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Publisher: Oxford University Press   (Total: 370 journals)

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Showing 1 - 200 of 370 Journals sorted alphabetically
Acta Biochimica et Biophysica Sinica     Hybrid Journal   (Followers: 6, SJR: 0.881, h-index: 38)
Adaptation     Hybrid Journal   (Followers: 9, SJR: 0.111, h-index: 4)
Aesthetic Surgery J.     Hybrid Journal   (Followers: 6, SJR: 1.538, h-index: 35)
African Affairs     Hybrid Journal   (Followers: 60, SJR: 1.512, h-index: 46)
Age and Ageing     Hybrid Journal   (Followers: 86, SJR: 1.611, h-index: 107)
Alcohol and Alcoholism     Hybrid Journal   (Followers: 18, SJR: 0.935, h-index: 80)
American Entomologist     Full-text available via subscription   (Followers: 6)
American Historical Review     Hybrid Journal   (Followers: 147, SJR: 0.652, h-index: 43)
American J. of Agricultural Economics     Hybrid Journal   (Followers: 39, SJR: 1.441, h-index: 77)
American J. of Epidemiology     Hybrid Journal   (Followers: 174, SJR: 3.047, h-index: 201)
American J. of Hypertension     Hybrid Journal   (Followers: 25, SJR: 1.397, h-index: 111)
American J. of Jurisprudence     Hybrid Journal   (Followers: 18)
American J. of Legal History     Full-text available via subscription   (Followers: 7, SJR: 0.151, h-index: 7)
American Law and Economics Review     Hybrid Journal   (Followers: 27, SJR: 0.824, h-index: 23)
American Literary History     Hybrid Journal   (Followers: 13, SJR: 0.185, h-index: 22)
Analysis     Hybrid Journal   (Followers: 23)
Annals of Botany     Hybrid Journal   (Followers: 35, SJR: 1.912, h-index: 124)
Annals of Occupational Hygiene     Hybrid Journal   (Followers: 28, SJR: 0.837, h-index: 57)
Annals of Oncology     Hybrid Journal   (Followers: 48, SJR: 4.362, h-index: 173)
Annals of the Entomological Society of America     Full-text available via subscription   (Followers: 8, SJR: 0.642, h-index: 53)
Annals of Work Exposures and Health     Hybrid Journal  
AoB Plants     Open Access   (Followers: 4, SJR: 0.78, h-index: 10)
Applied Economic Perspectives and Policy     Hybrid Journal   (Followers: 19, SJR: 0.884, h-index: 31)
Applied Linguistics     Hybrid Journal   (Followers: 53, SJR: 1.749, h-index: 63)
Applied Mathematics Research eXpress     Hybrid Journal   (Followers: 1, SJR: 0.779, h-index: 11)
Arbitration Intl.     Full-text available via subscription   (Followers: 20)
Arbitration Law Reports and Review     Hybrid Journal   (Followers: 13)
Archives of Clinical Neuropsychology     Hybrid Journal   (Followers: 27, SJR: 0.96, h-index: 71)
Aristotelian Society Supplementary Volume     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 20)
Arthropod Management Tests     Hybrid Journal   (Followers: 2)
Astronomy & Geophysics     Hybrid Journal   (Followers: 45, SJR: 0.144, h-index: 15)
Behavioral Ecology     Hybrid Journal   (Followers: 51, SJR: 1.698, h-index: 92)
Bioinformatics     Hybrid Journal   (Followers: 296, SJR: 4.643, h-index: 271)
Biology Methods and Protocols     Hybrid Journal  
Biology of Reproduction     Full-text available via subscription   (Followers: 9, SJR: 1.646, h-index: 149)
Biometrika     Hybrid Journal   (Followers: 20, SJR: 2.801, h-index: 90)
BioScience     Hybrid Journal   (Followers: 30, SJR: 2.374, h-index: 154)
Bioscience Horizons : The National Undergraduate Research J.     Open Access   (Followers: 1, SJR: 0.213, h-index: 9)
Biostatistics     Hybrid Journal   (Followers: 16, SJR: 1.955, h-index: 55)
BJA : British J. of Anaesthesia     Hybrid Journal   (Followers: 160, SJR: 2.314, h-index: 133)
BJA Education     Hybrid Journal   (Followers: 65, SJR: 0.272, h-index: 20)
Brain     Hybrid Journal   (Followers: 63, SJR: 6.097, h-index: 264)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 46, SJR: 4.086, h-index: 73)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 50)
British J. for the Philosophy of Science     Hybrid Journal   (Followers: 35, SJR: 1.267, h-index: 38)
British J. of Aesthetics     Hybrid Journal   (Followers: 27, SJR: 0.217, h-index: 18)
British J. of Criminology     Hybrid Journal   (Followers: 564, SJR: 1.373, h-index: 62)
British J. of Social Work     Hybrid Journal   (Followers: 84, SJR: 0.771, h-index: 53)
British Medical Bulletin     Hybrid Journal   (Followers: 7, SJR: 1.391, h-index: 84)
British Yearbook of Intl. Law     Hybrid Journal   (Followers: 29)
Bulletin of the London Mathematical Society     Hybrid Journal   (Followers: 3, SJR: 1.474, h-index: 31)
Cambridge J. of Economics     Hybrid Journal   (Followers: 59, SJR: 0.957, h-index: 59)
Cambridge J. of Regions, Economy and Society     Hybrid Journal   (Followers: 10, SJR: 1.067, h-index: 22)
Cambridge Quarterly     Hybrid Journal   (Followers: 11, SJR: 0.1, h-index: 7)
Capital Markets Law J.     Hybrid Journal   (Followers: 1)
Carcinogenesis     Hybrid Journal   (Followers: 2, SJR: 2.439, h-index: 167)
Cardiovascular Research     Hybrid Journal   (Followers: 12, SJR: 2.897, h-index: 175)
Cerebral Cortex     Hybrid Journal   (Followers: 44, SJR: 4.827, h-index: 192)
CESifo Economic Studies     Hybrid Journal   (Followers: 17, SJR: 0.501, h-index: 19)
Chemical Senses     Hybrid Journal   (Followers: 1, SJR: 1.436, h-index: 76)
Children and Schools     Hybrid Journal   (Followers: 6, SJR: 0.211, h-index: 18)
Chinese J. of Comparative Law     Hybrid Journal   (Followers: 3)
Chinese J. of Intl. Law     Hybrid Journal   (Followers: 21, SJR: 0.737, h-index: 11)
Chinese J. of Intl. Politics     Hybrid Journal   (Followers: 9, SJR: 1.238, h-index: 15)
Christian Bioethics: Non-Ecumenical Studies in Medical Morality     Hybrid Journal   (Followers: 11, SJR: 0.191, h-index: 8)
Classical Receptions J.     Hybrid Journal   (Followers: 24, SJR: 0.1, h-index: 3)
Clinical Infectious Diseases     Hybrid Journal   (Followers: 63, SJR: 4.742, h-index: 261)
Clinical Kidney J.     Open Access   (Followers: 4, SJR: 0.338, h-index: 19)
Community Development J.     Hybrid Journal   (Followers: 24, SJR: 0.47, h-index: 28)
Computer J.     Hybrid Journal   (Followers: 9, SJR: 0.371, h-index: 47)
Conservation Physiology     Open Access   (Followers: 2)
Contemporary Women's Writing     Hybrid Journal   (Followers: 11, SJR: 0.111, h-index: 3)
Contributions to Political Economy     Hybrid Journal   (Followers: 5, SJR: 0.313, h-index: 10)
Critical Values     Full-text available via subscription  
Current Legal Problems     Hybrid Journal   (Followers: 26)
Current Zoology     Full-text available via subscription   (Followers: 1, SJR: 0.999, h-index: 20)
Database : The J. of Biological Databases and Curation     Open Access   (Followers: 10, SJR: 1.068, h-index: 24)
Digital Scholarship in the Humanities     Hybrid Journal   (Followers: 13)
Diplomatic History     Hybrid Journal   (Followers: 19, SJR: 0.296, h-index: 22)
DNA Research     Open Access   (Followers: 5, SJR: 2.42, h-index: 77)
Dynamics and Statistics of the Climate System     Open Access   (Followers: 3)
Early Music     Hybrid Journal   (Followers: 15, SJR: 0.124, h-index: 11)
Economic Policy     Hybrid Journal   (Followers: 38, SJR: 2.052, h-index: 52)
ELT J.     Hybrid Journal   (Followers: 25, SJR: 1.26, h-index: 23)
English Historical Review     Hybrid Journal   (Followers: 55, SJR: 0.311, h-index: 10)
English: J. of the English Association     Hybrid Journal   (Followers: 13, SJR: 0.144, h-index: 3)
Environmental Entomology     Full-text available via subscription   (Followers: 11, SJR: 0.791, h-index: 66)
Environmental Epigenetics     Open Access   (Followers: 2)
Environmental History     Hybrid Journal   (Followers: 28, SJR: 0.197, h-index: 25)
EP-Europace     Hybrid Journal   (Followers: 2, SJR: 2.201, h-index: 71)
Epidemiologic Reviews     Hybrid Journal   (Followers: 9, SJR: 3.917, h-index: 81)
ESHRE Monographs     Hybrid Journal  
Essays in Criticism     Hybrid Journal   (Followers: 16, SJR: 0.1, h-index: 6)
European Heart J.     Hybrid Journal   (Followers: 52, SJR: 6.997, h-index: 227)
European Heart J. - Cardiovascular Imaging     Hybrid Journal   (Followers: 8, SJR: 2.044, h-index: 58)
European Heart J. - Cardiovascular Pharmacotherapy     Full-text available via subscription   (Followers: 1)
European Heart J. - Quality of Care and Clinical Outcomes     Hybrid Journal  
European Heart J. Supplements     Hybrid Journal   (Followers: 7, SJR: 0.152, h-index: 31)
European J. of Cardio-Thoracic Surgery     Hybrid Journal   (Followers: 8, SJR: 1.568, h-index: 104)
European J. of Intl. Law     Hybrid Journal   (Followers: 173, SJR: 0.722, h-index: 38)
