Takuro Mizukami1, Masaki Takahashi2, Yu Sunakawa1, Satoshi Yuki3, Yoshinori Kagawa4, Atsuo Takashima5, Kyoko Kato6, Hiroki Hara7, Tadamichi Denda8, Yoshiyuki Yamamoto9, Manabu Shiozawa10, Eiji Oki11, Wataru Okamoto12,13,14, Takayuki Yoshino14, Takako Eguchi Nakajima15. 1. Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan. 2. Medical Informatics, St. Marianna University School of Medicine, Kawasaki, Japan. 3. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan. 4. Department of Surgery, Osaka Prefectural General Medical Center, Osaka, Japan. 5. Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 6. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 7. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 8. Gastroenterology, Chiba Cancer Center, Chiba, Japan. 9. Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 10. Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. 11. Department of Surgery and Science, Kyushu University, Fukuoka, Japan. 12. Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan. 13. Translational Research Support Section, National Cancer Center Hospital East, Kashiwa, Japan. 14. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 15. Department of Early Clinical Development, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. tnakajima@kuhp.kyoto-u.ac.jp.
Abstract
BACKGROUND: Primary tumor site and genomic status are utilized for regimen selection in metastatic colorectal cancer; however, the impact on clinical practice is not well known. OBJECTIVE: We aimed to clarify the impact of primary tumor site and genomic status on clinical practice in metastatic colorectal cancer. METHODS: The relationship between primary tumor site, genomic alterations, and clinical outcomes was evaluated in patients with untreated metastatic colorectal cancer using real-world data of a prospective observational study, SCRUM-Japan GI-SCREEN with clinical and genomic data set in 1011 patients enrolled from February 2015 to March 2017. RESULTS: Five hundred and sixty-one patients were eligible for this study. Patients with right-sided tumors had a significantly worse survival, left-sided tumors with wild-type RAS had favorable outcomes when treated with anti-epidermal growth factor receptor monoclonal antibodies, and cecum tumors had poor prognosis when treated with bevacizumab. The rate of gene alterations varied considerably depending on the primary site. In addition, gene alterations of KRAS, BRAF, SMAD4, or TP53 had individually different contributions to survival from site to site. KRAS, BRAF, PTEN, or SMAD4 mutations were associated with efficacy of bevacizumab or anti-epidermal growth factor receptor monoclonal antibodies. CONCLUSIONS: Primary tumor site is a clinically useful biomarker to predict survival in patients with metastatic colorectal cancer treated with first-line chemotherapy. Moreover, the prognostic or predictive value of several gene alterations by primary tumor site should be considered in clinical practice.
BACKGROUND: Primary tumor site and genomic status are utilized for regimen selection in metastatic colorectal cancer; however, the impact on clinical practice is not well known. OBJECTIVE: We aimed to clarify the impact of primary tumor site and genomic status on clinical practice in metastatic colorectal cancer. METHODS: The relationship between primary tumor site, genomic alterations, and clinical outcomes was evaluated in patients with untreated metastatic colorectal cancer using real-world data of a prospective observational study, SCRUM-Japan GI-SCREEN with clinical and genomic data set in 1011 patients enrolled from February 2015 to March 2017. RESULTS: Five hundred and sixty-one patients were eligible for this study. Patients with right-sided tumors had a significantly worse survival, left-sided tumors with wild-type RAS had favorable outcomes when treated with anti-epidermal growth factor receptor monoclonal antibodies, and cecum tumors had poor prognosis when treated with bevacizumab. The rate of gene alterations varied considerably depending on the primary site. In addition, gene alterations of KRAS, BRAF, SMAD4, or TP53 had individually different contributions to survival from site to site. KRAS, BRAF, PTEN, or SMAD4 mutations were associated with efficacy of bevacizumab or anti-epidermal growth factor receptor monoclonal antibodies. CONCLUSIONS: Primary tumor site is a clinically useful biomarker to predict survival in patients with metastatic colorectal cancer treated with first-line chemotherapy. Moreover, the prognostic or predictive value of several gene alterations by primary tumor site should be considered in clinical practice.
Authors: Lee S Schwartzberg; Fernando Rivera; Meinolf Karthaus; Gianpiero Fasola; Jean-Luc Canon; J Randolph Hecht; Hua Yu; Kelly S Oliner; William Y Go Journal: J Clin Oncol Date: 2014-03-31 Impact factor: 44.544
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: D Arnold; B Lueza; J-Y Douillard; M Peeters; H-J Lenz; A Venook; V Heinemann; E Van Cutsem; J-P Pignon; J Tabernero; A Cervantes; F Ciardiello Journal: Ann Oncol Date: 2017-08-01 Impact factor: 32.976