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This content will become publicly available on March 1, 2026

Title: Early Circulating Tumor DNA Kinetics as a Dynamic Biomarker of Cancer Treatment Response
PURPOSECirculating tumor DNA (ctDNA) assays are promising tools for the prediction of cancer treatment response. Here, we build a framework for the design of ctDNA biomarkers of therapy response that incorporate variations in ctDNA dynamics driven by specific treatment mechanisms. These biomarkers are based on novel proposals for ctDNA sampling protocols, consisting of frequent sampling within a compact time window surrounding therapy initiation—which we hypothesize to hold valuable prognostic information on longer-term treatment response. METHODSWe develop mathematical models of ctDNA kinetics driven by tumor response to several therapy classes and use them to simulate randomized virtual patient cohorts to test candidate biomarkers. RESULTSUsing this approach, we propose specific biomarkers, on the basis of ctDNA longitudinal features, for targeted therapy and radiation therapy. We evaluate and demonstrate the efficacy of these biomarkers in predicting treatment response within a randomized virtual patient cohort data set. CONCLUSIONThis study highlights a need for tailoring ctDNA sampling protocols and interpretation methodology to specific biologic mechanisms of therapy response, and it provides a novel modeling and simulation framework for doing so. In addition, it highlights the potential of ctDNA assays for making early, rapid predictions of treatment response within the first days or weeks of treatment and generates hypotheses for further clinical testing.  more » « less
Award ID(s):
2052465 2228034
PAR ID:
10615169
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
ASCO
Date Published:
Journal Name:
JCO Clinical Cancer Informatics
Issue:
9
ISSN:
2473-4276
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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