomatoid; these classifications had prognostic significance. The entity called transitional mesothelioma was found to behave exactly like sarcomatoid mesothelioma. RNA-seq analysis of a large series of mesotheliomas from a public database showed that, genetically, the morphologic breakdown into epithelioid, sarcomatoid, or biphasic mesotheliomas is artificial because there is a continuous spectrum of genomic changes. There are now criteria for the diagnosis of mesothelioma in situ and this is potentially important, since such cases might be curable.ConclusionsThis session documented new morphological and molecular approaches to separating benign from malignant mesothelial proliferations and to subclassifying malignant mesoteheliomas in clinical relevant ways.
       
  • Exosomal RNA-profiling of pleural effusions identifies adenocarcinoma
           patients through elevated miR-200 and LCN2 expression
    • Abstract: Publication date: October 2018Source: Lung Cancer, Volume 124Author(s): Per Hydbring, Luigi De Petris, Yanming Zhang, Eva Brandén, Hirsh Koyi, Metka Novak, Lena Kanter, Petra Hååg, James Hurley, Vasisht Tadigotla, Baoli Zhu, Johan Skog, Kristina Viktorsson, Simon Ekman, Rolf Lewensohn HypothesisThe inherent challenges associated with tissue biopsies from lung have spurred an interest in the use of liquid biopsies. Pleural effusions are one source of liquid biopsy. Recently, extracellular vesicles of endocytic origin, exosomes, have attracted interest as liquid biopsy of tumors as they are thought to be a mirror of their tumor of origin. Here, we aimed to analyze if RNA profiling of exosomes isolated from pleural effusions could differentiate patients with lung adenocarcinoma from patients with benign inflammatory processes.MethodsExosomes were isolated from 36 pleural effusions from patients with adenocarcinoma (n = 18) and patients with benign inflammatory processes (n = 18). The two groups were balanced with respect to age and smoking history but with a gender bias towards males in the benign group. Profiling was conducted using RT-qPCR arrays covering 754 microRNAs and 624 mRNAs followed by statistical ranking of differentially regulated transcripts between the two patient cohorts.ResultsRNA profiling revealed differential expression of 17 microRNAs and 71 mRNAs in pleural effusions collected from patients with lung adenocarcinoma compared to pleural effusions from benign lung disease. Overall, top differentially expressed microRNAs, including miR-200 family microRNAs, provided a stronger diagnostic power compared to top differentially expressed mRNAs. However, the mRNA transcript encoding Lipocalin-2 (LCN2) displayed the strongest diagnostic power of all analyzed transcripts (AUC: 0.9916).ConclusionsOur study demonstrates that exosomal RNA profiling from pleural effusions can be used to identify patients with lung adenocarcinoma from individuals with benign processes and further proposes miR-200 microRNAs and LCN2 as diagnostic markers in lung cancer liquid biopsies.
       
  • Mechanisms of Primary Resistance to EGFR targeted therapy in
           advanced lung adenocarcinomas
    • Abstract: Publication date: Available online 29 July 2018Source: Lung CancerAuthor(s): Ying Jin, Xun Shi, Jun Zhao, Qiong He, Ming Chen, Junrong Yan, Qiuxiang Ou, Xue Wu, Yang W. Shao, Xinmin Yu IntroductionIncreasing evidence leads to a ratiocination that genetic heterogeneity of the lung adenocarcinoma with EGFR mutations may impact clinical responses and outcomes to EGFR tyrosine kinase inhibitor (TKI) treatments.MethodsWe performed genetic profiling of pre-treatment samples of 69 lung adenocarcinoma patients, including tumor FFPE and cell-free DNA (cfDNA), targeting 416 cancer-related genes using next generation sequencing. We analyzed mutation concordance across sample types and investigated potential mechanisms that confer primary resistance to EGFR-TKIs in patients with short progression-free survival (PFS) versus those with long PFS.ResultsWe detected a total of 200 actionable genetic alterations (mean: 2.9 variants/patient, range: 1-7 variants) in tumor FFPE and 140 actionable genetic alterations (mean: 2.0 variants/patient, range: 0-5 variants) in matched cfDNA, respectively. All patients had EGFR TKI-sensitizing mutations, including EGFR Ex19del, L858R, G719S/C, and L861Q. Concurrent TP53 mutations were most commonly observed in 72.5% of patients, followed by EGFR amplification (20.3%), RB1 (10.1%), PIK3CA (7.2%), and MYC (5.8%). For EGFR activating mutations, the concordance rate was 88.2% between cfDNA and FFPE samples. Furthermore, we identified genes that potentially confer primary resistance to EGFR-TKIs including CDC73, SMAD4, RB1 and PIK3CA. We also report signaling pathways enriched in patients with TKI primary resistance.ConclusionsWe note the genetic complexity and heterogeneity of EGFR-mutated lung adenocarcinoma and underscore that mutation status is highly concordant between tumor FFPE and cfDNA samples. This study also highlights the alterations that potentially confer primary resistance to EGFR TKI treatments in patients who demonstrated short PFS.
       
  • A new bronchoscopic catheter for the transbronchial ablation of pulmonary
           nodules
    • Abstract: Publication date: Available online 26 July 2018Source: Lung CancerAuthor(s): Seyer Safi, Jan op den Winkel, Steve Kramer, Thomas Keast, Henky Wibowo, Thomas Muley, Felix J.F. Herth ObjectivesWith the objective of simultaneous bronchoscopic biopsy and ablation of malignant solitary pulmonary nodules, we have developed a flexible monopolar radiofrequency (RF) catheter that can be deployed through the working channel of most bronchoscopes. Herein, we present the results of a benchtop study demonstrating the local control of ablation achieved using this RF device.Materials and MethodsFresh tumor specimens were heated in a water bath to 37 °C, and the RF catheter was inserted into the tumors within the specimen. Temperature sensors were positioned 3 mm, 5 mm and 7 mm from the electrode to measure the temperature of the surrounding tissue every 1 second. The ablation was conducted by applying RF energy for 8 minutes. The ablated specimens were evaluated by cutting the tissue samples along the top of the device and measuring the ablation zones.ResultsFive ablations were performed in 3 specimens. All of the ablation zones had a major axis length (along the electrode axis) between 18.9 mm and 22.8 mm and a minor axis length (perpendicular to the major axis) between 13.3 mm and 18.0 mm. The temperature data showed that all of the temperature sensors detected 60 °C or higher. These results demonstrate that the RF catheter was capable of generating ablation zones that were locally contained in ex vivo human cancerous lung specimens and that incorporated the tumor tissues.ConclusionThis study suggests that the ex vivo ablation of lung malignancy with a new bronchoscopic RF catheter is feasible and that in vivo tumor ablation with this method in humans merits further study.
       
  • Cost-Utility Analysis of a Potential Lung Cancer Screening Program for a
           High-Risk Population in Germany: A Modelling Approach
    • Abstract: Publication date: Available online 24 July 2018Source: Lung CancerAuthor(s): Florian Hofer, Hans-Ulrich Kauczor, Tom Stargardt BackgroundLung cancer is the leading cause of cancer death in Germany. Although several randomized trials in Europe have evaluated the effectiveness of lung cancer screening programs, evidence on the cost-effectiveness of lung cancer screening is scarce.ObjectiveTo evaluate the cost-effectiveness of a population-based lung cancer screening program from the perspective of a German payer.MethodsWe conducted a cost-effectiveness analysis from the public payer perspective for a high-risk population defined as heavy former and current smokers (≥ 20 cigarettes per day) between 55 and 75 years of age. The underlying model consisted of two Markov models. We differentiated between a population-based annual screening program and standard clinical care. Depending on stage at diagnosis, simulated patients were assigned to one of five treatment paths according to the German clinical guideline for the diagnosis and treatment of lung cancer. Costs, life years saved, and quality adjusted life years (QALYs) were used as outcomes. Values for input parameters were taken from the literature. The model was run for 60 cycles with a cycle length of three months. Deterministic and probabilistic sensitivity analyses were conducted.ResultsIn the base case, annual lung cancer screening led to an increase in incremental costs (€ 1,153 per person) compared to standard clinical care. However, the screening approach was associated with an incremental gain in life years (0.06 per person) and QALYs (0.04 per person). Thus, the incremental cost-effectiveness ratio (ICER) was € 19,302 per life year saved and € 30,291 per QALY. A probabilistic sensitivity analysis with 10,000 draws resulted in average ICERs of € 22,118 per life year and € 34,841 per QALY.ConclusionWe provide evidence that lung cancer screening for a high-risk population may be more effective, but also more costly, than standard clinical care from the perspective of a German payer.
       
