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Effects of Metastatic Sites on Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer.
Bando, Hideaki; Nakamura, Yoshiaki; Taniguchi, Hiroya; Shiozawa, Manabu; Yasui, Hisateru; Esaki, Taito; Kagawa, Yoshinori; Denda, Tadamichi; Satoh, Taroh; Yamazaki, Kentaro; Sunakawa, Yu; Kato, Takeshi; Goto, Masahiro; Yuki, Satoshi; Nishina, Tomohiro; Oki, Eiji; Shinozaki, Eiji; Matsuhashi, Nobuhisa; Takahashi, Naoki; Tsuji, Akihito; Ohtsubo, Koushiro; Wakabayashi, Masashi; Ikeno, Takashi; Hata, Masayuki; Odegaard, Justin I; Yoshino, Takayuki.
Affiliation
  • Bando H; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • Nakamura Y; Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
  • Taniguchi H; Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • Shiozawa M; Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
  • Yasui H; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
  • Esaki T; Department of Surgery, Kanagawa Cancer Center, Yokohama, Japan.
  • Kagawa Y; Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
  • Denda T; Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
  • Satoh T; Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan.
  • Yamazaki K; Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan.
  • Sunakawa Y; Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
  • Kato T; Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shunto-gun, Japan.
  • Goto M; Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan.
  • Yuki S; Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.
  • Nishina T; Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Takatsuki, Japan.
  • Oki E; Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.
  • Shinozaki E; Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
  • Matsuhashi N; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Takahashi N; Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
  • Tsuji A; Department of Gastroenterological Surgery, Graduate School of Medicine, Gifu University, Gifu, Japan.
  • Ohtsubo K; Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
  • Wakabayashi M; Department of Clinical Oncology, Kagawa University Hospital, Kita-gun, Japan.
  • Ikeno T; Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
  • Hata M; Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
  • Odegaard JI; Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
  • Yoshino T; Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan.
JCO Precis Oncol ; 6: e2100535, 2022 04.
Article in En | MEDLINE | ID: mdl-35544728
ABSTRACT

PURPOSE:

Low 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

METHODS:

We 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).

RESULTS:

Of 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%).

CONCLUSION:

Patients 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Circulating Tumor DNA Limits: Humans Language: En Journal: JCO Precis Oncol Year: 2022 Document type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Colorectal Neoplasms / Circulating Tumor DNA Limits: Humans Language: En Journal: JCO Precis Oncol Year: 2022 Document type: Article Affiliation country: Japan