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Publisher: Elsevier   (Total: 3177 journals)

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Showing 1 - 200 of 3177 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 30, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 86, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 35, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 386, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
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: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 242, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 7)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 132, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 29, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
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: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 14)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 43, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 53, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
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: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
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: 15, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
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: 0.324, h-index: 8)
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: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
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: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 384, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 9, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
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: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 337, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 10, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 435, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
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: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 51, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 42, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 196, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 62, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 14)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 168, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)

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Journal Cover Lung Cancer
  [SJR: 1.923]   [H-I: 98]   [14 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-5002
   Published by Elsevier Homepage  [3177 journals]
  • Associations of objectively assessed physical activity and sedentary time
           with health-related quality of life among lung cancer survivors: A
           quantile regression approach
    • Authors: Jeff K. Vallance; Gwyn D. Bebb; Terry Boyle; Steven T. Johnson; Paul A. Gardiner; Adrijana D'Silva
      Pages: 61 - 65
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Adrijana D’Silva, Paul A. Gardiner, Terry Boyle, D. Gwyn Bebb, Steven T. Johnson, Jeff K. Vallance
      Objectives No studies have examined objectively assessed physical activity, sedentary time, and patient-reported outcomes among lung cancer survivors. The objective of this study was to determine associations of objectively assessed moderate-to-vigorous intensity physical activity (MVPA) and sedentary time with health-related quality of life (HRQoL) and fatigue among lung cancer survivors. Materials and method Lung cancer survivors in Southern Alberta (N = 540) were invited to complete a mailed survey that assessed HRQoL [Functional Assessment of Cancer Therapy-Lung (FACT-L)], physical and functional well-being [Trial Outcome Index (TOI)], and fatigue [Fatigue Scale (FS)]. Physical activity and sedentary time data was collected using an Actigraph® GT3X+ accelerometer that was worn on the hip for seven consecutive days. Quantile regression was used to examine associations of HRQoL and fatigue with physical activity and sedentary time at the 25th, 50th, and 75th HRQoL and fatigue percentiles. Results A total of 127 lung cancer survivors participated for a 24% response rate (Mean age = 71 years; Mean time since diagnosis = 75 months). Total MVPA minutes was positively associated with fewer fatigue symptoms at the 25th percentile (β = 0.16, p = 0.046). Total sedentary time was inversely associated with HRQoL at the 75th percentile (β = −0.07, p = 0.014) and inversely associated with fatigue symptoms at the 50th percentile (β = −0.04, p = 0.009). Total sedentary time was also inversely associated with physical and functional well-being scores at the 25th (β = −0.07, p = 0.045), 50th (β = −0.07, p = 0.004) and 75th (β = −0.04, p = 0.035) percentiles. Conclusion Across the HRQoL, fatigue, and physical and functional well-being distributions, sedentary time was inversely associated with HRQoL, fatigue, and physical and functional well-being in lung cancer survivors. Small associations were observed between MVPA and fatigue, but no associations emerged with HRQoL or physical and functional well-being.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.mhpa.2018.02.002
      Issue No: Vol. 14 (2018)
       
  • Facility volume and postoperative outcomes for malignant pleural
           mesothelioma: A National Cancer Data Base analysis
    • Authors: Vivek Verma; Christopher A. Ahern; Christopher G. Berlind; William D. Lindsay; Surbhi Grover; Melissa J. Culligan; Joseph S. Friedberg; Charles B. Simone
      Pages: 7 - 13
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Vivek Verma, Christopher A. Ahern, Christopher G. Berlind, William D. Lindsay, Surbhi Grover, Melissa J. Culligan, Joseph S. Friedberg, Charles B. Simone
      Purpose This study of a large, contemporary national database evaluated postoperative outcomes and overall survival (OS) for malignant pleural mesothelioma (MPM) by facility volume. Methods The National Cancer Database was queried for newly-diagnosed non-metastatic MPM undergoing definitive surgery (extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D)). Patients were dichotomized into those receiving therapy at a high-volume facility (HVF), defined a priori at the 90th percentile of case volume, with all others categorized as lower-volume facilities (LVFs). Statistics included multivariable logistic regression, Kaplan-Meier analysis, propensity-matching, and multivariable Cox proportional hazards modeling. Sensitivity analysis varied the dichotomized HVF-LVF cutoff and evaluated effects on postoperative outcomes and OS. Results Of 1307 patients, 621 (48%) were treated at LVFs and 686 (52%) at HVFs. HVFs were more often in the Middle/South Atlantic regions, and less likely in New England, South, and Midwest. Notably, 75% of procedures at HVFs were P/Ds, versus 84% at LVFs (p < 0.001). Patients treated at HVFs experienced shorter length of postoperative hospitalization (p = 0.035), lower 30-day readmission rates (4.6% vs. 6.1%, p = 0.021), and lower 90-day mortality rates (10.0% vs. 14.6%, p = 0.029). Median OS for respective groups were 18 versus 15 months (p = 0.010), which were not significant following propensity-matching (p = 0.540). On multivariable analysis, facility volume did not independently predict for OS. Sensitivity analyses confirmed the postoperative outcomes and OS findings. Conclusions This is the largest investigation to date assessing facility volume and outcomes following surgery for MPM. Although no independent effects on OS were observed, postoperative outcomes were more favorable at HVFs. These findings have implications for postoperative management, patient counseling, referring providers, and cost-effectiveness.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.03.019
      Issue No: Vol. 120 (2018)
       
  • Tumor spread through air spaces is a useful predictor of recurrence and
           prognosis in stage I lung squamous cell carcinoma, but not in stage II and
           III
    • Authors: Naoki Yanagawa; Satoshi Shiono; Makoto Endo; Shin-ya Ogata
      Pages: 14 - 21
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Naoki Yanagawa, Satoshi Shiono, Makoto Endo, Shin-ya Ogata
      Objectives Tumor spread through air spaces (STAS) is a newly identified invasion pattern in lung adenocarcinoma. This study aimed to analyze and validate the clinical impact of tumor STAS in surgically resected lung squamous cell carcinoma (SQCC). Materials and methods We retrospectively reviewed 220 patients with lung SQCC. Tumor STAS was defined as detached tumor cells within the air spaces in the lung parenchyma beyond the edge of the main tumor. Statistical analyses were conducted to investigate the proportion of STAS and the relationship between the presence of STAS and clinicopathological factors, including clinical outcome. Results STAS was identified in 42 of 220 patients (19.1%). The patients with STAS had a significantly worse 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) than those without STAS (5-year RFS: 37.4% vs. 68.4%; p = 0.0006; 5-year OS: 50.2% vs. 71.4%, p = 0.0078) in stage I, but not in stage II and III. A multivariate analysis showed that the presence of STAS was an independent predictive factor of recurrence (hazard ratio = 3.27; 95% confidence interval, 1.7–6.29; p = 0.0004) and an independent prognostic factor (hazard ratio = 3.01; 95% confidence interval, 1.54–5.89; p = 0.0013) in stage I, but not in stage II and III. Conclusion We found that STAS was detected in 19.1% of surgical resected SQCC, and it was associated with recurrence and worse survival in stage I SQCC, but not in stage II and III SQCC. Therefore, we suggest that STAS is a useful predictor of recurrence and prognosis in stage I lung SQCC.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.03.018
      Issue No: Vol. 120 (2018)
       
  • Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural
           mesothelioma
    • Authors: Joanna Kopecka; Iris C. Salaroglio; Luisella Righi; Roberta Libener; Sara Orecchia; Federica Grosso; Vladan Milosevic; Preeta Ananthanarayanan; Luisa Ricci; Enrica Capelletto; Monica Pradotto; Francesca Napoli; Massimo Di Maio; Silvia Novello; Menachem Rubinstein; Giorgio V. Scagliotti; Chiara Riganti
      Pages: 34 - 45
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Joanna Kopecka, Iris C. Salaroglio, Luisella Righi, Roberta Libener, Sara Orecchia, Federica Grosso, Vladan Milosevic, Preeta Ananthanarayanan, Luisa Ricci, Enrica Capelletto, Monica Pradotto, Francesca Napoli, Massimo Di Maio, Silvia Novello, Menachem Rubinstein, Giorgio V. Scagliotti, Chiara Riganti
      Objectives Cisplatin-based chemotherapy is moderately active in malignant pleural mesothelioma (MPM) due to intrinsic drug resistance and to low immunogenicity of MPM cells. CAAT/enhancer binding protein (C/EBP)-β LIP is a pro-apoptotic and chemosensitizing transcription factor activated in response to endoplasmic reticulum (ER) stress. Materials and methods We investigated if LIP levels can predict the clinical response to cisplatin and survival of MPM patients receiving cisplatin-based chemotherapy. We studied the LIP-dependent mechanisms determining cisplatin-resistance and we identified pharmacological approaches targeting LIP, able to restore cisplatin sensitiveness, in patient-derived MPM cells and animal models. Results were analyzed by a one-way analysis of variance test. Results We found that LIP was degraded by constitutive ubiquitination in primary MPM cells derived from patients poorly responsive to cisplatin. LIP ubiquitination was directly correlated with cisplatin chemosensitivity and was associated with patients’ survival after chemotherapy. Overexpression of LIP restored cisplatin’s pro-apoptotic effect by activating CHOP/TRB3/caspase 3 axis and up-regulating calreticulin, that triggered MPM cell phagocytosis by dendritic cells and expanded autologous anti-tumor CD8+CD107+T-cytotoxic lymphocytes. Proteasome inhibitor carfilzomib and lysosome inhibitor chloroquine prevented LIP degradation. The triple combination of carfilzomib, chloroquine and cisplatin increased ER stress-triggered apoptosis and immunogenic cell death in patients’ samples, and reduced tumor growth in cisplatin-resistant MPM preclinical models. Conclusion The loss of LIP mediates cisplatin resistance, rendering LIP a possible predictor of cisplatin response in MPM patients. The association of proteasome and lysosome inhibitors reverses cisplatin resistance by restoring LIP levels and may represent a new adjuvant strategy in MPM treatment.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.03.022
      Issue No: Vol. 120 (2018)
       
