Longitudinal analysis of plasma cell-free DNA by ultra-deep sequencing in stage I-III colorectal cancer patients: a prospective observational study

Publikation: KonferencebidragPosterForskning

Longitudinal analysis of plasma cell-free DNA by ultra-deep sequencing in stage I-III colorectal cancer patients: a prospective observational study

Thomas Reinert1, Tenna V. Henriksen1, Emil Christensen1, Shruti Sharma2, Raheleh Salari2, Himanshu Sethi2, Hsin-Ta Wu2, Svetlana Shchegrova2, Alexander Olson2, Scott Dashner2, Shruti Goel2, Ryan Swenerton2, Prashanthi Natarajan2, Tony Tin2, Hemant Pawar2, Lene H. Iversen1, Anders Husted Madsen 3, Cheng-Ho Jimmy Lin2, Bernhard Zimmermann2, Claus L. Andersen1
1Aarhus University Hospital, Aarhus, Denmark; 2Natera Inc, San Carlos, CA, USA; 3Regional Hospital Herning, Herning, Denmark

Background
Early detection of disease recurrence has been shown to improve survival in patients with colorectal cancer (CRC). Previous studies have analyzed circulating tumor DNA (ctDNA) to monitor tumor burden in CRC using small gene panels and ddPCR. Here, we use a personalized multiplex-PCR and NGS platform (SignateraTM RUO) to detect ctDNA in serially collected plasma samples to assess if ctDNA detection defines the subset of patients with high risk of recurrence both before and after adjuvant chemotherapy (ACT).

Methods
A cohort of 125 patients with stage I–III CRC, treated according to standard of care was analyzed. For each patient, tumor-specific panels of 16 mutations were designed using somatic mutation signatures obtained from WES. Plasma samples (n=795) collected pre- and post-surgery, and during ACT were analyzed. Recurrence-free survival was calculated for patients stratified by ctDNA status post-surgery (n=94) and post-ACT (n=58).

Results
ctDNA status after surgery, but prior to ACT, was assessed in 94 patients. Relapse was observed for 70% (7/10) of the ctDNA+, and only for 12% (10/84) of the ctDNA- patients. Effective ACT treatment was observed for 30% (3/10) of the post-operative ctDNA+ patients. These were consistently ctDNA- in post-ACT serially collected blood samples, and concordantly relapse free at end of follow-up. ctDNA status post-ACT was assessed in 58 patients. Radiologically confirmed relapse was observed for 100% (7/7) of the ctDNA+ and for 14% (7/51) of ctDNA- patients. On average ctDNA detected relapse 8.7 months earlier than standard-of-care CT-imaging

Conclusions
Serial post-operative ctDNA analysis enables stratification of patients into high or low recurrence risk subgroups, assessment of ACT treatment efficacy, and early detection of recurrence. Importantly, it also indicates that ACT can eliminate residual disease in up to 30% of the post- operative ctDNA+ patients and therefore can be a treatment option for ctDNA+ patients. In summary, ctDNA analysis has great potential to guide treatment decisions, both in the adjuvant and post-adjuvant settings.
OriginalsprogEngelsk
Udgivelsesår23 maj 2019
StatusUdgivet - 23 maj 2019
Begivenhed4th International Meeting on Cell-Free DNA - Metropol Københavns Professionshøjskole/University College Copenhagen, Sigurdsgade 26, 2200 Copenhagen N. Building A room 310., København, Danmark
Varighed: 23 maj 201924 maj 2019
http://cfdna2019.eu/program.html

Konference

Konference4th International Meeting on Cell-Free DNA
LokationMetropol Københavns Professionshøjskole/University College Copenhagen, Sigurdsgade 26, 2200 Copenhagen N. Building A room 310.
LandDanmark
ByKøbenhavn
Periode23/05/201924/05/2019
Internetadresse

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