Vascular Invasion Signatures in cfDNA Support Re-staging of Small Liver Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 286
- 试验地点
- 1
- 主要终点
- Recurrence-free survival (RFS)
研究概览
简要总结
Tumor staging system based on clinicopathological charactertics has been used to guide treatment decisions. However, therapeutic outcomes of "early-stage" hepatocellular carcinoma (HCC) differs significantly, which strongly suggests the requirement for a re-staging of early HCC to inform treatment selection more precisely. Microvascular invasion (MVI) reflects malignant biological characteristics of early HCC, and has a potential role of guiding treatment selection. As such, the objective of this study is to investigate preoperative MVI prediction based on MVI-related genomic signatures of cell-free circulating tumor DNA (ctDNA) to establish a re-staging of early HCC. The investigators have detected 37 mutant genes associated with MVI in HCC tumor tissues. In this study, the investigators will design a gene panel based on these mutant genes to perform targeted gene sequencing on preoperatively collected ctDNA to identify genomic signatures associated with MVI. A nomogram to predict MVI before treatment will be generated by incorporating these genomic signatures. Based on a calculated optimal cut-off value of the nomogram, early HCC patients can be re-staged into subpopulations based on the nomogram-predicted risks of MVI. This study will develop a re-staging system of early HCC based on tumor biological charactertics, which is expected to accurately and individually guide treatment decisions and improve long-term survival outcomes.
详细描述
Study Design:
The genetic profiles associated with MVI in early-stage HCC was detected to generate a gene panel based on the WES and targeted gene NGS data of paired tumor and non-tumor tissues. Then, genomic alternations related to MVI in preoperative cfDNA were identified using targeted sequencing with the panel. Based on the genomic signatures in cfDNA, a nomogram model was constructed to predict MVI risks preoperatively, and a re-staging paradigm for early-stage HCC based on predicted high or low-risk of MVI by the nomogram was subsequently developed. Furthermore, the clinical relevance of the re-staging system in deciding on the optimal extent of surgical resection for HCC was examined. This study was approved by the Institutional Ethics Committee of each center, and informed consents were obtained from all patients for their tissues or blood samples and clinical data to be used for research purposes.
Patients, Surgical Treatment and Follow-up:
The eligibility criteria were patients aged 18-75 years, histopathologically confirmed HCC, tumor within the Milan criteria, Child-Pugh class A of liver function, no history of other malignancies, no previous anti-cancer treatment including neoadjuvant therapy before surgery, curative-intent surgical resection defined as complete removal of macroscopic nodules with microscopic tumor-free resection margins and without distant metastasis and major vascular invasion, and complete clinicopathological and follow-up data.
A total of 436 patients who underwent surgical resection for early-stage HCC between June 2015 and December 2017 and met the eligibility criteria were prospectively collected. Of these patients, 150 patients who were operated between June 2015 and May 2016 at the Eastern Hepatobiliary Surgery Hospital (EHBH) served as the panel discovery cohort. Paired tumor and adjacent non-tumor tissues from 81 patients were used for WES, and those from another 69 patients were for targeted gene NGS by using a commercial 123-gene-panel to detect MVI-related mutations.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged 18-75 years
- •histopathologically confirmed HCC
- •tumor within the Milan criteria
- •Child-Pugh class A of liver function
- •curative-intent surgical resection defined as complete removal of macroscopic nodules with microscopic tumor-free resection margins
- •complete clinicopathological and follow-up data
排除标准
- •history of other malignancies
- •previous anti-cancer treatment
- •distant metastasis and major vascular invasion
结局指标
主要结局
Recurrence-free survival (RFS)
时间窗: Between June 2016 and January 2022
The time from surgery to the first diagnosis of recurrence or patient death without recurrence
Overall survival (OS)
时间窗: Between June 2016 and January 2022
The time from surgery to patient death from any cause or the last follow-up
次要结局
- Local recurrence(Between June 2016 and January 2022)
研究者
Shen Feng
Professor and Chief Surgeon
Eastern Hepatobiliary Surgery Hospital