Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies

Yoshiaki Nakamura^#^{1

2}, Hiroya Taniguchi^#^{1

2}, Masafumi Ikeda³, Hideaki Bando⁴, Ken Kato^{5

6}, Chigusa Morizane⁷, Taito Esaki⁸, Yoshito Komatsu⁹, Yasuyuki Kawamoto⁹, Naoki Takahashi¹⁰, Makoto Ueno¹¹, Yoshinori Kagawa¹², Tomohiro Nishina¹³, Takeshi Kato¹⁴, Yoshiyuki Yamamoto¹⁵, Junji Furuse¹⁶, Tadamichi Denda¹⁷, Hisato Kawakami¹⁸, Eiji Oki¹⁹, Takako Nakajima²⁰, Naohiro Nishida²¹, Kensei Yamaguchi²², Hisateru Yasui²³, Masahiro Goto²⁴, Nobuhisa Matsuhashi²⁵, Koushiro Ohtsubo²⁶, Kentaro Yamazaki²⁷, Akihito Tsuji²⁸, Wataru Okamoto^{2

29}, Katsuya Tsuchihara^{2

30}, Takeharu Yamanaka³¹, Izumi Miki², Yasutoshi Sakamoto², Hiroko Ichiki², Masayuki Hata², Riu Yamashita³⁰, Atsushi Ohtsu¹, Justin I Odegaard³², Takayuki Yoshino³³

Affiliations

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 Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
⁴ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
⁵ Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Biobank Translational Research Support Section, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁸ Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
⁹ Department of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
¹⁰ Department of Gastroenterology, Saitama Cancer Center, Kitaadachi-gun, Japan.
¹¹ Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan.
¹² Department of Colorectal Surgery, Kansai Rosai Hospital, Amagasaki, Japan.
¹³ Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
¹⁴ Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.
¹⁵ Department of Gastroenterology and Hepatology, University of Tsukuba Hospital, Tsukuba, Japan.
¹⁶ Department of Medical Oncology, Kyorin University Hospital, Mitaka, Japan.
¹⁷ Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan.
¹⁸ Department of Medical Oncology, Kindai University Hospital, Osakasayama, Japan.
¹⁹ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²⁰ Department of Medical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.
²¹ Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Japan.
²² Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
²³ Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
²⁴ Cancer Chemotherapy Center, Osaka Medical College Hospital, Takatsuki, Japan.
²⁵ Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan.
²⁶ Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
²⁷ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shunto-gun, Japan.
²⁸ Department of Clinical Oncology, Kagawa University Hospital, Kita-gun, Japan.
²⁹ Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan.
³⁰ Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
³¹ Division of Biostatistics, National Cancer Center Hospital East, Kashiwa, Japan.
³² Guardant Health, Redwood City, CA, USA.
³³ Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. tyoshino@east.ncc.go.jp.

^# Contributed equally.

PMID: 33020649
DOI: 10.1038/s41591-020-1063-5

Clinical Trial

Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies

Yoshiaki Nakamura et al. Nat Med. 2020 Dec.

. 2020 Dec;26(12):1859-1864.

doi: 10.1038/s41591-020-1063-5. Epub 2020 Oct 5.

Authors

Affiliations

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 Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
⁴ Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
⁵ Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁶ Biobank Translational Research Support Section, National Cancer Center Hospital, Tokyo, Japan.
⁷ Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
⁸ Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
⁹ Department of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
¹⁰ Department of Gastroenterology, Saitama Cancer Center, Kitaadachi-gun, Japan.
¹¹ Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan.
¹² Department of Colorectal Surgery, Kansai Rosai Hospital, Amagasaki, Japan.
¹³ Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
¹⁴ Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan.
¹⁵ Department of Gastroenterology and Hepatology, University of Tsukuba Hospital, Tsukuba, Japan.
¹⁶ Department of Medical Oncology, Kyorin University Hospital, Mitaka, Japan.
¹⁷ Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan.
¹⁸ Department of Medical Oncology, Kindai University Hospital, Osakasayama, Japan.
¹⁹ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²⁰ Department of Medical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan.
²¹ Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Japan.
²² Department of Gastroenterological Chemotherapy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
²³ Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan.
²⁴ Cancer Chemotherapy Center, Osaka Medical College Hospital, Takatsuki, Japan.
²⁵ Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan.
²⁶ Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
²⁷ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shunto-gun, Japan.
²⁸ Department of Clinical Oncology, Kagawa University Hospital, Kita-gun, Japan.
²⁹ Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan.
³⁰ Division of Translational Informatics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
³¹ Division of Biostatistics, National Cancer Center Hospital East, Kashiwa, Japan.
³² Guardant Health, Redwood City, CA, USA.
³³ Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. tyoshino@east.ncc.go.jp.

^# Contributed equally.

PMID: 33020649
DOI: 10.1038/s41591-020-1063-5

Abstract

Comprehensive genomic profiling enables genomic biomarker detection in advanced solid tumors. Here, to evaluate the utility of circulating tumor DNA (ctDNA) genotyping, we compare trial enrollment using ctDNA sequencing in 1,687 patients with advanced gastrointestinal (GI) cancer in SCRUM-Japan GOZILA (no. UMIN000016343), an observational ctDNA-based screening study, to enrollment using tumor tissue sequencing in the same centers and network (GI-SCREEN, 5,621 patients). ctDNA genotyping significantly shortened the screening duration (11 versus 33 days, P < 0.0001) and improved the trial enrollment rate (9.5 versus 4.1%, P < 0.0001) without compromising treatment efficacy compared to tissue genotyping. We also describe the clonal architecture of ctDNA profiles in ~2,000 patients with advanced GI cancer, which reinforces the relevance of many targetable oncogenic drivers and highlights multiple new drivers as candidates for clinical development. ctDNA genotyping has the potential to accelerate innovation in precision medicine and its delivery to individual patients.

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Comment in

Liquid biopsy versus tumor biopsy for clinical-trial recruitment.
Corcoran RB. Corcoran RB. Nat Med. 2020 Dec;26(12):1815-1816. doi: 10.1038/s41591-020-01169-6. Nat Med. 2020. PMID: 33230339 No abstract available.

References

1. Bando, H. The current status and problems confronted in delivering precision medicine in Japan and Europe. Curr. Probl. Cancer 41, 166–175 (2017). - DOI
1. Spiegel, M. L. et al. Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges. Cancer 123, 4800–4807 (2017). - DOI
1. Lim, C. et al. Patients with advanced non-small cell lung cancer: are research biopsies a barrier to participation in clinical trials? J. Thorac. Oncol. 11, 79–84 (2016). - DOI
1. Nakamura, Y. & Yoshino, T. Clinical utility of analyzing circulating tumor DNA in patients with metastatic colorectal cancer. Oncologist 23, 1310–1318 (2018). - DOI
1. Nakamura, Y. & Shitara, K. Development of circulating tumour DNA analysis for gastrointestinal cancers. ESMO Open 5, e000600 (2020). - DOI

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Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies

Affiliations

Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies

Authors

Affiliations

Abstract

Comment in

References

Publication types

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Associated data

LinkOut - more resources

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