Advancing Evidence Generation for Circulating Tumor DNA: Lessons Learned from A Multi-Assay Study of Baseline Circulating Tumor DNA Levels across Cancer Types and Stages
Brittany A. McKelvey,
Hillary S. Andrews,
Frederick L. Baehner,
James Chen,
Carin R. Espenschied,
David Fabrizio,
Vanessa Gorton,
Claire Gould,
Justin Guinney,
Greg Jones,
Xiangyang Lv,
Michael S. Nahorski,
Melanie R. Palomares,
Gary A. Pestano,
Mark Sausen,
Alain Silk,
Nicole Zhang,
Zhihong Zhang,
Mark D. Stewart,
Jeff D. Allen
Affiliations
Brittany A. McKelvey
Friends of Cancer Research, Washington, DC 20036, USA
Hillary S. Andrews
Friends of Cancer Research, Washington, DC 20036, USA
Frederick L. Baehner
Exact Sciences Corp., Madison, WI 53719, USA
James Chen
Tempus AI, Inc., Chicago, IL 60654, USA
Carin R. Espenschied
Guardant Health, Inc., Redwood City, CA 94063, USA
David Fabrizio
Foundation Medicine, Inc., Cambridge, MA 02141, USA
Vanessa Gorton
Predicine, Hayward, CA 94545, USA
Claire Gould
Biodesix Inc., Louisville, CO 80027, USA
Justin Guinney
Tempus AI, Inc., Chicago, IL 60654, USA
Greg Jones
NeoGenomics Laboratories, Fort Myers, FL 33912, USA
Xiangyang Lv
Burning Rock, Irvine, CA 92617, USA
Michael S. Nahorski
NeoGenomics Laboratories, Fort Myers, FL 33912, USA
Melanie R. Palomares
Exact Sciences Corp., Madison, WI 53719, USA
Gary A. Pestano
Biodesix Inc., Louisville, CO 80027, USA
Mark Sausen
Personal Genome Diagnostics, Labcorp, Baltimore, MD 21224, USA
Alain Silk
Tempus AI, Inc., Chicago, IL 60654, USA
Nicole Zhang
Guardant Health, Inc., Redwood City, CA 94063, USA
Zhihong Zhang
Burning Rock, Irvine, CA 92617, USA
Mark D. Stewart
Friends of Cancer Research, Washington, DC 20036, USA
Jeff D. Allen
Friends of Cancer Research, Washington, DC 20036, USA
Circulating tumor DNA (ctDNA) holds promise as a biomarker for predicting clinical responses to therapy in solid tumors, and multiple ctDNA assays are in development. However, the heterogeneity in ctDNA levels prior to treatment (baseline) across different cancer types and stages and across ctDNA assays has not been widely studied. Friends of Cancer Research formed a collaboration across multiple commercial ctDNA assay developers to assess baseline ctDNA levels across five cancer types in early- and late-stage disease. This retrospective study included eight commercial ctDNA assay developers providing summary-level de-identified data for patients with non-small cell lung cancer (NSCLC), bladder, breast, prostate, and head and neck squamous cell carcinoma following a common analysis protocol. Baseline ctDNA levels across late-stage cancer types were similarly detected, highlighting the potential use of ctDNA as a biomarker in these cancer types. Variability was observed in ctDNA levels across assays in early-stage NSCLC, indicative of the contribution of assay analytical performance and methodology on variability. We identified key data elements, including assay characteristics and clinicopathological metadata, that need to be standardized for future meta-analyses across multiple assays. This work facilitates evidence generation opportunities to support the use of ctDNA as a biomarker for clinical response.