  • Definitive Treatment Patterns and Survival in Stage II Non-Small Cell Lung
           Cancer
    • Abstract: Publication date: Available online 24 July 2018Source: Lung CancerAuthor(s): Sherry X. Yan, Muhammad M. Qureshi, Kei Suzuki, Michael Dyer, Minh Tam Truong, Virginia Litle, Kimberley S. MakABSTRACTObjectivesThis study delineated definitive treatment patterns for Stage II non-small cell lung cancer (NSCLC) in the United States and evaluated survival by treatment approach.Materials and MethodsPatients with clinically-staged Stage II NSCLC treated with surgery-based therapy, chemoradiation, conventionally-fractionated radiation (CFR), or stereotactic body radiotherapy (SBRT) were identified using the National Cancer Database (NCDB). Median survival was estimated using Kaplan-Meier analysis. Crude and adjusted hazard ratios (HR) and 95% confidence intervals were computed using Cox regression modeling.ResultsBetween 2004-2012, 19,749 patients met study criteria: 13,382 (67.8%) underwent surgery-based treatment, 4,310 (21.8%) received chemoradiation, 1,606 (8.1%) received CFR, and 451 (2.3%) received SBRT. Surgery and SBRT utilization increased over time while CFR and chemoradiation decreased (all p ≤ 0.002). Patients receiving radiation-based treatments were older, with more comorbidities, and higher T/N stage (all p 
       
  • CAPACITY: A physical activity self-management program for patients
           undergoing surgery for lung cancer, a phase I feasibility study
    • Abstract: Publication date: Available online 23 July 2018Source: Lung CancerAuthor(s): Catherine L. Granger, Louis Irving, Phillip Antippa, Lara Edbrooke, Selina M. Parry, Mei Krishnasamy, Linda Denehy ObjectivesPhysical activity is important in lung cancer, yet the majority of patients do not meet minimum weekly recommended activity levels. The objectives of this study were to determine the: 1) feasibility and 2) exploratory effectiveness of a physical activity self-management program aiming to increase physical activity levels of patients undergoing surgery for lung cancer.Materials and MethodsProspective case series including patients with operable lung cancer. The physical activity self-management program, based on international cancer physical activity guidelines, commenced pre-operative (if recruitment occurred ≥7 days before surgery) or post-operative if not, and continued until 8-weeks after surgery. The program included prescription of an unsupervised home aerobic exercise program, taught in an initial face-to-face consultation and followed-up with weekly telephone consultations. This was supplemented with patient education, behaviour change techniques and provision of an activity monitor. The primary endpoint was program feasibility including consent rate and number of consultations delivered. In addition, self-reported physical activity levels, self-efficacy for physical activity, health-related quality of life (HRQoL) and mood was assessed pre- and 8-weeks post-operative.ResultsThe consent rate was 89%. Thirty-seven patients (54% male, mean age 66 ± 10 years) were included. Only six participants commenced the program before surgery, with most (n = 31) commencing post-operatively. The median [IQR] number of consultations was 4 [[3], [4], [5], [6]] per participant. There was no change in physical activity levels (total estimated mets/week pre-operative median [IQR] 1066 [0-2772], 8 weeks post-operative 924 [346-1752], p = 0.545) or sedentary time (television viewing hours/day pre-operative 4.5 [2.0-9.5], 8-weeks 4.0 [3.0-5.0], p = 0.527) after surgery.ConclusionThe physical activity program was feasible when implemented in the post-operative setting. Participants in this feasibility study demonstrated maintenance in physical activity levels 8-weeks after surgery, compared with published literature reporting decline after surgery. A randomised controlled trial is warranted to further investigate potential effectiveness of this intervention.
       
  • Does presentation at multidisciplinary team meetings improve lung cancer
           survival' Findings from a consecutive cohort study
    • Abstract: Publication date: Available online 23 July 2018Source: Lung CancerAuthor(s): Emily Stone, Nicole Rankin, Stephen Kerr, Kwun Fong, David C Currow, Jane Phillips, Tess Bewes, Lorena Zhang, Tim Shaw BackgroundMultidisciplinary team (MDT) presentation in lung cancer has the potential to improve longterm outcomes, although this varies between studies. This study aims to evaluate outcomes including survival, according to MDT presentation and to explore the utility of data obtained from local clinical sources.Patients and methodsProspective cases of lung cancer recorded in our institution’s cancer registry were analyzed according to MDT presentation for patient and tumour characteristics, adjusted survival and referral to palliative care.Results1197 cases were included, 295 (24.6%) with MDT presentation and 902 (75.4%) without. 60% of patients were male with median (IQR) age at diagnosis of 70 years (62-78). Histopathology distribution (non-small cell lung cancer and small-cell lung cancer) was similar between the two groups. Compared with the non-MDT group, the MDT group had (1) ECOG score recorded more often (71.9% vs. 47.6%), (2) higher proportion of ECOG 0 cases (31.2% vs. 11.9%) and ECOG 1 cases (28.8% vs. 20.3%), (3) higher proportion of early stage disease (stage I - 23.1% vs. 9.7% stage II - 10.2% vs. 4.8%, stage IIIA - 14.6% vs 6.3%) and (4) lower proportion of metastatic disease (stage IV - 39.3% vs. 56.1%). Referral to palliative care was incompletely recorded in both groups (MDT: n = 116/295, 39.3%; non-MDT: n = 430, 47.7%) but did not differ significantly for stage IV cases. Survival analyzed by stage was greater in the MDT group at 1, 2 and 5 years for all stages except stage IIIB at 1 year post-diagnosis. Adjusted survival analysis for the entire cohort showed improved survival at 5 years for the MDT group (HR 0.7 (0.58-0.85), p 
       
  • Elongation Factor-2 Kinase (eEF-2K) Expression Is Associated with Poor
           Patient Survival and Promotes Proliferation, Invasion and Tumor Growth of
           Lung Cancer
    • Abstract: Publication date: Available online 21 July 2018Source: Lung CancerAuthor(s): Ahmet Bircan, Nilgun Gurbuz, Apar Pataer, Ayse Caner, Nermin Kahraman, Emine Bayraktar, Recep Bayraktar, Mumin Alper Erdogan, Nashwa Kabil, Bulent Ozpolat ObjectivesLung cancer is the leading cause of cancer related deaths in worldwide. Despite recent advances in treatment options, patient survival has not improved substantially due to lack of commonly expressed molecular targets and effective targeted therapeutics. Thus, better understanding of the biology of lung cancer and identification of novel therapeutic targets are urgently needed for development of highly effective molecularly targeted therapies.Materials and MethodsViability, proliferation and metastatic ability of lung cancer cells were evaluated using methylthiazoltetrazolium (MTT), colony formation and matrigel invasion assays, respectively. Western blotting, RT-PCR, and gene knockdown by siRNA transfections were carried out to investigate the effects of eEF-2 K on lung cancer cells. Athymic Nu/Nu mice were treated with liposomal eEF-2 K or control siRNAs and tumor growth was evaluated in vivo tumor xenograft models of lung cancer.Results and discussionHere, we report that Eukaryotic Elongation Factor-2 kinase (eEF-2 K), a member of an atypical alpha kinases family, is significantly upregulated in lung cancer cell lines and its expression is associated with shorter overall patient survival in lung cancer. Inhibition eEF-2 K expression by siRNA or a chemical inhibitor significantly suppressed lung cancer cell proliferation, colony formation, survival, migration/invasion and tumorigenesis by inhibiting cyclin D1, Src and Mitogen-Activated Protein Kinases/Extracellular Signal-Regulated Kinase (MAPK/ERK) signaling. In vivo targeting of eEF-2 K by systemically injected nanoliposomal eEF-2 K siRNA resulted in a significant inhibition of tumor xenografts in nude mice. Our results suggest, for the first time, that expression of eEF-2 K is associated with poor patient prognosis and involved in regulation of critical pathways including Src and MAPK/ERK and cyclin D1, promoting tumor growth and progression, and thus may be a novel potential therapeutic target in lung cancer.
       
