Real-time genomic characterization utilizing circulating cell-free DNA in patients with anaplastic thyroid carcinoma.

Real-time genomic characterization utilizing circulating cell-free DNA in patients with anaplastic thyroid carcinoma.

Thyroid. 2016 Oct 27;

Authors: Sandulache VC, Williams MD, Lai SY, Lu C, William WN, Busaidy N, Cote GJ, Singh R, Luthra R, Cabanillas M

Abstract
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an aggressive disease which requires rapid diagnosis and multimodality treatment. Recent advances in targeted therapeutics provide ATC patients with previously unavailable treatment options, which may improve clinical outcomes in the coming years. Continued development of high throughput next generation sequencing provides clinicians with an unparalleled ability to characterize the genomic background of tumors in order to guide treatment selection and clinical trial enrollment.
METHODS: We evaluated 23 patients with ATC treated at the University of Texas MD Anderson Cancer Center (UTMDACC) between 8/2015 and 4/2016. All patients underwent next generation sequencing using an institutional tissue-based DNA platform (50 genes) and a commercially available cell-free circulating DNA (cfDNA) platform (70 genes).
RESULTS: Sequencing data was successfully obtained for both platforms on all patients. The most commonly mutated genes noted on both platforms were TP53 (15/23, 65%) and BRAF (11/23, 48%). Concordance between the tumor and cfDNA data was high for BRAF, PIK3CA, NRAS, PTEN and moderate for TP53. Concordance was highest in patients who underwent dual platform sequencing prior to initiation of definitive treatment and lowest in patients who underwent cfDNA analysis following treatment. Nineteen patients had treatment at UTMDACC following cfDNA sequencing. One patient was observed and 3 patients opted for hospice. At time of last contact 15/23 (65%) patients were alive.
CONCLUSIONS: Next generation sequencing platforms offer clinicians an opportunity to identify targetable oncogenic events in ATC. To our knowledge, this is the largest sequential cohort of ATC patients who have undergone targeted genomic profiling. Based on these data, we recommend utilization of both tumor-based and cfDNA analysis in the context of clinical trial development and application. Integration of these or similar platforms in clinical trials implementation may have the potential to transform clinical outcomes for patients with ATC.

PMID: 27785980 [PubMed - as supplied by publisher]

http://ift.tt/2eWLfLx