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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2023
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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. |
format | Online Article Text |
id | pubmed-10309506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
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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