  • Lung cancer screening – gaining consensus on next steps – proceedings
           of a closed workshop in the UK
    • Abstract: Publication date: Available online 21 July 2018Source: Lung CancerAuthor(s): J. Moffat, S. Hiom, H.S. Kumar, D.R. Baldwin Lung cancer is the most common cause of cancer death in the UK, and survival from the disease is persistently poor. Efforts to improve outcomes for patients have focused on ways of reducing late diagnosis of the disease, and access to optimal treatment. Research on lung cancer screening has so far provided some evidence of an impact on lung cancer mortality, but there is some debate about whether implementation of a national screening programme should await further trial data, principally that from the NELSON trial. The ongoing poor outcomes and the belief amongst some clinicians that there is sufficient evidence has prompted several local projects testing out lung screening in their communities, sometimes referred to as lung health checks or proactive approaches to high-risk individuals. Funding from NHS England has been forthcoming to support this. Acknowledging roll-out of such activities, which effectively constitute local lung screening in the absence of a NSC recommendation, it was timely to bring key national stakeholders together with academic and clinical experts, to agree a way forward. Cancer Research UK therefore convened a closed workshop in March 2018, involving national and international expertise. This paper outlines the proceedings, key discussion points, highlighted research gaps, and areas of consensus and next steps.
       
  • Circulating endothelial cells and microparticles as diagnostic and
           prognostic biomarkers in small-cell lung cancer
    • Abstract: Publication date: Available online 21 July 2018Source: Lung CancerAuthor(s): Fadi Najjar, Moosheer Alammar, Ghassan Al-Massarani, Nissreen Almalla, Abdulmunim Japawe, Adnan IkhtiarABSTRACTObjectivesIt has been proposed that circulating endothelial cells (CECs) and microparticles (MPs) may be useful for the assessment of patients with non-small-cell lung cancer (NSCLC). However, little is known about the potential clinical relevance of these biomarkers in small-cell lung cancer (SCLC). Therefore, we investigated the utility of baseline levels of CECs and MPs in SCLC patients.Materials and methodsAn immunomagnetic separation (IMS) technique was used to isolate and quantify CECs in the peripheral blood, while plasma samples were analyzed using flow cytometry for the measurement of circulating MPs.ResultsWe prospectively collected data from 56 patients and 41 healthy individuals. Forty-three patients presented at initial diagnosis and 13 patients presented at relapse. Baseline levels of CECs and MPs were significantly higher in SCLC patients either at initial diagnosis or at relapse than in healthy subjects (p < 0.0002 and p < 0.007, respectively). However, estimated tumor volume (ETV) was significantly correlated with basal MP values (p < 0.0001) but not with pretreatment CECs (p =  0.57). The amount of baseline CECs and MPs was significantly lower in patients with an objective response (OR, n = 23) than in those with progressive disease (PD, n = 15) after treatment (p =  0.016 and 0.05, respectively). With cut-off values of 110 cells/mL for CECs and 1257 events/µL for MPs according to receiver operating characteristics (ROC) analysis, baseline levels of these biomarkers were not significantly correlated with either progression-free survival (PFS) or overall survival (OS). However, patients with 6-month PFS displayed significantly decreased pretreatment CEC counts (p =  0.042), whereas basal MP values significantly increased in 1-year survivors compared with those in non-survivors (p =  0.05).ConclusionOur results suggest that baseline CECs and MPs may be predictive biomarkers of tumor response and long-term survival in SCLC patients.
       
  • Tumor-specific genetic variants can be detected in circulating cell-free
           DNA of malignant pleural mesothelioma patients
    • Abstract: Publication date: Available online 21 July 2018Source: Lung CancerAuthor(s): Marieke Hylebos, Ken Op de Beeck, Patrick Pauwels, Karen Zwaenepoel, Jan P. van Meerbeeck, Guy Van CampABSTRACTObjectivesPatients diagnosed with malignant pleural mesothelioma (MPM) face a poor prognosis, with an overall survival plateauing at a median of one year. This can be explained by difficulties in early diagnosis, effective treatment and treatment monitoring. Circulating cell-free tumor DNA (ctDNA) is emerging as an interesting biomarker addressing some of these issues. So far, the development of ctDNA in MPM lags behind that in other tumors. In this study, the possibility of tracing tumor-specific genetic variants, identified in MPM tissue, in circulating DNA of the corresponding patients is investigated.Materials and MethodsWhole exome sequencing was performed on paired tumor and germline DNA of ten MPM patients, of which five were treatment naïve. For each patient, a tumor-specific variant was selected and traced in tumor, germline and circulating DNA using droplet digital PCR in two independent runs.ResultsAll but one tumor-specific variants, selected after whole exome sequencing, were validated on primary tumor tissue using droplet digital PCR analysis. Patient-specific, selected variants could be detected in circulating DNA of three MPM patients, either in one or both independent droplet digital PCR runs. Mutated fractions in circulating DNA ranged from 0.28 to 0.9%. Interestingly, all patients whose circulating DNA samples contained tumor-specific variants, were treatment naïve.ConclusionWe demonstrated for the first time the presence of ctDNA within circulating DNA of treatment naïve MPM patients. This finding opens perspectives towards the use of ctDNA as a biomarker for (early and differential) diagnosis, treatment and treatment monitoring of MPM, which all remain challenging.
       
  • The intratumoral distribution influences the prognostic impact of CD68-
           and CD204-positive macrophages in non-small cell lung cancer
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Zhuo Li, Daichi Maeda, Makoto Yoshida, Michinobu Umakoshi, Hiroshi Nanjo, Kouya Shiraishi, Motonobu Saito, Takashi Kohno, Hayato Konno, Hajime Saito, Yoshihiro Minamiya, Akiteru Goto ObjectiveTumor-associated macrophages (TAMs) are believed to influence tumor progression and the prognosis of patients. The purpose of this study was to clarify the correlation between the TAM density or location and the clinicopathological features of non-small-cell lung cancer (NSCLC) as well as to explore the prognostic impact of TAMs in NSCLC.Materials and methodsCD68- and CD204-positive macrophages were detected in tumor islets, tumor stroma and alveolar space in 297 patients with NSCLC using immunochemistry. The clinicopathological and genetic factors surveyed were the disease-free survival, age, gender, smoking status, histological type, disease stage, histological grade, pleural invasion, lymph node metastasis, EGFR gene mutations and ALK rearrangements.ResultsThere were significantly more CD68-positive macrophages than CD204-positive macrophages in each location of the tumor islets, tumor stroma and alveolar spaces, and they were strongly correlated (P 
       
  • What you see is (not) what you get: tools for a non-radiologist to
           evaluate image quality in lung cancer
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Evelyn E.C. de Jong, Lizza E.L. Hendriks, Wouter van Elmpt, Hester A. Gietema, Paul A.M. Hofman, Dirk K.M. De Ruysscher, Anne-Marie C. Dingemans Medical images are an integral part of oncological patient records and they are reviewed by many different specialists. Therefore, it is important that besides imaging experts, other clinicians are also aware that the diagnostic value of a scan is influenced by the applied imaging protocol.Based on two clinical lung cancer trials, we experienced that, even within a study protocol, there is a large variability in imaging parameters, which has direct impact on the interpretation of the image. These two trials were: 1) the NTR3628 in which the added value of gadolinium magnetic resonance imaging (Gd-MRI) to dedicated contrast enhanced computed tomography (CE-CT) for detecting asymptomatic brain metastases in stage III non-small cell lung cancer (NSCLC) was investigated and 2) a sub-study of the NVALT 12 trial (NCT01171170) in which repeated 18 F-fludeoxyglucose positron emission tomography (18F-FDG-PET) imaging for early response assessment was investigated.Based on the problems encountered in the two trials, we provide recommendations for non-radiology clinicians, which can be used in daily interpretation of imaging. Variations in image parameters cannot only influence trial results, but sub-optimal imaging can also influence treatment decisions in daily lung cancer care, when a physician is not aware of the scanning details.
       
  • EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma
           harboring an NRG1 fusion
    • Abstract: Publication date: Available online 20 July 2018Source: Lung CancerAuthor(s): Hye Sook Kim, Ji-Youn Han, Dong Hoon Shin, Kun Young Lim, Geon Kook Lee, Jin Young Kim, Wolfgang Jacob, M. Ceppi, Martin Weisser, I. James Rearrangements of NRG1 have been identified in invasive mucinous adenocarcinoma of the lung (IMA), formerly referred to as mucinous bronchioloalveolar carcinoma. NRG1 ligand signals through induction of HER2-HER3 heterodimers, thus leading to PI3K–AKT pathway activation. Therefore, targeting HER2, HER3 and the downstream pathway may be a hypothesis-driven strategy for IMA with NRG1 fusion. Herein we reported two patients who benefited from lumretuzumab, a monoclonal anti-HER3 antibody, in combination of erlotinib during a clinical trial (NCT01482377). At least sixteen weeks of progression-free survival were achieved without any unacceptable toxicity.
       
