journal contribution
posted on 2023-04-01, 00:22 authored by Iris van 't Erve, Jamie E. Medina, Alessandro Leal, Eniko Papp, Jillian Phallen, Vilmos Adleff, Elaine Jiayuee Chiao, Adith S. Arun, Karen Bolhuis, John K. Simmons, Aanavi Karandikar, Kenneth C. Valkenburg, Mark Sausen, Samuel V. Angiuoli, Robert B. Scharpf, Cornelis J.A. Punt, Gerrit A. Meijer, Victor E. Velculescu, Remond J.A. Fijneman The Supplementary Figures file consists of Supplementary Figures 1 to 15 belonging to the manuscript: "Metastatic colorectal cancer treatment response evaluation by ultra-deep sequencing of cell-free DNA and matched white blood cells"
Funding
KWF Kankerbestrijding (DCS)
Stand Up To Cancer (SU2C)
Mark Foundation For Cancer Research (The Mark Foundation for Cancer Research)
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF)
Gray Foundation
Commonwealth Foundation for Cancer Research Foundation
Cole Foundation (CF)
Foundation for the National Institutes of Health (FNIH)
History
ARTICLE ABSTRACT
Circulating tumor DNA (ctDNA) has the potential to guide therapy selection and monitor treatment response in patients with metastatic cancer. However, germline and clonal hematopoiesis–associated alterations can confound identification of tumor-specific mutations in cell-free DNA (cfDNA), often requiring additional sequencing of tumor tissue. The current study assessed whether ctDNA-based treatment response monitoring could be performed in a tumor tissue–independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC)-derived DNA.
In total, 183 cfDNA and 49 WBC samples, along with 28 tissue samples, from 52 patients with metastatic colorectal cancer participating in the prospective phase III CAIRO5 clinical trial were analyzed using an ultra-deep targeted sequencing liquid biopsy assay.
The combined cfDNA and WBC analysis prevented false-positives due to germline or hematopoietic variants in 40% of patients. Patient-matched tumor tissue sequencing did not provide additional information. Longitudinal analyses of ctDNA were more predictive of overall survival than standard-of-care radiological response evaluation. ctDNA mutations related to primary or acquired resistance to panitumumab were identified in 42% of patients.
Accurate calling of ctDNA mutations for treatment response monitoring is feasible in a tumor tissue–independent manner by combined cfDNA and patient-matched WBC genomic DNA analysis. This tissue biopsy-independent approach simplifies sample logistics and facilitates the application of liquid biopsy ctDNA testing for evaluation of emerging therapy resistance, opening new avenues for early adaptation of treatment regimens.
