TY - JOUR
T1 - Postoperative circulating tumour DNA is associated with pathologic response and recurrence-free survival after resection of colorectal cancer liver metastases
AU - Bolhuis, Karen
AU - van 't Erve, Iris
AU - Mijnals, Clinton
AU - Delis – van Diemen, Pien M.
AU - Huiskens, Joost
AU - Komurcu, Aysun
AU - Lopez-Yurda, Marta
AU - van den Broek, Daan
AU - Swijnenburg, Rutger-Jan
AU - Meijer, Gerrit A.
AU - Punt, Cornelis J. A.
AU - Fijneman, Remond J. A.
N1 - Funding Information:
R.J.A.F. reports grants and non-financial support from Personal Genome Diagnostics, grants from MERCK BV, non-financial support from Pacific Biosciences, non-financial support from Cergentis BV, outside the submitted work; In addition, R.J.A.F. has several patents pending.
Funding Information:
G.A.M. reports non-financial support from Exact Sciences, non-financial support from Sysmex, non-financial support from Sentinel CH. SpA, non-financial support from Personal Genome Diagnostics (PGDX), other from Hartwig Medical Foundation, grants from CZ (OWM Centrale Zorgverzekeraars groep Zorgverzekeraar u.a), other from Royal Philips, other from GlaxoSmithKline, other from Keosys SARL, other from Open Clinica LLC, other from Roche Diagnostics Nederland BV, other from The Hyve BV, other from Open Text, other from SURFSara BV, other from Vancis BV, other from CSC Computer Sciences BV, outside the submitted work; In addition, G.A.M. has several patents pending.
Funding Information:
This study was supported by scientific grants from the Dutch Cancer Society (Grant No. 10438) and Amgen, The Netherlands. We thank Mirthe Lanfermeijer, Doroth? Linders, Kalpana Ramkisoensing, Margriet Lemmens, Anne Bolijn and Marianne Tijssen for laboratory assistance. We thank all participating hospitals and their research teams involved in the CAIRO5 study. We would like to acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for supplying NKI-AVL Biobank material.
Publisher Copyright:
© 2021 The Authors
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Background: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS). Methods: Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system. Findings: With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p < 0.001). In univariable Cox regression analyses both postoperative detectable ctDNA (HR = 3.3, 95%CI = 1.1–9.6, p = 0.03) and pathologic non-response (HR = 4.6, 95%CI = 1.4–15, p = 0.01) were associated with poorer RFS and were strongly correlated (r = 0.88, p < 0.001). After adjusting for clinical characteristics in pairwise multivariable analyses, postoperative ctDNA status remained associated with RFS. Interpretation: The detection of postoperative ctDNA after secondary resection of CRLM is a promising prognostic factor for RFS and appeared to be highly correlated with pathologic response.
AB - Background: Recurrence rates after resection of colorectal cancer liver metastases (CRLM) are high and correlate with worse survival. Postoperative circulating tumour DNA (ctDNA) is a promising prognostic biomarker. Focusing on patients with resected CRLM, this study aimed to evaluate the association between the detection of postoperative ctDNA, pathologic response and recurrence-free survival (RFS). Methods: Twenty-three patients were selected from an ongoing phase-3 trial who underwent resection of RAS-mutant CRLM after induction systemic treatment. CtDNA analysis was performed by droplet digital PCR using blood samples collected at baseline, before and after resection. Pathologic response of CRLM was determined via the Tumour Regression Grading system. Findings: With a median follow-up of 19.6 months, the median RFS for patients with detectable (N = 6, [26%]) and undetectable (N = 17, [74%]) postoperative ctDNA was 4.8 versus 12.1 months, respectively. Among 21 patients with available tumour tissue, pathologic response in patients with detectable compared to undetectable postoperative ctDNA was found in one of six (17%) and 15 of 15 (100%) patients, respectively (p < 0.001). In univariable Cox regression analyses both postoperative detectable ctDNA (HR = 3.3, 95%CI = 1.1–9.6, p = 0.03) and pathologic non-response (HR = 4.6, 95%CI = 1.4–15, p = 0.01) were associated with poorer RFS and were strongly correlated (r = 0.88, p < 0.001). After adjusting for clinical characteristics in pairwise multivariable analyses, postoperative ctDNA status remained associated with RFS. Interpretation: The detection of postoperative ctDNA after secondary resection of CRLM is a promising prognostic factor for RFS and appeared to be highly correlated with pathologic response.
KW - Circulating tumour DNA
KW - Colorectal cancer
KW - Liver metastases
KW - Recurrences
KW - Resection
UR - https://www.scopus.com/pages/publications/85111489300
U2 - 10.1016/j.ebiom.2021.103498
DO - 10.1016/j.ebiom.2021.103498
M3 - Article
C2 - 34333237
SN - 2352-3964
VL - 70
JO - EBioMedicine
JF - EBioMedicine
M1 - 103498
ER -
SDG 3 Good Health and Well-being