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Circulating tumour DNA (ctDNA) facilitates longitudinal study of the tumour genome, which, unlike tumour tissue biopsies, globally reflects intratumor and intermetastatis heterogeneity. Despite its costs, next-generation sequencing (NGS) has revolutionised the study of ctDNA, ensuring a more comprehensive and multimodal approach, increasing data collection, and introducing new variables that can be correlated with clinical outcomes. Current NGS strategies can comprise a tumour-informed set of genes or the entire genome and detect a tumour fraction as low as 10−5.
CA-125 | ctDNA |
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Non-invasive | |
Can be altered by other coexisting physiological and pathological conditions | |
Inexpensive and highly available | Expensive and restricted to specialist centres |
Simple methodology | Complex methodology |
Results in minutes-hours | Results in days and weeks |
Quantitative marker | Quantitative and qualitative markers |
One continuous variable | Can generate multiple continuous and discrete variables |
Only informative regarding the presence/absence of treatment response and recurrence | Yields more information regarding treatment response and tumour recurrence, like resistance mechanisms and targetable genetic alterations |
Directly interpreted by the clinician | Requires specialised interpretation |
Easily detected in blood and urine | Low concentrations in biological fluids |
The utility is limited to producing tumours (mainly restricted to HGSOC) | Theoretically applicable to all histological subtypes |
Established and recognised clinical utility in trials | Clinical utility is debatable and requires confirmation in prospective trials |