クラモチ　ヒデカズ   Kuramochi Hidekazu   倉持　英和    所属   医学部 医学科（東京女子医科大学病院）    職種   非常勤講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Analysis of Circulating DNA to Assess Prognoses for Metastatic Colorectal Cancer Patients Treated with Regorafenib Dose-Escalation Therapy: A Retrospective, Exploratory Analysis of the RECC Trial.
掲載誌名	正式名：Digestion 略　 称：Digestion ISSNコード：14219867/00122823
掲載区分	国外
巻・号・頁	pp.1-10
著者・共著者	Ohta Ryo, Yamada Takeshi, Nakamura Masato, Enomoto Masanobu, Takahashi Makoto, Yokomizo Hajime, Kosugi Chihiro, Ishimaru Kei, Sonoda Hiromichi, Kuramochi Hidekazu, Yoshida Yoichiro, Furuya Shinji, Hirata Keiji, Yoshida Hiroshi, Nozawa Keijiro, Hashiguchi Yojiro, Ishida Hideyuki, Koda Keiji, Katsumata Kenji, Sakamoto Kazuhiro
発行年月	2023/01/16
概要	INTRODUCTION:Regorafenib is a multi-kinase inhibitor approved for patients with metastatic colorectal cancer (mCRC) who were previously treated with standard therapies. A few reports showed the impact of KRAS mutation on therapeutic efficacy of regorafenib. Only one study reported poor prognoses for patients treated with regorafenib who had large amounts of circulating cell-free DNA (cfDNA). In the present study, we evaluated the impact of KRAS mutations in tissue or plasma and amounts of cfDNA on prognoses of mCRC patients treated with regorafenib.METHOD:This is a biomarker investigation of the RECC study, which evaluated efficacy of regorafenib dose-escalation therapy. Plasma samples were obtained just before initiation of treatment with regorafenib. KRAS mutations were evaluated using tissue and plasma samples. cfDNA was extracted from plasma samples and quantified.RESULTS:Forty-five patients were enrolled in this biomarker study. Median progression-free survival (PFS) and overall survival (OS) of patients without KRAS mutations in tissues were 1.9 months (95% confidence interval [CI] 1.7-2.0) and 8.9 months (95% CI: 6.5-11.2), and those of patients with KRAS mutations were 1.4 months (95% CI: 1.3-1.5) and 6.8 months (95% CI: 5.0-8.5). Median PFS and OS of patients with plasma KRAS mutations were 1.9 months (95% CI: 1.8-1.9) and 7.0 months (95% CI: 5.3-8.7), respectively. Median PFS and OS of patients without plasma KRAS mutations were 1.7 months (95% CI: 1.1-2.3) and 8.9 months (95% CI: 6.7-11.2), respectively. Prior to administration of regorafenib, KRAS mutations were detected in 6 of 16 (37.5%) patients who had no tissue KRAS mutations. Median OS of patients with high cfDNA concentration (>median) was significantly poorer than that of patients with low cfDNA.CONCLUSION:KRAS mutations in the tissue or plasma have no impact on efficacy of regorafenib. KRAS emerging mutations were observed in quite a few patients. Large amounts of cfDNA may indicate poorer progn
DOI	10.1159/000528283
PMID	36646047