Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

Purpose: Nearly 50% of patients recur within two years after curatively intended resection of colorectal cancer liver metastasis (CRLM). The optimal surveillance strategy is unknown due to the lack of evidence. Here, we explored the potential for improving postoperative CRLM surveillance by performing serial circulating tumour DNA (ctDNA) assessments parallel to standard-of-care surveillance. Experimental design: 499 prospectively collected serial plasma samples from 96 patients undergoing CRLM resection were analysed using the tumour-agnostic methylation multiplex droplet-digital PCR test ‘TriMeth’. Results: Patients with ctDNA postoperatively or post adjuvant chemotherapy experienced a significant lower recurrence-free survival than patients without ctDNA (hazard ratio (HR) 4.5; P < 0.0001 and HR 8.4, P < 0.0001). ctDNA status was a stronger predictor of recurrence than standard clinical risk factors and carcinoembryonic antigen. Serial TriMeth analysis detected ctDNA before radiological recurrence in 55.6% of ctDNA-positive patients, with up to 10.6 months lead-time (median 3.1 months). During surveillance, 24% of patients had inconclusive CT scans, which was associated with a significant delay in recurrence diagnosis (median 3.5 months versus 1.0 month, P < 0.0001). Uniquely, ctDNA status at the time of inconclusive CT scans predicted recurrence with positive and negative predictive values of 100%, and 75% (P = 0.0003). Serial TriMeth analysis allowed ctDNA growth rate assessment and revealed that fast ctDNA growth was associated with poor overall survival (HR: 1.6, P = 0.0052). Conclusions: Serial postoperative ctDNA analysis has a strong prognostic value and is more sensitive for recurrence detection than standard-of-care CRLM surveillance tools. Altogether, TriMeth provides several opportunities for improving postoperative surveillance of CRLM patients.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Cancer
Vol/bind163
Sider (fra-til)163-176
Antal sider14
ISSN0959-8049
DOI
StatusUdgivet - mar. 2022

Bibliografisk note

Funding Information:
This study was supported by the Novo Nordisk Foundation [NNF17OC0025052 (Andersen)]; the Danish Cancer Society [R133-A8520-00-S41 (Andersen), R146-A9466-16-S2 (Andersen), R231-A13845 (Andersen) and R257-A14700 (Andersen)]; Cancer Research UK [C6199/A26932 (Andersen)]; Innovation Fund Denmark [9068-00046B (Andersen)]; Aage & Johanne Louis-Hansens foundation [j.nr. 18-2B-2525 (Andersen)]; NEYE foundation [2018-02-23(?gaard)]; Dansk kr?ftforsknings fond [DKF-2018-14 - (207) (?gaard)]; Knud & Edith Eriksens foundation [j.nr. 62786 (?gaard)]; Eva & Henry Fr?nkels foundation [2018-09-09 (?gaard)]; Dagmar Marshall foundation [j.nr. 500020 (?gaard)]; Emil C. Hertz & Inger Hertz foundation [j.nr. KJR-13016 (?gaard)]; Frimodt Heineke foundation [2018-05-02 (?gaard)]; Aarhus University, and Aarhus University Hospital. The opinions, results, and conclusions reported in this article are those of the authors, and are independent from the funding sources.

Funding Information:
This study was supported by the Novo Nordisk Foundation [ NNF17OC0025052 (Andersen)]; the Danish Cancer Society [ R133-A8520-00-S41 (Andersen), R146-A9466-16-S2 (Andersen), R231-A13845 (Andersen) and R257-A14700 (Andersen)]; Cancer Research UK [ C6199/A26932 (Andersen)]; Innovation Fund Denmark [ 9068-00046B (Andersen)]; Aage & Johanne Louis-Hansens foundation [j.nr. 18-2B-2525 (Andersen)]; NEYE foundation [ 2018-02-23 (Øgaard)]; Dansk kræftforsknings fond [ DKF-2018-14 - (207) (Øgaard)]; Knud & Edith Eriksens foundation [j.nr. 62786 (Øgaard)]; Eva & Henry Frænkels foundation [ 2018-09-09 (Øgaard)]; Dagmar Marshall foundation [j.nr. 500020 (Øgaard)]; Emil C. Hertz & Inger Hertz foundation [j.nr. KJR-13016 (Øgaard)]; Frimodt Heineke foundation [ 2018-05-02 (Øgaard)]; Aarhus University , and Aarhus University Hospital . The opinions, results, and conclusions reported in this article are those of the authors, and are independent from the funding sources.

Publisher Copyright:
© 2022 The Authors

Se relationer på Aarhus Universitet Citationsformater

ID: 262030890