  • Lorlatinib – Induced pulmonary arterial hypertension
    • Authors: Alexandre Chabrol; Marie Mayenga; Abdul Momen Hamid; Sylvie Friard; Hélène Salvator; Hélèe Doubre; Séverine Fraboulet; Anne-Cécile Metivier; Emilie Catherinot; Elisabeth Rivaud; Marie Camille Chaumais; David Montani; Louis Jean Couderc; Colas Tcherakian
      Pages: 60 - 61
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Alexandre Chabrol, Marie Mayenga, Abdul Momen Hamid, Sylvie Friard, Hélène Salvator, Hélèe Doubre, Séverine Fraboulet, Anne-Cécile Metivier, Emilie Catherinot, Elisabeth Rivaud, Marie Camille Chaumais, David Montani, Louis Jean Couderc, Colas Tcherakian
      We report here the first cases, to our knowledge, of pulmonary arterial hypertension induced by lorlatinib. It s the first time that a tyrosine kinase inhibitor for lung cancer is associated with pulmonary arteriel hypertension.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.03.023
      Issue No: Vol. 120 (2018)
       
  • Antiangiogenic therapy for patients with aggressive or refractory advanced
           non-small cell lung cancer in the second-line setting
    • Authors: Martin Reck; Marina Chiara Garassino; Martina Imbimbo; Frances A. Shepherd; Mark A. Socinski; Jin-Yuan Shih; Anne Tsao; Pablo Lee; Katherine B. Winfree; Andreas Sashegyi; Rebecca Cheng; Rocio Varea; Benjamin Levy; Edward Garon
      Pages: 62 - 69
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Martin Reck, Marina Chiara Garassino, Martina Imbimbo, Frances A. Shepherd, Mark A. Socinski, Jin-Yuan Shih, Anne Tsao, Pablo Lee, Katherine B. Winfree, Andreas Sashegyi, Rebecca Cheng, Rocio Varea, Benjamin Levy, Edward Garon
      A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.03.025
      Issue No: Vol. 120 (2018)
       
  • Long-term survival with erlotinib in advanced lung adenocarcinoma
           harboring synchronous EGFR G719S and KRAS G12C mutations
    • Authors: Biagio Ricciuti; Sara Baglivo; Vienna Ludovini; Angelo Sidoni; Giulio Metro; Marta Brambilla; Annamaria Siggillino; Maria Sole Reda; Alberto Rebonato; Daniele Maiettini; Rita Chiari
      Pages: 70 - 74
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Biagio Ricciuti, Sara Baglivo, Vienna Ludovini, Angelo Sidoni, Giulio Metro, Marta Brambilla, Annamaria Siggillino, Maria Sole Reda, Alberto Rebonato, Daniele Maiettini, Rita Chiari
      Although epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) mutations were thought to be mutually exclusive in patients with non-small cell lung cancer (NSCLC), the development of high sensitive large-scale mutation analysis, has increasingly shown that activating EGFR mutations occasionally coexist with other dominant genetic alterations. Herein, we discuss the case of a patient with advanced NSCLC harboring both the uncommon EGFR G719S and the KRAS G12C mutations, who was treated for 9 years with erlotinib achieving a long-term survival. In light of their rarity, multiple mutations are very challenging for the decision of tyrosine kinase inhibitors (TKIs) treatment, especially when EGFR mutations occur together with mutations known to provide resistance to EGFR TKIs, such as KRAS.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.002
      Issue No: Vol. 120 (2018)
       
  • EGFR-TKIs plus chemotherapy demonstrated superior efficacy than EGFR-TKIs
           alone as first-line setting in advanced NSCLC patients with EGFR mutation
           and BIM deletion polymorphism
    • Authors: Sangtian Liu; Yayi He; Tao Jiang; Shengxiang Ren; Fei Zhou; Chao Zhao; Xuefei Li; Jie Zhang; Chunxia Su; Xiaoxia Chen; Weijing Cai; Guanghui Gao; Wei Li; Fengying Wu; Jiayu Li; Jing Zhao; Qiong Hu; Mingchuan Zhao; Caicun Zhou; Fred R. Hirsch
      Pages: 82 - 87
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Sangtian Liu, Yayi He, Tao Jiang, Shengxiang Ren, Fei Zhou, Chao Zhao, Xuefei Li, Jie Zhang, Chunxia Su, Xiaoxia Chen, Weijing Cai, Guanghui Gao, Wei Li, Fengying Wu, Jiayu Li, Jing Zhao, Qiong Hu, Mingchuan Zhao, Caicun Zhou, Fred R. Hirsch
      Background Non–small-cell lung cancer (NSCLC) patients with both epidermal growth factor receptor (EGFR) positive mutation and B-cell chronic lymphocytic leukemia/lymphoma-like 11 (BIM) deletion polymorphism had a poor clinical response to EGFR-tyrosine kinase inhibitors (TKIs). The current study aimed to investigate the clinical efficacy and tolerability of EGFR-TKIs plus chemotherapy versus EGFR-TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletion polymorphism. Methods A retrospective, non-randomized analysis was conducted. BIM deletion polymorphism was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from peripheral blood cells. Clinical characteristics, overall survival (OS), progress-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared between EGFR-TKIs alone versus EGFR-TKIs plus chemotherapy group. Results 65 patients were enrolled. 36 of them received EGFR-TKIs and 29 received EGFR-TKIs plus chemotherapy. EGFR-TKIs plus chemotherapy had significantly higher ORR than TKIs alone (65.5% vs. 38.9%, P = 0.046). Median PFS was significantly longer in EGFR-TKIs plus chemotherapy group than in TKIs group (7.2 vs 4.7 m; P = 0.008). Median OS was numerically longer in EGFR-TKIs plus chemotherapy group than in TKIs alone (18.5 vs 14.2 m; P = 0.107). EGFR-TKIs plus chemotherapy was associated with more grade 3 or 4 hematological toxic effects than EGFR-TKIs alone. Conclusion EGFR-TKIs plus chemotherapy conferred a significantly higher ORR, prolonged PFS and numerically longer OS in advanced NSCLC patients with EGFR mutation and BIM deletion polymorphism. Further prospective studies are needed to validate these findings.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.004
      Issue No: Vol. 120 (2018)
       
  • Cost-effectiveness analysis of policy options on first-line treatments for
           advanced, non-small cell lung cancer in Thailand
    • Authors: Chulaporn Limwattananon; Supon Limwattananon; Onanong Waleekhachonloet; Thananan Rattanachotphanit
      Pages: 91 - 97
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Chulaporn Limwattananon, Supon Limwattananon, Onanong Waleekhachonloet, Thananan Rattanachotphanit
      Objectives Tyrosine kinase inhibitors (TKIs) have shown to be better for progression-free survival than chemotherapy as the first-line treatment for advanced, non-small cell lung cancer (NSCLC), especially in patients with epidermal growth factor receptor mutation (EGFR M+). This study evaluates under the Thai health system context, cost-effectiveness of (A) the use of platinum doublets for all without EGFR testing, and (B) an EGFR test followed by TKIs or platinum doublets conditional on test results. Materials and methods A decision analysis model was constructed to estimate quality-adjusted life years (QALYs) and total cost for each option. Cancer progression and death were pooled from randomized, controlled trials. Quality of life was obtained from patient interview, using the European Quality-of-Life, 5-Dimension questionnaire. Costs associated with treatment outcomes were derived from patient chart reviews. Results Combining the EGFR test with each TKI, gefitinib, erlotinib and afatinib if M+ or otherwise platinum doublets, resulted in higher effectiveness than the use of platinum doublets for all by 0.15, 0.19 and 0.21 QALYs, respectively. Among the three TKIs, gefitinib was dominated economically by erlotinib, which incurred an incremental cost-effectiveness ratio (ICER) of $46,783/QALY over the platinum doublets for all. Moving to the next best, afatinib resulted in the ICER of $198,961/QALY over erlotinib. Probabilities for any TKIs being cost-effective when compared with platinum doublets over a wide range of willingness to pay were modest. Conclusion In Thailand, the first-line treatment for advanced NSCLC with TKIs conditional on EGFR test results was not cost-effective as compared with platinum doublets for all.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.003
      Issue No: Vol. 120 (2018)
       
