Liquid biopsies have become a reality as part of the diagnostic toolbox for oncology. Assays based on targeted next-generation sequencing of circulating tumor DNA (ctDNA) are now reimbursed for genotyping of advanced disease and can be used to identify resistance mechanisms. I will describe some of our work in developing and validating such tests. I will also describe methods we have developed that leverage the characteristic fragment sizes of ctDNA to aid in detecting and monitoring cancer, using shallow whole-genome sequencing and by analysis of dried blood spots. Applications of ctDNA analysis as a diagnostic tool for earlier-stage disease are making exciting progress. Recent studies have shown potential for detection of minimal residual disease and monitoring for relapse in patients who have undergone treatment with curative intent. Current tests have shown excellent specificity and positive predictive value, and most patients relapse within 6-12 months after ctDNA is detected. These findings have supported the launching of clinical trials to test the utility of ctDNA-guided adjuvant treatment. Patients for whom ctDNA has not been detected with current methods still face an uncertain prognosis. I will describe our ongoing efforts to develop tests with enhanced sensitivity, which aim to identify a larger fraction of patients destined to recur, and to provide a longer lead time prior to clinically overt recurrence, when the residual disease has had less time to grow and evolve.

Citation Format: Nitzan Rosenfeld. Enhancing detection of ctDNA in patients with early-stage or residual disease [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA16.