Targeted Sequencing of Circulating Tumor DNA to Monitor Genetic Variants and Therapeutic Response in Metastatic Colorectal Cancer

Molecular Cancer Therapeutics
Hung-Chih HsuTsai Sheng Yang

Abstract

Substantial improvements have been made in the management of metastatic colorectal cancer (mCRC) in the last two decades, but disease monitoring remains underdeveloped. Circulating tumor DNA (ctDNA) is a promising prognostic and predictive biomarker; however, ctDNA as a marker for mCRC patients is not well established, and there is still no consensus about how to utilize it most cost-effectively. In this study, we aim to investigate plasma ctDNA levels as a biomarker for therapeutic response of mCRC patients. We performed next-generation sequencing (NGS) by using a 12-gene panel to identify genetic variants in 136 tumor tissue and ctDNA samples from 32 mCRC patients. Genetic variants were detected in approximately 70% of samples, and there was a high concordance (85%) between tumor tissue and plasma ctDNA. We observed ctDNA changes in 18 follow-up patients, including the emergence of new variants. Changes in ctDNA levels significantly correlated with tumor shrinkage (P = 0.041), and patients with a ctDNA decrease >80% after treatment had a longer progression-free survival compared with patients with a ctDNA decrease of <80% (HR, 0.22; P = 0.015). The objective response rate among patients with a ctDNA decrease of >80% was bette...Continue Reading

References

May 15, 2002·Diseases of the Colon and Rectum·C GloverT G Allen-Mersh
Dec 4, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Halfdan Sørbye, Olav Dahl
Aug 2, 2008·Nature Medicine·Frank DiehlLuis A Diaz
Nov 11, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael Chao, Peter Gibbs
Jun 24, 2010·Cancer Research·Manickam JanakiramanDavid B Solit
Dec 17, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joost S VermaatEmile E Voest
Jul 20, 2012·Nature·UNKNOWN Cancer Genome Atlas Network
Feb 21, 2014·Science Translational Medicine·Chetan BettegowdaLuis A Diaz
Mar 19, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Jun 14, 2014·Journal of the National Comprehensive Cancer Network : JNCCN·Anya LitvakLeonard Saltz
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Apr 9, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J TieP Gibbs
May 9, 2015·PloS One·Kazuko SakaiKazuto Nishio
Jun 2, 2015·Nature Medicine·Giulia SiravegnaAlberto Bardelli
Oct 2, 2015·EBioMedicine·Daniela KandiolerUNKNOWN p53 Research Group and the Austrian Breast and Colorectal Study Group (ABCSG)
Mar 19, 2016·International Journal of Cancer. Journal International Du Cancer·Inger Marie LøesPer Eystein Lønning
Apr 28, 2016·The New England Journal of Medicine·H Gilbert Welch, Douglas J Robertson
Aug 16, 2016·Acta Medica (Hradec Králové)·Martin BeránekVladimír Palička
Apr 21, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jian-Ming XuZhi-Rong Qian
May 10, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jeremy C JonesAxel Grothey
Jun 4, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fanny GarlanAziz Zaanan
Jun 11, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lone V SchølerClaus L Andersen
Aug 30, 2017·PloS One·Allan A Lima PereiraVan Morris
Dec 3, 2017·Cancer Discovery·John H StricklerScott Kopetz

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Citations

Jan 12, 2019·F1000Research·Fabian Grass, Kellie Mathis
Aug 3, 2020·Journal of Translational Medicine·Jiaping LiYanhong Deng
Jan 17, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aparna R ParikhRyan B Corcoran
Jan 28, 2021·Annual Review of Medicine·Van K Morris, John H Strickler
Jan 11, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Robert P JonesJorge Barriuso
Feb 7, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paolo MancaFilippo Pietrantonio

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