  • Expression of brain-derived neurotrophic factor and its receptor TrkB is
           associated with poor prognosis and a malignant phenotype in small cell
           lung cancer
    • Authors: Shinichi Kimura; Taishi Harada; Kayo Ijichi; Kentaro Tanaka; Renpeng Liu; Daisuke Shibahara; Yuko Kawano; Kohei Otsubo; Yasuto Yoneshima; Eiji Iwama; Yoichi Nakanishi; Isamu Okamoto
      Pages: 98 - 107
      Abstract: Publication date: June 2018
      Source:Lung Cancer, Volume 120
      Author(s): Shinichi Kimura, Taishi Harada, Kayo Ijichi, Kentaro Tanaka, Renpeng Liu, Daisuke Shibahara, Yuko Kawano, Kohei Otsubo, Yasuto Yoneshima, Eiji Iwama, Yoichi Nakanishi, Isamu Okamoto
      Objectives TrkB is a receptor for brain-derived neurotrophic factor (BDNF) and is highly expressed in various cancers, with BDNF-TrkB signaling having been implicated in tumor progression and metastasis. The role of the BDNF-TrkB system in small cell lung cancer (SCLC), a neuroendocrine cancer, has remained unclear, however. We examined BDNF and TrkB expression in SCLC patients as well as the function of BDNF-TrkB signaling in SCLC cell lines. Materials and methods BDNF and TrkB expression in tumor specimens of 58 SCLC patients and 20 non–small cell lung cancer (NSCLC) patients was examined by immunohistochemistry and was scored on the basis of the distribution and intensity of staining. TrkB-overexpressing SCLC (SBC5TrkB) cells were established by retrovirus transduction and were examined for the effects of BDNF on intracellular signaling, cell proliferation, and cell migration in vitro. Results The staining score for TrkB in NSCLC and SCLC specimens was 2.80 ± 0.19 and 3.60 ± 0.15, respectively, whereas that for BDNF was 1.95 ± 0.32 and 2.76 ± 0.14, respectively. High levels of both TrkB and BDNF expression in SCLC tumors were significantly associated with poor overall survival in multivariate analysis (hazard ratio = 1.821, P = 0.036). BDNF activated AKT and ERK signaling pathways in and promoted the migration of SBC5TrkB cells, and these effects were attenuated by the pan-Trk inhibitor GNF-5837. GNF-5837 also inhibited the proliferation of SBC5TrkB cells in the presence of BDNF. Conclusion Coexpression of BDNF and TrkB was associated with poor prognosis in SCLC patients, and BDNF promoted the migration of TrkB-overexpressing SCLC cells. TrkB is thus a potential therapeutic target for SCLC.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.005
      Issue No: Vol. 120 (2018)
       
  • PD-L1 expression in circulating tumor cells of advanced non-small cell
           lung cancer patients treated with nivolumab
    • Authors: Nicolas Guibert; Myriam Delaunay; Amélie Lusque; Nadia Boubekeur; Isabelle Rouquette; Estelle Clermont; Jean Mourlanette; Sandrine Gouin; Inge Dormoy; Gilles Favre; Julien Mazieres; Anne Pradines
      Pages: 108 - 112
      Abstract: Publication date: Available online 3 April 2018
      Source:Lung Cancer
      Author(s): Nicolas Guibert, Myriam Delaunay, Amélie Lusque, Nadia Boubekeur, Isabelle Rouquette, Estelle Clermont, Sandrine Gouin, Inge Dormoy, Gilles Favre, Julien Mazieres, Anne Pradines
      Background Inhibitors of the PD-1/PD-L1 immune checkpoint have become a standard of care in non-small cell lung cancer (NSCLC). Patient selection, currently based on PD-L1 expression on tumor tissue, is limited by its temporal and spatial heterogeneity. We hypothesized that liquid biopsy with PD-L1 analysis on circulating tumor cells (CTCs) might overcome this limitation. Methods Blood samples were prospectively collected from patients with advanced NSCLC before nivolumab treatment and at the time of progression. CTCs were isolated using a cell size-based technology. PD-L1 expression was assessed by immunofluorescence on CTCs and immunohistochemistry on tissue biopsies. Results 113 specimens from 96 patients were collected. Baseline PD-L1 expression could be assessed on 72% and 93% of tissue and CTC, respectively. CTCs were more frequently found to be PD-L1 positive than tissue (83% vs. 41%) and no correlation was observed between tissue and CTC PD-L1 expression (r = 0.04, p = 0.77). Pre-treatment high CTC number was associated with increased risk of death and progression (HR1.06, p = 0.03 for OS; HR1.05, p = 0.02 for PFS). The presence of pre-treatment PD-L1+CTC was not significantly correlated with outcomes but a higher baseline PD-L1+ CTC number (≥1%) was observed in the “non-responders” group (PFS <6 months) (p = 0.04) and PD-L1+CTC were seen in all patients at progression. Conclusion Assessment of PD-L1 expression in CTCs is feasible and CTCs are more often positive than in tissue. Pre-treatment PD-L1+CTCs are associated with bad prognosis in patients treated with PD-1 inhibitors.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.001
      Issue No: Vol. 120 (2018)
       
  • Genomic alterations of plasma cell-free DNAs in small cell lung cancer and
           their clinical relevance
    • Authors: Meijun Du; Jonathan Thompson; Hannah Fisher; Peng Zhang; Chiang-Ching Huang; Liang Wang
      Pages: 113 - 121
      Abstract: Publication date: Available online 12 April 2018
      Source:Lung Cancer
      Author(s): Meijun Du, Jonathan Thompson, Hannah Fisher, Peng Zhang, Chiang-Ching Huang, Liang Wang
      Objectives To identify genomic variations in cell-free DNA (cfDNA) and evaluate their clinical utility in small cell lung cancer (SCLC). Materials and methods We performed whole genome sequencing using plasma cfDNAs derived from 24 SCLC patients for copy number variation (CNV) analysis, and targeted sequencing using 17 pairs of plasma cfDNA and their matched gDNA for mutation analysis. We defined somatic mutations by comparing cfDNA to its matched gDNA with 5% variant alleles as the cutoff for mutation calls. We applied Kaplan-Meier to correlate the genomic alterations with overall survival (OS) and progression-free survival (PFS). Results We observed widespread somatic copy-number alterations and mutations, including amplification of MYC at 8q24, FGF10 at 5p13, SOX2 at 3q26 and FGFR1 at 8p12, as well as deletion of TP53 at 17p13, RASSF1 at 3p21.3, RB1 at 13q14.2, FHIT at 3p14, and PTEN at 10q23. The most frequent mutations were genes involved in chromatin regulation (KMT2D, ARID1A, SETBP1 and PBRM1), PI3K/MTOR pathway(MTOR,PIK13G), Notch1 signalling pathway (NOTCH1), and DNA repair related gene ATRX. Kaplan-Meier analysis revealed poor OS and PFS in patients with somatic mutations in gene SETBP1 (P = 0.0061/0.0264, HR = 4.785/3.841, 95% CI = 2.014–28.25/1.286–16.58) and PBRM1 (P = 0.0276/0.0286, HR = 3.532/3.506, 95% CI = 1.275 to 25.34/1.26–24.87). Poor OS was also associated with somatic mutations in ATRX (P = 0.0099, HR = 4.024, 95% CI = 1.926–42.95), EP300 (P = 0.025/0.0622, HR = 3.382/2.891, 95% CI = 1.448–27.76/1.013-17.29), while poor PFS was associated with ATM mutation (P = 0.0038, HR = 4.604, 95% CI = 2.211–40.93). The mutation index produced by summing up the number of mutations in the five genes was significantly associated with the poor OS/PFS (P = 0.0185/0.0294) after adjusting the effect of the stage. Conclusions Our result supports blood plasma as a promising sample source for the genomic analysis in SCLC patients whose tumor tissues are scarcely available and demonstrates potential clinical utilities of cfDNA-based liquid biopsy for clinical management of this deadly disease.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.008
      Issue No: Vol. 120 (2018)
       
  • Prognostic stratification model for patients with stage I non-small cell
           lung cancer adenocarcinoma treated with surgical resection without
           adjuvant therapies using metabolic features measured on F-18 FDG PET and
           postoperative pathologic factors
    • Authors: Yeon-koo Kang; Yoo Sung Song; Sukki Cho; Sanghoon Jheon; Won Woo Lee; Kwhanmien Kim; Sang Eun Kim
      Pages: 1 - 6
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Yeon-koo Kang, Yoo Sung Song, Sukki Cho, Sanghoon Jheon, Won Woo Lee, Kwhanmien Kim, Sang Eun Kim
      Purpose In the management of non-small cell lung cancer (NSCLC), the prognostic stratification of stage I tumors without indication of adjuvant therapy, remains to be elucidated in order to better select patients who can benefit from additional therapies. We aimed to stratify the prognosis of patients with stage I NSCLC adenocarcinoma using clinicopathologic factors and F-18 FDG PET. Materials and methods We retrospectively enrolled 128 patients with stage I NSCLC without any high-risk factors, who underwent curative surgical resection without adjuvant therapies. Preoperative clinical and postoperative pathologic factors were evaluated by medical record review. Standardized uptake value corrected with lean body mass (SULmax) was measured on F-18 FDG PET. Among the factors, independent predictors for recurrence-free survival (RFS) were selected using univariate and stepwise multivariate survival analyses. A prognostic stratification model for RFS was designed using the selected factors. Results Tumors recurred in nineteen patients (14.8%). Among the investigated clinicopathologic and FDG PET factors, SULmax on PET and spread through air spaces (STAS) on pathologic review were determined to be independent prognostic factors for RFS. A prognostic model was designed using these two factors in the following manner: (1) Low-risk: SULmax ≤ 1.9 and no STAS, (2) intermediate-risk: neither low-risk nor high-risk, (3) high-risk: SULmax>1.9 and observed STAS. This model exhibited significant predictive power for RFS. Conclusion We showed that FDG uptake and STAS are significant prognostic markers in stage I NSCLC adenocarcinoma treated with surgical resection without adjuvant therapies.

