TY - JOUR
T1 - Effects of Metastatic Sites on Circulating Tumor DNA in Patients with Metastatic Colorectal Cancer
AU - Bando, Hideaki
AU - Nakamura, Yoshiaki
AU - Taniguchi, Hiroya
AU - Shiozawa, Manabu
AU - Yasui, Hisateru
AU - Esaki, Taito
AU - Kagawa, Yoshinori
AU - Denda, Tadamichi
AU - Satoh, Taroh
AU - Yamazaki, Kentaro
AU - Sunakawa, Yu
AU - Kato, Takeshi
AU - Goto, Masahiro
AU - Yuki, Satoshi
AU - Nishina, Tomohiro
AU - Oki, Eiji
AU - Shinozaki, Eiji
AU - Matsuhashi, Nobuhisa
AU - Takahashi, Naoki
AU - Tsuji, Akihito
AU - Ohtsubo, Koushiro
AU - Wakabayashi, Masashi
AU - Ikeno, Takashi
AU - Hata, Masayuki
AU - Odegaard, Justin I.
AU - Yoshino, Takayuki
N1 - Funding Information:
Supported by grants from the Japan Agency for Medical Research and Development (AMED) (no. 19ck0106445h0002 to Y.N.), National Cancer Center Research and Development Fund (no. 31-A-5 to Atsushi Ohtsu), and SCRUM-Japan Funds.
Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - PURPOSELow concordance between plasma-based and tissue-based tests for determining the RAS mutational status have been reported in some but not all patients with limited-extent metastatic colorectal cancer (mCRC). In this study, we investigated the relationship between metastatic site and circulating tumor DNA (ctDNA) detection using ctDNA genotyping, an alternative to tissue genotyping for precision oncology.MATERIALS AND METHODSWe investigated the relationship between metastatic site and ctDNA detection using Guardant360, a next-generation sequencing ctDNA assay, in mCRC patients with single-organ metastasis in the SCRUM-Japan GOZILA study (UMIN000029315).RESULTSOf 1,187 patients with mCRC enrolled in GOZILA, 138 were eligible (49 with liver-only, 15 with lymph node-only, 27 with peritoneum-only, and 47 with lung-only metastases). The concordance of RAS/BRAF status between Guaradant360 and tissue in vitro diagnostic tests was 95.9% in patients with liver-only, 80.0% in lymph node-only, 56.0% in peritoneum-only, and 65.9% in lung-only metastases. ctDNA fraction, as measured by the median maximum variant allelic fraction (max VAF), and median number of detected variants were 23.1% and five in liver-only, 6.0% and five in lymph node-only, 0.4% and three in peritoneum-only, and 0.4% and three in lung-only metastases, respectively (all P <.001, Kruskal-Wallis test). Few patients with liver-only (2.0%) and lymph node-only metastasis (13.3%) had a max VAF < 0.2%, which is required to ensure a detection limit of 95%, but max VAF was more frequently < 0.2% in patients with lung-only (27.7%) or peritoneum-only metastasis (29.6%).CONCLUSIONPatients with lung-only and peritoneum-only metastatic disease have significantly lower levels of ctDNA, suggesting decreased clinical sensitivity for subclonal variants. This observation suggests that such patients may benefit from concurrent tissue and plasma testing to provide optimal genotyping for subsequent therapy selection.
AB - PURPOSELow concordance between plasma-based and tissue-based tests for determining the RAS mutational status have been reported in some but not all patients with limited-extent metastatic colorectal cancer (mCRC). In this study, we investigated the relationship between metastatic site and circulating tumor DNA (ctDNA) detection using ctDNA genotyping, an alternative to tissue genotyping for precision oncology.MATERIALS AND METHODSWe investigated the relationship between metastatic site and ctDNA detection using Guardant360, a next-generation sequencing ctDNA assay, in mCRC patients with single-organ metastasis in the SCRUM-Japan GOZILA study (UMIN000029315).RESULTSOf 1,187 patients with mCRC enrolled in GOZILA, 138 were eligible (49 with liver-only, 15 with lymph node-only, 27 with peritoneum-only, and 47 with lung-only metastases). The concordance of RAS/BRAF status between Guaradant360 and tissue in vitro diagnostic tests was 95.9% in patients with liver-only, 80.0% in lymph node-only, 56.0% in peritoneum-only, and 65.9% in lung-only metastases. ctDNA fraction, as measured by the median maximum variant allelic fraction (max VAF), and median number of detected variants were 23.1% and five in liver-only, 6.0% and five in lymph node-only, 0.4% and three in peritoneum-only, and 0.4% and three in lung-only metastases, respectively (all P <.001, Kruskal-Wallis test). Few patients with liver-only (2.0%) and lymph node-only metastasis (13.3%) had a max VAF < 0.2%, which is required to ensure a detection limit of 95%, but max VAF was more frequently < 0.2% in patients with lung-only (27.7%) or peritoneum-only metastasis (29.6%).CONCLUSIONPatients with lung-only and peritoneum-only metastatic disease have significantly lower levels of ctDNA, suggesting decreased clinical sensitivity for subclonal variants. This observation suggests that such patients may benefit from concurrent tissue and plasma testing to provide optimal genotyping for subsequent therapy selection.
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U2 - 10.1200/PO.21.00535
DO - 10.1200/PO.21.00535
M3 - Article
C2 - 35544728
AN - SCOPUS:85131328647
SN - 2473-4284
VL - 6
JO - JCO Precision Oncology
JF - JCO Precision Oncology
M1 - e2100535
ER -
