Early, molecular detection of cancer utilizing circulating cell-free DNA assay with ultra high accuracy and sensitivity.

Tumor Biology
Session Type and Session Title: 
Poster Session, Tumor Biology
Abstract Number: 


Poster Board Number: 
Board #237
J Clin Oncol 34, 2016 (suppl; abstr 11540)
Stefanie Mortimer, Katharine Dilger, Diana Abdueva, Darya Chudova, Ankit Sarin, Chloe Evelyn Atreya, Jim Leng, Jeeyun Lee, Helmy Eltoukhy, Pamela N. Munster, AmirAli Talasaz; Guardant Health, Inc., Redwood City, CA; Guardant Health Inc, Redwood City, CA; University of California San Francisco, San Francisco, CA; University of California, San Francisco, San Francisco, CA; Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea

Abstract Disclosures


Background: Analysis of cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is a promising method for early detection of cancer. Applications include screening high risk populations and detection of post-operative residual disease for adjuvant therapy decision-making and early detection of cancer recurrence. However, to be applicable, tests must cover a broad enough genomic footprint to not require a priori knowledge of mutations to have clinical sensitivity higher than conventional methods Methods: We developed a 20kb panel ctDNA capture panel based on the landscape of genomic alterations in ctDNA of over 10,000 advanced cancer patients, with high theoretical clinical sensitivity for: colorectal (96%), ovarian (95%), lung (90%), and pancreatic cancers (90%). Analytical sensitivity of 0.01% for single nucleotide variants (SNVs) and indels was achieved. We used the panel to monitor advanced cancer patients (n = 120pts with longitudinal samples) and then applied it to a clinical study of 14 early stage (II/III) CRC patients with both pre- and post-tumor resection blood draws (up to 7 days post surgery). A subset (6 patients) also had tumor samples collected at the time of the surgical resection. Results: Overall, the detection rate of ctDNA in pre-op blood draws was 93%. In the post-op blood draws ctDNA was detectable in 43% of cases. When tumor tissue was available and used as a reference, the clinical sensitivity, specificity, and accuracy in pre-op blood samples were 83%, 99.995%, and 99.99%, respectively. The clinical specificity of variants detected in post-op blood samples using pre-op samples as the reference is 99.996%. Cohort expansion of CRC and recently diagnosed ovarian cancer patients is ongoing. Conclusions: In conclusion, we have leverage emerging knowledge of the cancer genome to educate the development of a non-invasive multigene cfDNA NGS test with ultra-high sensitivity and high accuracy for the early detection of ctDNA across many of the most deadly and difficult to detect cancers.