转移部位对转移性结直肠癌患者循环肿瘤DNA的影响。

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

作者信息

Bando Hideaki, Nakamura Yoshiaki, Taniguchi Hiroya, Shiozawa Manabu, Yasui Hisateru, Esaki Taito, Kagawa Yoshinori, Denda Tadamichi, Satoh Taroh, Yamazaki Kentaro, Sunakawa Yu, Kato Takeshi, Goto Masahiro, Yuki Satoshi, Nishina Tomohiro, Oki Eiji, Shinozaki Eiji, Matsuhashi Nobuhisa, Takahashi Naoki, Tsuji Akihito, Ohtsubo Koushiro, Wakabayashi Masashi, Ikeno Takashi, Hata Masayuki, Odegaard Justin I, Yoshino Takayuki

机构信息

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

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

出版信息

JCO Precis Oncol. 2022 Apr;6:e2100535. doi: 10.1200/PO.21.00535.

DOI:10.1200/PO.21.00535

PMID:35544728

Abstract

PURPOSE

Low concordance between plasma-based and tissue-based tests for determining the 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 / 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 < .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.

摘要

目的

在部分但并非所有局限性转移性结直肠癌（mCRC）患者中，已报道基于血浆和基于组织的检测在确定突变状态方面的一致性较低。在本研究中，我们使用循环肿瘤DNA（ctDNA）基因分型研究转移部位与ctDNA检测之间的关系，ctDNA基因分型是一种用于精准肿瘤学的组织基因分型替代方法。

材料与方法

在SCRUM - 日本GOZILA研究（UMIN000029315）中，我们使用Guardant360（一种下一代测序ctDNA检测方法）研究单器官转移的mCRC患者中转移部位与ctDNA检测之间的关系。

结果

在GOZILA研究纳入的1187例mCRC患者中，138例符合条件（49例仅肝转移，15例仅淋巴结转移，27例仅腹膜转移，47例仅肺转移）。仅肝转移患者中Guardant360与组织体外诊断检测的一致性/状态为95.9%，仅淋巴结转移患者中为80.0%，仅腹膜转移患者中为56.0%，仅肺转移患者中为65.9%。通过中位最大变异等位基因分数（max VAF）测量的ctDNA分数以及检测到的变异中位数，仅肝转移患者分别为23.1%和5个，仅淋巴结转移患者为6.0%和5个，仅腹膜转移患者为0.4%和3个，仅肺转移患者为0.4%和3个（所有P <.001，Kruskal - Wallis检验）。仅肝转移（2.0%）和仅淋巴结转移（13.3%）的患者中很少有max VAF < 0.2%（这是确保95%检测限所必需的），但仅肺转移（27.7%）或仅腹膜转移（29.6%）的患者中max VAF更频繁地< 0.2%。