Effects of Metastatic Sites on Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer-Reference-Cited by-同舟云学术

Effects of Metastatic Sites on Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer

Published:2022-05 Issue:6 Volume: Page:
ISSN:2473-4284
Container-title:JCO Precision Oncology
language:en
Short-container-title:JCO Precision Oncology

Author:

Bando Hideaki¹²^ORCID,Nakamura Yoshiaki¹²,Taniguchi Hiroya³^ORCID,Shiozawa Manabu⁴,Yasui Hisateru⁵^ORCID,Esaki Taito⁶,Kagawa Yoshinori⁷,Denda Tadamichi⁸^ORCID,Satoh Taroh⁹^ORCID,Yamazaki Kentaro¹⁰^ORCID,Sunakawa Yu¹¹^ORCID,Kato Takeshi¹²,Goto Masahiro¹³,Yuki Satoshi¹⁴,Nishina Tomohiro¹⁵^ORCID,Oki Eiji¹⁶^ORCID,Shinozaki Eiji¹⁷^ORCID,Matsuhashi Nobuhisa¹⁸,Takahashi Naoki¹⁹,Tsuji Akihito²⁰^ORCID,Ohtsubo Koushiro²¹,Wakabayashi Masashi²²,Ikeno Takashi²²,Hata Masayuki²,Odegaard Justin I.²³,Yoshino Takayuki¹²^ORCID

Affiliation:

1. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

2. Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan

3. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

4. Department of Surgery, Kanagawa Cancer Center, Yokohama, Japan

5. Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan

6. Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

7. Department of Surgery, Kansai Rosai Hospital, Amagasaki, Japan

8. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan

9. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

10. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shunto-gun, Japan

11. Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan

12. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan

13. Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University Hospital, Takatsuki, Japan

14. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan

15. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan

16. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

17. Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

18. Department of Gastroenterological Surgery, Graduate School of Medicine, Gifu University, Gifu, Japan

19. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan

20. Department of Clinical Oncology, Kagawa University Hospital, Kita-gun, Japan

21. Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

22. Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan

23. Guardant Health, Redwood City, CA

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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Link

https://ascopubs.org/doi/pdfdirect/10.1200/PO.21.00535

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