Can circulating tumor DNA be used for direct and early stage cancer detection?

Eleftherios P Diamandis,Clare Fiala

doi:10.12688/f1000research.13440.1

Eleftherios P Diamandis, Clare Fiala

Open Access

https://doi.org/10.12688/f1000research.13440.1

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Abstract

In the August 16th issue of Science Translational Medicine, Phallen et al propose a method for early cancer diagnosis by using circulating tumor DNA (1). One major advance of this paper includes optimized sequencing of cell-free/circulating tumor DNA (ctDNA) without knowledge of tumor mutations. Evaluation of 200 patients with colorectal, breast, lung and ovarian cancer revealed mutations in ctDNA in approx. 60-70% of all patients, including stage 1 and stage 2 disease. If this data can be reproduced in asymptomatic individuals, they will likely have a major impact on early cancer detection and patient outcomes. In this commentary, we examine the feasibility of this approach for detecting small, asymptomatic tumors, based on previously published empirical data.

Highlights

In the August 16th issue of Science Translational Medicine, Phallen et al propose a method for early cancer diagnosis by using circulating tumor DNA (1)
Correspondence Phallen et al recently proposed a method for early cancer diagnosis by using circulating tumor DNA1
Evaluation of 200 patients with colorectal, breast, lung and ovarian cancer revealed mutations in circulating tumor DNA (ctDNA) in approximately 60–70% of all patients, including stage 1 and stage 2 disease. If this data can be reproduced in asymptomatic individuals, they will likely have a major impact on early cancer detection and patient outcomes

Summary

13 Dec 2017 report report

If we assume that the overall positivity of this test is 50%, the overall sensitivity will likely be less than 40% This would make screening of asymptomatic individuals less efficient, since the majority of patients will receive incorrect screening results (false negatives) due to either lack of the targeted mutations or sampling error. Our analysis shows that measurement of ctDNA for early cancer diagnosis is problematic, due to the limited capability of deep whole genome sequencing to reveal mutations, but because the amount of circulating tumor DNA retrieved from a 10mL blood draw will be extremely small, or even nonexistent, making efficient diagnosis of cancer unlikely. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Garber K

Findings

Del Monte U