European J. of Orthodontics     Hybrid Journal   (Followers: 4, SJR: 1.09, h-index: 60)
European J. of Public Health     Hybrid Journal   (Followers: 23, SJR: 1.284, h-index: 64)
European Review of Agricultural Economics     Hybrid Journal   (Followers: 11, SJR: 1.549, h-index: 42)
European Review of Economic History     Hybrid Journal   (Followers: 29, SJR: 0.628, h-index: 24)
European Sociological Review     Hybrid Journal   (Followers: 41, SJR: 2.061, h-index: 53)
Evolution, Medicine, and Public Health     Open Access   (Followers: 11)
Family Practice     Hybrid Journal   (Followers: 12, SJR: 1.048, h-index: 77)
Fems Microbiology Ecology     Hybrid Journal   (Followers: 9, SJR: 1.687, h-index: 115)
Fems Microbiology Letters     Hybrid Journal   (Followers: 21, SJR: 1.126, h-index: 118)
Fems Microbiology Reviews     Hybrid Journal   (Followers: 26, SJR: 7.587, h-index: 150)
Fems Yeast Research     Hybrid Journal   (Followers: 14, SJR: 1.213, h-index: 66)
Foreign Policy Analysis     Hybrid Journal   (Followers: 22, SJR: 0.859, h-index: 10)
Forestry: An Intl. J. of Forest Research     Hybrid Journal   (Followers: 15, SJR: 0.903, h-index: 44)
Forum for Modern Language Studies     Hybrid Journal   (Followers: 6, SJR: 0.108, h-index: 6)
French History     Hybrid Journal   (Followers: 32, SJR: 0.123, h-index: 10)
French Studies     Hybrid Journal   (Followers: 20, SJR: 0.119, h-index: 7)
French Studies Bulletin     Hybrid Journal   (Followers: 10, SJR: 0.102, h-index: 3)
Gastroenterology Report     Open Access   (Followers: 2)
Genome Biology and Evolution     Open Access   (Followers: 12, SJR: 3.22, h-index: 39)
Geophysical J. Intl.     Hybrid Journal   (Followers: 35, SJR: 1.839, h-index: 119)
German History     Hybrid Journal   (Followers: 27, SJR: 0.437, h-index: 13)
GigaScience     Open Access   (Followers: 3)
Global Summitry     Hybrid Journal  
Glycobiology     Hybrid Journal   (Followers: 14, SJR: 1.692, h-index: 101)
Health and Social Work     Hybrid Journal   (Followers: 52, SJR: 0.505, h-index: 40)
Health Education Research     Hybrid Journal   (Followers: 14, SJR: 0.814, h-index: 80)
Health Policy and Planning     Hybrid Journal   (Followers: 22, SJR: 1.628, h-index: 66)
Health Promotion Intl.     Hybrid Journal   (Followers: 21, SJR: 0.664, h-index: 60)
History Workshop J.     Hybrid Journal   (Followers: 29, SJR: 0.313, h-index: 20)
Holocaust and Genocide Studies     Hybrid Journal   (Followers: 26, SJR: 0.115, h-index: 13)
Human Molecular Genetics     Hybrid Journal   (Followers: 9, SJR: 4.288, h-index: 233)
Human Reproduction     Hybrid Journal   (Followers: 80, SJR: 2.271, h-index: 179)
Human Reproduction Update     Hybrid Journal   (Followers: 19, SJR: 4.678, h-index: 128)
Human Rights Law Review     Hybrid Journal   (Followers: 62, SJR: 0.7, h-index: 21)
ICES J. of Marine Science: J. du Conseil     Hybrid Journal   (Followers: 54, SJR: 1.233, h-index: 88)
ICSID Review     Hybrid Journal   (Followers: 11)
ILAR J.     Hybrid Journal   (Followers: 1, SJR: 1.099, h-index: 51)
IMA J. of Applied Mathematics     Hybrid Journal   (SJR: 0.329, h-index: 26)
IMA J. of Management Mathematics     Hybrid Journal   (Followers: 1, SJR: 0.351, h-index: 20)
IMA J. of Mathematical Control and Information     Hybrid Journal   (Followers: 2, SJR: 0.661, h-index: 28)
IMA J. of Numerical Analysis - advance access     Hybrid Journal   (SJR: 2.032, h-index: 44)
Industrial and Corporate Change     Hybrid Journal   (Followers: 9, SJR: 1.37, h-index: 81)
Industrial Law J.     Hybrid Journal   (Followers: 32, SJR: 0.184, h-index: 15)
Information and Inference     Free  
Integrative and Comparative Biology     Hybrid Journal   (Followers: 8, SJR: 1.911, h-index: 90)
Interacting with Computers     Hybrid Journal   (Followers: 11, SJR: 0.529, h-index: 59)
Interactive CardioVascular and Thoracic Surgery     Hybrid Journal   (Followers: 5, SJR: 0.743, h-index: 35)
Intl. Affairs     Hybrid Journal   (Followers: 52, SJR: 1.264, h-index: 53)
Intl. Data Privacy Law     Hybrid Journal   (Followers: 30)
Intl. Health     Hybrid Journal   (Followers: 5, SJR: 0.835, h-index: 15)
Intl. Immunology     Hybrid Journal   (Followers: 3, SJR: 1.613, h-index: 111)
Intl. J. for Quality in Health Care     Hybrid Journal   (Followers: 34, SJR: 1.593, h-index: 69)
Intl. J. of Constitutional Law     Hybrid Journal   (Followers: 61, SJR: 0.613, h-index: 19)
Intl. J. of Epidemiology     Hybrid Journal   (Followers: 158, SJR: 4.381, h-index: 145)
Intl. J. of Law and Information Technology     Hybrid Journal   (Followers: 4, SJR: 0.247, h-index: 8)
Intl. J. of Law, Policy and the Family     Hybrid Journal   (Followers: 29, SJR: 0.307, h-index: 15)
Intl. J. of Lexicography     Hybrid Journal   (Followers: 8, SJR: 0.404, h-index: 18)
Intl. J. of Low-Carbon Technologies     Open Access   (Followers: 1, SJR: 0.457, h-index: 12)
Intl. J. of Neuropsychopharmacology     Open Access   (Followers: 3, SJR: 1.69, h-index: 79)
Intl. J. of Public Opinion Research     Hybrid Journal   (Followers: 9, SJR: 0.906, h-index: 33)
Intl. J. of Refugee Law     Hybrid Journal   (Followers: 34, SJR: 0.231, h-index: 21)
Intl. J. of Transitional Justice     Hybrid Journal   (Followers: 13, SJR: 0.833, h-index: 12)
Intl. Mathematics Research Notices     Hybrid Journal   (Followers: 1, SJR: 2.052, h-index: 42)
Intl. Political Sociology     Hybrid Journal   (Followers: 32, SJR: 1.339, h-index: 19)
Intl. Relations of the Asia-Pacific     Hybrid Journal   (Followers: 18, SJR: 0.539, h-index: 17)
Intl. Studies Perspectives     Hybrid Journal   (Followers: 7, SJR: 0.998, h-index: 28)
Intl. Studies Quarterly     Hybrid Journal   (Followers: 40, SJR: 2.184, h-index: 68)
Intl. Studies Review     Hybrid Journal   (Followers: 18, SJR: 0.783, h-index: 38)
ISLE: Interdisciplinary Studies in Literature and Environment     Hybrid Journal   (Followers: 1, SJR: 0.155, h-index: 4)
ITNOW     Hybrid Journal   (Followers: 2, SJR: 0.102, h-index: 4)
J. of African Economies     Hybrid Journal   (Followers: 15, SJR: 0.647, h-index: 30)
J. of American History     Hybrid Journal   (Followers: 45, SJR: 0.286, h-index: 34)
J. of Analytical Toxicology     Hybrid Journal   (Followers: 14, SJR: 1.038, h-index: 60)
J. of Antimicrobial Chemotherapy     Hybrid Journal   (Followers: 14, SJR: 2.157, h-index: 149)
J. of Antitrust Enforcement     Hybrid Journal   (Followers: 1)
J. of Applied Poultry Research     Hybrid Journal   (Followers: 4, SJR: 0.563, h-index: 43)
J. of Biochemistry     Hybrid Journal   (Followers: 42, SJR: 1.341, h-index: 96)
J. of Chromatographic Science     Hybrid Journal   (Followers: 18, SJR: 0.448, h-index: 42)
J. of Church and State     Hybrid Journal   (Followers: 11, SJR: 0.167, h-index: 11)
J. of Competition Law and Economics     Hybrid Journal   (Followers: 36, SJR: 0.442, h-index: 16)
J. of Complex Networks     Hybrid Journal   (Followers: 1, SJR: 1.165, h-index: 5)
J. of Conflict and Security Law     Hybrid Journal   (Followers: 13, SJR: 0.196, h-index: 15)
J. of Consumer Research     Full-text available via subscription   (Followers: 43, SJR: 4.896, h-index: 121)
J. of Crohn's and Colitis     Hybrid Journal   (Followers: 10, SJR: 1.543, h-index: 37)
J. of Cybersecurity     Hybrid Journal   (Followers: 3)
J. of Deaf Studies and Deaf Education     Hybrid Journal   (Followers: 9, SJR: 0.69, h-index: 36)
J. of Design History     Hybrid Journal   (Followers: 18, SJR: 0.166, h-index: 14)
J. of Economic Entomology     Full-text available via subscription   (Followers: 6, SJR: 0.894, h-index: 76)
J. of Economic Geography     Hybrid Journal   (Followers: 24, SJR: 2.909, h-index: 69)
J. of Environmental Law     Hybrid Journal   (Followers: 24, SJR: 0.457, h-index: 20)
J. of European Competition Law & Practice     Hybrid Journal   (Followers: 20)
J. of Experimental Botany     Hybrid Journal   (Followers: 14, SJR: 2.798, h-index: 163)
J. of Financial Econometrics     Hybrid Journal   (Followers: 22, SJR: 1.314, h-index: 27)
J. of Global Security Studies     Hybrid Journal   (Followers: 4)
J. of Heredity     Hybrid Journal   (Followers: 4, SJR: 1.024, h-index: 76)
J. of Hindu Studies     Hybrid Journal   (Followers: 8, SJR: 0.186, h-index: 3)
J. of Hip Preservation Surgery     Open Access  
J. of Human Rights Practice     Hybrid Journal   (Followers: 20, SJR: 0.399, h-index: 10)
J. of Infectious Diseases     Hybrid Journal   (Followers: 41, SJR: 4, h-index: 209)
J. of Insect Science     Open Access   (Followers: 9, SJR: 0.388, h-index: 31)

