Abstract
PurposeAccess to genomic tumor material is required to select patients for targeted therapies. However, tissue biopsies are not always feasible and therefore circulating cell-free DNA (cfDNA) has emerged as an alternative. Here we investigate the utility of cfDNA for genomic tumor profiling in the phase I setting.Study designPeripheral blood was collected from patients with advanced solid cancers eligible for phase I treatment. Patients failing the initial tissue biopsy due to inaccessible lesions or insufficient tumor cellularity (<10%) were included in the study. Genomic profiling of cfDNA including whole exome sequencing (WES) and somatic copy number alterations (SCNAs) analysis (OncoScan).ResultsPlasma cfDNA was pro- and retrospectively profiled from 24 and 20 patients, respectively. The median turnaround time was 29 days (N= 24, range 13-87 days) compared to tissue re-analyses of median 60 days (N= 6, range 29-98). Selected cancer-associated alterations (SCAAs) were identified in 70% (31/44) of patients, predominantly by WES due to the low sensitivity of OncoScan on cfDNA. Primarily, inaccessible cases of prostate and lung cancers could benefit from cfDNA profiling. In contrast, breast cancer patients showed a low level of tumor-specific cfDNA which might be due to cancer type and/or active treatment at the time of plasma collection.ConclusionPlasma cfDNA profiling using WES is feasible within a clinically relevant timeframe and represents an alternative to invasive tissue biopsies to identify possible treatment targets. Especially, difficult-to-biopsy cancers can benefit from cfDNA profiling, but tumor tissue remains the gold standard for molecular analyses.
Highlights
Knowledge of the genomic makeup of tumors is essential for cancer diagnosis, prognosis, and selection of treatment
Inaccessible cases of prostate and lung cancers could benefit from cell-free DNA (cfDNA) profiling
Difficult-to-biopsy cancers can benefit from cfDNA profiling, but tumor tissue remains the gold standard for molecular analyses
Summary
Knowledge of the genomic makeup of tumors is essential for cancer diagnosis, prognosis, and selection of treatment. Fresh tissue is used to characterize the tumor but often archival material such as formalin-fixed paraffin-embedded (FFPE) tissue is used introducing several problems. Archival tissue might not represent www.oncotarget.com the current malignancy due to clonal evolution of the disease over time and in response to previous therapies [3, 4]. Either fresh or archival, represent standard for molecular testing, poor quality or inadequate quantity of tissue and DNA is often challenging besides the discomfort and risks of complications related to biopsy procedures. In NSCLC, tissue biopsies are unusable in 20-30% of patients [7], highlighting the need for an alternative source of tumor material
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