Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies
Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies
复制标题
DOI：
10.1038/s41591-020-1063-5
复制
发表时间：
2020-10-05
期刊：
影响因子：
82.9
通讯作者：
Yoshino, Takayuki
中科院分区：
文献类型：
--
作者：
Nakamura, Yoshiaki;Taniguchi, Hiroya;Yoshino, Takayuki
全面的基因组分析使晚期实体瘤中的基因组生物标志物检测成为可能。在此，为了评价循环肿瘤DNA（ctDNA）基因分型的效用，我们比较了SCRUM-Japan GOZILA（编号UMIN 000016343）中使用ctDNA测序的1，687例晚期胃肠道（GI）癌患者的试验入组情况，这是一项基于ctDNA的观察性筛查研究，与相同中心和网络中使用肿瘤组织测序的入组情况（GI-SCREEN，5，621例患者）。与组织基因分型相比，ctDNA基因分型显著缩短了筛选时间（11天对33天，P < 0.0001），提高了试验入组率（9.5%对4.1%，P < 0.0001），而不影响治疗效果。我们还描述了类似于2,000例晚期GI癌症患者的ctDNA谱的克隆结构，这加强了许多可靶向致癌驱动因素的相关性，并突出了多种新驱动因素作为临床开发的候选者。ctDNA基因分型有可能加速精准医学的创新及其向个体患者的交付。
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 similar to 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.