Table 1 Applications of ctDNA in cancer diagnostics

Prognosis determination

• Absence of ctDNA after surgery is associated with a much better prognosis and smaller chances of relapse

• Prognosis determination aids in selecting aggressiveness of treatment as well as determining the necessity for adjuvant therapy; patients at high risk of relapse could receive targeted treatment, while low risk patients are spared unnecessary chemotherapy

[2,3,4,5,6,7, 10, 21, 29]

Monitoring for treatment efficacy/relapse

• ctDNA can be analyzed through a blood test; this ‘liquid biopsy’ can be repeated more often, enabling consistent monitoring of response to treatment

• Raised ctDNA concentrations or increased number of mutations indicate treatment failure/relapse earlier than clinical relapse

[4, 8,9,10,11,12,13,14,15,16,17,18,19,20,21,22, 29]

Selection of treatment

• Sequencing the ctDNA informs choice of therapy to target specific mutations

• Traditional tumor biopsies only allow for the analysis of a certain part of the tumor, which ignores intratumor heterogeneity, while ctDNA analysis provides a more holistic view of the tumor to inform more targeted treatment

[1, 19,20,21, 28]

Tumor size/disease burden

• Larger amount of ctDNA in blood correlates with advanced tumor stage/greater metastatic burden

• Blood testing does not carry the risk of radiation exposure or poor accuracy of imaging; ctDNA can provide a snapshot of disease burden, which can be repeated more often than imaging or traditional biopsies

[19, 21, 23, 24, 30]

Detection in asymptomatic individuals

• 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

• However, reliable ctDNA tests for early diagnosis would allow for early intervention and curative surgery and higher cure rates

[16, 20, 25, 30, 32,33,34,35,36,37,38]