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Journal Cover Annals of Oncology
  [SJR: 4.362]   [H-I: 173]   [48 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0923-7534 - ISSN (Online) 1569-8041
   Published by Oxford University Press Homepage  [370 journals]
  • LAG-3: another brake to release in breast cancer'
    • Authors: Kok M.
      Abstract: Upregulation of inhibitory immune checkpoints is critical for the control of T-cell activation in order to prevent autoimmunity and tissue damage. It is now clear that tumors can hijack immune checkpoint mechanisms as protection against the anticancer T-cell response. Blockade of the PD-1/PD-L1 immune checkpoint pathway has created a revolution in the treatment of melanoma, lung cancer and several other cancer types. In metastatic breast cancer patients, the response rates to PD-1 blocking antibodies are modest (4%–25%), but durable responses are seen [1–7]. Given that the majority of patients do not have clinical benefit, there is an urgent need to improve immunotherapy for breast cancer patients. This optimization is not a paved road and requires the integration of different parallel approaches, such as the search for predictive biomarkers [8], combination treatment with conventional therapies [9, 10], strategies to convert cold tumors into hot tumors [4, 11] and development of novel immunomodulatory compounds.
      PubDate: Mon, 30 Oct 2017 00:00:00 GMT
       
  • Incremental improvement in osteosarcoma chemotherapy'
    • Authors: Schuetze S.
      Abstract: Osteosarcoma is one of the first solid cancers for which a survival benefit from adjuvant chemotherapy was established [1, 2]. After decades of clinical research to improve on results obtained in the 1980s, the long-standing chemotherapy regimen of doxorubicin and cisplatin with or without methotrexate remains a standard treatment of osteosarcoma, resulting in a 5-year survival rate of more than 60% in patients with localized disease [3, 4]. In patients with metastatic osteosarcoma at diagnosis, or with distant disease relapse after treatment of localized disease, the long-term survival rate is <20%, and new therapies are much needed for this group of patients [5]. Neither the intensification of chemotherapy by adding ifosfamide and etoposide nor the use of muramyl tripeptide or traztuzumab has improved the survival of patients with metastatic osteosarcoma [6–8]. However, cure can be achieved in patients with metastatic osteosarcoma who undergo metastasectomy [5, 9].
      PubDate: Mon, 30 Oct 2017 00:00:00 GMT
       
  • Understanding personal risk of oropharyngeal cancer: risk-groups for
           oncogenic oral HPV infection and oropharyngeal cancer
    • Authors: D’Souza G; McNeel T, Fakhry C.
      Abstract: AbstractBackgroundIncidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing. There is interest in identifying healthy individuals most at risk for development of oropharyngeal cancer to inform screening strategies.Patients and methodsAll data are from 2009 to 2014, including 13 089 people ages 20–69 in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18) registries (representing ∼28% of the US population), and oropharyngeal cancer mortality from National Center for Health Statistics (NCHS). Primary study outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle sample, and (ii) incident oropharyngeal squamous cell cancer.ResultsOncogenic oral HPV DNA is detected in 3.5% of all adults age 20–69 years; however, the lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50–59 years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16 infection, yet only 0.7% will ‘ever’ develop oropharyngeal cancer in their lifetime. Oncogenic oral HPV prevalence was higher in men than women, and increased with number of lifetime oral sexual partners and tobacco use. Men who currently smoked and had ≥5 lifetime oral sexual partners had ‘elevated risk’ (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked and had 2–4 partners or did not smoke and had ≥5 partners) had ‘medium risk’ (7.3%). Regardless of what other risk factors participants had, oncogenic oral HPV prevalence was ‘low’ among those with only ≤1 lifetime oral sexual partner (women = 0.7% and men = 1.7%).ConclusionsScreening based upon oncogenic oral HPV detection would be challenging. Most groups have low oncogenic oral HPV prevalence. In addition to the large numbers of individuals who would need to be screened to identify prevalent oncogenic oral HPV, the lifetime risk of developing oropharyngeal caner among those with infection remains low.
      PubDate: Thu, 19 Oct 2017 00:00:00 GMT
       
  • Emerging treatment paradigms for brain metastasis in non-small-cell lung
           cancer: an overview of the current landscape and challenges ahead
    • Authors: Ulahannan D; Khalifa J, Faivre-Finn C, et al.
      Abstract: AbstractAdvances in the last decade in genomic profiling and the identification of druggable targets amenable to biological agents have transformed the management and survival of a subgroup of patients with brain metastasis in non-small-cell lung cancer. In parallel, clinicians have reevaluated the role of whole brain radiotherapy in selected patients with brain metastases to reduce neurocognitive toxicity. Continual progress in this understudied field is required: optimization of the sequence of schedules for therapies in patients with brain metastases of differing genomic profiles, focusing on new strategies to overcome mechanisms of biological resistance and increasing drug penetrability into the central nervous system. This review summarizes the field to date and possible treatment strategies based on current evidence.
      PubDate: Tue, 17 Oct 2017 00:00:00 GMT
       
  • Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an
           analysis of patients treated on the RICOVER-60 trial
    • Authors: Glass B; Dohm A, Truemper L, et al.
      Abstract: AbstractBackgroundThe prognosis of elderly patients with aggressive B-non-Hodgkin’s lymphoma after first lymphoma-related treatment failure (TF-L) is not well described.MethodsWe analysed patient characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial.ResultsTF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen.ConclusionMYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.
      PubDate: Fri, 06 Oct 2017 00:00:00 GMT
       
