Clinical outcomes after whole-genome sequencing in patients with metastatic non-small-cell lung cancer.

Autor:	Tsang ES; Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Shen Y; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Chooback N; Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Ho C; Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Jones M; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Renouf DJ; Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Lim H; Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Sun S; Division of Medical Oncology, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Yip S; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada., Pleasance E; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Ionescu DN; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada., Mungall K; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Kasaian K; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Ma Y; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Zhao Y; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Mungall A; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Moore R; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Jones SJM; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada., Marra M; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada., Laskin J; Canada's Michael Smith Genome Sciences Center, BC Cancer, Vancouver, British Columbia V5Z 4E6, Canada.
Jazyk:	angličtina
Zdroj:	Cold Spring Harbor molecular case studies [Cold Spring Harb Mol Case Stud] 2019 Feb 01; Vol. 5 (1). Date of Electronic Publication: 2019 Feb 01 (Print Publication: 2019).
DOI:	10.1101/mcs.a002659
Abstrakt:	The Personalized Onco-Genomics (POG) program at BC Cancer integrates whole-genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examined the subgroup of patients with metastatic non-small-cell lung cancer (NSCLC) and report the prevalence of actionable targets, treatments, and outcomes. We identified patients who were enrolled in the POG program between 2012 and 2016 who had a tumor biopsy and blood samples with comprehensive DNA (80×, 40× normal) and RNA sequencing followed by in-depth bioinformatics to identify potential cancer drivers and actionable targets. In NSCLC cases, we compared the progression-free survival (PFS) of "POG-informed therapies" with the PFS of the last regimen prior to POG (PFS ratio). In 29 NSCLC cases, 11 were male (38%), the median age was 60.2 yr (range: 39.4-72.6), and histologies included were adenocarcinoma (93%) and squamous cell carcinoma (7%). Potential molecular targets (i.e., cancer drivers including TP53 mutations) were identified in 26 (90%), and 21 (72%) had actionable targets. Therapies based on standard-of-care mutation analysis, such as EGFR mutations, were not considered POG-informed therapies. Thirteen received POG-informed therapies, of which three had no therapy before POG; therefore a comparator PFS could not be obtained. Of 10 patients with POG-informed therapy, median PFS ratio was 0.94 (IQR 0.2-3.4). Three (30%) had a PFS ratio ≥1.3, and three (30%) had a PFS ratio ≥0.8 and <1.3. In this small cohort of NSCLC, 30% demonstrated longer PFS with POG-informed therapies. Larger studies will help clarify the role of whole-genome analysis in clinical practice. (© 2019 Tsang et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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