  • Smoking, alcohol, and nutritional status in relation to one-year mortality
           in Danish stage I lung cancer patients
    • Abstract: Publication date: Available online 20 July 2018Source: Lung CancerAuthor(s): Niels Lyhne Christensen, Anders Løkke, Susanne Oksbjerg Dalton, Jane Christensen, Torben Riis Rasmussen IntroductionIn addition to the highest incidence rate of lung cancer among the Nordic countries, Denmark has the highest mortality rate. Moreover, rates of tobacco and alcohol consumption are among the highest in these countries. Method: In a population-based matched case/control study, we aimed to assess the association between one-year all-cause mortality and a number of smoking-related parameters, high-risk alcohol intake, and nutritional status in clinical stage I lung cancer patients. Results: We included 221 patients who died within one year after diagnosis (early death) and 410 matched controls who survived more than one year (survivor). The odds ratio (OR) for early death among never-smokers was 0.3 (CI 95%: 0.1–0.9). There was no significant difference between patients who died early and survivors in proportions of current smokers (49 vs. 45%), number of cumulated pack-years (45 vs. 46), daily tobacco consumption (15 vs. 14 cigarettes/day), patients who quit smoking after diagnosis (25 vs. 40%) and the prevalence of chronic obstructive pulmonary disease (COPD) (43 vs. 38%). Patients that died early received more medications for COPD (p = 0.03) and smoked more after diagnosis, 14 vs. 10 cigarettes per day (p = 0.03). The unadjusted OR for high-risk alcohol intake was 2.2 (CI 95% 1.3–3.7) in the early death group vs. the survivors. However, in a treatment-stratified analysis this was observed only for surgically treated patients (OR, 3.2; CI 95% 1.7–6.1). Low nutritional status was associated with early death, unadjusted (OR 2.3; CI 95% 1.4–3.7), while OR was 1.8 (95% CI 1.0–2.3) adjusted for high-risk alcohol intake and COPD. Treatment selection according to and interventions against these factors before and after lung cancer diagnosis may improve outcomes.
       
  • Applicability of a prognostic CT-based radiomic signature model trained on
           stage I-III non-small cell lung cancer in stage IV non-small cell lung
           cancer
    • Abstract: Publication date: Available online 20 July 2018Source: Lung CancerAuthor(s): Evelyn E.C. de Jong, Wouter van Elmpt, Stefania Rizzo, Anna Colarieti, Gianluca Spitaleri, Ralph T.H. Leijenaar, Arthur Jochems, Lizza E.L. Hendriks, Esther G.C. Troost, Bart Reymen, Anne-Marie C. Dingemans, Philippe Lambin ObjectivesRecently it has been shown that radiomic features of computed tomography (CT) have prognostic information in stage I-III non-small cell lung cancer (NSCLC) patients. We aim to validate this prognostic radiomic signature in stage IV adenocarcinoma patients undergoing chemotherapy.Materials and MethodsTwo datasets of chemo-naive stage IV adenocarcinoma patients were investigated, dataset 1: 285 patients with CTs performed in a single center; dataset 2: 223 patients included in a multicenter clinical trial. The main exclusion criteria were EGFR mutation or unknown mutation status and non-delineated primary tumor. Radiomic features were calculated for the primary tumor. The c-index of cox regression was calculated and compared to the signature performance for overall survival (OS).ResultsIn total CT scans from 195 patients were eligible for analysis. Patients having a Prognostic Index (PI) lower than the signature median (n = 92) had a significantly better OS than patients with a PI higher than the median (n = 103, HR 1.445, 95% CI 1.07-1.95, p = 0.02, c-index 0.576, 95% CI 0.527-0.624).ConclusionThe radiomic signature, derived from daily practice CT scans, has prognostic value for stage IV NSCLC, however the signature performs less than previously described for stage I-III NSCLC stages. In the future, machine learning techniques can potentially lead to a better prognostic imaging based model for stage IV NSCLC.
       
  • KRAS-Mutant Non-Small Cell Lung Cancer: From Biology to Therapy
    • Abstract: Publication date: Available online 19 July 2018Source: Lung CancerAuthor(s): Irene Ferrer, Jon Zugazagoitia, Stephan Herbertz, William John, Luis Paz-Ares, Gerald Schmid-Bindert In patients with non-small cell lung cancer (NSCLC), the most frequent oncogene driver mutation in Western countries is Kirsten rat sarcoma viral oncogene homolog (KRAS), and KRAS-mutant NSCLC is associated with smoking. There are various sources of biological heterogeneity of KRAS-mutant NSCLC, including different genotypes that may be associated with specific clinical outcomes, the presence of other co-mutations that exhibit different biological features and drug sensitivity patterns, and mutant allelic content. The efficacy of chemotherapy in patients with KRAS-mutant NSCLC is generally poor and numerous novel therapeutic strategies have been developed. These approaches include targeting KRAS membrane associations, targeting downstream signalling pathways, the use of KRAS synthetic lethality, direct targeting of KRAS, and immunotherapy. Of these, immunotherapy may be one of the most promising treatment approaches for patients with KRAS-mutant NSCLC. Recent data also suggest the potential for distinct efficacy of immunotherapy according to the presence of other co-mutations. In view of the biological heterogeneity of KRAS-mutant NSCLC, treatment will likely need to be individualised and, in future, may require the use of rational combinations of treatment, many of which are currently under investigation.
       
  • Antibody Drug Conjugates in Thoracic Malignancies
    • Abstract: Publication date: Available online 19 July 2018Source: Lung CancerAuthor(s): Jose M. Pacheco, D. Ross Camidge Antibody drug conjugates (ADCs) have the potential to alter the efficacy: toxicity ratio of cytotoxic therapy utilizing surface markers on cancer cells as antibody targets to preferentially deliver toxic payloads to tumor cells while limiting systemic toxicity. Multiple ADCs, differing in their antibody targets, cytotoxic payloads and linker molecules are currently being evaluated in non-small-cell lung cancer, small-cell lung cancer and malignant pleural mesothelioma. Here we review the available data in thoracic malignancies and the potential issues influencing the efficacy and toxicity of these approaches.
       
  • Synchronous multiple non-small cell lung cancers in an allograftlung
           recipient
    • Abstract: Publication date: Available online 19 July 2018Source: Lung CancerAuthor(s): Jean-Louis Pujol, Sandy Jean-Baptiste, Sébastien Bommart, Benoît Roch We described a case report of synchronous non-small cell lungcancers arising in lung transplants after allograft.Immunosuppressive therapy of the recipient induced an accelerated growth rate of primarytumour and metastases as was been observed in orthotopic liverallograft for hepatocellular carcinoma.
       
  • Acute Kidney Injury after Lung Cancer Surgery: Incidence and clinical
           relevance, predictors, and role of N-terminal pro B-type natriuretic
           peptide
    • Abstract: Publication date: Available online 17 July 2018Source: Lung CancerAuthor(s): Daniela Cardinale, Nicola Cosentino, Marco Moltrasio, Maria Teresa Sandri, Francesco Petrella, Alessandro Colombo, Giulia Bacchiani, Adele Tessitore, Alice Bonomi, Fabrizio Veglia, Michela Salvatici, Carlo M. Cipolla, Giancarlo Marenzi, Lorenzo SpaggiariABSTRACTBackgroundAcute kidney injury (AKI) frequently occurs in several medical and surgical settings, and it is associated with increased morbidity and mortality. In patients undergoing lung cancer surgery, AKI has not been fully investigated. We prospectively evaluated the incidence, clinical relevance, and risk factors of AKI in patients undergoing lung cancer surgery. Moreover, we estimated the accuracy of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prediction of AKI.MethodsPatients undergoing lung cancer surgery were included in the study. Plasma NT-proBNP was measured before and soon after surgery. Postoperative AKI was defined according to the Acute Kidney Injury Network (AKIN) classification.ResultsA total of 2179 patients were enrolled. Of them, 222 (10%) developed AKI and had a more complicated in-hospital clinical course (overall complication rate: 35% vs. 16%; P 
       