  • DPYD genotype-guided fluoropyrimidines dose: is it ready for prime
           time'
    • Authors: Páez D; Salazar R, Tabernero J.
      Abstract: For over 50 years, fluoropyrimidines have been the cornerstone of anticancer drugs for various types of solid cancers. Treatment with these drugs—5-fluorouracil (FU) and its oral prodrugs, capecitabine and tegafur—is generally well-tolerated, except in a small proportion of patients who develop severe and life-threatening early toxicity. This toxicity is mainly associated with a deficiency of the primary fluoropyrimidine detoxifying enzyme, dihydropryrimidine dehydrogenase (DPD) [1]. The drug labels of FU and capecitabine state DPD deficiency as a contraindication, but they give no warning for the 3%–8% of the population who are partially DPD deficient.
      PubDate: Thu, 05 Oct 2017 00:00:00 GMT
       
  • SELECT-2: a phase II, double-blind, randomized, placebo-controlled study
           to assess the efficacy of selumetinib plus docetaxel as a second-line
           treatment of patients with advanced or metastatic non-small-cell lung
           cancer
    • Authors: Soria J; Fülöp A, Maciel C, et al.
      Abstract: AbstractBackgroundCombination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC.Patients and methodsPatients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations.ResultsA total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified.ConclusionThe primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported.Trial identifierClinicaltrials.gov NCT01750281.
      PubDate: Tue, 03 Oct 2017 00:00:00 GMT
       
  • Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment
    • Authors: Teyssonneau D; Cousin S, Italiano A.
      Abstract: A 36-year-old female patient with no significant medical history except hypothyroidism was diagnosed with left parotid acinic cell carcinoma that was treated by radical parotidectomy followed by adjuvant radiotherapy (50 Gy) in 2004. Seven years after the initial diagnosis, the patient developed histologically confirmed metastases on the left adrenal gland and the lung, for which systemic therapy was indicated. The patient participated in two successive studies and received lapatinib and then an EZH-2 inhibitor. In March 2016, the patient’s adrenal lesion progressed, and she started treatment with pembrolizumab, 200 mg, every 3 weeks. At the time of the 11th injection, the patient experienced a retinal detachment that was linked to her myopia. The detachment was treated by surgery and amoxicillin for 7 days. Subsequently, the patient developed an oral candidiasis that was treated with systemic fungizone. At the time of the 13th injection, in December 2016, the patient experienced a debilitating grade 2 dry-eye syndrome that was associated with grade 1 conjunctival hyperemia, grade 2 xerostomia, and grade 1 skin rash on both hands. Therefore, serum protein electrophoresis (SPEP) and determination of antinuclear antibodies (ANA) [particularly Sjogren’s syndrome A/Sjogren’s syndrome B (SSA/SSB)] were carried out. A salivary gland biopsy could not be conducted because of the patient’s radiation history. The SPEP and the ANA were normal. Concomitantly, the CT-scan showed a stable disease using the RECIST criteria v1.1.
      PubDate: Thu, 28 Sep 2017 00:00:00 GMT
       
  • Molecular Tumor Boards: current practice and future needs
    • Authors: van der Velden D; van Herpen C, van Laarhoven H, et al.
      Abstract: AbstractBackgroundDue to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as whole-exome and whole-genome sequencing will soon be applied in standard care. Clinicians will thus be confronted with increasingly complex genetic information and multiple test-platforms to choose from. General medical training, meanwhile, can hardly keep up with the pace of innovation. Consequently, there is a rapidly growing gap between clinical knowledge and genetic potential in cancer care. Multidisciplinary Molecular Tumor Boards (MTBs) have been suggested as a means to address this disparity, but shared experiences are scarce in literature and no quality requirements or guidelines have been published to date.MethodsBased on literature review, a survey among hospitals in The Netherlands, and our own experience with the establishment of a nationally operating MTB, this article evaluates current knowledge and unmet needs and lays out a strategy for successful MTB implementation.ResultsHaving access to an MTB can improve and increase the application of genetics-guided cancer care. In our survey, however, <50% of hospitals and only 5% of nonacademic hospitals had access to an MTB. In addition, current MTBs vary widely in terms of composition, tasks, tools, and workflow. This may not only lead to variation in quality of care but also hinders data sharing and thus creation of an effective learning community.ConclusionsThis article acknowledges a leading role for MTBs to govern (extensive) tumor sequencing into daily practice and proposes three basic necessities for successful MTB implementation: (i) global harmonization in cancer sequencing practices and procedures, (ii) minimal member and operational requirements, and (iii) an appropriate unsolicited findings policy. Meeting these prerequisites would not only optimize MTB functioning but also improve general interpretation and application of genomics-guided cancer care.
      PubDate: Wed, 27 Sep 2017 00:00:00 GMT
       
  • Clinical and molecular characterization of patients with cancer of unknown
           primary in the modern era
    • Authors: Varghese A; Arora A, Capanu M, et al.
      Abstract: AbstractBackgroundOn the basis of historical data, patients with cancer of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than 1 year. Treatment is typically cytotoxic chemotherapy guided by histologic features and the pattern of metastatic spread. The purpose of this study was to provide a clinical and pathologic description of patients with CUP in the modern era, to define the frequency of clinically actionable molecular alterations in this population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of next-generation sequencing in the evaluation and treatment of patients with CUP.Patients and methodsUnder Institutional Review Board approval, we identified all CUP patients evaluated at our institution over a recent 2-year period. We documented demographic information, clinical outcomes, pathologic evaluations, next-generation sequencing of available tumor tissue, use of targeted therapies, and clinical trial enrollment.ResultsWe identified 333 patients with a diagnosis of CUP evaluated at our institution from 1 January 2014 through 30 June 2016. Of these patients, 150 had targeted next-generation sequencing carried out on available tissue. Median overall survival in this cohort was 13 months. Forty-five of 150 (30%) patients had potentially targetable genomic alterations identified by tumor molecular profiling, and 15 of 150 (10%) received targeted therapies. Dominant mutation signatures were identified in 21 of 150 (14%), largely implicating exogenous mutagen exposures such as ultraviolet radiation and tobacco.ConclusionsPatients with CUP represent a heterogeneous population, harboring a variety of potentially targetable alterations. Next-generation sequencing may provide an opportunity for CUP patients to benefit from novel personalized therapies.
      PubDate: Tue, 26 Sep 2017 00:00:00 GMT
       
  • Clinical benefit of systemic treatment in patients with advanced
           pancreatic and gastrointestinal neuroendocrine tumours according to
           ESMO-MCBS and ASCO framework
    • Authors: de Hosson L; Veenendaal L, Schuller Y, et al.
      Abstract: AbstractBackgroundAssessment of clinical benefit of systemic treatments of rare diseases including gastroenteropancreatic neuroendocrine tumours (GEP-NET) is challenging. Recently several tools have been developed to grade the clinical benefit of cancer drugs. The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). The American Society of Clinical Oncology (ASCO) has developed and revised the ASCO framework consisting of the Net Health Benefit (NHB) score juxtaposed against the costs of the treatment. In this review, we graded systemic treatments for GEP-NET patients with both frameworks.MethodsThe electronic databases (PubMed and EMBASE) were searched for papers reporting comparative trials, conducted in adult GEP-NET patients in the English language. Papers were assessed according to the ESMO-MCBS and the NHB part of the ASCO revised Framework (NHB-ASCO-F) by four independent assessors, and discrepancies were discussed.ResultsThe search yielded 32 trials of which 6 were eligible for grading with the ESMO-MCBS resulting in scores of 2 or 3. Eight trials were eligible for grading with the NHB-ASCO-F, resulting in scores between 37.6 and 57.4. Trials that were not primary assessable by the tools were analysed separately. Consensus between assessors was reached in 68% of trials with the ESMO-MCBS and in 23% of trials with the NHB-ASCO-F.ConclusionThe currently used systemic treatments for GEP-NET patients had low scores according to the NHB-ASCO-F and none could be graded as meaningful clinical beneficial according to the ESMO-MCBS. Despite the low incidence, the heterogeneous patient population and relatively long natural course of NET, future studies on new treatment modalities should aim for high clinical benefit outcomes.
      PubDate: Tue, 26 Sep 2017 00:00:00 GMT
       
