Clinical and molecular characterization of patients with cancer of unknown primary in the modern era Journal Article


Authors: Varghese, A. M.; Arora, A.; Capanu, M.; Camacho, N.; Won, H. H.; Zehir, A.; Gao, J.; Chakravarty, D.; Schultz, N.; Klimstra, D. S.; Ladanyi, M.; Hyman, D. M.; Solit, D. B.; Berger, M. F.; Saltz, L. B.
Article Title: Clinical and molecular characterization of patients with cancer of unknown primary in the modern era
Abstract: Background: On 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 methods: Under 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, nextgeneration sequencing of available tumor tissue, use of targeted therapies, and clinical trial enrollment. Results: We 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. Conclusions: Patients 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. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Keywords: next-generation sequencing; cancer of unknown primary
Journal Title: Annals of Oncology
Volume: 28
Issue: 12
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2017-12-01
Start Page: 3015
End Page: 3021
Language: English
DOI: 10.1093/annonc/mdx545
PROVIDER: scopus
PUBMED: 29045506
PMCID: PMC5834064
DOI/URL:
Notes: Article -- Export Date: 1 March 2018 -- Source: Scopus
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MSK Authors
  1. Leonard B Saltz
    791 Saltz
  2. David Solit
    779 Solit
  3. Anna Mary Varghese
    145 Varghese
  4. Marinela Capanu
    385 Capanu
  5. David S Klimstra
    978 Klimstra
  6. Marc Ladanyi
    1328 Ladanyi
  7. David Hyman
    354 Hyman
  8. Ahmet Zehir
    343 Zehir
  9. Michael Forman Berger
    765 Berger
  10. Jianjiong Gao
    132 Gao
  11. Nikolaus D Schultz
    487 Schultz
  12. Helen Hyeong-Eun Won
    109 Won
  13. Arshi Arora
    36 Arora