Kataoka Kozo, Yamada Takeshi, Shiozawa Manabu, Takase Naoto, Ito Kazuma, Yamazaki Kentaro, Watanabe Jun, Kudo Toshihiro, Suto Takeshi, Matsumoto Toshihiko, Murata Kohei, Suwa Yusuke, Boku Shogen, Yasui Hisateru, Matsuhashi Nobuhisa, Maeda Atsuyuki, Sugimoto Kiichi, Matsumoto Yusuke, Yokota Mitsuru, Fredebohm Johannes, Mori Keita, Ikeda Masataka
Division of Lower GI Surgery, Department of Gastroenterological Surgery, Hyogo Medical University, Nishinomiya, Japan.
Department of Gastrointestinal and Hepato-Billiary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
J Anus Rectum Colon. 2024 Apr 25;8(2):132-136. doi: 10.23922/jarc.2023-051. eCollection 2024.
Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy.
METHODS/DESIGN: RAS-trace study is an observational study to monitor ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks using the Plasma-SeqSensei™ CRC RUO Kit (Sysmex Inostics GmbH) in mCRC with RAS/BRAF wild-type (wt) on tumor tissue. The primary endpoint was the time to the acquired RAS mutations. A total of 42 patients has been accrued. RAS-trace-2 study is also an observational study aimed at comparing the efficacy of the anti-EGFR mAb in ctDNA RAS/BRAF wt with ctDNA RAS or BRAF mutant mCRC patients, whose RAS/BRAF are wt in tumor tissue. The primary endpoint was progression-free survival in patients with ctDNA RAS/BRAF wt and RAS or BRAF mutant. A total of 240 patients will be accrued over 2 years.
These trials will help us understanding the clinical significance of spatial and temporal heterogeneities of RAS, BRAF and other genes, while optimizing the anti-EGFR mAb treatment strategies in mCRC.
在使用抗表皮生长因子受体（EGFR）单克隆抗体（mAb）治疗转移性结直肠癌（mCRC）时，应考虑RAS和其他分子基因的时空异质性；在抗EGFR mAb治疗疾病进展时，有时会观察到获得性RAS突变。同时，有时会观察到同一患者组织和循环肿瘤DNA（ctDNA）的RAS状态存在差异。基于此，我们开展了两项观察性研究，使用液体活检的下一代测序技术来阐明mCRC中RAS和BRAF的这些异质性。
方法/设计：RAS-trace研究是一项观察性研究，使用Plasma-SeqSensei™ CRC RUO试剂盒（Sysmex Inostics GmbH），每4-12周监测一次mCRC患者肿瘤组织中RAS/BRAF/PIK3CA野生型（wt）患者的ctDNA RAS/BRAF/PIK3CA状态。主要终点是获得性RAS突变的时间。共纳入了42例患者。RAS-trace-2研究也是一项观察性研究，旨在比较抗EGFR mAb在ctDNA RAS/BRAF wt与ctDNA RAS或BRAF突变的mCRC患者中的疗效，这些患者肿瘤组织中的RAS/BRAF为wt。主要终点是ctDNA RAS/BRAF wt和RAS或BRAF突变患者的无进展生存期。在2年内将共纳入240例患者。
这些试验将帮助我们了解RAS、BRAF和其他基因时空异质性的临床意义，同时优化mCRC的抗EGFR mAb治疗策略。
