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Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy

PURPOSE: Circulating tumor DNA (ctDNA) genotyping on the basis of next-generation sequencing (NGS) may guide targeted therapy for metastatic colorectal cancer (mCRC). However, the validity of NGS-based ctDNA genotyping for RAS/BRAF V600E mutation assessment and the efficacy of anti-EGFR and BRAF-tar...

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Autores principales: Aoki, Yu, Nakamura, Yoshiaki, Denda, Tadamichi, Ohta, Takashi, Esaki, Taito, Shiozawa, Manabu, Yamaguchi, Kensei, Yamazaki, Kentaro, Sunakawa, Yu, Kato, Takeshi, Okano, Naohiro, Taniguchi, Hiroya, Sato, Taro, Oki, Eiji, Nishina, Tomohiro, Komatsu, Yoshito, Matsuhashi, Nobuhisa, Goto, Masahiro, Yasui, Hisateru, Ohtsubo, Koushiro, Moriwaki, Toshikazu, Takahashi, Naoki, Horita, Yosuke, Boku, Shogen, Wakabayashi, Masashi, Ikeno, Takashi, Mitani, Ryuta, Yuasa, Mihoko, Yoshino, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309506/
https://www.ncbi.nlm.nih.gov/pubmed/37343204
http://dx.doi.org/10.1200/PO.22.00688
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author Aoki, Yu
Nakamura, Yoshiaki
Denda, Tadamichi
Ohta, Takashi
Esaki, Taito
Shiozawa, Manabu
Yamaguchi, Kensei
Yamazaki, Kentaro
Sunakawa, Yu
Kato, Takeshi
Okano, Naohiro
Taniguchi, Hiroya
Sato, Taro
Oki, Eiji
Nishina, Tomohiro
Komatsu, Yoshito
Matsuhashi, Nobuhisa
Goto, Masahiro
Yasui, Hisateru
Ohtsubo, Koushiro
Moriwaki, Toshikazu
Takahashi, Naoki
Horita, Yosuke
Boku, Shogen
Wakabayashi, Masashi
Ikeno, Takashi
Mitani, Ryuta
Yuasa, Mihoko
Yoshino, Takayuki
author_facet Aoki, Yu
Nakamura, Yoshiaki
Denda, Tadamichi
Ohta, Takashi
Esaki, Taito
Shiozawa, Manabu
Yamaguchi, Kensei
Yamazaki, Kentaro
Sunakawa, Yu
Kato, Takeshi
Okano, Naohiro
Taniguchi, Hiroya
Sato, Taro
Oki, Eiji
Nishina, Tomohiro
Komatsu, Yoshito
Matsuhashi, Nobuhisa
Goto, Masahiro
Yasui, Hisateru
Ohtsubo, Koushiro
Moriwaki, Toshikazu
Takahashi, Naoki
Horita, Yosuke
Boku, Shogen
Wakabayashi, Masashi
Ikeno, Takashi
Mitani, Ryuta
Yuasa, Mihoko
Yoshino, Takayuki
author_sort Aoki, Yu
collection PubMed
description PURPOSE: Circulating tumor DNA (ctDNA) genotyping on the basis of next-generation sequencing (NGS) may guide targeted therapy for metastatic colorectal cancer (mCRC). However, the validity of NGS-based ctDNA genotyping for RAS/BRAF V600E mutation assessment and the efficacy of anti-EGFR and BRAF-targeted therapies on the basis of ctDNA results remains unclear. PATIENTS AND METHODS: The performance of NGS-based ctDNA genotyping for RAS/BRAF V600E mutation assessment was compared with that of a validated polymerase chain reaction–based tissue testing in patients with mCRC enrolled in the GOZILA study, a nationwide plasma genotyping study. The primary end points were concordance rate, sensitivity, and specificity. The efficacy of anti-EGFR and BRAF-targeted therapies on the basis of ctDNA were also evaluated. RESULTS: In 212 eligible patients, the concordance rate, sensitivity, and specificity were 92.9% (95% CI, 88.6 to 96.0), 88.7% (95% CI, 81.1 to 94.0), and 97.2% (95% CI, 92.0 to 99.4) for RAS and 96.2% (95% CI, 92.7 to 98.4), 88.0% (95% CI, 68.8 to 97.5), and 97.3% (95% CI, 93.9 to 99.1) for BRAF V600E, respectively. In patients with a ctDNA fraction of ≥1.0%, sensitivity rose to 97.5% (95% CI, 91.2 to 99.7) and 100% (95% CI, 80.5 to 100.0) for RAS and BRAF V600E mutations, respectively. In addition to a low ctDNA fraction, previous chemotherapy, lung and peritoneal metastases, and interval between dates of tissue and blood collection were associated with discordance. The progression-free survival of anti-EGFR therapy and BRAF-targeted treatment was 12.9 months (95% CI, 8.1 to 18.5) and 3.7 (95% CI, 1.3 to not evaluated) months, respectively, for matched patients with RAS/BRAF V600E results by ctDNA. CONCLUSION: ctDNA genotyping effectively detected RAS/BRAF mutations, especially with sufficient ctDNA shedding. Clinical outcomes support ctDNA genotyping for determining the use of anti-EGFR and BRAF-targeted therapies in patients with mCRC.