      PubDate: 2018-03-08T01:07:14Z
      DOI: 10.1016/j.lungcan.2018.02.013
      Issue No: Vol. 119 (2018)
       
  • The burden of lung cancer in Latin-America and challenges in the access to
           genomic profiling, immunotherapy and targeted treatments
    • Authors: Luis E. Raez; Andrés F. Cardona; Edgardo S. Santos; Heath Catoe; Christian Rolfo; Gilberto Lopes; Carlos Barrios; Luis A. Mas; Carlos Vallejos; Zyanya Lucia Zatarain-Barrón; Christian Caglevic; Oscar Arrieta
      Pages: 7 - 13
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Luis E. Raez, Andrés F. Cardona, Edgardo S. Santos, Heath Catoe, Christian Rolfo, Gilberto Lopes, Carlos Barrios, Luis A. Mas, Carlos Vallejos, Zyanya Lucia Zatarain-Barrón, Christian Caglevic, Oscar Arrieta
      Lung cancer is a public health problem worldwide and Latin America (LATAM) cannot escape this reality. This malignant disease has not only a high prevalence in the region, but is also the main cause of cancer related deaths, and in other emerging countries, the incidence rates are still on the rise. Interestingly in most LATAM countries, lung cancer mortality has been decreasing in men but not in women, reflecting smoking patterns in countries such as Chile, Bolivia, and Brazil. Despite the fact that these issues are well known to government agencies, physicians and patients in the region, current efforts still fall behind those needed in order to face this problem of epidemic proportions. Tobacco control and smoking cessation are the most important interventions against lung cancer, but even with their optimal implementation (which is far from reality at this time) the number of cases in the foreseeable future would still be significant. Beyond tobacco control, advances in our understanding of the molecular component of lung cancer have resulted in new targeted therapies and immune check point inhibitors, which have improved clinical outcomes but at a considerably higher financial cost. LATAM has not widely and speedily adopted these strategies, including new technology and approved novel drugs, due to a number of facts, and therefore only a dismal proportion of LATAḾs patient population have benefited from these new advances. A keen focus on a heterogeneous education system for caregivers in lung cancer treatment would likely help standardize care and improve future potential gains from domestic research. In this review we discuss the challenges of treatment implementation, focusing on new technologies.

      PubDate: 2018-03-08T01:07:14Z
      DOI: 10.1016/j.lungcan.2018.02.014
      Issue No: Vol. 119 (2018)
       
  • Tumor associated macrophages support the growth of FGF9-induced lung
           adenocarcinoma by multiple mechanisms
    • Authors: Ahmed E. Hegab; Mari Ozaki; Shizuko Kagawa; Junko Hamamoto; Hiroyuki Yasuda; Katsuhiko Naoki; Kenzo Soejima; Yongjun Yin; Tomonari Kinoshita; Tomonori Yaguchi; Yutaka Kawakami; David M. Ornitz; Tomoko Betsuyaku
      Pages: 25 - 35
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Ahmed E. Hegab, Mari Ozaki, Shizuko Kagawa, Junko Hamamoto, Hiroyuki Yasuda, Katsuhiko Naoki, Kenzo Soejima, Yongjun Yin, Tomonari Kinoshita, Tomonori Yaguchi, Yutaka Kawakami, David M. Ornitz, Tomoko Betsuyaku
      Objectives Tumor-associated macrophages (TAMs) are known to promote tumorigenesis but the mechanism(s) remain elusive. We have developed a mouse model of lung cancer that is initiated through an inducible overexpression of fibroblast growth factor 9 (FGF9) in type-2 pneumocytes. Expression of FGF9 in adult lungs resulted in a rapid development of multiple adenocarcinoma-like tumor nodules, and is associated with an intense immunological reaction. The purpose of this study is to characterize the immune response to the FGF9-induced lung adenocarcinoma and to determine the contribution of TAMs to growth and survival of these tumors. Materials and methods We used flow cytometry, immunostaining, RT-PCR and in vitro culture system on various cell populations isolated from the FGF9-induced adenocarcinoma mouse lungs. Results Immunostaining demonstrated that the majority of the inflammatory cells recruited to FGF9-induced lung tumors were macrophages. These TAMs were enriched for the alternatively activated (M2) macrophage subtype. TAMs performed a significantly high immune suppressive function on T-cells and displayed high levels of arginase-1 expression and activity. The growth and colony forming potential of tumor cells was induced by co-culture with TAMs. Additionally, TAMs were shown to promote fibroblast proliferation and angiogenesis. TAMs had high expression of Tgf-β, Vegf, Fgf2, Fgf10, Fgfr2 and several matrix metalloproteinases; factors that play multiple roles in supporting tumor growth, immune protection, fibroblast activation and angiogenesis. Conclusion Our results provide evidence that the Fgf9-induced lung adenocarcinoma is associated with recruitment and activation of M2-biased TAMs, which provided multiple means of support to the tumor. This model represents an excellent means to further study the complex interactions between TAMs, their related chemokines, and progression of lung adenocarcinoma, and adds further evidence to support the importance of TAMs in tumorigenesis.

      PubDate: 2018-03-08T01:07:14Z
      DOI: 10.1016/j.lungcan.2018.02.015
      Issue No: Vol. 119 (2018)
       
  • Circulating Tumor DNA Testing in Advanced Non-Small Cell Lung Cancer
    • Authors: Everett J. Moding; Maximilian Diehn; Heather A. Wakelee
      Pages: 42 - 47
      Abstract: Publication date: Available online 2 March 2018
      Source:Lung Cancer
      Author(s): Everett J. Moding, Maximilian Diehn, Heather A. Wakelee
      Circulating tumor DNA (ctDNA) shed from cancer cells into the peripheral blood can be non-invasively collected and tested for the presence of tumor-specific mutations. Mutations identified in ctDNA can predict responses to targeted therapies and emerging evidence suggests that changes in ctDNA levels over time can be used to monitor response to therapy and detect disease recurrence. Given the emergence of targeted therapies in advanced non-small cell lung cancer (NSCLC), liquid biopsies utilizing ctDNA testing represent a powerful approach to genotype tumors and monitor for the development of resistance. Here, we review current and potential future clinical applications of ctDNA testing for patients with advanced NSCLC.

      PubDate: 2018-03-08T01:07:14Z
      DOI: 10.1016/j.lungcan.2018.02.019
      Issue No: Vol. 119 (2018)
       
  • Extraction of radiomic values from lung adenocarcinoma with near-pure
           subtypes in the International Association for the Study of Lung Cancer/the
           American Thoracic Society/the European Respiratory Society (IASLC/ATS/ERS)
           classification
    • Authors: Shun-Mao Yang; Li-Wei Chen; Hao-Jen Wang; Leng-Rong Chen; Kuo-Lung Lor; Yi-Chang Chen; Mong-Wei Lin; Min-Shu Hsieh; Jin-Shing Chen; Yeun-Chung Chang; Chung-Ming Chen
      Pages: 56 - 63
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Shun-Mao Yang, Li-Wei Chen, Hao-Jen Wang, Leng-Rong Chen, Kuo-Lung Lor, Yi-Chang Chen, Mong-Wei Lin, Min-Shu Hsieh, Jin-Shing Chen, Yeun-Chung Chang, Chung-Ming Chen
      Introduction Histological subtypes of lung adenocarcinomas (ADCs) classified by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) system have been investigated using radiomic approaches. However, the results have had limitations since <80% of invasive lung ADCs were heterogeneous, with two or more subtypes. To reduce the influence of heterogeneity during radiomic analysis, computed tomography (CT) images of lung ADCs with near-pure ADC subtypes were analyzed to extract representative radiomic features of different subtypes. Methods We enrolled 95 patients who underwent complete resection for lung ADC and a pathological diagnosis of a “near-pure” (≥70%) IASLC/ATS/ERS histological subtype. Conventional histogram/morphological features and complex radiomic features (grey-level-based statistical features and component variance-based features) of thin-cut CT data of tumor regions were analyzed. A prediction model based on leave-one-out cross-validation (LOOCV) and logistic regression (LR) was used to classify all five subtypes and three pathologic grades (lepidic, acinar/papillary, micropapillary/solid) of ADCs. The validation was performed using 36 near-pure ADCs in a later cohort. Results A total of 31 lepidic, 14 papillary, 32 acinar, 10 micropapillary, and 8 solid ADCs were analyzed. With 21 conventional and complex radiomic features, for 5 subtypes and 3 pathological grades, the prediction models achieved accuracy rates of 84.2% (80/95) and 91.6% (87/95), respectively, while accuracy was 71.6% and 85.3%, respectively, if only conventional features were used. The accuracy rate for the validation set (n = 36) was 83.3% (30/36) and 94.4% (34/36) in 5 subtypes and 3 pathological grades, respectively, using conventional and complex features, while it was 66.7% and 77.8% only using conventional features, respectively. Conclusion Lung ADC with high purity pathological subtypes demonstrates strong stratification of radiomic values, which provide basic information for accurate pathological subtyping and image parcellation of tumor sub-regions.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.004
      Issue No: Vol. 119 (2018)
       
