1. Comparing single-target and multitarget approaches for postoperative circulating tumour DNA detection in stage II-III colorectal cancer patients
- Author
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Tenna Vesterman Henriksen, Thomas Reinert, Mads Heilskov Rasmussen, Christina Demuth, Uffe Schou Løve, Anders Husted Madsen, Kåre Andersson Gotschalck, Lene Hjerrild Iversen, and Claus Lindbjerg Andersen
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Cancer Research ,liquid biopsy ,circulating tumour DNA ,colorectal cancer ,General Medicine ,Circulating Tumor DNA ,Oncology ,Genetics ,Biomarkers, Tumor ,residual disease ,Molecular Medicine ,Humans ,Neoplasm Recurrence, Local ,Colorectal Neoplasms - Abstract
Circulating tumour DNA (ctDNA) detection for postoperative risk stratification in cancer patients has great clinical potential. However, low ctDNA abundances complicates detection. Multitarget (MT) detection strategies have been developed to increase sensitivity. Yet, empirical evidence supporting performance gains of MT vs. single-target (ST) strategies in a postoperative setting is limited. We compared ctDNA detection in 379 paired plasma samples from 112 stage II–III colorectal cancer patients by ST digital PCR and MT sequencing of 16 patient-specific variants. The strategies exhibited good concordance (90%, Cohen's Kappa 0.79), with highly correlated ctDNA quantifications (Pearson r = 0.985). A difference was observed in ctDNA detection preoperatively (ST 72/92, MT 88/92). However, no difference was observed immediately after surgery in recurrence (ST 11/22, MT 10/22) or nonrecurrence (both 2/34) patients. In serial samples, detection was similar within recurrence (ST 13/16, MT 14/16) and nonrecurrence (ST 3/49, MT 1/49) patients. Both approaches yielded similar lead times to standard-of-care radiology (ST 4.0 months, MT 4.1 months). Our findings do not support significant performance gains of the MT strategy over the ST strategy for postoperative ctDNA detection. Circulating tumour DNA (ctDNA) detection for postoperative risk stratification in cancer patients has great clinical potential. However, low ctDNA abundances complicates detection. Multitarget (MT) detection strategies have been developed to increase sensitivity. Yet, empirical evidence supporting performance gains of MT vs. single-target (ST) strategies in a postoperative setting is limited. We compared ctDNA detection in 379 paired plasma samples from 112 stage II-III colorectal cancer patients by ST digital PCR and MT sequencing of 16 patient-specific variants. The strategies exhibited good concordance (90%, Cohen's Kappa 0.79), with highly correlated ctDNA quantifications (Pearson r = 0.985). A difference was observed in ctDNA detection preoperatively (ST 72/92, MT 88/92). However, no difference was observed immediately after surgery in recurrence (ST 11/22, MT 10/22) or nonrecurrence (both 2/34) patients. In serial samples, detection was similar within recurrence (ST 13/16, MT 14/16) and nonrecurrence (ST 3/49, MT 1/49) patients. Both approaches yielded similar lead times to standard-of-care radiology (ST 4.0 months, MT 4.1 months). Our findings do not support significant performance gains of the MT strategy over the ST strategy for postoperative ctDNA detection.
- Published
- 2022
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