2018 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
Type: Oral Abstract Session
Time: Monday June 4, 8:00 AM to 11:00 AM
Location: Hall B1
Genome-wide sequencing for early stage lung cancer detection from plasma cell-free DNA (cfDNA): The Circulating Cancer Genome Atlas (CCGA) study.
Local-Regional Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr LBA8501)
Author(s): Geoffrey R. Oxnard, Tara Maddala, Earl Hubbell, Alex Aravanis, Nan Zhang, Oliver Venn, Anton Valouev, Ling Shen, Shilpen Patel, Arash Jamshidi, Karthik Jagadeesh, Samuel Gross, Darya Filippova, John F. Beausang, Minetta C. Liu, Donald A. Richards, Sylvia Plevritis, Richard Thomas Williams, Anne-Renee Hartman, Charles Swanton; Dana-Farber Cancer Institute, Boston, MA; GRAIL, Inc., Menlo Park, CA; Stanford University, Stanford, CA; Mayo Clinic, Rochester, MN; US Oncology Research, Tyler, TX; Stanford University, Stanford, CA; Translation Cancer Therapeutics Laboratory, The Francis Crick Institute, London, United Kingdom
Background: Plasma cfDNA genomic analysis is used widely for the care of advanced lung cancer, but its suitability for early stage lung cancer detection is not well established. CCGA (NCT02889978) is a prospective, multi-center, observational study launched for the development of a noninvasive assay for cancer detection. Methods: Blood was prospectively collected (N = 1627) from 749 controls (no cancer diagnosis) and 878 participants (pts) with newly-diagnosed untreated cancer in this preplanned substudy, including 127 pts with lung cancer. Three prototype sequencing assays were performed: paired cfDNA and white blood cell (WBC) targeted sequencing (507 genes, 60,000X) for single nucleotide variants/indels; paired cfDNA and WBC whole genome sequencing (WGS) for copy number variation (30X); and cfDNA whole genome bisulfite sequencing (WGBS) for methylation (30X). For each assay, a classification model using 10-fold cross-validation was developed for all pts with cancer, then evaluated in the pts with lung cancer; sensitivity was estimated at 95% specificity. Results: We evaluated pts with lung cancer (127) and a subset of controls (580) with similar ages (mean±SD yrs: 67±9, 60±13), 85% and 43% were ever-smokers, and 46% and 22% were men, respectively. Of 3055 nonsynonymous mutations detected across 122 evaluable pts with lung cancer, > 50% were detected in WBC consistent with clonal hematopoiesis (CH). Accounting for CH, sensitivity in 63 stage I-IIIA pts evaluable across all 3 assays was 48% (35-61, targeted), 54% (41-67, WGS), and 56% (43-68, WGBS); in 54 stage IIIB-IV pts it was 85% (73-93, targeted), 91% (80-97, WGS), and 93% (82-98, WGBS) . Similar sensitivities were observed across histological subtypes (adenocarcinoma, squamous cell, small cell). Comparison to tumor WGS and multi-assay classification will be reported. Conclusions: Early stage lung cancers are detectable in cfDNA using a genome-wide sequencing approach. For lung cancer detection using targeted assays, CH must be accounted for to minimize false positives. Assay optimization is ongoing to allow further clinical development in the intended use population. Clinical trial information: NCT02889978
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