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Research ArticleSpecial Report

Circulating Tumor DNA for Early Cancer Detection

Clare Fiala, Vathany Kulasingam, Eleftherios P. Diamandis
DOI: 10.1373/jalm.2018.026393 Published August 2018
Clare Fiala
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada;
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Vathany Kulasingam
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada.
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Eleftherios P. Diamandis
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada.
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  • For correspondence: Eleftherios.diamandis@sinaihealthsystem.ca
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    Fig. 1. Likelihood of detecting tumors of various sizes through ctDNA quantification.

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    Table 1.

    Potential applications of ctDNA in cancer diagnostics and management.

    ApplicationSummaryPotential for clinical utilityReferences
    Prognosis
    • Undetectable ctDNA in the bloodstream after surgery are correlated with improved prognosis and smaller chances of relapse

    • Strength and type of chemotherapy can be informed by ctDNA analysis showing likelihood of relapse

    Excellent13–31, 70, 88, 89
    Monitoring treatment efficacy and early relapse detection
    • Increased number of mutations or rising ctDNA concentration can indicate treatment failure, resistance, and relapse

    Excellent, maybe in combination with protein markers13–20, 23–29
    Selection of treatment
    • Knowledge of mutations in the ctDNA informs choice of therapy (personalized treatments)

    • ctDNA avoids tumor heterogeneity issues by providing overview of all the mutations in the tumor (assuming all tumor cells secrete DNA at the same rate)

    Excellent17, 28, 30–33, 73
    Tumor size/disease burden
    • Larger amount of ctDNA in blood denotes advanced tumor stage and volume

    • Blood testing does not carry the risk of radiation exposure or poor accuracy of imaging and can be repeated more often than traditional biopsies

    Excellent, especially in combination with imaging15, 17, 18, 20–29, 88, 89
    Detection of cancer in asymptomatic individuals/population screening
    • Most studies show poor sensitivity, especially for early-stage tumors

    • For small tumors, there is not enough ctDNA present to allow for an accurate test result

    • Threshold appears to be 1-cm-diameter tumors

    Under intense investigation; could be used in combination with protein biomarkers13, 30, 70, 88, 89
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The Journal of Applied Laboratory Medicine: 3 (2)
Vol. 3, Issue 2
September 2018
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Circulating Tumor DNA for Early Cancer Detection
Clare Fiala, Vathany Kulasingam, Eleftherios P. Diamandis
The Journal of Applied Laboratory Medicine Sep 2018, 3 (2) 300-313; DOI: 10.1373/jalm.2018.026393
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Circulating Tumor DNA for Early Cancer Detection
Clare Fiala, Vathany Kulasingam, Eleftherios P. Diamandis
The Journal of Applied Laboratory Medicine Sep 2018, 3 (2) 300-313; DOI: 10.1373/jalm.2018.026393

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    • CLINICAL APPLICATIONS OF ctDNA LIQUID BIOPSIES
    • CTDNA COMPARED WITH BLOOD-BASED PROTEIN MARKERS
    • ctDNA IN OTHER BIOLOGICAL FLUIDS
    • ctDNA TESTING FOR EARLY DETECTION
    • CHALLENGES OF USING CTDNA FOR EARLY DIAGNOSIS
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