  • Genetic and clinicopathologic characteristics of lung adenocarcinoma with
           tumor spread through air spaces
    • Abstract: Publication date: Available online 17 July 2018Source: Lung CancerAuthor(s): Jae Seok Lee, Eun Kyung Kim, Moonsik Kim, Hyo Sup Shim ObjectiveThe World Health Organization Classification of Lung Tumors considers “Spread Through Air Spaces (STAS)” as a form of invasion in lung adenocarcinoma. However, its existence as an independent pathologic entity rather than an artifact caused by spreading through a knife surface is still controversial. Therefore, we performed comprehensive analyses on the genetic and clinicopathologic characteristics of lung adenocarcinoma with STAS.Materials and MethodsA total of 316 surgically resected lung adenocarcinoma cases were analyzed retrospectively. Detailed analyses were performed on clinical-histological-molecular features. Tumor STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor.ResultsSTAS was observed in 160 cases (50.6%). STAS was significantly related to lymphovascular invasion, lymph node metastasis, higher stage, and high-grade histologic subtype. STAS was frequently found in tumors with wild-type EGFR or ALK-rearrangement. Logistic regression analysis showed that STAS was significantly associated with absence of lepidic component, presence of micropapillary component, cribriform predominant type, lymphovascular invasion, and wild-type EGFR. Multivariate survival analysis demonstrated that STAS was independently associated with shorter recurrence-free survival. STAS was also associated with recurrences to extrathoracic sites as well as intrathoracic sites.ConclusionSTAS is associated with certain pathological and molecular subtypes. STAS might be a parameter for tumor aggressiveness in that it is strongly associated with poor prognostic factors and recurrence, including to extrathoracic sites.
       
  • EORTC QLQ-C30 Summary Score reliably detects changes in QoL three months
           after anatomic lung resection for Non-Small Cell Lung Cancer (NSCLC)
    • Abstract: Publication date: Available online 17 July 2018Source: Lung CancerAuthor(s): Cecilia Pompili, Michael Koller, Galina Velikova, Kevin Franks, Kate Absolom, Matthew Callister, Jonathan Robson, Andrea Imperatori, Alessandro Brunelli IntroductionWe tested the European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) summary score (SumSC) to detect changes in the HRQOL after Non-small-cell lung cancer (NSCLC) surgery and compared its performance to the traditional scales.MethodEORTC QLQ-C30 data was obtained from 326 consecutive pre-operative patients submitted for anatomical lung resections for NSCLC.66 patients completed post-operative assessments 3 months after surgery. The data was analysed to evaluate the ability of the SumSC compared to the traditional scales to [1] preoperatively differentiate between clinical groups [2]; detect post-op changes and to [3] compare pre and post-op changes in clinically different groups.The importance of perioperative changes was measured by calculating the effect size (ES).ResultsOf the 326 patients, those older than 70 years, with higher DLCO value and Performance Status (PS) ≤1 had a significantly better preoperative SumScore.Physical function (PF) showed a large and significant decline (ES 0.91). Role and social function also showed a significant and medium decline (ES 0.62 and 0.41).Postoperatively some symptoms scales showed significant increases in the values, implying worse symptoms with the largest increase in dyspnoea (ES -0.88). The change in General Health score (GH) was not significant after surgery (ES 0.26, p = 0.062).The SumSc, decreased significantly postoperatively. In particular, medium or large postoperative declines of SumSc were observed in both males and females, in patients with lower FEV1, lower performance score, and in those older than 70 years. Interestingly the decline of SumSc was observed irrespective of the preoperative DLCO level.DiscussionThe Summary Score was more sensitive to changes in subjects' HRQOL, than the GH score. The SumSc can be used as a parsimonious and easy to interpreted patient-reported-outcome measure in multi-institutional database and future clinical trials.
       
  • Are working practices of lung cancer nurse specialists associated with
           variation in peoples’ receipt of anticancer therapy'
    • Abstract: Publication date: Available online 17 July 2018Source: Lung CancerAuthor(s): Iain Stewart, Aamir Khakwani, Richard B. Hubbard, Paul Beckett, Diana Borthwick, Angela Tod, Alison Leary, Laila J. Tata ObjectivesTreatment choices for people with lung cancer may be influenced by contact and engagement with lung cancer nurse specialists (LCNSs). We investigated how service factors, LCNS workload, and LCNS working practices may influence the receipt of anticancer treatment.Materials and methodsEnglish National Lung Cancer Audit data and inpatient Hospital Episode Statistics for 109,079 people with lung cancer surviving 30 days from diagnosis were linked along with LCNS workforce census data and a bespoke nationwide LCNS survey. Multinomial logistic regression was used to determine adjusted relative risk ratios (RRRs) for receipt of anticancer therapies associated with LCNS assessment, LCNS workforce composition, caseload, LCNS reported working practices, treatment facilities at the patients’ attending hospitals, and the size of the lung cancer service.ResultsAssessment by an LCNS was the strongest independent predictor for receipt of anticancer therapy, with early LCNS assessments being particularly associated with greater receipt of surgery (RRR 1.85, 95%CI 1.63–2.11). For people we considered clinically suitable for surgery, receipt was 55%. Large LCNS caseloads were associated with decreased receipt of surgery among suitable patients (RRR 0.71, 95%CI 0.51–0.97) for caseloads>250 compared to ≤150. Reported LCNS working practices were associated with receipt of surgery, particularly provision of psychological support (RRR 1.60, 95%CI 1.02–2.51) and social support (RRR 1.56, 95%CI 1.07–2.28).ConclusionLCNS assessment, workload, and working practices are associated with the likelihood of patients receiving anticancer therapy. Enabling and supporting LCNSs to undertake key case management interventions offers an opportunity to improve treatment uptake and reduce the apparent gap in receipt of surgery for those suitable.
       
  • Corrigendum to “Validation of the 8th TNM classification for small-cell
           lung cancer in a retrospective material from Sweden” [Lung Cancer 120
           (June) (2018) 75–81]
    • Abstract: Publication date: Available online 14 July 2018Source: Lung CancerAuthor(s): Salomon Tendler, Vitali Grozman, Rolf Lewensohn, Georgios Tsakonas, Kristina Viktorsson, Luigi De Petris
       
  • Response to: Low level evidence supporting the choice of optimal
           multimodality treatment approach in patients with stage IIIA NSCLC- ain't
           no mountain high enough…. to keep me getting to you by Jeremic Branislav
           
    • Abstract: Publication date: Available online 13 July 2018Source: Lung CancerAuthor(s): F. Couñago, N. Rodriguez de Dios, S. Montemuiño, J. Jové-Teixidó, M. Martin, P. Calvo-Crespo, M. López-Mata, M.P. Samper-Ots, J.L. López-Guerra, T. García-Cañibano, V. Díaz-Díaz, L. de Ingunza-Barón, M. Murcia-Mejía, P. Alcántara, J. Corona, M.M. Puertas, M. Chust, M.L. Couselo, E. Del Cerro, J. Moradiellos
       
  • The prognostic effect of single and multiple cancer-related somatic
           mutations in resected non-small-cell lung cancer
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Kevin Jao, Pascale Tomasini, Suzanne Kamel-Reid, Gregorz J. Korpanty, Céline Mascaux, Shingo Sakashita, Catherine Labbé, Natasha B. Leighl, Geoffrey Liu, Ronald Feld, Penelope A. Bradbury, David M. Hwang, Melania Pintilie, Ming-Sound Tsao, Frances A. Shepherd IntroductionSomatic mutations are becoming increasingly important biomarkers for treatment selection and outcome in patients with non-small-cell lung cancer (NSCLC). The role of multiple somatic mutations in early-stage NSCLC is unclear.MethodsTissue from 214 patients with resected NSCLC at the Princess Margaret Cancer Centre was analyzed by next-generation sequencing by Mi-SEQ or Sequenom multiplex platforms. Associations between mutation status, baseline patient characteristics and outcomes (disease-free survival (DFS) after surgical resection and overall survival (OS)) were investigated.ResultsSomatic mutations were identified in 184 patients with resected stage I-III NSCLC: None (n = 30), single (n = 101) and multiple (≥2, n = 83). Multiple mutations were significantly associated with younger age (p = 0.0006), female sex (p = 0.012), smoking status (p = 0.002) and adenocarcinoma histology (p = 0.0001).TP53, KRAS and EGFR were the most common mutations. TP53 mutation was the most frequent co-mutation occurring in 72% of patients with multiple mutations. In resected stage I-III patients, multiple mutations were significantly associated with worse DFS (HR = 2.56, p = 0.003) but not OS on univariate analysis. Patients with KRAS and EGFR mutations were also associated with shorter DFS (HR = 2.52, p = 0.016 and HR = 4.37, p = 0.001 respectively) but no OS difference. TP53 mutation was associated with both shorter DFS (HR = 2.21, p = 0.02) and OS (HR = 3.08, p = 0.02). In subgroup univariate analysis, poorer DFS was associated with multiple mutations (p = 0.0015), EGFR (HR = 3.14, p = 0.006), and TP53 (HR = 2.46, p = 0.018) in patients with stage I disease.ConclusionThe presence of known somatic mutations is associated with worse DFS in resected NSCLC. The differences are both statistically significant and clinically relevant. The presence of EGFR, KRAS and TP53 mutations was also associated with adverse outcomes. Larger datasets are required to validate whether mutational status is an independent prognostic factor in early stage NSCLC.
       
