Cargando…

Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study

Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the sign...

Descripción completa

Detalles Bibliográficos
Autores principales: Takada, Kohichi, Kubo, Tomohiro, Kikuchi, Junko, Yoshida, Makoto, Murota, Ayako, Arihara, Yohei, Nakamura, Hajime, Nagashima, Hiroyuki, Tanabe, Hiroki, Sugita, Shintaro, Tanaka, Yumi, Miura, Ayana, Ohhara, Yoshihito, Ishiguro, Atsushi, Yokouchi, Hiroshi, Kawamoto, Yasuyuki, Mizukami, Yusuke, Ohnishi, Hirofumi, Kinoshita, Ichiro, Sakurai, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478541/
https://www.ncbi.nlm.nih.gov/pubmed/36119486
http://dx.doi.org/10.3389/fonc.2022.988527
_version_ 1784790596435574784
author Takada, Kohichi
Kubo, Tomohiro
Kikuchi, Junko
Yoshida, Makoto
Murota, Ayako
Arihara, Yohei
Nakamura, Hajime
Nagashima, Hiroyuki
Tanabe, Hiroki
Sugita, Shintaro
Tanaka, Yumi
Miura, Ayana
Ohhara, Yoshihito
Ishiguro, Atsushi
Yokouchi, Hiroshi
Kawamoto, Yasuyuki
Mizukami, Yusuke
Ohnishi, Hirofumi
Kinoshita, Ichiro
Sakurai, Akihiro
author_facet Takada, Kohichi
Kubo, Tomohiro
Kikuchi, Junko
Yoshida, Makoto
Murota, Ayako
Arihara, Yohei
Nakamura, Hajime
Nagashima, Hiroyuki
Tanabe, Hiroki
Sugita, Shintaro
Tanaka, Yumi
Miura, Ayana
Ohhara, Yoshihito
Ishiguro, Atsushi
Yokouchi, Hiroshi
Kawamoto, Yasuyuki
Mizukami, Yusuke
Ohnishi, Hirofumi
Kinoshita, Ichiro
Sakurai, Akihiro
author_sort Takada, Kohichi
collection PubMed
description Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.
format Online
Article
Text
id pubmed-9478541
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-94785412022-09-17 Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study Takada, Kohichi Kubo, Tomohiro Kikuchi, Junko Yoshida, Makoto Murota, Ayako Arihara, Yohei Nakamura, Hajime Nagashima, Hiroyuki Tanabe, Hiroki Sugita, Shintaro Tanaka, Yumi Miura, Ayana Ohhara, Yoshihito Ishiguro, Atsushi Yokouchi, Hiroshi Kawamoto, Yasuyuki Mizukami, Yusuke Ohnishi, Hirofumi Kinoshita, Ichiro Sakurai, Akihiro Front Oncol Oncology Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC. Frontiers Media S.A. 2022-09-02 /pmc/articles/PMC9478541/ /pubmed/36119486 http://dx.doi.org/10.3389/fonc.2022.988527 Text en Copyright © 2022 Takada, Kubo, Kikuchi, Yoshida, Murota, Arihara, Nakamura, Nagashima, Tanabe, Sugita, Tanaka, Miura, Ohhara, Ishiguro, Yokouchi, Kawamoto, Mizukami, Ohnishi, Kinoshita and Sakurai https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Takada, Kohichi
Kubo, Tomohiro
Kikuchi, Junko
Yoshida, Makoto
Murota, Ayako
Arihara, Yohei
Nakamura, Hajime
Nagashima, Hiroyuki
Tanabe, Hiroki
Sugita, Shintaro
Tanaka, Yumi
Miura, Ayana
Ohhara, Yoshihito
Ishiguro, Atsushi
Yokouchi, Hiroshi
Kawamoto, Yasuyuki
Mizukami, Yusuke
Ohnishi, Hirofumi
Kinoshita, Ichiro
Sakurai, Akihiro
Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study
title Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study
title_full Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study
title_fullStr Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study
title_full_unstemmed Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study
title_short Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study
title_sort effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: a prospective multicenter study
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478541/
https://www.ncbi.nlm.nih.gov/pubmed/36119486
http://dx.doi.org/10.3389/fonc.2022.988527
work_keys_str_mv AT takadakohichi effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT kubotomohiro effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT kikuchijunko effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT yoshidamakoto effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT murotaayako effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT ariharayohei effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT nakamurahajime effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT nagashimahiroyuki effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT tanabehiroki effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT sugitashintaro effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT tanakayumi effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT miuraayana effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT ohharayoshihito effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT ishiguroatsushi effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT yokouchihiroshi effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT kawamotoyasuyuki effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT mizukamiyusuke effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT ohnishihirofumi effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT kinoshitaichiro effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy
AT sakuraiakihiro effectofcomprehensivecancergenomicprofilingontherapeuticstrategiesandclinicaloutcomesinpatientswithadvancedbiliarytractcanceraprospectivemulticenterstudy