دورية أكاديمية

Metastatic Colorectal Cancer Treatment Response Evaluation by Ultra-Deep Sequencing of Cell-Free DNA and Matched White Blood Cells.

التفاصيل البيبلوغرافية
العنوان: Metastatic Colorectal Cancer Treatment Response Evaluation by Ultra-Deep Sequencing of Cell-Free DNA and Matched White Blood Cells.
المؤلفون: van 't Erve I; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Medina JE; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Leal A; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Papp E; Personal Genome Diagnostics, Baltimore, Maryland., Phallen J; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Adleff V; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Chiao EJ; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Arun AS; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Bolhuis K; Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands., Simmons JK; Personal Genome Diagnostics, Baltimore, Maryland., Karandikar A; Personal Genome Diagnostics, Baltimore, Maryland., Valkenburg KC; Personal Genome Diagnostics, Baltimore, Maryland., Sausen M; Personal Genome Diagnostics, Baltimore, Maryland., Angiuoli SV; Personal Genome Diagnostics, Baltimore, Maryland., Scharpf RB; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Punt CJA; Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands., Meijer GA; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., Velculescu VE; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Fijneman RJA; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
المصدر: Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Mar 01; Vol. 29 (5), pp. 899-909.
نوع المنشور: Clinical Trial, Phase III; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Denville, NJ : The Association, c1995-
مواضيع طبية MeSH: Cell-Free Nucleic Acids*/genetics , Circulating Tumor DNA*/genetics , Colonic Neoplasms* , Rectal Neoplasms*, Humans ; Biomarkers, Tumor/genetics ; DNA, Neoplasm/genetics ; High-Throughput Nucleotide Sequencing ; Mutation ; Prospective Studies
مستخلص: 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.
(©2022 The Authors; Published by the American Association for Cancer Research.)
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المشرفين على المادة: 0 (Biomarkers, Tumor)
0 (Cell-Free Nucleic Acids)
0 (Circulating Tumor DNA)
0 (DNA, Neoplasm)
تواريخ الأحداث: Date Created: 20221219 Date Completed: 20230310 Latest Revision: 20230330
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9975664
DOI: 10.1158/1078-0432.CCR-22-2538
PMID: 36534496
قاعدة البيانات: MEDLINE
الوصف
تدمد:1557-3265
DOI:10.1158/1078-0432.CCR-22-2538