  • Next generation sequencing reveals a novel ALK G1128A mutation resistant
           to crizotinib in an ALK-Rearranged NSCLC patient
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Xinghao Ai, Xiaomin Niu, Lianpeng Chang, Rongrong Chen, Sai-Hong Ignatius Ou, Shun Lu ObjectiveAcquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged non–small cell lung cancer (NSCLC) patients who are resistant to treatment with the ALK inhibitor crizotinib. We sought to uncover novel mutations that contribute to resistance in these patients.Materials and MethodsFollowing clinical diagnosis and development of crizotinib treatment resistance, tissue and ctDNA samples were obtained from the 60-year-old patient and subjected to next-generation sequencing for identification of mutations contributing to drug resistance.ResultsWe identified a novel acquired NSCLC ALK G1128A mutation in the ALK + NSCLC patient who progressed on crizotinib after a short partial response to the drug. This mutation, ALK G1128A, is located at the glycine loop (the P-loop) of the ALK tyrosine kinase domain. As a gain-of-function mutation, ALK G1128A increases kinase activity and transformation ability, perhaps conferring resistance to crizotinib.ConclusionsThis case further illustrates the importance of comprehensive genomic profiling of resistant tumors for tailoring treatment decisions after disease progression on crizotinib in ALK + NSCLC in the era of rapidly developing new-generation ALK inhibitors and other therapeutic strategies.
       
  • Computed tomography characteristics of lung adenocarcinomas with epidermal
           growth factor receptor mutation: A propensity score matching study
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Young Joo Suh, Hyun-Ju Lee, Young Jae Kim, Kwang Gi Kim, Heekyung Kim, Yoon Kyung Jeon, Young Tae Kim ObjectivesWe investigated the relationship between computed tomography (CT) characteristics and epidermal growth factor receptor (EGFR) mutations in a large Asian cohort who received surgical resection of invasive lung adenocarcinoma.Materials and MethodsWe retrospectively included 864 patients (524 with EGFR mutation and 340 with EGFR wild-type) who received surgical resections for invasive lung adenocarcinomas. After applying propensity score matching, 312 patients with mutated EGFR were matched with 312 patients with wild-type EGFR. CT characteristics, predominant histologic subtype, and CT measurement parameters (volume and estimated diameter of the total tumor and inner solid portion and ground-glass opacity [GGO] proportion) were compared within matched pairs.ResultsTumors in the EGFR mutation group showed higher proportions of pure ground-glass nodules (4.1% vs 1.3%), GGO-predominant (23.7% vs 14.7%), and solid-predominant part-solid nodules (37.2% vs 31.7%) CT characteristics, whereas EGFR wild-type tumors predominantly presented as pure solid nodules (34.6% vs 52.2%, P 
       
  • Inhibition of IGF1R enhances 2-deoxyglucose in the treatment of non-small
           cell lung cancer
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Fakeng Liu, Yuan Liu, Xiuju Liu, Kaisheng Mao, Diansheng Zhong, Adam I. Marcus, Fadlo R. Khuri, Shi-Yong Sun, Yulong He, Wei Zhou ObjectiveWe previously postulated that 2-deoxyglucose (2-DG) activates multiple pro-survival pathways through IGF1R to negate its inhibitory effect on glycolysis. Here, we evaluated whether IGF1R inhibitor synergizes with 2-DG to impede the growth of non-small cell lung cancer (NSCLC).Materials and methodsThe activation of IGF1R signaling was assessed by the phosphorylation of IGF1R and its downstream target AKT using immunoblot. Drug dose response and combination index analyses were carried out according to the method of Chou and Talalay. Flow cytometry was used to evaluate cell cycle progression. Apoptosis was monitored by caspase-3/PARP cleavages or Annexin V staining. A subcutaneous xenograft model was used to assess this combination in vivo.Results2-DG induces the phosphorylation of IGF1R in its kinase domain, which can be abolished by the IGF1R inhibitor BMS-754807. Furthermore, the combination of 2-DG and BMS-754807 synergistically inhibited the survival of several non-small cell lung cancer (NSCLC) cell lines both in vitro and in vivo. The mechanistic basis of this synergy was cell line-dependent, and LKB1-inactivated EKVX cells underwent apoptosis following treatment with a subtoxic dose of 2-DG and BMS-754807. For these cells, the restoration of LKB1 kinase activity suppressed apoptosis induced by this combination but enhanced G1 arrest. In H460 cells, the addition of 2-DG did not enhance the low level of apoptosis induced by BMS-754807. However, treatment with 0.75 μM of BMS-754807 resulted in the accumulation of H460 cells with 8n-DNA content without affecting cell density increases. Hence, H460 cells may escape BMS-754807-induced G2/M cell cycle arrest through polyploidy. The inclusion of 2-DG blocked formation of the 8n-DNA cell population and restored G2/M phase cell cycle arrest.ConclusionThe combination of 2-DG and IGF1R inhibitor BMS-754807 may be used to suppress the proliferation of NSCLC tumors through different mechanisms.
       
  • Phase Ib/II study of the pan-cyclin-dependent kinase inhibitor roniciclib
           in combination with chemotherapy in patients with extensive-disease
           small-cell lung cancer
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Byoung Chul Cho, Grace K. Dy, Ramaswamy Govindan, Dong-Wan Kim, Nathan A. Pennell, Gerard Zalcman, Benjamin Besse, Joo-Hang Kim, Goekben Koca, Prabhu Rajagopalan, Simon Langer, Matthias Ocker, Hendrik Nogai, Fabrice Barlesi ObjectivesThis phase Ib/II study evaluated safety, pharmacokinetics, maximum tolerated dose (MTD), and efficacy of the pan-cyclin-dependent kinase inhibitor roniciclib with cisplatin-etoposide (CIS-ETOP) or carboplatin-etoposide (CARBO-ETOP) in patients with extensive-disease small-cell lung cancer (ED-SCLC).Patients and methodsIn this open-label, non-randomized study, patients with previously untreated ED-SCLC received roniciclib twice daily (BID) in a 3 days on/4 days off schedule. Cisplatin 75 mg/m2 or carboplatin (AUC5) dose was administered on day 1, and etoposide 100 mg/m2 on days 1–3, of 21-day cycles. Phase Ib used a dose-escalation design to define the MTD for phase II. Pharmacokinetics were assessed.ResultsForty-three patients received treatment (roniciclib 2.5 mg BID [+ CARBO-ETOP, n = 4; + CIS-ETOP, n = 3] and roniciclib 5 mg BID [+ CARBO-ETOP, n = 24; + CIS-ETOP, n = 12]). The MTD of roniciclib was 5 mg BID with CARBO-ETOP or CIS-ETOP. Common adverse events were nausea (90.7%) and vomiting (69.8%). Roniciclib was readily absorbed following oral administration at the MTD (median tmax 0.5–1 h), with a 30–40% reduction in exposure when co-administered with CARBO-ETOP or CIS-ETOP; administration of roniciclib had no effect on etoposide or platinum pharmacokinetics. The response rate was 81.4% (35/43) overall and 86.1% (31/36) in the pooled roniciclib 5 mg BID population (all partial responses).ConclusionRoniciclib co-administered with chemotherapy in patients with ED-SCLC demonstrated tolerability, acceptable pharmacokinetics, and promising efficacy. An observed safety signal in a related phase II study resulted in discontinuation of the present study and termination of further roniciclib development.
       