  • Malignant cells from pleural fluids in malignant mesothelioma patients
           reveal novel mutations
    • Authors: Sophie Sneddon; Ian Dick; Y.C. Gary Lee; A.W. (Bill) Musk; Ann-Marie Patch; John V. Pearson; Nicola Waddell; Richard J.N. Allcock; Robert A. Holt; Bruce W.S. Robinson; Jenette Creaney
      Pages: 64 - 70
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Sophie Sneddon, Ian Dick, Y.C. Gary Lee, A.W. (Bill) Musk, Ann-Marie Patch, John V. Pearson, Nicola Waddell, Richard J.N. Allcock, Robert A. Holt, Bruce W.S. Robinson, Jenette Creaney
      Objectives Malignant mesothelioma (MM) is an asbestos related tumour affecting cells of serosal cavities. More than 70% of MM patients develop pleural effusions which contain tumour cells, representing a readily accessible source of malignant cells for genetic analysis. Although common somatic mutations and losses have been identified in solid MM tumours, the characterization of tumour cells within pleural effusions could provide novel insights but is little studied. Materials and methods DNA and RNA were extracted from cells from short term cultures of 27 human MM pleural effusion samples. Whole exome and transcriptome sequencing was performed using the Ion Torrent platform. Somatic mutations were identified using VarScan2 and SomaticSniper. Copy number alterations were identified using ExomeCNV in R. Significant copy number alterations were identified across all samples using GISTIC2.0. The association between tumour intrinsic properties and survival was analyzed using the Cox proportional hazards regression model. Results We identified BAP1, CDKN2A and NF2 alterations in the cells from MM pleural effusions at a higher frequency than what is typically seen in MM tumours from surgical series. The median mutation rate was 1.09 mutations/Mb. TRAF7 and LATS2 alterations were also identified at a high frequency (66% and 59% respectively). Novel regions of interest were identified, including alterations in FGFR3, and the regions 19p13.3, 8p23.1 and 1p36.32. Conclusion Short term cultures of tumour cells from MM pleural effusions offer an accessible alternative to surgical tumour biopsies in the study of MM genomics and reveal novel mutations of interest. Pleural effusion tumour cells provide an opportunity for the monitoring of tumour dynamics, treatment response and the clonal evolution of MM tumours.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.009
      Issue No: Vol. 119 (2018)
       
  • Correlation of tumor-related immunity with 18F-FDG-PET in pulmonary
           squamous-cell carcinoma
    • Authors: Norimitsu Kasahara; Kyoichi Kaira; Pinjie Bao; Tetsuya Higuchi; Yukiko Arisaka; Bilguun Erkhem-Ochir; Noriaki Sunaga; Yoichi Ohtaki; Toshiki Yajima; Takayuki Kosaka; Tetsunari Oyama; Takehiko Yokobori; Takayuki Asao; Masahiko Nishiyama; Yoshito Tsushima; Hiroyuki Kuwano; Kimihiro Shimizu; Akira Mogi
      Pages: 71 - 77
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Norimitsu Kasahara, Kyoichi Kaira, Pinjie Bao, Tetsuya Higuchi, Yukiko Arisaka, Bilguun Erkhem-Ochir, Noriaki Sunaga, Yoichi Ohtaki, Toshiki Yajima, Takayuki Kosaka, Tetsunari Oyama, Takehiko Yokobori, Takayuki Asao, Masahiko Nishiyama, Yoshito Tsushima, Hiroyuki Kuwano, Kimihiro Shimizu, Akira Mogi
      Objectives 2-Deoxy-2-[fluorine-18] fluoro-d-glucose with positron emission tomography (18F-FDG-PET) is a clinically useful tool for cancer evaluation. 18F-FDG accumulation in tumor cells is known to be correlated with the presence of glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1α (HIF-1α). Although anti-programmed death-1 (PD-1) antibody treatments have been approved, no suitable predictor of significant responders has been identified. Based on the existing information, we investigated the relationship between tumor immunity (including PD-L1) and 18F-FDG uptake in patients with surgically resected pulmonary squamous-cell carcinoma (SQC). Materials and methods This study included 167 patients (153 men and 14 women) with SQC who underwent 18F-FDG PET. Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1α, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and 18F-FDG uptake was analyzed. Student’s t-test, the χ2 test, non-parametric Spearman’s rank test and the Kaplan–Meier method were used to show associations between variables. Results The rate of positive PD-L1 expression was 79% (132/167), and PD-L1 expression was significantly associated with GLUT1 (P < 0.01), HIF-1α (P < 10−4), and CD8 (P < 1 × 10−3) expression. The SUVmax of 18F-FDG was significantly correlated with PD-L1 (P = 0.02) and GLUT1 (P < 0.01) expression. Multivariate analysis demonstrated that advanced stage, elevated PD-L1 expression, and elevated SUVmax were independent prognostic factors for predicting poor OS. Among patients with a high SUVmax, multivariate analysis confirmed that advanced stage and high PD-L1 expression were independent prognostic factors for poor OS; however, there was no significant difference among patients with a low SUVmax. Conclusion High SUVmax on 18F-FDG-PET is associated with PD-L1 expression but is an independent prognostic factor for OS in our population of surgically resected pulmonary squamous-cell carcinoma.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.001
      Issue No: Vol. 119 (2018)
       
  • Feasibility of endobronchial ultrasound transbronchial needle aspiration
           for massively parallel next-generation sequencing in thoracic cancer
           patients
    • Authors: Simon R. Turner; Darren Buonocore; Patrice Desmeules; Natasha Rekhtman; Snjezana Dogan; Oscar Lin; Maria E. Arcila; David R. Jones; James Huang
      Pages: 85 - 90
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Simon R. Turner, Darren Buonocore, Patrice Desmeules, Natasha Rekhtman, Snjezana Dogan, Oscar Lin, Maria E. Arcila, David R. Jones, James Huang
      Introduction Next-generation sequencing (NGS) allows for the identification of a growing number of therapeutic and prognostic molecular targets. However, NGS typically requires greater quantities of DNA than traditional molecular testing does. Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure used to sample central thoracic lesions, but it is not well established whether this technique provides sufficient material for NGS. Methods We performed a retrospective review of EBUS-TBNA at our institution (3/1/14-9/28/16). NGS was performed using a comprehensive hybrid-capture based assay (MSK-IMPACT) that detects >340 gene mutations. Samples found to be diagnostic for malignancy and for which MSK-IMPACT had been attempted were identified. Pathologic and clinical data were obtained from the medical record, and the results of MSK-IMPACT were examined. Results In total, 784 EBUS-TBNA procedures were performed during the study period. MSK-IMPACT was requested for 115 malignant samples and was successful for 99 (86.1%), identifying an average of 12.7 mutations at a mean coverage depth of 806X. NGS was performed on paraffin-embedded cell blocks in 93 cases (93.9%) and on cell-free DNA in needle rinse fluid in 6 cases. The success rate of the assay improved significantly from the first third of cases (76.3%), to 92.3% for the final one-third of cases (p < 0.05). Conclusions EBUS-TBNA reliably provided adequate tissue for hybrid capture NGS, and is a suitable option for comprehensive NGS testing in patients with thoracic malignancies.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.003
      Issue No: Vol. 119 (2018)
       
  • Physical behavior and associations with health outcomes in operable NSCLC
           patients: A prospective study
    • Authors: J.G. (Josien) Timmerman; M.G.H. (Marit) Dekker-van Weering; M.W.J.M. (Michel) Wouters; M.M. (Martijn) Stuiver; W. (Wanda) de Kanter; M.M.R. (Miriam) Vollenbroek-Hutten
      Pages: 91 - 98
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): J.G. (Josien) Timmerman, M.G.H. (Marit) Dekker-van Weering, M.W.J.M. (Michel) Wouters, M.M. (Martijn) Stuiver, W. (Wanda) de Kanter, M.M.R. (Miriam) Vollenbroek-Hutten
      Objectives Our objectives were to 1) characterize daily physical behavior of operable non-small cell lung cancer (NSCLC) patients, from preoperative to six months postoperative using accelerometry, and explore if physical behavior preoperative or one month postoperative is associated with better health outcomes at six months postoperative. Methods A prospective study with 23 patients (13 female) diagnosed with primary NSCLC and scheduled for curative lung resection was performed. Outcome measures were assessed two weeks preoperative, and one, three and six months postoperative, and included accelerometer-derived physical behavior measures and the following health outcomes: six minute walking distance (6MWD), questionnaires concerning health-related quality of life (HRQOL), fatigue and distress. Results On group average, physical behavior showed significant changes over time. Physical behavior worsened following surgery, but improved between one and six months postoperative, almost reaching preoperative levels. However, physical behavior showed high variability between patients in both amount as well as change over time. More time in moderate-to-vigorous physical activity in bouts of 10 min or longer in the first month postoperative was significantly associated with better 6MWD, HRQOL, distress, and fatigue at six months postoperative. Conclusion As expected, curative lung resection impacts physical behavior. Patients who were more active in the first month following surgery reported better health outcome six months postoperative. The large variability in activity patterns over time observed between patients, suggests that physical behavior ‘profiling’ through detailed monitoring of physical behavior could facilitate tailored goal setting in interventions that target change in physical behavior.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.006
      Issue No: Vol. 119 (2018)
       
