# A Novel Cell-Free DNA Fragmentomic Assay and Its Application for Monitoring Disease Progression in Real Time for Stage IV Cancer Patients

## TL;DR

A new blood test can detect if cancer treatments are failing in just 2-3 weeks, helping doctors make quicker decisions for stage IV cancer patients.

## Contribution

A novel cell-free DNA fragmentomic assay provides early treatment response monitoring across multiple cancer types without relying on specific genetic mutations.

## Key findings

- The Progression Score (PS) model achieved an AUC of 0.93 in predicting radiographic progression.
- 92% of patients with PS > 90 progressed, while 95% with PS < 10 did not.
- The assay's performance was unaffected by tumor genomic profile.

## Abstract

For patients with advanced (stage IV) cancer, imaging can take 6 to 8 weeks to show whether a new treatment is helping—a stressful delay that can keep them on ineffective therapies. A new blood test has been developed to detect treatment failure in just 2–3 weeks. The test measures tiny tumor-derived DNA fragments in the blood and reports a “Progression Score” from 0 to 100. High scores flag likely rapid cancer growth, while low scores suggest the therapy is effective. Because the test is quick, is noninvasive, and does not rely on specific genetic mutations, it can be used across many cancer types and treatments, helping doctors decide sooner whether to continue, modify, or discontinue a patient’s therapy.

Background/Objectives: Conventional imaging assesses therapy response in stage IV solid-tumor patients in 8- to 12-week intervals, delaying detection of non-responders. We evaluated a quantitative PCR (qPCR) assay that interrogates size-distributed cell-free DNA (cfDNA) fragments to provide earlier insights into treatment efficacy. Methods: In this prospective study, 128 patients with metastatic lung, breast, or colorectal cancer provided plasma 12–21 days after the first dose of a new systemic regimen. The qPCR targets multi-copy retrotransposon element fragments of greater than 80 bp, greater than 105 bp, and greater than 265 bp, as well as an internal control. A model integrates these quantities into a Progression Score (PS) ranging from 0 to 100; higher values indicate probable disease progression. Results: The PS model yielded an area under (AUC) the receiver-operating-characteristic (ROC) curve of 0.93 for predicting radiographic progression at first imaging. Scores were strongly bimodal: 92% of patients with PS > 90 progressed, whereas 95% with PS < 10 did not. Intermediate scores (10–90) comprised a mixed cohort. Assay performance was unaffected by tumor genomic profile. Conclusions: This cfDNA-based Progression Score (PS) assay enables tumor- and therapy-agnostic, non-invasive monitoring of treatment response as early as two weeks after initiation. By flagging ineffective regimens well before standard imaging, the test can accelerate clinical decision-making, reduce exposure to futile therapy, and potentially improve outcomes in stage IV cancer. Early treatment plan changes may also avoid the high costs of ineffective treatments, prevent downstream toxicity-related hospitalizations, and free up limited imaging and infusion-suite capacity—yielding savings for patients, payers, and healthcare systems.