  • Clinicopathological implications of MET exon 14 mutations in non-small
           cell lung cancer – A systematic review and meta-analysis
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Huy Gia Vuong, An Thi Nhat Ho, Ahmed M.A. Altibi, Tadao Nakazawa, Ryohei Katoh, Tetsuo Kondo MET exon 14 mutation is an uncommon genomic alteration in non-small cell lung cancer (NSCLC). This meta-analysis aimed at investigating the clinicopathological and prognostic features of NSCLCs with MET exon 14 mutation in comparison with other genetic events. We performed a search in four electronic databases including PubMed, Web of Science, Scopus, and Virtual Health Library from inception to February 2018. Relevant data were extracted and pooled into odds ratio (OR), mean differences (MD), and corresponding 95% confidence intervals (CI) using the random-effect model. From 168 studies, we included 12 studies comprising of 18,464 NSCLCs for final analyses. Overall, the prevalence of MET exon 14 mutation in NSCLC was 3% (95% CI = 2–3), with being most commonly found in pulmonary sarcomatoid carcinoma (13%; 95% CI = 4–21). The mutation was more likely to occur in females (OR = 0.55; 95% CI = 0.33 – 0.90), patients with advanced age (MD = 7.48; 95% CI = 3.99–10.98), non-smoker (OR = 0.48; 95% CI = 0.28 – 0.83), and was associated with a worse prognosis (HR = 1.82; 95% CI = 1.04–3.19). Patients with MET exon 14 mutation had a distinct clinicopathological profile compared to other NSCLC genetic events. To summarize, MET exon 14 is a rare mutation in NSCLC and might be associated with a dismal survival. Patients harboring MET exon 14 skipping are eligible for targeted therapy with c-MET inhibitors, thus emphasizing the need to screen for this mutation in advanced NSCLCs.
       
  • The prognostic value of TP53 and its correlation with EGFR mutation in
           advanced non-small cell lung cancer, an analysis based on cBioPortal data
           base
    • Abstract: Publication date: September 2018Source: Lung Cancer, Volume 123Author(s): Xiao-Dong Jiao, Bao-Dong Qin, Pu You, Jian Cai, Yuan-Sheng Zang ObjectivesThe prognostic value of TP53 in advanced non-small-cell lung cancer (NSCLC) is unclear. Whether different mutated exon has different prognostic value is unknown. We sought to reveal the prognostic value of TP53 in advanced NSCLC, as well as the correlation with EGFR mutation.Materials and MethodsInformation regarding TP53 and EGFR alterations and patients’ survival time in advanced NSCLC was downloaded from the Cancer Genome Atlas Database. We further subdivided TP53 and EGFR mutation into subgroups based on different mutation exon, and then evaluated the distribution of different mutation exon as well as the prognostic value.Results and ConclusionOverall, 1441 pieces of data from 1441 metastatic NSCLC patient were collected. Mutation rate of TP53 was 56.1% (809/1441). TP53 mutation was a negative prognostic factor for OS. The estimated survival time for wild type TP53 and mutated TP53 was 27.0 months (95% CI, not reached) and 19 months (95% CI, 16.62 to 21.38), respectively, (p 
       
  • Common Cancer-Driver Mutations and their Association with Abnormally
           Methylated Genes in Lung Adenocarcinoma from Never-Smokers
    • Abstract: Publication date: Available online 11 July 2018Source: Lung CancerAuthor(s): Mathewos Tessema, Michael R. Rossi, Maria A. Picchi, Christin M. Yingling, Yong Lin, Suresh S. Ramalingam, Steven A. Belinsky ObjectivesLung adenocarcinoma in never-smokers accounts for 15-20% of all lung cancer. Although targetable mutations are more prevalent in these tumors, the biological and clinical importance of coexisting and/or mutually exclusive abnormalities is just emerging. This study evaluates the relationships between common genetic and epigenetic aberrations in these tumors.Materials and methodsNext-generation sequencing was employed to screen 20 commonly mutated cancer-driver genes in 112 lung adenocarcinomas from never-smokers. The relationship of these mutations with cancer-related methylation of 59 genes, and geographical/ethnic differences in the prevalence for mutations compared to multiple East Asian never-smoker lung adenocarcinoma cohorts was studied.ResultsThe most common driver mutation detected in 40% (45/112) of the tumors was EGFR, followed by TP53 (18%), SETD2 (11%), and SMARCA4 (11%). Over 72% (81/112) of the cases have mutation of at least one driver gene. While 30% (34/112) of the tumors have co-mutations of two or more genes, 42% (47/112) have only one driver gene mutation. Differences in the prevalence for some of these mutations were seen between adenocarcinomas in East Asian versus US (mainly Caucasian) never-smokers including a significantly lower rate of EGFR mutation among the US patients. Interestingly, aberrant methylation of multiple cancer-related genes was significantly associated with EGFR wildtype tumors. Among 15 differentially methylated genes by EGFR mutation, 14 were more commonly methylated in EGFR wildtype compared to mutant tumors. These findings were independently validated using publicly available data.ConclusionMost lung adenocarcinomas from never-smokers harbor targetable mutation/co-mutations. In the absence of EGFR mutation that drives 40% of these tumors, EGFR wildtype tumors appear to develop by acquiring aberrant promoter methylation that silences tumor-suppressor genes.
       
  • First-line pembrolizumab in PD-L1 positive non-small-cell lung cancer: a
           cost-effectiveness analysis from the UK health care perspective
    • Abstract: Publication date: Available online 11 July 2018Source: Lung CancerAuthor(s): Xiaohan Hu, Joel W. Hay BackgroundPembrolizumab has shown significant survival benefits in treating chemotherapy-naïve non-small-cell lung cancer patients (NSCLC) with increased level of PD-L1 expression. This analysis aimed to evaluate the cost-effectiveness of pembrolizumab as a first-line treatment for patients with PD-L1 positive NSCLC from the UK health care perspective.MethodsA Markov model with progression-free, progressive disease and death states was developed. Clinical parameters were informed by the KEYNOTE-024 trial. Utility values were sourced from published literature. Cost data including drug acquisition costs, disease management costs, and adverse event costs were derived from British National Formulary and published literature. The model was run until 99% patients died. Both health outcomes and costs were discounted at an annual rate of 3.5%. Deterministic and probabilistic sensitivity analyses were performed to address the uncertainties around model parameters.ResultsIn the base case, pembrolizumab is projected to increase patient’s life expectancy by 1.32 life-years over chemotherapy (2.45 vs. 1.13) and 0.83 QALYs (1.55 vs. 0.71) at an additional cost of £72,465, yielding an incremental cost-effectiveness ratio of £86,913/QALY. When parameters were varied in the deterministic sensitivity analyses, results are most sensitive to duration of median overall survival in both groups.ConclusionUsing a willingness-to-pay threshold of £50,000, pembrolizumab is not cost-effective at its current list price and a discount of 50% or more is required for it to be cost-effective comparing to commonly prescribed chemotherapy.
       
  • At last we can go ahead with low-dose CT screening for lung cancer in
           Europe
    • Abstract: Publication date: Available online 10 July 2018Source: Lung CancerAuthor(s): Giulia Veronesi, Javier J. Zulueta, Patrick Maisonneuve, Claudia Henschke
       
  • Prediagnosis weight loss, a stronger factor than BMI, to predict survival
           in patients with lung cancer
    • Abstract: Publication date: Available online 5 July 2018Source: Lung CancerAuthor(s): Hugues Morel, Bruno Raynard, Michel d’Arlhac, Pierre-Alexandre Hauss, Emmanuelle Lecuyer, Gérard Oliviero, Clothilde Marty, Jean-Pierre Gury, Bernard Asselain, Michel Grivaux, Didier Debieuvre
       
  • Stereotactic ablative radiotherapy (SABR) for early-stage central lung
           tumors: New insights and approaches
    • Abstract: Publication date: Available online 4 July 2018Source: Lung CancerAuthor(s): H. Tekatli, F.O.B. Spoelstra, M. Palacios, J. van Sornsen de Koste, B.J. Slotman, S. Senan The use of stereotactic ablative radiotherapy (SABR) for central lung tumors is increasing. Centrally located lung tumors can be subdivided into two categories, namely the 'moderately central' tumors where the planning target volume is located within 2 cm in of the proximal bronchial tree, and the 'ultracentral' tumors where a planning target volume (PTV) overlaps the trachea or main stem bronchi. The toxicity of SABR appears acceptable when 'moderately central' tumors are treated using techniques that comply with organs at risk tolerance doses used for prospective trials and in recent publications. A high toxicity is seen when ultracentral tumors are treated using SABR, and conventional radiotherapy appears more appropriate as the true normal organ tolerance doses remain unknown. When ultracentral tumors are treated with non-SABR hypofractionated radiotherapy, a homogenous dose distribution in the planning target volume and limitation of both normal organ maximum point doses and volumes receiving high doses seems to be needed.
       