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spelling pubmed-103095062023-06-30 Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy Aoki, Yu Nakamura, Yoshiaki Denda, Tadamichi Ohta, Takashi Esaki, Taito Shiozawa, Manabu Yamaguchi, Kensei Yamazaki, Kentaro Sunakawa, Yu Kato, Takeshi Okano, Naohiro Taniguchi, Hiroya Sato, Taro Oki, Eiji Nishina, Tomohiro Komatsu, Yoshito Matsuhashi, Nobuhisa Goto, Masahiro Yasui, Hisateru Ohtsubo, Koushiro Moriwaki, Toshikazu Takahashi, Naoki Horita, Yosuke Boku, Shogen Wakabayashi, Masashi Ikeno, Takashi Mitani, Ryuta Yuasa, Mihoko Yoshino, Takayuki JCO Precis Oncol ORIGINAL REPORTS PURPOSE: Circulating tumor DNA (ctDNA) genotyping on the basis of next-generation sequencing (NGS) may guide targeted therapy for metastatic colorectal cancer (mCRC). However, the validity of NGS-based ctDNA genotyping for RAS/BRAF V600E mutation assessment and the efficacy of anti-EGFR and BRAF-targeted therapies on the basis of ctDNA results remains unclear. PATIENTS AND METHODS: The performance of NGS-based ctDNA genotyping for RAS/BRAF V600E mutation assessment was compared with that of a validated polymerase chain reaction–based tissue testing in patients with mCRC enrolled in the GOZILA study, a nationwide plasma genotyping study. The primary end points were concordance rate, sensitivity, and specificity. The efficacy of anti-EGFR and BRAF-targeted therapies on the basis of ctDNA were also evaluated. RESULTS: In 212 eligible patients, the concordance rate, sensitivity, and specificity were 92.9% (95% CI, 88.6 to 96.0), 88.7% (95% CI, 81.1 to 94.0), and 97.2% (95% CI, 92.0 to 99.4) for RAS and 96.2% (95% CI, 92.7 to 98.4), 88.0% (95% CI, 68.8 to 97.5), and 97.3% (95% CI, 93.9 to 99.1) for BRAF V600E, respectively. In patients with a ctDNA fraction of ≥1.0%, sensitivity rose to 97.5% (95% CI, 91.2 to 99.7) and 100% (95% CI, 80.5 to 100.0) for RAS and BRAF V600E mutations, respectively. In addition to a low ctDNA fraction, previous chemotherapy, lung and peritoneal metastases, and interval between dates of tissue and blood collection were associated with discordance. The progression-free survival of anti-EGFR therapy and BRAF-targeted treatment was 12.9 months (95% CI, 8.1 to 18.5) and 3.7 (95% CI, 1.3 to not evaluated) months, respectively, for matched patients with RAS/BRAF V600E results by ctDNA. CONCLUSION: ctDNA genotyping effectively detected RAS/BRAF mutations, especially with sufficient ctDNA shedding. Clinical outcomes support ctDNA genotyping for determining the use of anti-EGFR and BRAF-targeted therapies in patients with mCRC. Wolters Kluwer Health 2023-06-21 /pmc/articles/PMC10309506/ /pubmed/37343204 http://dx.doi.org/10.1200/PO.22.00688 Text en © 2023 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle ORIGINAL REPORTS
Aoki, Yu
Nakamura, Yoshiaki
Denda, Tadamichi
Ohta, Takashi
Esaki, Taito
Shiozawa, Manabu
Yamaguchi, Kensei
Yamazaki, Kentaro
Sunakawa, Yu
Kato, Takeshi
Okano, Naohiro
Taniguchi, Hiroya
Sato, Taro
Oki, Eiji
Nishina, Tomohiro
Komatsu, Yoshito
Matsuhashi, Nobuhisa
Goto, Masahiro
Yasui, Hisateru
Ohtsubo, Koushiro
Moriwaki, Toshikazu
Takahashi, Naoki
Horita, Yosuke
Boku, Shogen
Wakabayashi, Masashi
Ikeno, Takashi
Mitani, Ryuta
Yuasa, Mihoko
Yoshino, Takayuki
Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy
title Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy
title_full Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy
title_fullStr Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy
title_full_unstemmed Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy
title_short Clinical Validation of Plasma-Based Genotyping for RAS and BRAF V600E Mutation in Metastatic Colorectal Cancer: SCRUM-Japan GOZILA Substudy
title_sort clinical validation of plasma-based genotyping for ras and braf v600e mutation in metastatic colorectal cancer: scrum-japan gozila substudy
topic ORIGINAL REPORTS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309506/
https://www.ncbi.nlm.nih.gov/pubmed/37343204
http://dx.doi.org/10.1200/PO.22.00688
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