  • Response to ‘Survival advantage for etoposide/cisplatin over
           paclitaxel/carboplatin concurrent chemoradiation in patients with
           inoperable stage III NSCLC: a subgroup analysis for ECOG 2 patients would
           be of great interest’
    • Authors: Bi N; Liang J, Wang L.
      Abstract: We thank Farkhad Manapov and Chukwuka Eze [1] for their interest in our phase III trial of etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small-cell lung cancer [2]. We have addressed here, and hope to clarify, a few points that they raised in their letter.
      PubDate: Mon, 25 Sep 2017 00:00:00 GMT
       
  • LAG-3+ tumor infiltrating lymphocytes in breast cancer: clinical
           correlates and association with PD-1/PD-L1+ tumors
    • Authors: Burugu S; Gao D, Leung S, et al.
      Abstract: AbstractBackgroundNovel immune checkpoint blockade strategies are being evaluated in clinical trials and include targeting the lymphocyte activation gene 3 (LAG-3) checkpoint, alone or in combination with PD-1/PD-L1 blockade. We investigated LAG-3 expression and its prognostic value in a large series of breast cancer patients, and correlated LAG-3 expression with key biomarkers including PD-1 and PD-L1.Experimental designLAG-3 expression was evaluated by immunohistochemistry on two tissue microarray series incorporating 4322 breast cancer primary excision specimens (N = 330 in the training and N= 3992 in the validation set) linked to detailed clinicopathologic, biomarker and long-term clinical outcome data. PD-1 and PD-L1 expressions were also evaluated by immunohistochemistry. Stromal or intra-epithelial tumor infiltrating lymphocytes (sTILs or iTILs) expressing LAG-3 or PD-1 were assessed by absolute count. PD-L1 expression was evaluated as the percentage of positive carcinoma cells per core. Kaplan–Meier curves and Cox proportional hazard models were used for survival analyses.ResultsAfter locking down interpretation cut-offs on the training set, LAG-3+ iTILs were found in 11% of cases in the validation set. In both sets, LAG-3+ iTILs were significantly associated with negative prognostic factors: young age, large tumor size, high proliferation, HER2E and basal-like breast cancer subtypes. In multivariate analyses, breast cancer patients with LAG-3+ iTILs had a significantly improved breast cancer-specific survival [hazard ratio (HR): 0.71, 95% CI 0.56–0.90], particularly among estrogen receptor-negative patients (HR: 0.50, 95% CI 0.36–0.69). Furthermore, we found that 53% of PD-L1+ and 61% of PD-1+ cases were also positive for LAG-3+ iTILs. Concurrent infiltration of LAG-3+ and CD8+ iTILs was significantly associated with increased breast cancer-specific survival (HR: 0.49, 95% CI 0.32–0.74).ConclusionLAG-3+ iTILs are enriched in estrogen receptor-negative breast cancers and represent an independent favorable prognostic factor. In addition, a high proportion of PD-1/PD-L1+ tumors are co-infiltrated with LAG-3+ TILs, supporting potential immune checkpoint blockade combination strategies as a treatment option for breast cancer patients.
      PubDate: Mon, 25 Sep 2017 00:00:00 GMT
       
  • Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma
           patients after standard chemotherapy: a multicenter, single-arm phase II
           trial of Spanish Group for Research on Sarcoma (GEIS)
    • Authors: Martin-Broto J; Redondo A, Valverde C, et al.
      Abstract: AbstractBackgroundPatients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients.Patients and methodsA multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome.ResultsThirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3–4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival.ConclusionGemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.
      PubDate: Mon, 25 Sep 2017 00:00:00 GMT
       
  • Negative hyper-selection of metastatic colorectal cancer patients for
           anti-EGFR monoclonal antibodies: the PRESSING case–control study
    • Authors: Cremolini C; Morano F, Moretto R, et al.
      Abstract: AbstractBackgroundRefining the selection of metastatic colorectal cancer patients candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies beyond RAS and BRAF testing is a challenge of precision oncology. Several uncommon genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than EGFR or downstream signalling pathways, have been suggested by preclinical and retrospective studies.Patients and methodsWe conducted this multicentre, prospective, case–control study to demonstrate the negative predictive impact of a panel of rare genomic alterations [PRESSING (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations. Hypothesizing a prevalence of candidate alterations of 15% and 0% in resistant and sensitive RAS and BRAF wild-type patients, respectively, with two-sided α and β errors of 0.05 and 0.20, 47 patients per group were needed.ResultsForty-seven patients per group were included. PRESSING panel alterations were significantly more frequent in resistant (24 out of 47, 51.1%) than in sensitive (1 out of 47, 2.1%) patients (P < 0.001) and in right- (12 out of 29, 41.4%) than left-sided (13 out of 65, 20.0%) tumours (P = 0.03). The predictive accuracy of PRESSING panel and sidedness was 75.3% and 70.2%, respectively. Among hyper-selected patients, right-sidedness was still associated with resistance (P = 0.002). The predictive accuracy of the combined evaluation of PRESSING panel and sidedness was 80.4%. As a secondary analysis, 8 (17.0%) resistant and 0 sensitive patients showed microsatellite instability (P < 0.001).ConclusionThe investigated panel of genomic alterations allows refining the selection of RAS and BRAF wild-type metastatic colorectal cancer patients candidates for anti-EGFRs, partially explaining and further corroborating the predictive ability of primary tumour sidedness.
      PubDate: Mon, 25 Sep 2017 00:00:00 GMT
       
  • The antibody–drug conjugate target landscape across a broad range of
           tumour types
    • Authors: Moek K; de Groot D, de Vries E, et al.
      Abstract: AbstractBackgroundAntibody–drug conjugates (ADCs), consisting of an antibody designed against a specific target at the cell membrane linked with a cytotoxic agent, are an emerging class of therapeutics. Because ADC tumour cell targets do not have to be drivers of tumour growth, ADCs are potentially relevant for a wide range of tumours currently lacking clear oncogenic drivers. Therefore, we aimed to define the landscape of ADC targets in a broad range of tumours.Materials and methodsPubMed and ClinicalTrials.gov were searched for ADCs that are or were evaluated in clinical trials. Gene expression profiles of 18 055 patient-derived tumour samples representing 60 tumour (sub)types and 3520 healthy tissue samples were collected from the public domain. Next, we applied Functional Genomic mRNA-profiling to predict per tumour type the overexpression rate at the protein level of ADC targets with healthy tissue samples as a reference.ResultsWe identified 87 ADCs directed against 59 unique targets. A predicted overexpression rate of ≥ 10% of samples for multiple ADC targets was observed for high-incidence tumour types like breast cancer (n = 31 with n = 23 in triple negative breast cancer), colorectal cancer (n = 18), lung adenocarcinoma (n = 18), squamous cell lung cancer (n = 16) and prostate cancer (n = 5). In rare tumour types we observed, amongst others, a predicted overexpression rate of 55% of samples for CD22 and 55% for ENPP3 in adrenocortical carcinomas, 81% for CD74 and 81% for FGFR3 in osteosarcomas, and 95% for c-MET in uveal melanomas.ConclusionThis study provides a data-driven prioritization of clinically available ADCs directed against 59 unique targets across 60 tumour (sub)types. This comprehensive ADC target landscape can guide clinicians and drug developers which ADC is of potential interest for further evaluation in which tumour (sub)type.
      PubDate: Mon, 25 Sep 2017 00:00:00 GMT
       
