Dataset Information

Circulating Tumor DNA Profiling in Small-Cell Lung Cancer Identifies Potentially Targetable Alterations.

ABSTRACT: PURPOSE:Patients with SCLC rarely undergo biopsies at relapse. When pursued, tissue obtained can be inadequate for molecular testing, posing a challenge in identifying potentially targetable alterations in a clinically meaningful time frame. We examined the feasibility of circulating tumor DNA (ctDNA) testing in identifying potentially targetable alterations in SCLC. EXPERIMENTAL DESIGN:ctDNA test results were prospectively collected from patients with SCLC between 2014 and 2017 and analyzed. ctDNA profiles of SCLC at diagnosis and relapse were also compared. RESULTS:A total of 609 samples collected from 564 patients between 2014 and 2017 were analyzed. The median turnaround time for test results was 14 days. Among patients with data on treatment status, there were 61 samples from 59 patients and 219 samples from 206 patients collected at diagnosis and relapse, respectively. The number of mutations or amplifications detected per sample did not differ by treatment status. Potentially targetable alterations in DNA repair, MAPK and PI3K pathways, and genes such as MYC and ARID1A were identifiable through ctDNA testing. Furthermore, our results support that it may be possible to reconstruct the clonal relationship between detected variants through ctDNA testing. CONCLUSIONS:Patients with relapsed SCLC rarely undergo biopsies for molecular testing and often require prompt treatment initiation. ctDNA testing is less invasive and capable of identifying alterations in relapsed disease in a clinically meaningful timeframe. ctDNA testing on an expanded gene panel has the potential to advance our knowledge of the mechanisms underlying treatment resistance in SCLC and aid in the development of novel treatment strategies.

SUBMITTER: Devarakonda S

PROVIDER: S-EPMC7373320 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Circulating Tumor DNA Profiling in Small-Cell Lung Cancer Identifies Potentially Targetable Alterations.

Devarakonda Siddhartha S Sankararaman Sumithra S Herzog Brett H BH Gold Kathryn A KA Waqar Saiama N SN Ward Jeffrey P JP Raymond Victoria M VM Lanman Richard B RB Chaudhuri Aadel A AA Owonikoko Taofeek K TK Li Bob T BT Poirier John T JT Rudin Charles M CM Govindan Ramaswamy R Morgensztern Daniel D

Clinical cancer research : an official journal of the American Association for Cancer Research 20190712 20

<h4>Purpose</h4>Patients with SCLC rarely undergo biopsies at relapse. When pursued, tissue obtained can be inadequate for molecular testing, posing a challenge in identifying potentially targetable alterations in a clinically meaningful time frame. We examined the feasibility of circulating tumor DNA (ctDNA) testing in identifying potentially targetable alterations in SCLC.<h4>Experimental design</h4>ctDNA test results were prospectively collected from patients with SCLC between 2014 and 2017 a ...[more]

PMID: 31300452

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Project description:Guidelines advocate molecular profiling in the evaluation of advanced non-small-cell lung cancer (NSCLC) and support the use of plasma circulating tumor DNA (ctDNA)-based profiling for patients with insufficient tissue. Thorough prospective clinical validation studies of next-generation sequencing (NGS)-based ctDNA assays are lacking. We report the multicentered prospective clinical validation of the InVision ctDNA assay in patients with advanced untreated NSCLC. A total of 264 patients with untreated advanced NSCLC were prospectively recruited, and their plasma was analyzed using a ctDNA NGS assay for detection of genomic alterations in 36 commonly mutated genes. Tumor tissue was available in 178 patients for molecular profiling for comparison with plasma profiling. The remaining 86 patients were included to compare ctDNA profiles in patients with and without tissue for profiling. Concordance of InVisionFirst with matched tissue profiling was 97.8%, with 82.9% positive predictive value, 98.5% negative predictive value, 70.6% sensitivity, and 99.2% specificity. Considering specific alterations in eight genes that most influence patient management, the positive predictive value was 97.8%, with 97.1% negative predictive value, 73.9% sensitivity, and 99.8% specificity. Across the entire study, 48 patients with actionable alterations were identified by ctDNA testing compared with only 38 by tissue testing. ctDNA NGS reported either an actionable alteration or an alteration generally considered mutually exclusive for such actionable changes in 53% of patients. The liquid biopsy NGS assay demonstrated excellent concordance with tissue profiling in this multicenter, prospective, clinical validation study, with sensitivity and specificity equivalent to Food and Drug Administration-approved single-gene ctDNA assays. The use of plasma-based molecular profiling using NGS led to the detection of 26% more actionable alterations compared with standard-of-care tissue testing in this study.

Dataset Information

Circulating Tumor DNA Profiling in Small-Cell Lung Cancer Identifies Potentially Targetable Alterations.

Publications

Circulating Tumor DNA Profiling in Small-Cell Lung Cancer Identifies Potentially Targetable Alterations.

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