  • Successful treatment with brigatinib in a patient with ALK-rearranged lung
           
    • Authors: Marta Doménech; Maria Jové; Samantha Aso; Mar Marín; Ernest Nadal
      Pages: 99 - 102
      Abstract: Publication date: Available online 17 March 2018
      Source:Lung Cancer
      Author(s): Marta Doménech, Maria Jové, Samantha Aso, Mar Marín, Ernest Nadal
      We present a 45-year-old patient diagnosed with anaplastic lymphoma kinase (ALK)-rearranged metastatic lung cancer who developed grade 4 interstitial lung disease (ILD) while on crizotinib treatment and was lately treated with brigatinib with no reappearance of ILD. To our knowledge, this is the first case report of successful treatment with brigatinib after crizotinib-induced ILD. Even though ILD secondary to brigatinib has been reported in clinical trials, no pulmonary toxicity has been seen in our patient, suggesting no crosslink lung toxicity between crizotinib and brigatinib.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.014
      Issue No: Vol. 119 (2018)
       
  • Severe adverse events impact overall survival and costs in elderly
           patients with advanced non-small cell lung cancer on second-line therapy
    • Authors: Hossein Borghaei; Yeun Mi Yim; Annie Guerin; Irina Pivneva; Sherry Shi; Mayank Gandhi; Raluca Ionescu-Ittu
      Pages: 112 - 119
      Abstract: Publication date: May 2018
      Source:Lung Cancer, Volume 119
      Author(s): Hossein Borghaei, Yeun Mi Yim, Annie Guerin, Irina Pivneva, Sherry Shi, Mayank Gandhi, Raluca Ionescu-Ittu
      Objectives Elderly patients with advanced non-small lung cancer (aNSCLC) represent a high-risk patient population due to disease burden, comorbidities, and performance status, particularly after progressing on first-line therapy. Among elderly patients who receive second-line therapy, treatment related toxicities can have substantial impact on both clinical and economic outcomes. This study assessed the impact of severe adverse events (AEs) during second-line therapy on overall survival (OS) and all-cause heathcare costs in elderly with aNSCLC. Materials and methods Patients with aNSCLC aged ≥65 years who initiated second-line chemotherapy/targeted therapy were identified in the SEER-Medicare database (2007–2011). Fifty-seven AEs were identified by literature review and consultation with two oncologists. Severe AEs were defined as AEs that required a hospitalization and were operationalized based on AE diagnosis(es) recorded during hospitalizations. OS post-second-line initiation and healthcare costs during second-line were compared between patients with and without severe AEs. Results Among 3967 patients initiating second-line therapy, 1624 (41%) had ≥1 severe AE, where hypertension (26%), anemia (24%), and pneumonia (23%) were most commonly reported. Patients with and without severe AEs had similar demographic and cancer characteristics at diagnosis and similar second-line treatment regimens, but patients with severe AEs had more comorbidities at second-line initiation. Median OS was lower in patients with versus without severe AEs (6 vs. 11 months). After multivariate adjustment, hazard of death was more than twice higher in patients with versus without severe AEs (adjusted hazard ratio [HR] 2.31, 95% CI 2.16–2.47). Healthcare costs were more than twice higher in patients with versus without severe AEs ($16,135 vs. $7559 per-patient-per-month). Conclusion Severe AEs among elderly patients with aNSCLC treated with second-line chemotherapy/targeted therapy were found to be associated with decreased OS and increased healthcare costs. Results suggest a potential link between severe AEs in second-line treated aNSCLC elderly and patient survival and economic burden to the healthcare system.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.02.011
      Issue No: Vol. 119 (2018)
       
  • Phase II trial of preoperative pemetrexed plus carboplatin in patients
           with stage IB-III nonsquamous non-small cell lung cancer (NSCLC)
    • Authors: John D. Hainsworth; David M. Waterhouse; Kent C. Shih; Ralph V. Boccia; Victor M. Priego; Michael J. McCleod; Fred J. Kudrik; Reed Brian Mitchell; Howard A. Burris; F. Anthony Greco; David R. Spigel
      Pages: 6 - 12
      Abstract: Publication date: April 2018
      Source:Lung Cancer, Volume 118
      Author(s): John D. Hainsworth, David M. Waterhouse, Kent C. Shih, Ralph V. Boccia, Victor M. Priego, Michael J. McCleod, Fred J. Kudrik, Reed Brian Mitchell, Howard A. Burris, F. Anthony Greco, David R. Spigel
      Objectives The combination of pemetrexed and carboplatin is a standard first-line treatment for patients with advanced NSCLC. In this pilot phase II trial, we evaluated the feasibility of using pemetrexed and carboplatin as neoadjuvant therapy, prior to definitive surgical resection, for patients with localized NSCLC. Patients and methods Patients with potentially resectable, previously untreated, clinical stage IB-III, nonsquamous NSCLC were eligible for this trial. All patients received 4 cycles of pemetrexed (500 mg/m2) and carboplatin (AUC 6.0) administered at 21 day intervals. Three to 6 weeks after completion of chemotherapy, definitive surgical resection was attempted. The primary endpoint of this trial was the 3-year survival rate. Results Forty-six patients began protocol treatment, and 40 completed 4 courses of pemetrexed/carboplatin. Surgical resection was performed in 27 patients (59%); all had pathologic partial responses. The estimated 3-year survival rate for the entire group was 46%. Toxicity of neoadjuvant therapy was consistent with toxicity previously reported with pemetrexed/carboplatin. Conclusions Administration of 4 courses of pemetrexed/carboplatin was feasible. The efficacy was similar to neoadjuvant regimens previously investigated. A significant number of patients 19 of 46 (41%) in this trial did not have surgical resection after neoadjuvant therapy. Further investigation of the role of neoadjuvant pemetrexed/carboplatin requires a larger, randomized clinical trial.

      PubDate: 2018-02-05T16:58:01Z
      DOI: 10.1016/j.lungcan.2018.01.009
      Issue No: Vol. 118 (2018)
       
  • Is heterogeneity in stage 3 non-small cell lung cancer obscuring the
           potential benefits of dose-escalated concurrent chemo-radiotherapy in
           clinical trials'
    • Authors: Andrew Hudson; Clara Chan; David Woolf; Alan McWilliam; Crispin Hiley; James O’Connor; Neil Bayman; Fiona Blackhall; Corinne Faivre-Finn
      Pages: 139 - 147
      Abstract: Publication date: April 2018
      Source:Lung Cancer, Volume 118
      Author(s): Andrew Hudson, Clara Chan, David Woolf, Alan McWilliam, Crispin Hiley, James O’Connor, Neil Bayman, Fiona Blackhall, Corinne Faivre-Finn
      The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.02.006
      Issue No: Vol. 118 (2018)
       
  • Optimal surgical approach to thymic malignancies: New trends challenging
           old dogmas
    • Authors: Enrico Ruffini; Pier Luigi Filosso; Francesco Guerrera; Paolo Lausi; Paraskevas Lyberis; Alberto Oliaro
      Pages: 161 - 170
      Abstract: Publication date: April 2018
      Source:Lung Cancer, Volume 118
      Author(s): Enrico Ruffini, Pier Luigi Filosso, Francesco Guerrera, Paolo Lausi, Paraskevas Lyberis, Alberto Oliaro
      Until recently, the surgical approach to thymic tumors has remained basically unchanged. The collaborative effort led by ITMIG with the collaboration of regional and society-based interest groups (ESTS, JART) produced an enthusiastic surge of interest in testing the new technological advances in thoracic surgery and many historical dogmas in thymic surgery have been questioned and challenged. The present review addresses the new trends in the optimal surgical management of thymic tumors based on the review of the current literature. 1. Minimally-invasive techniques (MIT) including video-assisted thoracic surgery (VATS) and robotic-assisted thoracic Surgery (RATS) are now to be considered the standard of care in early-stage thymic tumors. MIT are no inferior to open approaches in terms of postoperative complications, loco-regional recurrence rates and survival. MIT are associated with a shorter length of stay, reduced intraoperative blood loss and better cosmetic results. 2. The adoption of the ITMIG/IASLC TNM staging system for thymic tumors requires a paradigm shift among thoracic surgeons to include regional lymphadenectomy according to the IASLC/ITMIG nodal map in the surgical management of thymic tumors. 3. A limited thymectomy instead of total thymectomy along with the removal of the thymic tumor in nonmyasthenic Stage I–II tumors has been proposed by some authors, although the results are not uniform. Until more mature data is available, adherence to the current guidelines recommending total thymectomy in addition to thymomectomy is always indicated. 4. In locally-advanced Stage IVa patients with pleural involvement, major pleural resections, including pleurectomy/decortication or extrapleural pneumonectomy are indicated, provided a complete resection of the pleural deposits is anticipated, usually in a multidisciplinary setting, with excellent long-term results. The incorporation of these new concepts and techniques in the surgical armamentarium of the thoracic surgeons dealing with thymic malignancies will certainly be of help in the optimal management of these patients.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.01.025
      Issue No: Vol. 118 (2018)
       
