2018 ASCO Annual Meeting!
Session: Tumor Biology
Type: Poster Session
Time: Monday June 4, 1:15 PM to 4:45 PM
Location: Hall A
Session: Tumor Biology
Type: Poster Discussion Session
Time: Monday June 4, 4:45 PM to 6:00 PM
Development of a comprehensive cell-free DNA (cfDNA) assay for early detection of multiple tumor types: The Circulating Cell-free Genome Atlas (CCGA) study.
2018 ASCO Annual Meeting
Poster Board Number:
Poster Discussion Session (Board #134)
J Clin Oncol 36, 2018 (suppl; abstr 12021)
Author(s): Eric A. Klein, Earl Hubbell, Tara Maddala, Alex Aravanis, John F. Beausang, Darya Filippova, Samuel Gross, Arash Jamshidi, Kathryn Kurtzman, Ling Shen, Anton Valouev, Oliver Venn, Nan Zhang, David A. Smith, Timothy Joseph Yeatman, Robert Tibshirani, Richard Thomas Williams, Anne-Renee Hartman, Michael Seiden, Minetta C. Liu; Cleveland Clinic Glickman Urology and Kidney Institute, Cleveland, OH; GRAIL, Inc., Menlo Park, CA; Compass Oncology, Vancouver, WA; Gibbs Cancer Center and Research Institute, Spartanburg, SC; Stanford University, Stanford, CA, US; US Oncology Research, The Woodlands, TX; Mayo Clinic, Rochester, MN
Background: Globally most cancers are detected at advanced stages with high treatment burden and low cure rates. A noninvasive cfDNA blood test detecting multiple cancers at early stages when curative treatment is more likely to succeed is desirable. CCGA (NCT02889978) is a prospective multi-center observational study for development of a noninvasive cfDNA-based multi-cancer detection assay. Methods: Prospectively collected samples (N = 1627) from 749 controls (no cancer diagnosis, C) and 878 participants (pts) with newly diagnosed untreated cancer (20 tumor types, all stages) were analyzed in a preplanned substudy. 3 prototype sequencing assays were performed: paired cfDNA and white blood cell (WBC, 60,000X) targeted sequencing (507 genes) for single nucleotide variants/indels; paired cfDNA and WBC whole genome sequencing (WGS, 30X) for copy number variation; cfDNA whole genome bisulfite sequencing (WGBS, 30X) for methylation. For each assay a detection model was developed for all cancer pts; sensitivity was estimated at 95% specificity. Results: Pts w/cancer and C had similar age, smoking status and gender. WGBS had the highest sensitivity and is reported here; results were consistent across assays. Detected (sensitivity [95% CI]) cancers (stage I-III) included 28 colorectal (66% [48-84]), 19 esophageal (63% [38-84]), 5 head and neck (56% [21-86]), 5 hepatobiliary (80% [28-99]), 73 lung (59% [47-70]), 17 lymphoma (77% [50-93]), 11 multiple myeloma (73% [39-94]), 10 ovarian (90% [56-99]), and 10 pancreatic (80% [44-98]). Breast cancer-specific assay results are reported separately. Cancers with low signal ( < 10% sensitivity) include low gleason score prostate cancer, thyroid, uterine, melanoma, and renal. Comparison to tumor WGS and multi-assay classification will be reported. Conclusions: A cfDNA-based blood test detected multiple cancers at various stages with high specificity, indicating this approach is promising as a multi-cancer screening test, including for lethal unscreened cancers where stage shift can impact mortality. Further assay and clinical development of a multi-cancer cfDNA test in an asymptomatic population is ongoing. Clinical trial information: NCT02889978