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Characterization of cell-free circulating tumor DNA in patients with brain metastases.
Background: Brain metastases are the most common malignant brain tumor and a significant cause of morbidity and mortality. As patients live longer from more effective systemic therapies, they are at increased risk of developing brain metastases. Genetic profiling of tumor tissue allows for targeted therapy, though biopsy of brain metastases is not always feasible. Cell-free circulating tumor DNA (ctDNA) testing carries diagnostic potential for targeted therapy without the need for repeat biopsies, and the ability to rapidly respond to changes in the molecular profile. Methods: 37 patients with brain metastases (15 lung, 12 breast, 5 ovarian, 3 renal, 2 melanoma) were tested prospectively with the Guardant360 ctDNA panel at a CLIA-certified, CAP-accredited clinical laboratory. Samples were analyzed for amplifications in 18 genes, single nucleotide variants in 68 genes, and select fusions, rearrangements and indels. Results: 29/37 (78.4%) patients tested harbored at least one detectable genomic alteration. The median number of alterations was 3 (range, 1-12). The most frequently detected alterations were in EGFR (19), TP53 (18), APC (6), NF1 (6), PIK3CA(6). The median ctDNA concentration was 0.50% (range, 0.10-43.80%). 11/37 patients had a subsequent test. 4/11 patients were tested within 50 days of initial testing; the median number of new alterations detected was 0.5 (range, 0-1). 7/11 patients were tested greater than 50 days of initial testing; the median number of new alterations detected was 2 (range, 0-4). Conclusions: CtDNA testing was able to detect alterations in a majority of patients with brain metastases. An increasing number of alterations were observed with time, suggesting the utility of ctDNA analysis in monitoring changes in tumor biology, response to therapy, and the ability to refine treatment plans with changes in the molecular profile.
Abstracts by Nadia Faiq:
- Meeting: 2015 ASCO Annual Meeting | Abstract No: 2074