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Date publication
avril 2022
Journal
Analytical chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent
Tous les auteurs :
Callens C, Bidard FC, Curto-Taribo A, Trabelsi-Grati O, Melaabi S, Delaloge S, Hardy-Bessard AC, Bachelot T, Clatot F, De La Motte Rouge T, Canon JL, Arnould L, Andre F, Marques S, Stern MH, Pierga JY, Vincent-Salomon A, Benoist C, Jeannot E, Berger F, Bieche I, Pradines A
Lien Pubmed
Résumé
The clinical actionability of circulating tumor DNA requires sensitive detection methods with a short turnaround time. In the PADA-1 phase 3 trial (NCT03079011), metastatic breast cancer patients treated with an aromatase inhibitor and palbociclib were screened every 2 months for activating mutations in blood (). We report the feasibility of the droplet digital polymerase chain reaction (ddPCR) and cross-validation with next-generation sequencing (NGS). testing was centralized in two platforms using the same ddPCR assay. Results were reported as copies/mL of plasma and mutant allele frequency (MAF). We analyzed 200 positive ddPCR samples with an NGS assay (0.5-1% sensitivity). Overall, 12,552 blood samples were collected from 1017 patients from 83 centers. Among the 12,525 available samples with ddPCR results, 11,533 (92%) were -negative. A total of 267 patients newly displayed (26% patients/2% samples) with a median copy number of 14/mL (range: 4-1225) and a median MAF of 0.83% (0.11-35), 648 samples (20% patients/5% samples) displayed persistent , and 77 (<1%) samples encountered a technical failure. The median turnaround time from blood drawing to result notification was 13 days (Q1:9; Q3:21 days). Among 200 ddPCR-positive samples tested, NGS detected in 168 (84%); 25 of the 32 cases missed by NGS had low MAF and/or low coverage. In these 200 samples, MAF by both techniques had an excellent intraclass correlation coefficient (ICC = 0.93; 95% CI [0.85; 0.97]). These results from a large-scale trial support the feasibility and accuracy of real-time tracking by ddPCR, opening new opportunities for therapeutic interventions.
Référence
Anal Chem. 2022 Apr 13;:
