Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR

Abstract Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were e...

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Autores principales:	Yoojoo Lim, Sheehyun Kim, Jun-Kyu Kang, Hwang-Phill Kim, Hoon Jang, Hyojun Han, Hyoki Kim, Min Jung Kim, Kyung-Hun Lee, Seung-Bum Ryoo, Ji Won Park, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/743bbc06cf9748eeaadef63b4ff5bb41
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spelling	oai:doaj.org-article:743bbc06cf9748eeaadef63b4ff5bb412021-12-02T18:50:51ZCirculating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR10.1038/s41598-021-95345-42045-2322https://doaj.org/article/743bbc06cf9748eeaadef63b4ff5bb412021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95345-4https://doaj.org/toc/2045-2322Abstract Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (< 1%) at the first evaluation showed significantly better PFS (p < 0.001), and the average VAF change further discriminated the PFS in the patients in partial response (p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome.Yoojoo LimSheehyun KimJun-Kyu KangHwang-Phill KimHoon JangHyojun HanHyoki KimMin Jung KimKyung-Hun LeeSeung-Bum RyooJi Won ParkSeung-Yong JeongKyu Joo ParkGyeong Hoon KangSae-Won HanTae-You KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoojoo Lim Sheehyun Kim Jun-Kyu Kang Hwang-Phill Kim Hoon Jang Hyojun Han Hyoki Kim Min Jung Kim Kyung-Hun Lee Seung-Bum Ryoo Ji Won Park Seung-Yong Jeong Kyu Joo Park Gyeong Hoon Kang Sae-Won Han Tae-You Kim Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR
description	Abstract Circulating tumor DNA (ctDNA) may reveal dynamic tumor status during therapy. We conducted serial ctDNA analysis to investigate potential association with clinical outcome in metastatic colorectal cancer (mCRC) patients receiving chemotherapy. Tissue KRAS/NRAS wild-type mCRC patients were enrolled and treated with first-line cetuximab-containing chemotherapy. ctDNA isolated from plasma were analyzed by next generation sequencing (NGS) with 16 targeted gene panel. Among 93 patients, 84 (90.3%) had at least 1 somatic mutation in baseline ctDNA samples (average 2.74). Five patients with KRAS or NRAS hotspot mutation in the ctDNA showed significantly worse progression-free survival (PFS) (p = 0.029). Changes in average variant allele frequency (VAF) in ctDNA showed significant correlation with tumor size change at the time of first response evaluation (p = 0.020) and progressive disease (PD) (p = 0.042). Patients whose average VAF decreased below cutoff (< 1%) at the first evaluation showed significantly better PFS (p < 0.001), and the average VAF change further discriminated the PFS in the patients in partial response (p = 0.018). At the time of PD, 54 new mutations including KRAS and MAP2K1 emerged in ctDNA. ctDNA sequencing can provide mutation profile that could better reflect tumor mutation status and predict treatment outcome.
format	article
author	Yoojoo Lim Sheehyun Kim Jun-Kyu Kang Hwang-Phill Kim Hoon Jang Hyojun Han Hyoki Kim Min Jung Kim Kyung-Hun Lee Seung-Bum Ryoo Ji Won Park Seung-Yong Jeong Kyu Joo Park Gyeong Hoon Kang Sae-Won Han Tae-You Kim
author_facet	Yoojoo Lim Sheehyun Kim Jun-Kyu Kang Hwang-Phill Kim Hoon Jang Hyojun Han Hyoki Kim Min Jung Kim Kyung-Hun Lee Seung-Bum Ryoo Ji Won Park Seung-Yong Jeong Kyu Joo Park Gyeong Hoon Kang Sae-Won Han Tae-You Kim
author_sort	Yoojoo Lim
title	Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR
title_short	Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR
title_full	Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR
title_fullStr	Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR
title_full_unstemmed	Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR
title_sort	circulating tumor dna sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-egfr
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/743bbc06cf9748eeaadef63b4ff5bb41
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Circulating tumor DNA sequencing in colorectal cancer patients treated with first-line chemotherapy with anti-EGFR

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