  • Role of adjuvant chemotherapy in early-stage endometrioid and clear-cell
           ovarian cancer
    • Authors: Lorusso D; Pignata S.
      Abstract: With more than 200 000 new cases annually worldwide [1], ovarian cancer represents the sixth most common cancer among women and the most lethal gynecologic malignancy.
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • Trastuzumab use in patients with durable complete response in
           HER2-amplified metastatic breast cancer: to continue or not to continue
    • Authors: Butterbaugh S; Patel R, Romond E, et al.
      Abstract: Exceptional response to trastuzumab, a monoclonal antibody against human epidermal growth factor receptor-2 (HER2/ERBB2), as manifested by prolonged absence of radiographic evidence of disease (durable complete response, DCR) is uncommon.
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • Risks and benefits from CDK inhibitors for advanced HR+ Her 2−
           breast cancer
    • Authors: Messina C; Messina M, Zanardi E.
      Abstract: Targeting the estrogen-receptor signalling pathway represented for many decades the standard of care for both locally and advanced hormone receptor positive (HR+) breast cancer. Deregulation of cyclin-D/cyclin-dependent kinase 4/6/retinoblastoma gene product pathway is implicated in resistance to endocrine therapy (ET). Three randomized trials showed that adding the CDK inhibitors (CDKi) palbociclib/ribociclib to letrozole significantly improved progression-free survival (PFS) than letrozole in upfront treatment of postmenopausal women with advanced HR+/Her2− breast cancer [1–3]. Moreover, combining palbociclib plus fulvestrant meaningfully prolonged PFS compared with fulvestrant in women with any menopausal status and advanced HR+/Her 2− breast cancer who had progressed to prior ET [4].
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • Checkpoint blockade for metastatic melanoma and Merkel cell carcinoma in
           HIV-positive patients
    • Authors: Heppt M; Schlaak M, Eigentler T, et al.
      Abstract: Immune checkpoint blockade (ICB) has shown dramatic survival benefits in advanced melanoma. Nevertheless, there are patient populations of unmet need in whom the efficacy and safety of ICB is less established. HIV-positive individuals were widely excluded from pivotal trials due to the risk of exacerbating the infection and triggering immune-related adverse events (AEs). We report a series of HIV-positive patients who received ICB for metastatic melanoma (MM) or Merkel cell carcinoma (MCC). This retrospective evaluation was approved by the institutional review board of the University Hospital of Munich, Germany.
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • Adjuvant chemotherapy in patients with stage I endometrioid or clear cell
           ovarian cancer in the platinum era: a Surveillance, Epidemiology, and End
           Results Cohort Study, 2000–2013
    • Authors: Oseledchyk A; Leitao M, Jr, Konner J, et al.
      Abstract: AbstractBackgroundWe sought to evaluate the impact of adjuvant chemotherapy on overall survival (OS) in patients with stage I endometrioid epithelial ovarian cancer (EEOC) or ovarian clear cell cancer (OCCC) using a national database.Patients and methodsThe Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I EEOC or OCCC from 2000 to 2013. We sought to identify predictors of chemotherapy use and to assess the impact of chemotherapy on OS in these patients. OS was compared using the log-rank test and the Cox proportional hazards model.ResultsIn all, 3552 patients with FIGO stage I EEOC and 1995 patients with stage I OCCC were identified. Of the 1600 patients (45%) with EEOC who underwent adjuvant chemotherapy, the 5-year OS rate was 90%, compared with 89% for those who did not undergo adjuvant chemotherapy (P = 0.807). Of the 1374 (69%) patients with OCCC who underwent adjuvant chemotherapy, the 5-year OS rate was 85%, compared with 83% (P = 0.439) for those who did not undergo adjuvant chemotherapy. Chemotherapy use was associated with younger age, higher substage, and more recent year of diagnosis for both the EEOC and OCCC groups. Only in the subgroup of patients with FIGO substage IC, grade 3 EEOC (n = 282) was chemotherapy associated with an improved 5-year OS—81% compared with 62% (P = 0.003) in untreated patients (HR: 0.583; 95% CI: 0.359–0.949; P = 0.030). In patients with OCCC, there was no significant effect of adjuvant chemotherapy on OS in any substage.ConclusionsAdjuvant chemotherapy was associated with improved OS only in patients with substage IC, grade 3 EEOC. In stage I OCCC, adjuvant chemotherapy was not associated with improved OS.
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • Activity and safety of crizotinib in patients with advanced clear-cell
           sarcoma with MET alterations: European Organization for Research and
           Treatment of Cancer phase II trial 90101 ‘CREATE’
    • Authors: Schöffski P; Wozniak A, Stacchiotti S, et al.
      Abstract: AbstractBackgroundClear-cell sarcoma (CCSA) is an orphan malignancy, characterized by a specific t(12;22) translocation, leading to rearrangement of the EWSR1 gene and overexpression of MET. We prospectively investigated the efficacy and safety of the tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic CCSA.Patients and methodsPatients with CCSA received oral crizotinib 250 mg twice daily. Primary end point was objective response rate (ORR), secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate (PFR), overall survival (OS), OS rate and safety. The study design focused on MET+ disease with documented rearrangement of the EWSR1 gene by fluorescence in situ hybridization.ResultsAmong 43 consenting patients with the local diagnosis of CCSA, 36 had centrally confirmed CCSA, 28 of whom were eligible, treated and assessable. Twenty-six out of the 28 patients had MET+ disease, of whom one achieved a confirmed partial response and 17 had stable disease (SD) (ORR 3.8%, 95% confidence interval: 0.1–19.6). Further efficacy end points in MET+ CCSA were DCR: 69.2% (48.2% to 85.7%), median PFS: 131 days (49–235), median OS: 277 days (232–442). The 3-, 6-, 12- and 24-month PFR was 53.8% (34.6–73.0), 26.9% (9.8–43.9), 7.7% (1.3–21.7) and 7.7% (1.3–21.7), respectively. Among two assessable MET− patients, one had stable disease and one had progression. The most common treatment-related adverse events were nausea [18/34 (52.9%)], fatigue [17/34 (50.0%)], vomiting [12/34 (35.3%)], diarrhoea [11/34 (32.4%)], constipation [9/34 (26.5%)] and blurred vision [7/34 (20.6%)].ConclusionsThe PFS with crizotinib in MET+ CCSA is similar to results achieved first-line in non-selected metastatic soft tissue sarcomas with single-agent doxorubicin. The PFS is similar to results achieved with pazopanib in previously treated sarcoma patients.Clinical trial numberEORTC 90101, EudraCT number 2011-001988-52, NCT01524926.
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or
           without cixutumumab (IMC-A12) in patients with advanced non-squamous,
           non-small-cell lung cancer: a trial of the ECOG-ACRIN Cancer Research
           Group (E3508)
    • Authors: Argiris A; Lee J, Stevenson J, et al.
      Abstract: AbstractBackgroundCixutumumab is a fully human IgG1 monoclonal antibody to the insulin-like growth factor type I receptor that can potentially reverse resistance and enhance the efficacy of chemotherapy.MethodsBevacizumab-eligible patients with stage IV or recurrent non-squamous, non-small-cell lung cancer and good performance status were randomized to receive standard doses of paclitaxel, carboplatin, and bevacizumab to a maximum of six cycles followed by bevacizumab maintenance (CPB) until progression (arm A) or CPB plus cixutumumab 6 mg/kg i.v. weekly (arm B).ResultsOf 175 patients randomized, 153 were eligible and treated (78 in arm A; 75 in arm B). The median progression-free survival was 5.8 months (95% CI 5.4–7.1) in arm A versus 7 months (95% CI 5.7–7.6) in arm B (P = 0.33); hazard ratio 0.92 (95% CI 0.65–1.31). Objective response was 46.2% versus 58.7% in arm A versus arm B (P = 0.15). The median overall survival was 16.2 months in arm A versus 16.1 months in arm B (P = 0.95). Grade 3/4 neutropenia and febrile neutropenia, thrombocytopenia, fatigue, and hyperglycemia were increased with cixutumumab.ConclusionsThe addition of cixutumumab to CPB increased toxicity without improving efficacy and is not recommended for further development in non-small-cell lung cancer. Both treatment groups had longer OS than historical controls which may be attributed to several factors, and emphasizes the value of a comparator arm in phase II trials.ClinicalTrials.gov IdentifierNCT00955305
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • The predictive role of interim PET after the first chemotherapy cycle and
           sequential evaluation of response to ABVD in Hodgkin’s lymphoma
           patients—the Polish Lymphoma Research Group (PLRG) Observational Study
    • Authors: Zaucha J; Małkowski B, Chauvie S, et al.
      Abstract: AbstractBackgroundInterim PET after two ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin’s lymphoma. To test whether an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value of iPET after one ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning.Patients and methodsConsecutive patients with newly diagnosed classical Hodgkin’s lymphoma underwent interim PET scan after one ABVD course (iPET1). PETs were interpreted according to the Deauville score (DS) as negative (−) (DS 1–3) and positive (+) (DS 4, 5). Patients with iPET1 DS 3–5 underwent iPET2.ResultsAbout 106 early (I–IIA) and 204 advanced (IIB–IV) patients were enrolled between January 2008 and October 2014. iPET1 was (−) in 87/106 (82%) or (+) in 19/106 (18%) of early, and (−) in 133/204 (65%) or (+) in 71/204 (35%) of advanced stage patients, respectively. Twenty-four patients were excluded from response analysis due to treatment escalation. After a median follow-up of 38.2 (3.2–90.2) months, 9/102 (9%) early and 43/184 (23%) advanced patients experienced a progression-free survival event. At 36 months, negative and positive predictive value for iPET1 were 94% and 41% (early) and 84% and 43% (advanced), respectively. The kinetics of PET response was assessed in 198 patients with both iPETs. All 116 patients with iPET1(−) remained iPET2(−) (fast responders), 41/82 with IPET1(+) became iPET2(−) (slow responders), and the remaining 41 stayed iPET2(+) (non-responders); progression-free survival at 36 months for fast, slow and non-responders was 0.88, 0.79 and 0.34, respectively.ConclusionThe optimal tool to predict ABVD outcome in HL remains iPET2 because it distinguishes responders, whatever their time to response, from non-responders. However, iPET1 identified fast responders with the best outcome and might guide early treatment de-escalation in both early and advanced-stage HL.
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • Successful targeting of the NRG1 pathway indicates novel treatment
           strategy for metastatic cancer
    • Authors: Jones M; Lim H, Shen Y, et al.
      Abstract: AbstractBackgroundNRG1 fusion-positive lung cancers have emerged as potentially actionable events in lung cancer, but clinical support is currently limited and no evidence of efficacy of this approach in cancers beyond lung has been shown.Patients and methodsHere, we describe two patients with advanced cancers refractory to standard therapies. Patient 1 had lung adenocarcinoma and patient 2 cholangiocarcinoma. Whole-genome and transcriptome sequencing were carried out for these cases with select findings validated by fluorescence in situ hybridization.ResultsBoth tumors were found to be positive for NRG1 gene fusions. In patient 1, an SDC4–NRG1 gene fusion was detected, similar gene fusions having been described in lung cancers previously. In patient 2, a novel ATP1B1–NRG1 gene fusion was detected. Cholangiocarcinoma is not a disease type in which NRG1 fusions had been described previously. Integrative genome analysis was used to assess the potential functional significance of the detected genomic events including the gene fusions, prioritizing therapeutic strategies targeting the HER-family of growth factor receptors. Both patients were treated with the pan HER-family kinase inhibitor afatinib and both displayed significant and durable response to treatment. Upon progression sites of disease were sequenced. The lack of obvious genomic events to describe the disease progression indicated that broad transcriptomic or epigenetic mechanisms could be attributed to the lack of prolonged response to afatinib.ConclusionThese observations lend further support to the use of pan HER-tyrosine kinase inhibitors for the treatment of NRG1 fusion-positive in both cancers of lung and hepatocellular origin and indicate more broadly that cancers found to be NRG1 fusion-positive may benefit from such a clinical approach regardless of their site of origin.Clinical trial informationPersonalized Oncogenomics (POG) Program of British Columbia: Utilization of Genomic Analysis to Better Understand Tumour Heterogeneity and Evolution (NCT02155621).
      PubDate: Mon, 18 Sep 2017 00:00:00 GMT
       
