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Peripheral Circulating Tumor DNA Detection Predicts Poor Outcomes After Liver Resection for Metastatic Colorectal Cancer

  • Raja R. Narayan
  • Debra A. Goldman
  • Mithat Gonen
  • Jonathan Reichel
  • Kety H. Huberman
  • Sandeep Raj
  • Agnes Viale
  • Nancy E. Kemeny
  • Peter J. Allen
  • Vinod P. Balachandran
  • Michael I. D’Angelica
  • Ronald P. DeMatteo
  • Jeffrey A. Drebin
  • William R. Jarnagin
  • T. Peter KinghamEmail author
Hepatobiliary Tumors

Abstract

Background

Liver resection can be curative for well-selected metastatic colorectal cancer (CRC) patients. Circulating tumor DNA (ctDNA) has shown promise as a biomarker for tumor dynamics and recurrence following CRC resection. This prospective pilot study investigated the use of ctDNA to predict disease outcome in resected CRC patients.

Methods

Between November 2014 and November 2015, 60 patients with CRC were identified and prospectively enrolled. During liver resection, blood was drawn from peripheral (PERIPH), portal (PV), and hepatic (HV) veins, and 3–4 weeks postoperatively from a peripheral vein (POSTOP). Kappa statistics were used to compare mutated (mt) genes in tissue and ctDNA. Disease-specific and disease-free survival (DSS and DFS) were assessed from surgery with Kaplan–Meier and Cox methods.

Results

For the 59 eligible patients, the most commonly mutated genes were TP53 (mtTP53: 47.5%) and APC (mtAPC: 50.8%). Substantial to almost-perfect agreement was seen between ctDNA from PERIPH and PV (mtTP53: 89.8%, κ = 0.73, 95% confidence interval [CI] 0.53–0.93; mtAPC: 94.9%, κ = 0.83, 95% CI 0.64–1.00), as well as HV (mtTP53: 91.5%, κ = 0.78, 95% CI 0.60–0.96; mtAPC: 91.5%, κ = 0.73, 95% CI 0.51–0.95). Tumor mutations and PERIPH ctDNA had fair-to-moderate agreement (mtTP53: 72.9%, κ = 0.44, 95% CI 0.23–0.66; mtAPC: 61.0%, κ = 0.23, 95% CI 0.04–0.42). Detection of PERIPH mtTP53 was associated with worse 2-year DSS (mt+ 79% vs. mt− 90%, P = 0.024).

Conclusions

Peripheral blood reflects the perihepatic ctDNA signature. Disagreement between tissue and ctDNA mutations may reflect the true natural history of tumor genes or an assay limitation. Peripheral ctDNA detection before liver resection is associated with worse DSS.

Notes

Funding

This work was supported in part by the NIH/NCI P30 CA008748 Cancer Center Support Grant.

Disclosure

The authors declare that they have no conflict of interest.

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Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Raja R. Narayan
    • 1
    • 2
  • Debra A. Goldman
    • 3
  • Mithat Gonen
    • 3
  • Jonathan Reichel
    • 4
  • Kety H. Huberman
    • 4
  • Sandeep Raj
    • 4
  • Agnes Viale
    • 4
  • Nancy E. Kemeny
    • 5
  • Peter J. Allen
    • 1
  • Vinod P. Balachandran
    • 1
  • Michael I. D’Angelica
    • 1
  • Ronald P. DeMatteo
    • 1
  • Jeffrey A. Drebin
    • 1
  • William R. Jarnagin
    • 1
  • T. Peter Kingham
    • 1
    Email author
  1. 1.Department of Surgery, Hepatopancreatobiliary ServiceMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Department of SurgeryStanford University School of MedicineStanfordUSA
  3. 3.Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkUSA
  4. 4.Marie-Josée and Henry R. Kravis Center for Molecular OncologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  5. 5.Department of Medicine, Gastrointestinal Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkUSA

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