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Circulating cell-free tumor DNA (cfDNA) testing in small cell lung cancer.
Background: The diagnosis of small cell lung cancer (SCLC) is often made using fine needle aspiration or small biopsy specimens, which may be insufficient for next generation sequencing (NGS). Guardant360 (G360), a blood-based liquid biopsy that analyzes circulating tumor DNA, may allow the detection of targetable gene abnormalities without the need for repeated biopsies. Methods: Peripheral blood samples from patients with SCLC were collected in two 10 mL tubes and cell-free DNA was analyzed by digital sequencing for the detection of single nucleotide variants (SNVs), copy number amplifications (CNAs), indels, and fusions. The Tumor Alterations Relevant for Genomics Driven Therapy (TARGET) curated database (http://www.broadinstitute.org/cancer/cga/target) was queried for potentially actionable mutations. Results: 143 consecutive samples from 134 de-identified patients were collected between June 2014 and December 2015. 6 patients had more than one sample. During the accrual time, the number of genes evaluated increased from 54 (6 tests) to 68 (98 tests) and finally to 70 (43 tests). The median time from collection to report was 15 days (range 9-27 days). Alterations in at least one gene were found in 132 (92.3%) of samples and 124 (92.5%) of patients. Inactivating mutations in TP53 and RB1 were seen in 70% and 32% of patients with detectable alterations respectively. Potentially targetable alterations were observed in 66 patients (49%). Amplifications in CCNE1 (12.0%) and FGFR1 (8.6%), and PIK3CAmutation (6.7%) were the most common potentially targetable alterations. Conclusions: G360 is non-invasive and rapid sequencing method, which may be particularly useful in patients with advanced stage SCLC where archival tissue samples may be suboptimal for NGS or no longer reflective of an evolving genomic profile. Due to the limited treatment options in this patient population, G360 may provide valuable information to guide treatment decisions.
Abstracts by Daniel Morgensztern:
Broadening response rates to PD-1 therapy in advanced lung adenocarcinoma: Viagenpumatucel-l (HS-110) in combination with nivolumab in the ongoing DURGA trial.Meeting: 2016 ASCO Annual Meeting | Abstract No: TPS9102
Clinical characteristics and treatment outcomes of patients with pulmonary salivary gland-like tumors.Meeting: 2016 ASCO Annual Meeting | Abstract No: 8534