  • ClonEvol: clonal ordering and visualization in cancer sequencing
    • Authors: Dang H; White B, Foltz S, et al.
      Abstract: AbstractBackgroundReconstruction of clonal evolution is critical for understanding tumor progression and implementing personalized therapies. This is often done by clustering somatic variants based on their cellular prevalence estimated via bulk tumor sequencing of multiple samples. The clusters, consisting of the clonal marker variants, are then ordered based on their estimated cellular prevalence to reconstruct clonal evolution trees, a process referred to as ‘clonal ordering’. However, cellular prevalence estimate is confounded by statistical variability and errors in sequencing/data analysis, and therefore inhibits accurate reconstruction of the clonal evolution. This problem is further complicated by intra- and inter-tumor heterogeneity. Furthermore, the field lacks a comprehensive visualization tool to facilitate the interpretation of complex clonal relationships. To address these challenges we developed ClonEvol, a unified software tool for clonal ordering, visualization, and interpretation.Materials and methodsClonEvol uses a bootstrap resampling technique to estimate the cellular fraction of the clones and probabilistically models the clonal ordering constraints to account for statistical variability. The bootstrapping allows identification of the sample founding- and sub-clones, thus enabling interpretation of clonal seeding. ClonEvol automates the generation of multiple widely used visualizations for reconstructing and interpreting clonal evolution.ResultsClonEvol outperformed three of the state of the art tools (LICHeE, Canopy and PhyloWGS) for clonal evolution inference, showing more robust error tolerance and producing more accurate trees in a simulation. Building upon multiple recent publications that utilized ClonEvol to study metastasis and drug resistance in solid cancers, here we show that ClonEvol rediscovered relapsed subclones in two published acute myeloid leukemia patients. Furthermore, we demonstrated that through noninvasive monitoring ClonEvol recapitulated the emerging subclones throughout metastatic progression observed in the tumors of a published breast cancer patient.ConclusionsClonEvol has broad applicability for longitudinal monitoring of clonal populations in tumor biopsies, or noninvasively, to guide precision medicine.AvailabilityClonEvol is written in R and is available at https://github.com/ChrisMaherLab/ClonEvol.
      PubDate: Mon, 11 Sep 2017 00:00:00 GMT
       
  • Atezolizumab in platinum-treated locally advanced or metastatic urothelial
           carcinoma: post-progression outcomes from the phase II IMvigor210 study
    • Authors: Necchi A; Joseph R, Loriot Y, et al.
      Abstract: AbstractBackgroundConventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator’s discretion: this analysis assessed post-progression outcomes in these patients.Patients and methodsPatients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively.ResultsIn total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression.ConclusionIn this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of metastatic urothelial carcinoma.ClinicalTrials.gov IDNCT02108652.
      PubDate: Sun, 10 Sep 2017 00:00:00 GMT
       
  • Meta-analysis of individual patient safety data from six randomized,
           placebo-controlled trials with the antiangiogenic VEGFR2-binding
           monoclonal antibody ramucirumab
    • Authors: Arnold D; Fuchs C, Tabernero J, et al.
      Abstract: AbstractBackgroundRamucirumab, the human immunoglobulin G1 monoclonal antibody receptor antagonist of vascular endothelial growth factor receptor 2, has been approved for treating gastric/gastroesophageal junction, non-small-cell lung, and metastatic colorectal cancers. With the completion of six global, randomized, double-blind, placebo-controlled, phase III trials across multiple tumor types, an opportunity now exists to further establish the safety parameters of ramucirumab across a large patient population.Materials and methodsAn individual patient meta-analysis across the six completed phase III trials was conducted and the relative risk (RR) and associated 95% confidence intervals (CIs) were derived using fixed-effects or mixed-effects models for all-grade and high-grade adverse events (AEs) possibly related to vascular endothelial growth factor pathway inhibition. The number needed to harm was also calculable due to the placebo-controlled nature of all six registration standard trials.ResultsA total of 4996 treated patients (N = 2748 in the ramucirumab arm and N = 2248 in the control, placebo arm) were included in this meta-analysis. Arterial thromboembolic events [ATE; all-grade, RR: 0.8, 95% CI 0.5–1.3; high-grade (grade ≥3), RR: 0.9, 95% CI 0.5–1.7], venous thromboembolic events (VTE; all-grade, RR: 0.7, 95% CI 0.5–1.1; high-grade, RR: 0.7, 95% CI 0.4–1.2), high-grade bleeding (RR: 1.1, 95% CI 0.8–1.5), and high-grade gastrointestinal (GI) bleeding (RR: 1.1, 95% CI 0.7–1.7) did not demonstrate a definite increased risk with ramucirumab. A higher percentage of hypertension, proteinuria, low-grade (grade 1–2) bleeding, GI perforation, infusion-related reaction, and wound-healing complications were observed in the ramucirumab arm compared with the control arm.ConclusionsRamucirumab may be distinct among antiangiogenic agents in terms of ATE, VTE, high-grade bleeding, or high-grade GI bleeding by showing no clear evidence for an increased risk of these AEs in this meta-analysis of a large and diverse patient population. Ramucirumab is consistent with other angiogenic inhibitors in the risk of developing certain AEs.Clinical Trial Numbers: NCT00917384 (REGARD), NCT01170663 (RAINBOW), NCT01168973 (REVEL), NCT01183780 (RAISE), NCT01140347 (REACH), and NCT00703326 (ROSE).
      PubDate: Sun, 10 Sep 2017 00:00:00 GMT
       
  • HBV-related acute hepatitis due to immune checkpoint inhibitors in a
           patient with malignant melanoma
    • Authors: Koksal A; Toka B, Eminler A, et al.
      Abstract: Immune checkpoint inhibitors are antibodies that reactivate cytotoxic T cells by blocking immunosuppressive molecules such as cytotoxic T-lymphocyte-associated antigen 4 (e.g. ipilimumab) and programmed cell death protein (e.g. nivolumab). They are increasingly used in the treatment of various cancers including melanoma, renal cell carcinoma, non-small-cell lung cancer, hepatocellular carcinoma, etc. [1]. Unbalancing the immune system leads to immune-related adverse events involving all of the tissues, including the liver. Herein we present a melanoma patient who developed moderate HBV-related acute hepatitis due to exaggerated immune response after ipilimumab and nivolumab use.
      PubDate: Mon, 04 Sep 2017 00:00:00 GMT
       
