Clinical and molecular characterization of patients with cancer of unknown primary in the modern era
| Autor: | Ahmet Zehir, Anna M. Varghese, David S. Klimstra, Michael F. Berger, Marinela Capanu, Nikolaus Schultz, David M. Hyman, Debyani Chakravarty, Arshi Arora, L. B. Saltz, Jianjiong Gao, Niedzica Camacho, David B. Solit, M. Ladanyi, Helen Won |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Population Cohort Studies 03 medical and health sciences 0302 clinical medicine Internal medicine Exome Sequencing Overall survival Humans Medicine education Aged Aged 80 and over education.field_of_study business.industry High-Throughput Nucleotide Sequencing Original Articles Hematology Middle Aged Cytotoxic chemotherapy Institutional review board Clinical trial Heterogeneous population 030104 developmental biology Cancer of unknown primary 030220 oncology & carcinogenesis Cohort Neoplasms Unknown Primary Female business |
| Zdroj: | Annals of Oncology. 28:3015-3021 |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdx545 |
| Popis: | 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, next-generation 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. |
| Databáze: | OpenAIRE |
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