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Journal of Cancer Research and Clinical Oncology

Published in:

01-09-2018 | Original Article – Cancer Research

Relationship between post-surgery detection of methylated circulating tumor DNA with risk of residual disease and recurrence-free survival

Authors: David H. Murray, Erin L. Symonds, Graeme P. Young, Susan Byrne, Philippa Rabbitt, Amitesh Roy, Kathryn Cornthwaite, Christos S. Karapetis, Susanne K. Pedersen

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2018

Abstract

Purpose

Methylation in IKZF1 and BCAT1 are common events in colorectal cancer (CRC). They are often detected in blood as circulating tumor DNA (ctDNA) at diagnosis and disappear after surgery in most CRC patients. A prospective study was conducted to determine the relationship between detection of these markers following surgery and risk for residual disease and for recurrence.

Methods

ctDNA status with methylated BCAT1 and IKZF1 was determined within 12 months of surgical resection of CRC, and was related to presence of or risk for residual disease (margins involved, metastases present or nature of node involvement), and to recurrence-free survival.

Results

Blood was collected from 172 CRC patients after surgery and 28 (16%) were ctDNA positive. Recurrence was diagnosed in 23 of the 138 with clinical follow-up after surgery (median follow-up 23.3 months, IQR 14.3–29.5). Multivariate modeling indicated that features suggestive of residual disease were an independent predictor of post-surgery ctDNA status: cases with any of three features (close resection margins, apical node involved, or distant metastases) were 5.3 times (95% CI 1.5–18.4, p = 0.008) more likely to be ctDNA positive. Multivariate analysis showed that post-surgery ctDNA positivity was independently associated with an increased risk of recurrence (HR 3.8, 1.5–9.5, p = 0.004).

Conclusions

CRC cases positive for methylated ctDNA after surgery are at increased risk of residual disease and subsequently recurrence. This could have implications for guiding recommendations for adjuvant therapy and surveillance strategies. Randomized studies are now indicated to determine if monitoring cases with these biomarkers leads to survival benefit.

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Title: Relationship between post-surgery detection of methylated circulating tumor DNA with risk of residual disease and recurrence-free survival
Authors: David H. Murray
Erin L. Symonds
Graeme P. Young
Susan Byrne
Philippa Rabbitt
Amitesh Roy
Kathryn Cornthwaite
Christos S. Karapetis
Susanne K. Pedersen
Publication date: 01-09-2018
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 9/2018
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-018-2701-x

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