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Clinical and Molecular Characterisation of CUP

Next-generation sequencing may provide an opportunity for patients with carcinoma of unknown primary to benefit from precision medicine
21 Dec 2017
Targeted Therapy
Carcinoma of Unknown Primary Site (CUP)

The researchers from the Memorial Sloan Kettering Cancer Center in New York, USA led by Dr Anna Varghese of the Solid Tumor Oncology Division, Department of Medicine performed next-generation sequencing (NGS) in patients with carcinoma of unknown primary (CUP) evaluated at their institution over a two-year period. The results are published in December 2017 issue of the Annals of Oncology. Patients with CUP represent a heterogeneous population and NGS may provide an opportunity to these patients to benefit from novel personalised therapies.

On the basis of historical data, patients with CUP have a dismal prognosis with overall survival (OS) 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.

The authors aimed to define the frequency of clinically actionable molecular alterations in this patient population, to determine how molecular testing can alter therapeutic decisions, and to investigate novel uses of NGS in the evaluation and treatment of patients with CUP.

Under Institutional Review Board approval, the investigators identified all CUP patients evaluated at their institution over a recent period. They documented demographic information, clinical outcomes, pathologic evaluations, NGS of available tumour tissue, use of targeted therapies, and clinical trial enrolment.

The study team identified 333 patients with a diagnosis of CUP, of these patients, 150 had targeted NGS carried out on available tissue. Median OS in this cohort was 13 months. They found in 30% of patients who undergone NGS testing potentially targetable genomic alterations identified by tumour molecular profiling, with 10% who received targeted therapies.

Dominant mutation signatures were identified in 14%, largely implicating exogenous mutagen exposures such as ultraviolet radiation and tobacco.

The authors concluded that patients with CUP represent a heterogeneous population, harbouring a variety of potentially targetable alterations. 

Reference

Varghese AM, Arora A, Capanu M, et al. Clinical and molecular characterization of patients with cancer of unknown primary in the modern era. Annals of Oncology 2017; 28(12):3015-3021.

Last update: 21 Dec 2017

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