  • Incorporating BEAMing technology as a liquid biopsy into clinical practice
           for the management of colorectal cancer patients: an expert taskforce
           review
    • Authors: García-Foncillas J; Alba E, Aranda E, et al.
      Abstract: AbstractThe importance of mutation identification for advanced colorectal cancer treatment with anti-epidermal growth factor receptor agents is well established. However, due to delays in turnaround time, low-quality tissue samples, and/or lack of standardization of testing methods a significant proportion of patients are being treated without the information that Kirsten rat sarcoma and neuroblastoma rat sarcoma (RAS) testing can provide. The detection of mutated circulating tumor DNA by BEAMing technology addresses this gap in care and allows these patients to receive international guideline-recommended expanded RAS testing with rapid turnaround times. Furthermore, the overall concordance between OncoBEAM RAS colorectal cancer testing and standard of care tissue testing is very high (93.3%). This article presents an overview of the clinical utility and potential applications of this minimally invasive method, such as early detection of emergent resistance to anti-epidermal growth factor receptor therapy. If appropriately implemented, BEAMing technology holds considerable promise to enhance the quality of patient care and improve clinical outcomes.
      PubDate: Mon, 04 Sep 2017 00:00:00 GMT
       
  • Immunotherapy in pancreatic ductal adenocarcinoma: an emerging entity'
    • Authors: Sahin I; Askan G, Hu Z, et al.
      Abstract: AbstractThe genomic-plasticity of the immune system creates a broad immune repertoire engaged to tackle cancer cells. Promising clinical activity has been observed with several immune therapy strategies in solid tumors including melanoma, lung, kidney, and bladder cancers, albeit as yet immunotherapy-based treatment approaches in pancreatic ductal adenocarcinoma (PDAC) remain to have proven value. While translational and early clinical studies have demonstrated activation of antitumor immunity, most recent late-phase clinical trials have not confirmed the early promise in PDAC except in MSI-High PDAC patients. These results may in part be explained by multiple factors, including the poorly immunogenic nature of PDAC along with immune privilege, the complex tumor microenvironment, and the genetic plasticity of PDAC cells. These challenges have led to disappointments in the field, nonetheless they have also advanced our understanding that may tailor the future steps for immunotherapy for PDAC. Therefore, there is significant hope that progress is on the horizon.
      PubDate: Mon, 04 Sep 2017 00:00:00 GMT
       
  • Absence of evidence is not evidence of absence: the case of
           non-inferiority
    • Authors: Klingbiel D; Thürlimann B, Brauchli P, et al.
      Abstract: With interest we read the recent article by Kwakman et al. [1] reporting on S-1 and capecitabine in Western patients with metastatic colorectal cancer.
      PubDate: Thu, 31 Aug 2017 00:00:00 GMT
       
  • Two cases of late-onset secondary adrenal insufficiency after
           discontinuation of nivolumab
    • Authors: Otsubo K; Nakatomi K, Furukawa R, et al.
      Abstract: Nivolumab, a monoclonal antibody to the immune-checkpoint protein PD-1 (programmed cell death-1) has been approved for the treatment of several tumors. On the basis of the results of randomized phase III trials, nivolumab is now administered as a standard therapy for patients with advanced, previously treated non-small-cell lung cancer (NSCLC) [1, 2]. Given that nivolumab promotes the response of effector T cells to tumor and self-antigens, it can elicit immune-related adverse events. We now report two cases of secondary adrenal insufficiency that developed several months after discontinuation of nivolumab treatment in patients with advanced NSCLC.
      PubDate: Thu, 31 Aug 2017 00:00:00 GMT
       
  • DPYD genotype-guided dose individualization to improve patient safety of
           fluoropyrimidine therapy: call for a drug label update
    • Authors: Henricks L; Opdam F, Beijnen J, et al.
      Abstract: AbstractThe fluoropyrimidine anticancer drugs, especially 5-fluorouracil (5-FU) and capecitabine, are frequently prescribed for several types of cancer, including breast, colorectal, head and neck and gastric cancer. In the current drug labels of 5-FU and capecitabine in the European Union and the United States, no adaptive dosing strategies are incorporated for polymorphic metabolism of 5-FU. Although treatment with fluoropyrimidines is generally well tolerated, a major clinical limitation is that a proportion of the treated population experiences severe, sometimes life-threatening, fluoropyrimidine-related toxicity. This toxicity is strongly affected by interindividual variability in activity of dihydropyrimidine dehydrogenase (DPD), the main metabolic enzyme for inactivation of fluoropyrimidines, with an estimated 3%–8% of the population being partially DPD deficient. A reduced functional or abrogated DPD enzyme is often caused by genetic polymorphisms in DPYD, the gene encoding for DPD, and heterozygous carriers of such DPYD polymorphisms have a partial DPD deficiency. When these partially DPD deficient patients are treated with a full dose of fluoropyrimidines, they are generally exposed to toxic levels of 5-FU and its metabolites, and the risk of developing severe treatment-related toxicity is therefore significantly increased.Currently, functional and clinical validity is well established for four DPYD variants (DPYD*2A, c.2846A>T, c.1679T>G and c.1236G>A), as those variants have retrospectively and in a large population study prospectively been shown to be associated with increased risk of fluoropyrimidine-associated toxicity. Patient safety of fluoropyrimidine treatment can be significantly improved by pre-emptive screening for DPYD genotype variants and dose reductions in heterozygous DPYD variant allele carriers, thereby normalizing 5-FU exposure. Based on the critical appraisal of currently available data, adjusting the labels of capecitabine and 5-FU by including recommendations on pre-emptive screening for DPYD variants and DPYD genotype-guided dose adjustments should be the new standard of care.
      PubDate: Wed, 02 Aug 2017 00:00:00 GMT
       
  • Combined irradiation and targeted therapy or immune checkpoint blockade in
           brain metastases: toxicities and efficacy
    • Authors: Tallet A; Dhermain F, Le Rhun E, et al.
      Abstract: AbstractBackgroundTargeted therapies (TT) and immune checkpoint inhibitors (ICI) are currently modifying the landscape of metastatic cancer management and are increasingly used over the course of many cancers treatment. They allow long-term survival with controlled extra-cerebral disease, contributing to the increasing incidence of brain metastases (BMs). Radiation therapy remains the cornerstone of BMs treatment (either whole brain irradiation or stereotactic radiosurgery), and investigating the safety profile of radiation therapy combined with TT or ICI is of high interest. Discontinuing an efficient systemic therapy, when BMs irradiation is considered, might allow systemic disease progression and, on the other hand, the mechanisms of action of these two therapeutic modalities might lead to unexpected toxicities and/or greater efficacy, when combined.Patients and methodsWe carried out a systematic literature review focusing on the safety profile and the efficacy of BMs radiation therapy combined with targeted agents or ICI, emphasizing on the role (if any) of the sequence of combination scheme (drug given before, during, and/or after radiation therapy).ResultsWhereas no relevant toxicity has been noticed with most of these drugs, the concomitant use of some other drugs with brain irradiation requires caution.ConclusionMost of available studies appear to advocate for TT or ICI combination with radiation therapy, without altering the clinical safety profiles, allowing the maintenance of systemic treatments when stereotactic radiation therapy is considered. Cognitive functions, health-related quality of life and radiation necrosis risk remain to be assessed. The results of prospective studies are awaited in order to complete and validate the above discussed retrospective data.
      PubDate: Wed, 02 Aug 2017 00:00:00 GMT
       
  • Power and limits of modern cancer diagnostics: cancer of unknown primary
    • Authors: Hemminki K; Liu H, Hemminki A, et al.
      Abstract: Ann Oncol 2012; 23: 760–764 (doi:10.1093/annonc/mdr369)
      PubDate: Mon, 27 Mar 2017 00:00:00 GMT
       
  • Phase III trial comparing 3–6 months of adjuvant FOLFOX4/XELOX in stage
           II–III colon cancer: safety and compliance in the TOSCA trial
    • Authors: Lonardi S; Sobrero A, Rosati G, et al.
      Abstract: Ann Oncol 2016; 27: 2074–2081 (doi: 10.1093/annonc/mdw404)
      PubDate: Thu, 23 Feb 2017 00:00:00 GMT
       
  • Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice
           Guidelines for diagnosis, treatment and follow-up
    • Authors: Dreyling M; Ghielmini M, Rule S, et al.
      Abstract: Ann Oncol 2016; 27(Suppl 5): v83–v90 (doi: 10.1093/annonc/mdw400)
      PubDate: Sun, 19 Feb 2017 00:00:00 GMT
       
  • 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast
           Cancer (ABC 3)
    • Authors: Cardoso F; Costa A, Senkus E, et al.
      Abstract: Ann Oncol 2016; 28(1): 16–33 (doi: 10.1093/annonc/mdw544)
      PubDate: Sun, 19 Feb 2017 00:00:00 GMT
       
 
 
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