Peripheral circulating tumor DNA detection predicts poor outcomes after liver resection for metastatic colorectal cancer Journal Article

Authors: Narayan, R. R.; Goldman, D. A.; Gonen, M.; Reichel, J.; Huberman, K. H.; Raj, S.; Viale, A.; Kemeny, N. E.; Allen, P. J.; Balachandran, V. P.; D’Angelica, M. I.; DeMatteo, R. P.; Drebin, J. A.; Jarnagin, W. R.; Kingham, T. P.
Article Title: Peripheral circulating tumor DNA detection predicts poor outcomes after liver resection for metastatic colorectal cancer
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. © 2019, Society of Surgical Oncology.
Keywords: adult; cancer survival; human tissue; treatment outcome; aged; gene mutation; major clinical study; cancer adjuvant therapy; cancer patient; disease free survival; antineoplastic agent; prospective study; tumor volume; protein p53; liver metastasis; blood sampling; pilot study; liver resection; tumor gene; disease specific survival; apc protein; predictive value; metastatic colorectal cancer; next generation sequencing; human; male; female; article; circulating tumor dna
Journal Title: Annals of Surgical Oncology
Volume: 26
Issue: 6
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2019-06-01
Start Page: 1824
End Page: 1832
Language: English
DOI: 10.1245/s10434-019-07201-5
PUBMED: 30706231
PROVIDER: scopus
PMCID: PMC6511310
Notes: Article -- Source: Scopus
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MSK Authors
  1. Ronald P DeMatteo
    610 DeMatteo
  2. Mithat Gonen
    726 Gonen
  3. Peter Allen
    449 Allen
  4. William R Jarnagin
    600 Jarnagin
  5. T Peter Kingham
    297 Kingham
  6. Agnes Viale
    208 Viale
  7. Nancy Kemeny
    364 Kemeny
  8. Debra Alyssa Goldman
    99 Goldman
  9. Jonathan Brett Reichel
    12 Reichel
  10. Sandeep Sunder Raj
    3 Raj
  11. Jeffrey Adam Drebin
    16 Drebin