Clinical and molecular characterization of patients with cancers of unknown primary in the modern era.

Clinical and molecular characterization of patients with cancers of unknown primary in the modern era.

Ann Oncol. 2017 Sep 26;:

Authors: Varghese AM, Arora A, Capanu M, Camacho N, Won HH, Zehir A, Gao J, Chakravarty D, Schultz N, Klimstra DS, Ladanyi M, Hyman DM, Solit DB, Berger MF, Saltz LB

Abstract
Background: On the basis of historical data, patients with cancers of unknown primary (CUP) are generally assumed to have a dismal prognosis with overall survival of less than one 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 two-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 January 1st 2014 through June 30th 2016. 150 of these patients had targeted next generation sequencing performed on available tissue. Median overall survival in this cohort was 13 months. 45/150 (30%) patients had potentially targetable genomic alterations identified by tumor molecular profiling, and 15/150 (10%) received targeted therapies. Dominant mutation signatures were identified in 21/150 (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.

PMID: 29045506 [PubMed – as supplied by publisher]

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