@article{vanterve2023,
  title = {Metastatic {{Colorectal Cancer Treatment Response Evaluation}} by {{Ultra-Deep Sequencing}} of {{Cell-Free DNA}} and {{Matched White Blood Cells}}},
  author = {{van 't Erve}, Iris and Medina, Jamie E. and Leal, Alessandro and Papp, Eniko and Phallen, Jillian and Adleff, Vilmos and Chiao, Elaine Jiayuee and Arun, Adith S. and Bolhuis, Karen and Simmons, John K. and Karandikar, Aanavi and Valkenburg, Kenneth C. and Sausen, Mark and Angiuoli, Samuel V. and Scharpf, Robert B. and Punt, Cornelis J. A. and Meijer, Gerrit A. and Velculescu, Victor E. and Fijneman, Remond J. A.},
  year = {2023},
  month = mar,
  journal = {Clin Cancer Res},
  volume = {29},
  number = {5},
  pages = {899--909},
  issn = {1557-3265},
  doi = {10.1158/1078-0432.CCR-22-2538},
  abstract = {PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.},
  langid = {english},
  pmcid = {PMC9975664},
  pmid = {36534496},
  keywords = {{Biomarkers, Tumor},Cell-Free Nucleic Acids,Circulating Tumor DNA,Colonic Neoplasms,{DNA, Neoplasm},High-Throughput Nucleotide Sequencing,Humans,Mutation,Prospective Studies,Rectal Neoplasms},
  file = {/Users/rscharpf/Zotero/storage/2VGIA7HE/van 't Erve et al. - 2023 - Metastatic Colorectal Cancer Treatment Response Ev.pdf}
}