  • The novel microRNA smR-164 regulates cell proliferation and apoptosis in
           human lung cancer by targeting XIAP
    • Authors: 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
      Abstract: Publication date: Available online 13 April 2018
      Source:Lung Cancer
      Author(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
      Objectives MicroRNAs 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 XIAP Material and methods Novel 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. Results Expression 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. Conclusion Taken 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.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.011
       
  • Building the case for comprehensive hospital-based tobacco addiction
           services: Applying the Ottawa Model to the City of Manchester
    • Authors: Matthew Evison; Sanjay Agrawal; Matthew Conroy; Neil Bendel; Navin Sewak; Andrew Fitzgibbon; Lorna McWilliams; Julie Jerram; David Regan; David Shackley; Richard Preece; Louise Brown; Phil Barber
      Abstract: Publication date: Available online 13 April 2018
      Source:Lung Cancer
      Author(s): Matthew Evison, Sanjay Agrawal, Matthew Conroy, Neil Bendel, Navin Sewak, Andrew Fitzgibbon, Lorna McWilliams, Julie Jerram, David Regan, David Shackley, Richard Preece, Louise Brown, Phil Barber


      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.010
       
  • Predicting Outcomes in Patients with Advanced Non-Small Cell Lung Cancer
           Enrolled in Early Phase Immunotherapy Trials
    • Authors: Hossein Maymani; Kenneth Hess; Roman Groisberg; David S. Hong; Aung Naing; Sarina Piha-Paul; Filip Janku; Siqing Fu; Apostolia M. Tsimberidou; Shubham Pant; Daniel Karp; Shuang Liu; Ming Sun; John Heymach; George Simon; Funda Meric-Bernstam; Vivek Subbiah
      Abstract: Publication date: Available online 11 April 2018
      Source:Lung Cancer
      Author(s): Hossein Maymani, Kenneth Hess, Roman Groisberg, David S. Hong, Aung Naing, Sarina Piha-Paul, Filip Janku, Siqing Fu, Apostolia M. Tsimberidou, Shubham Pant, Daniel Karp, Shuang Liu, Ming Sun, John Heymach, George Simon, Funda Meric-Bernstam, Vivek Subbiah
      Objectives Immunotherapy (IO) has altered the non-small cell lung cancer (NSCLC) therapeutic landscape. However, the majority of patients do not respond to immune-checkpoint blockade, and subsequently either receive further chemotherapy or are referred for clinical trials. Here we examined the outcomes and predictors of response to IO in early phase clinical trials. Materials and methods We analyzed the records of 74 patients with metastatic NSCLC that were enrolled on phase 1 IO trials within MD Anderson Cancer Center from 1/2010 to 7/2017. Results The median age was 68, with a median follow-up of 12.3 months. The median lines of prior therapy was three. There were 53 patients who did not receive any IO as a prior line of treatment with a mOS of 8.2 months and mPFS of 3.4 months. There were 21 patients who progressed on a prior IO agent and subsequently went on an IO study with a mOS of 10.5 months and mPFS of 4.3 months, which was similar to patients who did not receive IO HR 0.81 (P = 0.51) and PFS HR 0.85 (P = 0.59). Royal Marsden Hospital (RMH) prognostic score >1 was predictive of decreased OS HR 3.59 (P = 0.014) although PFS was not statistically different. MDACC prognostic score was predictive of both OS HR 3.39 (P = 0.0002) and PFS HR 1.9 (P = 0.030). ANC/ALC ratio (NLR) of >6 was predictive of decreased survival mOS 3.2 months compared to NLR <6 mOS 11 months; HR 3.0 (P = 0.0023). Conclusions In our heavily pretreated patient population with NSCLC, early phase clinical trials with IO demonstrated similar outcomes to those seen in larger clinical studies that also used immune checkpoint inhibitors. The addition of NLR to RMH and MDACC prognostic scores can identify patients with poor overall outcomes treated with early phase IO studies.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.03.020
       
  • Case Report: Osimertinib achieved remarkable and sustained disease control
           in an advanced non-small-cell lung cancer harboring EGFR H773L/V774M
           mutation complex
    • Authors: Minglei Yang; Xiaoling Tong; Xiang Xu; Enkuo Zheng; Junjun Ni; Junfang Li; Junrong Yan; Yang W. Shao; Guofang Zhao
      Abstract: Publication date: Available online 5 April 2018
      Source:Lung Cancer
      Author(s): Minglei Yang, Xiaoling Tong, Xiang Xu, Enkuo Zheng, Junjun Ni, Junfang Li, Junrong Yan, Yang W. Shao, Guofang Zhao
      Missense mutations in EGFR exon 20 are rare in non-small-cell lung cancer (NSCLC), and mostly insensitive to the first generation tyrosine kinase inhibitors (TKIs) of EGFR. However, their responses to the third generation TKI are unclear. Here, we reported a patient with advanced NSCLC harboring a rare EGFR H773L/V774M mutation complex. Although he was irresponsive to the first generation TKI gefitinib, he demonstrated sustained disease control to osimertinib, suggesting that this complex is an activating mutation of EGFR and can be suppressed by osimertinib. The follow-up genetic profiling revealed multiple acquired new mutations that might be related to his resistance to osimertinib. This finding would provide valuable experience for future treatment of the same mutations.

      PubDate: 2018-04-15T04:26:45Z
      DOI: 10.1016/j.lungcan.2018.04.006
       
  • Corrigendum to “Inhibition of protein phosphatase 5 suppresses non-small
           cell lung cancer through AMP-activated kinase activation” [Lung Cancer
           112, (October) (2017) 81–89]
    • Authors: Feng-Shu Hsieh; Man-Hsin Hung; Cheng-Yi Wang; Yen-Lin Chen; Yung-Jen Hsiao; Ming-Hsien Tsai; Jia-Rong Li; Li-Ju Chen; Chih-Ting Shih; Tzu-I Chao; Kuen-Feng Chen
      Abstract: Publication date: Available online 19 March 2018
      Source:Lung Cancer
      Author(s): Feng-Shu Hsieh, Man-Hsin Hung, Cheng-Yi Wang, Yen-Lin Chen, Yung-Jen Hsiao, Ming-Hsien Tsai, Jia-Rong Li, Li-Ju Chen, Chih-Ting Shih, Tzu-I Chao, Kuen-Feng Chen


      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.012
       
  • The Combination of the Blood Based Tumor Biomarkers Cytokeratin 19
           Fragments (CYFRA 21-1) and Carcinoembryonic Antigen (CEA) as a Potential
           Predictor of Benefit from Adjuvant Chemotherapy in Early Stage Squamous
           Cell Carcinoma of the Lung (SCC)
    • Authors: Thomas Muley; Vinzent Rolny; Ying He; Birgit Wehnl; Achim Escherich; Arne Warth; Christa Stolp; Marc A. Schneider; Hendrik Dienemann; Michael Meister; Felix J. Herth; Farshid Dayyani
      Abstract: Publication date: Available online 17 March 2018
      Source:Lung Cancer
      Author(s): Thomas Muley, Vinzent Rolny, Ying He, Birgit Wehnl, Achim Escherich, Arne Warth, Christa Stolp, Marc A. Schneider, Hendrik Dienemann, Michael Meister, Felix J. Herth, Farshid Dayyani
      Objectives To determine whether the tumor biomarkers cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), which are prognostic in early-stage non-small cell lung cancer (NSCLC), can predict which patients benefit from adjuvant chemotherapy (CTx). Materials and Methods Serum samples were collected preoperatively from patients with NSCLC who underwent resection. Samples were retrospectively analyzed for CYFRA 21-1 and CEA via electrochemiluminescence immunoassay. Recurrence-free survival (RFS) was compared for patients who received adjuvant CTx versus surgery alone, stratified based on the following prognostic classifications: (1) tumor stage (pT1‐2/N0 [stage I] or pT3/N0 or pT1‐2/N1 [stage II]), (2) biomarker-based risk score, (3) clinical characteristics. Absolute 2-year RFS rates were calculated via Kaplan-Meier estimations; statistical significance level: 0.05. Results 227 patients were included (stage I: 69%; male: 67%; median age 65 years); 70 received adjuvant CTx. Median duration of sample collection was 58.8 months. All high-risk patients (by all three prognostic classifications) who received adjuvant CTx had a longer RFS versus those who received surgery alone. In patients with squamous cell carcinoma (SCC) classified as high risk by all three prognostic classifications, there was a benefit from adjuvant CTx versus surgery alone (tumor stage hazard ratio [HR] 4.9, p = 0.004; biomarker levels HR 9.4, p = 0.002; clinical characteristics HR 9.0, p = 0.003). None of the prognostic classifications were able to predict a benefit from adjuvant CTx in patients with adenocarcinoma. Conclusion Baseline CYFRA 21-1 and CEA levels may provide further information to help clinicians decide which patients with SCC should receive adjuvant CTx. Further evaluation of these biomarkers is warranted.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.015
       
