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Testing the same patients again and again after surgery, and after chemotherapy, and during follow-up, showed the blood test gets more powerful the later you use it, and found relapses up to 16 months before a scan did.
In a prospective, multicentre cohort study, circulating tumour DNA was quantified before and after surgery, during and after adjuvant chemotherapy and during surveillance in stage I to III colorectal cancer by personalised multiplex PCR-based next-generation sequencing. 130 patients were enrolled at three Danish hospitals from 2014 to 2017, with 829 plasma samples collected before surgery, at postoperative day 30 and every three months for up to three years; 125 were analysable. Preoperatively, ctDNA was detectable in 108 of 122 patients (88.5%). After definitive treatment, longitudinal analysis identified 14 of 16 relapses (87.5%). At postoperative day 30, ctDNA-positive patients were 7 times more likely to relapse (hazard ratio 7.2); shortly after adjuvant chemotherapy, 17 times (hazard ratio 17.5), and all 7 patients who were positive after chemotherapy relapsed. During surveillance, ctDNA-positive patients were more than 40 times more likely to recur (hazard ratio 43.5). ctDNA status was independently associated with relapse after adjustment for known risk factors, and serial analysis revealed recurrence up to 16.5 months ahead of standard imaging.
It showed that serial rather than single testing is what makes residual disease detection work, and it set the sampling schedule most later studies have used.
Shares Aarhus University Hospital, Continuous and near-continuous ctDNA monitoring, Tumour-informed versus tumour-naive ctDNA assays, Cell-free DNA (cfDNA).
Shares Tumour-informed versus tumour-naive ctDNA assays, Cell-free DNA (cfDNA), ctDNA MRD positivity (molecular residual disease after curative treatment), DYNAMIC.
Shares Tumour-informed versus tumour-naive ctDNA assays, JAMA Oncology, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).
Shares Cell-free DNA (cfDNA), ctDNA MRD positivity (molecular residual disease after curative treatment), Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).
Shares Continuous and near-continuous ctDNA monitoring, Tumour-informed versus tumour-naive ctDNA assays, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera.
Shares Tumour-informed versus tumour-naive ctDNA assays, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera, Minimal / molecular residual disease (MRD).
Shares DYNAMIC, Signatera, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).
Shares Tumour-informed versus tumour-naive ctDNA assays, Signatera, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).