Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers

PurposePatients with advanced/relapsed rare cancers have few treatment options. Analysis of circulating tumor DNA in plasma may identify actionable genomic biomarkers using a non-invasive approach.Patients and MethodsRare cancer patients underwent prospective plasma-based NGS testing. Tissue NGS to...

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Autores principales:	Hitomi Sumiyoshi Okuma, Kan Yonemori, Yuki Kojima, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Susumu Hijioka, Keiko Wakakuwa, Ken Kato, Akihiro Hirakawa, Aya Kuchiba, Takashi Kubo, Hitoshi Ichikawa, Akihiko Yoshida, Yasushi Yatabe, Kenichi Nakamura, Hiroyuki Mano, Noboru Yamamoto, Yasuhiro Fujiwara
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	rare cancer CtDNA (circulating tumor DNA) precision medicine soft tissue sarcoma targeted therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/35ecf0472ced44858aa96591a8e7fa2a
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spelling	oai:doaj.org-article:35ecf0472ced44858aa96591a8e7fa2a2021-11-30T18:58:15ZClinical Utility of Circulating Tumor DNA in Advanced Rare Cancers2234-943X10.3389/fonc.2021.732525https://doaj.org/article/35ecf0472ced44858aa96591a8e7fa2a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.732525/fullhttps://doaj.org/toc/2234-943XPurposePatients with advanced/relapsed rare cancers have few treatment options. Analysis of circulating tumor DNA in plasma may identify actionable genomic biomarkers using a non-invasive approach.Patients and MethodsRare cancer patients underwent prospective plasma-based NGS testing. Tissue NGS to test concordance was also conducted. Plasma DNA alterations were assessed for incidence, functional impact, therapeutic implications, correlation to survival, and comparison with tissue NGS.ResultsNinety-eight patients were analyzed. Diseases included soft-tissue sarcoma, ovarian carcinoma, and others. Mean turn-around-time for results was 9.5 days. Seventy-six patients had detectable gene alterations in plasma, with a median of 2.8 alterations/patient. Sixty patients had a likely pathogenic alteration. Five received matched-therapy based on plasma NGS results. Two developed known resistance mutations while on targeted therapy. Patients with an alteration having VAF ≥5% had a significantly shorter survival compared to those of lower VAF. Tissue NGS results from eleven of 22 patients showed complete or partial concordance with plasma NGS.ConclusionPlasma NGS testing is less invasive and capable of identifying alterations in advanced rare cancers in a clinically meaningful timeframe. It should be further studied as a prospective enrollment assay in interventional studies for patients with rare advanced stage cancers.Clinical Registration[https://www.umin.ac.jp/ctr/index-j.htm], identifier UMIN000034394. Hitomi Sumiyoshi OkumaHitomi Sumiyoshi OkumaKan YonemoriYuki KojimaMaki TaniokaKazuki SudoEmi NoguchiSusumu HijiokaKeiko WakakuwaKen KatoAkihiro HirakawaAya KuchibaTakashi KuboHitoshi IchikawaAkihiko YoshidaYasushi YatabeKenichi NakamuraHiroyuki ManoNoboru YamamotoYasuhiro FujiwaraYasuhiro FujiwaraFrontiers Media S.A.articlerare cancerCtDNA (circulating tumor DNA)precision medicinesoft tissue sarcomatargeted therapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	rare cancer CtDNA (circulating tumor DNA) precision medicine soft tissue sarcoma targeted therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	rare cancer CtDNA (circulating tumor DNA) precision medicine soft tissue sarcoma targeted therapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hitomi Sumiyoshi Okuma Hitomi Sumiyoshi Okuma Kan Yonemori Yuki Kojima Maki Tanioka Kazuki Sudo Emi Noguchi Susumu Hijioka Keiko Wakakuwa Ken Kato Akihiro Hirakawa Aya Kuchiba Takashi Kubo Hitoshi Ichikawa Akihiko Yoshida Yasushi Yatabe Kenichi Nakamura Hiroyuki Mano Noboru Yamamoto Yasuhiro Fujiwara Yasuhiro Fujiwara Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers
description	PurposePatients with advanced/relapsed rare cancers have few treatment options. Analysis of circulating tumor DNA in plasma may identify actionable genomic biomarkers using a non-invasive approach.Patients and MethodsRare cancer patients underwent prospective plasma-based NGS testing. Tissue NGS to test concordance was also conducted. Plasma DNA alterations were assessed for incidence, functional impact, therapeutic implications, correlation to survival, and comparison with tissue NGS.ResultsNinety-eight patients were analyzed. Diseases included soft-tissue sarcoma, ovarian carcinoma, and others. Mean turn-around-time for results was 9.5 days. Seventy-six patients had detectable gene alterations in plasma, with a median of 2.8 alterations/patient. Sixty patients had a likely pathogenic alteration. Five received matched-therapy based on plasma NGS results. Two developed known resistance mutations while on targeted therapy. Patients with an alteration having VAF ≥5% had a significantly shorter survival compared to those of lower VAF. Tissue NGS results from eleven of 22 patients showed complete or partial concordance with plasma NGS.ConclusionPlasma NGS testing is less invasive and capable of identifying alterations in advanced rare cancers in a clinically meaningful timeframe. It should be further studied as a prospective enrollment assay in interventional studies for patients with rare advanced stage cancers.Clinical Registration[https://www.umin.ac.jp/ctr/index-j.htm], identifier UMIN000034394.
format	article
author	Hitomi Sumiyoshi Okuma Hitomi Sumiyoshi Okuma Kan Yonemori Yuki Kojima Maki Tanioka Kazuki Sudo Emi Noguchi Susumu Hijioka Keiko Wakakuwa Ken Kato Akihiro Hirakawa Aya Kuchiba Takashi Kubo Hitoshi Ichikawa Akihiko Yoshida Yasushi Yatabe Kenichi Nakamura Hiroyuki Mano Noboru Yamamoto Yasuhiro Fujiwara Yasuhiro Fujiwara
author_facet	Hitomi Sumiyoshi Okuma Hitomi Sumiyoshi Okuma Kan Yonemori Yuki Kojima Maki Tanioka Kazuki Sudo Emi Noguchi Susumu Hijioka Keiko Wakakuwa Ken Kato Akihiro Hirakawa Aya Kuchiba Takashi Kubo Hitoshi Ichikawa Akihiko Yoshida Yasushi Yatabe Kenichi Nakamura Hiroyuki Mano Noboru Yamamoto Yasuhiro Fujiwara Yasuhiro Fujiwara
author_sort	Hitomi Sumiyoshi Okuma
title	Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers
title_short	Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers
title_full	Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers
title_fullStr	Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers
title_full_unstemmed	Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers
title_sort	clinical utility of circulating tumor dna in advanced rare cancers
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/35ecf0472ced44858aa96591a8e7fa2a
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Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers

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