  • Randomized Phase II Study of Fulvestrant and Erlotinib Compared With
           Erlotinib Alone in Patients with Advanced or Metastatic Non-Small Cell
           Lung Cancer
    • Abstract: Publication date: Available online 22 June 2018Source: Lung CancerAuthor(s): Edward B. Garon, Jill M. Siegfried, Laura P. Stabile, Patricia A. Young, Diana C. Marquez-Garban, David J. Park, Ravi Patel, Eddie H. Hu, Saeed Sadeghi, Rupesh J. Parikh, Karen L. Reckamp, Brad Adams, Robert M. Elashoff, David Elashoff, Tristan Grogan, He-Jing Wang, Sanja Dacic, Meghan Brennan, Yacgley Valdes, Simon Davenport ObjectivesThis open-label, randomized phase II trial evaluated antitumor efficacy of an antiestrogen, fulvestrant, in combination with human epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in advanced non-small cell lung cancer (NSCLC) patients.Materials and MethodsPatients with advanced or metastatic NSCLC, ECOG 0-2, previous chemotherapy unless patient refusal, and no prior EGFR-directed therapy were randomized 2:1 to erlotinib 150 mg oral daily plus 500 mg intramuscular fulvestrant on day 1, 15, 29 and every 28 days thereafter or erlotinib alone 150 mg oral daily. The primary end point was objective response rate (ORR); secondary endpoints included progression free survival (PFS) and overall survival (OS).ResultsAmong 106 randomized patients, 100 received at least one dose of study drug. ORR was 16.4% (11 of 67 patients) for the combination versus 12.1% (4 of 33 patients) for erlotinib (p = 0.77). PFS median 3.5 versus 1.9 months [HR = 0.86, 95% CI (0.52-1.43), p = 0.29] and OS median 9.5 versus 5.8 months [HR = 0.92, 95% CI (0.57-1.48), p = 0.74] numerically favored the combination. In an unplanned subset analysis, among EGFR wild type patients (n = 51), but not EGFR mutant patients (n = 17), median PFS was 3.5 versus 1.7 months [HR = 0.35, 95% CI (0.14-0.86), p = 0.02] and OS was 6.2 versus 5.2 months [HR = 0.72, 95% CI (0.35 to 1.48), p = 0.37] for combined therapy versus erlotinib, respectively. Notably, EGFR WT patients were more likely to be hormone receptor-positive (either estrogen receptor α- and/or progesterone receptor-positive) compared to EGFR mutant patients (50% versus 9.1%, respectively) (p = 0.03). Treatment was well tolerated with predominant grade 1-2 dermatologic and gastrointestinal adverse effects.ConclusionAddition of fulvestrant to erlotinib was well tolerated, with increased activity noted among EGFR wild type patients compared to erlotinib alone, albeit in an unplanned subset analysis.
       
  • Low level evidence supporting the choice of optimal multimodality
           treatment approach in patients with stage IIIA NSCLC– Ain’t no
           mountain high enough…. to keep me getting to you
    • Abstract: Publication date: Available online 18 June 2018Source: Lung CancerAuthor(s): Branislav Jeremic, Antonio Gomez-Caamano, Pavol Dubinsky, Nikola Cihoric, Ivan Igrutinovic, Gregory Videtic
       
  • Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in
           France, Germany and the United Kingdom: A retrospective observational
           study (LuCaBIS)
    • Abstract: Publication date: Available online 9 June 2018Source: Lung CancerAuthor(s): Stefan Andreas, Christos Chouaid, Sarah Danson, Obukohwo Siakpere, Laure Benjamin, Rainer Ehness, Marie-Hélène Dramard-Goasdoue, Janina Barth, Hans Hoffmann, Vanessa Potter, Fabrice Barlesi, Costel Chirila, Kelly Hollis, Carolyn Sweeney, Mark Price, Sorrel Wolowacz, James A. Kaye, Ilias Kontoudis ObjectivesNew adjuvant treatments are being developed for patients with resected non-small cell lung cancer (NSCLC). Due to scarcity of real-world data available for treatment costs and resource utilization, health technology and cost-effectiveness assessments can be limited. We estimated the burden and cost-of-illness associated with completely resected stage IB-IIIA NSCLC in France, Germany and the United Kingdom (UK).Materials and methodsEligible patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC between August 2009 and July 2012. Patients (living or deceased) were enrolled at clinical sites by a systematic sampling method. Data were obtained from medical records and patient surveys. Direct, indirect and patient out-of-pocket expenses were estimated by multiplying resource use by country-specific unit costs. National annual costs were estimated based on disease prevalence data available from published sources.Results39 centers provided data from 831 patients of whom patient surveys were evaluable in 306 patients. Median follow-up was 26 months. The mean total direct costs per patient during follow-up were: €19,057 (France), €14,185 (Germany), and €8377 (UK). The largest cost drivers were associated with therapies received (€12,375 France; €3694 UK), and hospitalization/emergency costs (€7706 Germany). Monthly direct costs per patient were the highest during the distant metastasis/terminal illness phase in France (€15,562) and Germany (€6047) and during the adjuvant treatment period in the UK (€2790). Estimated mean total indirect costs per patient were: €696 (France), €2476 (Germany), and €1414 (UK). Estimates for the annual national direct cost were €478.4 million (France), €574.6 million (Germany) and €325.8 million (UK).ConclusionTo our knowledge, this is the first comprehensive study describing the burden of illness for patients with completely resected stage IB-IIIA NSCLC. The economic burden was substantial in all three countries. Treatment of NSCLC is associated with large annual national costs, mainly incurred during disease progression.
       
  • Relationship between the number of new nodules and lung cancer probability
           in incidence screening rounds of CT lung cancer screening: The NELSON
           study
    • Abstract: Publication date: Available online 14 May 2018Source: Lung CancerAuthor(s): Joan E. Walter, Marjolein A. Heuvelmans, Geertruida H. de Bock, Uraujh Yousaf-Khan, Harry J.M. Groen, Carlijn M. van der Aalst, Kristiaan Nackaerts, Peter M.A. van Ooijen, Harry J. de Koning, Rozemarijn Vliegenthart, Matthijs Oudkerk BackgroundNew nodules are regularly found after the baseline round of low-dose computed tomography (LDCT) lung cancer screening. The relationship between a participant’s number of new nodules and lung cancer probability is unknown.MethodsParticipants of the ongoing Dutch-Belgian Randomized Lung Cancer Screening (NELSON) Trial with (sub)solid nodules detected after baseline and registered as new by the NELSON radiologists were included. The correlation between a participant’s new nodule count and the largest new nodule size was assessed using Spearman's rank correlation. To evaluate the new nodule count as predictor for new nodule lung cancer together with largest new nodule size, a multivariable logistic regression analysis was performed.ResultsIn total, 705 participants with 964 new nodules were included. In 48% (336/705) of participants no nodule had been found previously during baseline screening and in 22% (154/705) of participants>1 new nodule was detected (range 1-12 new nodules). Eventually, 9% (65/705) of the participants had lung cancer in a new nodule. In 100% (65/65) of participants with new nodule lung cancer, the lung cancer was the largest or only new nodule at initial detection. The new nodule lung cancer probability did not differ significantly between participants with 1 (10% [56/551], 95%CI 8–13%) or>1 new nodule (6% [9/154], 95%CI 3–11%, P = 0.116). An increased number of new nodules positively correlated with a participant’s largest nodule size (P 
       
  • 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.
       
  • Heterogeneous MET gene copy number and EGFR mutation elicit discordant
           responses to crizotinib between primary and metastatic lesions in
           erlotinib-resistant lung adenocarcinoma
    • Abstract: Publication date: Available online 17 March 2018Source: Lung CancerAuthor(s): Katsuhiro Yoshimura, Masato Karayama, Yusuke Inoue, Tomoaki Kahyo, Naoki Inui, Masato Maekawa, Haruhiko Sugimura, Takafumi Suda
       
  • 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.
       
 
 
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