  • A phase I study of nintedanib combined with cisplatin/gemcitabine as
           first-line therapy for advanced squamous non-small cell lung cancer
           (LUME-Lung 3)
    • Authors: Martin Forster; Allan Hackshaw; Tommaso De Pas; Manuel Cobo; Pilar Garrido; Yvonne Summers; Anne-Marie C. Dingemans; Michael Flynn; David Schnell; Ute von Wangenheim; Arsene-Bienvenu Loembé; Rolf Kaiser; Siow Ming Lee
      Abstract: Publication date: Available online 9 March 2018
      Source:Lung Cancer
      Author(s): Martin Forster, Allan Hackshaw, Tommaso De Pas, Manuel Cobo, Pilar Garrido, Yvonne Summers, Anne-Marie C. Dingemans, Michael Flynn, David Schnell, Ute von Wangenheim, Arsene-Bienvenu Loembé, Rolf Kaiser, Siow Ming Lee
      Background There are limited treatment options for squamous non-small cell lung cancer (sqNSCLC) and prognosis remains poor. The safety and pharmacokinetics (PK) of nintedanib, a triple angiokinase inhibitor, plus cisplatin/gemcitabine as first-line treatment for advanced sqNSCLC patients, were evaluated. Materials and Methods A phase I, dose-escalation study administering drugs in a 21-day cycle: cisplatin (75 mg/m2, Day 1), gemcitabine (1250 mg/m2, Days 1 and 8) and nintedanib (Days 2–7, 9–21) were given for 4–6 cycles, followed by monotherapy until disease progression or adverse events (AEs). Two nintedanib doses were tested, 150 mg twice daily (bid) and 200 mg bid, to determine maximum tolerated dose (MTD) based on occurrence of dose-limiting toxicities (DLTs) during Cycle 1. DLTs were primarily defined as drug-related non-hematologic (grade ≥3) or hematologic (grade 4) AEs. Results Sixteen patients were treated with nintedanib; n = 4 for 150 mg bid, n = 12 for 200 mg bid. No DLTs were observed in Cycle 1; therefore, the MTD was 200 mg bid. In subsequent cycles, two patients had DLTs: renal failure and reduced blood magnesium levels. The most common AEs were gastrointestinal. Three patients discontinued last study medication due to AEs and one had a nintedanib dose reduction. No relevant PK interactions were observed. Five patients had partial responses (31.3%) and eight had stable disease (50.0%); disease control rate was 81.3%. There were three long-term survivors (17–35 months). Conclusions The safety profile of nintedanib 200 mg bid plus cisplatin/gemcitabine was manageable, with AEs consistent with previous observations. PK data demonstrated no interaction, and preliminary antitumor activity was observed.

      PubDate: 2018-03-20T02:00:39Z
      DOI: 10.1016/j.lungcan.2018.03.007
       
  • Large cell neuroendocrine lung carcinoma induces peripheral T-cell
           repertoire alterations with predictive and prognostic significance
    • Authors: Petros Christopoulos; Marc A. Schneider; Farastuk Bozorgmehr; Jonas Kuon; Walburga Engel-Riedel; Jens Kollmeier; Volker Baum; Thomas Muley; Philipp A. Schnabel; Helge Bischoff; Christian Grohé; Monika Serke; Michael Thomas; Paul Fisch; Michael Meister
      Abstract: Publication date: Available online 6 March 2018
      Source:Lung Cancer
      Author(s): Petros Christopoulos, Marc A. Schneider, Farastuk Bozorgmehr, Jonas Kuon, Walburga Engel-Riedel, Jens Kollmeier, Volker Baum, Thomas Muley, Philipp A. Schnabel, Helge Bischoff, Christian Grohé, Monika Serke, Michael Thomas, Paul Fisch, Michael Meister
      Objectives This study was performed to evaluate for a potentially important role of T cells in the pathophysiology and treatment sensitivity of large cell neuroendocrine lung carcinoma (LCNEC), an orphan disease with poor prognosis and scarce data to guide novel therapeutic strategies. Materials and Methods We performed T-cell receptor (TCR) β-chain spectratyping on blood samples of patients treated within the CRAD001KDE37 trial (n = 35) using age-matched current or former (n = 11) and never smokers (n = 10) as controls. The data were analyzed in conjunction with the complete blood counts of the probands as well as the data about response to treatment and overall survival in the clinical trial. Results and Conclusion Untreated stage IV LCNEC patients had significant T-cell repertoire alterations (p < 0.001) compared to age-matched smokers. These changes correlated positively with blood lymphocyte counts (r = 0.49, p < 0.01), suggesting antigen-induced T-cell proliferation as the causative mechanism. At the same time, LCNEC patients showed mild lymphopenia (1.54 vs. 2.51/nl in median, p < 0.01), which reveals a second, antigen-independent mechanism of systemic immune dysregulation. More pronounced T-cell repertoire alterations and higher blood lymphocyte counts at diagnosis were associated with a better treatment response by RECIST and with a longer overall survival (441 vs. 157 days in median, p = 0.019). A higher degree of T-cell repertoire normalization after 3 months of therapy also distinguished a patient group with more favourable prognosis (median overall survival 617 vs. 316 days, p = 0.036) independent of radiological response. Thus, LCNEC induces clinically relevant changes of the T-cell repertoire, which are measurable in the blood and could be exploited for prognostic, predictive and therapeutic purposes. Their pathogenesis appears to involve antigen-induced oligoclonal T-cell expansions superimposed on TCR-independent lymphopenia.

      PubDate: 2018-03-08T01:07:14Z
      DOI: 10.1016/j.lungcan.2018.03.002
       
  • Nivolumab-induced severe pancytopenia in a patient with lung
           adenocarcinoma
    • Authors: Kentaro Tokumo; Takeshi Masuda; Takahiko Miyama; Shinichiro Miura; Kakuhiro Yamaguchi; Shinjiro Sakamoto; Yasushi Horimasu; Taku Nakashima; Shintaro Miyamoto; Takashi Yoshida; Hiroshi Iwamoto; Kazunori Fujitaka; Hironobu Hamada; Noboru Hattori
      Abstract: Publication date: Available online 2 March 2018
      Source:Lung Cancer
      Author(s): Kentaro Tokumo, Takeshi Masuda, Takahiko Miyama, Shinichiro Miura, Kakuhiro Yamaguchi, Shinjiro Sakamoto, Yasushi Horimasu, Taku Nakashima, Shintaro Miyamoto, Takashi Yoshida, Hiroshi Iwamoto, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori
      Severe leukopenia, thrombocytopenia, and bi-cytopenia due to nivolumab have been reported. In this report, we present the first case of nivolumab-induced severe pancytopenia in a patient with lung adenocarcinoma. A 56-year-old Japanese man with lung adenocarcinoma received nivolumab therapy as second-line treatment. After 3 cycles of this therapy, although computed tomography (CT) showed a reduced tumor size, laboratory findings revealed pancytopenia and a bone marrow biopsy showed a severely hypoplastic marrow. The pancytopenia was diagnosed as an adverse effect of nivolumab; filgrastim (75 μg/day), steroid-pulse therapy (intravenous methylprednisolone: 500 mg/day), and subsequently intravenous prednisolone (50 mg/day) were administered. Furthermore, intravenous administration of immunoglobulins was also performed. However, these treatments were ineffective. He was further diagnosed with fungal pneumonia and a catheter-related bloodstream infection. Anti-bacterial chemotherapy was administered. Two months after hospitalization, the neutrophil count improved to 1000/μL, but multiple red blood cell and platelet transfusions were needed. Therefore, further chemotherapy for lung adenocarcinoma could not be initiated, and the patient died due to progression of lung cancer 118 days after the onset of pancytopenia. The possibility of severe pancytopenia as an immune-related adverse event should be considered as a mandatory prerequisite for nivolumab therapy.

      PubDate: 2018-03-08T01:07:14Z
      DOI: 10.1016/j.lungcan.2018.02.018
       
  • Challenges and Future Direction of Molecular Research in Air
           Pollution-Related Lung Cancers
    • Authors: M.S. Shahadin; N.S. Ab Mutalib; M.T. Latif; Greene M. Catherine; Hassan Tidi
      Abstract: Publication date: Available online 31 January 2018
      Source:Lung Cancer
      Author(s): M.S. Shahadin, N.S. Ab Mutalib, M.T. Latif, Greene M. Catherine, Hassan Tidi
      Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field.

      PubDate: 2018-02-05T16:58:01Z
      DOI: 10.1016/j.lungcan.2018.01.016
       
 
 
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