通过循环肿瘤 DNA 分析指导晚期胃肠道肿瘤的靶向治疗

IF 58.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yoshiaki Nakamura, Hiroshi Ozaki, Makoto Ueno, Yoshito Komatsu, Satoshi Yuki, Taito Esaki, Hiroya Taniguchi, Yu Sunakawa, Kensei Yamaguchi, Ken Kato, Tadamichi Denda, Tomohiro Nishina, Naoki Takahashi, Taroh Satoh, Hisateru Yasui, Hironaga Satake, Eiji Oki, Takeshi Kato, Takashi Ohta, Nobuhisa Matsuhashi, Masahiro Goto, Naohiro Okano, Koushiro Ohtsubo, Kentaro Yamazaki, Riu Yamashita, Naoko Iida, Mihoko Yuasa, Hideaki Bando, Takayuki Yoshino
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引用次数: 0

摘要

尽管全面的基因组图谱分析已成为晚期实体瘤的肿瘤学标准,但基于循环肿瘤DNA(ctDNA)的图谱分析在捕捉肿瘤异质性和指导治疗选择方面的全部潜力仍未得到充分利用,其特点是缺乏有关其临床影响和瘤内异质性评估的证据。GOZILA 研究是一项全国范围的前瞻性观察性 ctDNA 图谱研究,与组织筛查相比,该研究曾证实使用液体活检的临床试验入选率更高。这项对4037名患者进行的最新分析进一步明确了ctDNA图谱分析在晚期实体瘤中的临床应用,显示患者的治疗效果显著提高,靶向治疗匹配率达到24%。与未接受匹配治疗的患者相比,根据ctDNA图谱接受匹配靶向治疗的患者总生存率明显提高(危险比为0.54)。值得注意的是,生物标记物的克隆性和调整后的血浆拷贝数被确定为疗效的预测因子,从而加强了ctDNA在反映肿瘤异质性以做出精确治疗决策方面的价值。这些关于ctDNA特征与治疗结果之间关系的新见解,使我们的认识超越了最初的入组获益。我们的研究结果主张更广泛地采用ctDNA指导治疗,这标志着精准肿瘤学的进步,并能改善晚期实体瘤患者的生存预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors

Targeted therapy guided by circulating tumor DNA analysis in advanced gastrointestinal tumors

Although comprehensive genomic profiling has become standard in oncology for advanced solid tumors, the full potential of circulating tumor DNA (ctDNA)-based profiling in capturing tumor heterogeneity and guiding therapy selection remains underexploited, marked by a scarcity of evidence on its clinical impact and the assessment of intratumoral heterogeneity. The GOZILA study, a nationwide, prospective observational ctDNA profiling study, previously demonstrated higher clinical trial enrollment rates using liquid biopsy compared with tissue screening. This updated analysis of 4,037 patients further delineates the clinical utility of ctDNA profiling in advanced solid tumors, showcasing a significant enhancement in patient outcomes with a 24% match rate for targeted therapy. Patients treated with matched targeted therapy based on ctDNA profiling demonstrated significantly improved overall survival compared with those receiving unmatched therapy (hazard ratio, 0.54). Notably, biomarker clonality and adjusted plasma copy number were identified as predictors of therapeutic efficacy, reinforcing the value of ctDNA in reflecting tumor heterogeneity for precise treatment decisions. These new insights into the relationship between ctDNA characteristics and treatment outcomes advance our understanding beyond the initial enrollment benefits. Our findings advocate for the broader adoption of ctDNA-guided treatment, signifying an advancement in precision oncology and improving survival outcomes in advanced solid tumors.

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来源期刊
Nature Medicine
Nature Medicine 医学-生化与分子生物学
CiteScore
100.90
自引率
0.70%
发文量
525
审稿时长
1 months
期刊介绍: Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors. Nature Medicine consider all types of clinical research, including: -Case-reports and small case series -Clinical trials, whether phase 1, 2, 3 or 4 -Observational studies -Meta-analyses -Biomarker studies -Public and global health studies Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.
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