Precision Screening for Hepatocellular Carcinoma in Patients with Cirrhosis

肝硬化患者肝癌精准筛查

基本信息

批准号：
10543119
负责人：
Amit Singal
金额：
$ 25万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10543119
关键词：
Abdomen Algorithms Biological Markers Blood Body mass index Cancer Etiology Cessation of life Characteristics Cirrhosis Clinical Colorectal Cancer Data Detection Diagnosis Early Detection Research Network Early Diagnosis Effectiveness Etiology Evaluation Funding Goals Heterogeneity Incidence Individual Liver diseases Michigan Modeling Molecular Profiling Patient risk Patients Performance Primary carcinoma of the liver cells Professional Organizations Prognosis Prospective cohort Prospective, cohort study Public Health Quality-Adjusted Life Years Recommendation Risk Risk Factors Serum Severities Severity of illness Testing United States Universities alpha-Fetoproteins biomarker performance clinical risk cohort comparative cost effectiveness compare effectiveness cost cost effective cost effectiveness detection test early detection biomarkers high risk improved individual patient liver cancer model malignant breast neoplasm models and simulation mortality novel novel marker patient oriented patient subsets performance tests personalized screening phase 3 study precision medicine risk prediction model risk stratification screening screening guidelines sex tumor ultrasound

项目摘要

PROJECT SUMMARY / ABSTRACT The mortality of hepatocellular carcinoma (HCC) is rising, and it is projected to become the 3rd leading cause of cancer death in the U.S. by 2030. Given the association between early tumor detection and improved survival, multiple national professional societies recommend screening using abdominal ultrasound with or without a serum biomarker, alpha fetoprotein (AFP), every 6 months in at-risk individuals, including all patients with cirrhosis. However, most HCC patients are diagnosed at a late stage due to limitations in our current early detection strategy. The strategy of ultrasound and AFP for all cirrhosis patients is inadequate for 3 reasons: 1) It ignores heterogeneity in HCC risk between cirrhosis patients; 2) It ignores the poor accuracy of current screening tests; and 3) It ignores poor reliability of screening test performance between patients. Our proposal’s goal is to develop and evaluate a precision medicine strategy for early HCC detection in patients with cirrhosis that matches the best screening test to individual risk and screening test performance. We will leverage prospective cohort studies among 2000 patients with cirrhosis to evaluate the performance of risk stratification and early detection models incorporating novel biomarkers. Specifically, we propose to: Aim 1: Develop and validate the performance of risk stratification models incorporating a blood-based molecular signature panel to risk stratify cirrhosis patients for developing HCC Aim 2: Characterize and compare the performance of two biomarker-based early HCC detection strategies, the Doylestown Plus and a longitudinal biomarker algorithm, in a diverse cohort of patients with cirrhosis Aim 3: Compare the cost effectiveness, using micro-simulation modeling, of a tailored early detection strategy based on individual HCC risk and expected screening test performance to the current standard strategy of ultrasound and AFP in all patients with cirrhosis Our proposal leverages two prospective cohort studies with 2000 cirrhosis patients, to evaluate novel biomarker-based models for HCC risk stratification and early detection. We use these data to compare the effectiveness of a tailored early detection strategy to the current strategy of ultrasound and AFP for all patients using micro-simulation modeling. Tailoring early HCC detection efforts to individual risk and screening test performance moves beyond the current “one-size-fits-all” strategy and aligns HCC screening with the principles of precision medicine. Our proposed HCC early detection strategy would maximize screening benefits and minimize screening harms for each patient, thereby optimizing HCC screening value in the United States.

项目概要/摘要肝细胞癌（HCC）的死亡率正在上升，预计将成为第三大原因到 2030 年，美国的癌症死亡人数将增加。考虑到早期肿瘤检测与提高生存率之间的关联，多个国家专业协会建议使用腹部超声进行筛查，无论是否有每 6 个月对高危个体进行血清生物标志物甲胎蛋白 (AFP) 检测，包括所有患有然而，由于我们目前早期诊断的局限性，大多数 HCC 患者确诊时已处于晚期。针对所有肝硬化患者的超声和 AFP 检测策略并不充分，原因有 3 个：1) 2）它忽略了电流精度差的问题筛查测试；3) 它忽略了患者之间筛查测试表现的较差可靠性。我们提案的目标是开发和评估早期 HCC 检测的精准医学策略与个人风险和筛查测试表现相匹配的最佳筛查测试的肝硬化患者。我们将利用 2000 名肝硬化患者的前瞻性队列研究来评估具体来说，我们建议：目标 1：开发并验证包含基于血液的风险分层模型的性能分子特征面板对肝硬化患者发生 HCC 的风险进行分层目标 2：表征并比较两种基于生物标志物的早期 HCC 检测策略的性能， Doylestown Plus 和纵向生物标志物算法，在不同的肝硬化患者队列中目标 3：使用微观仿真模型比较定制的早期检测策略的成本效益基于个体 HCC 风险和预期筛查测试表现，采用当前标准策略所有肝硬化患者的超声和 AFP 我们的提案利用了两项针对 2000 名肝硬化患者的前瞻性队列研究来评估新的我们使用这些数据来比较基于生物标志物的 HCC 风险分层和早期检测模型。针对所有患者当前超声和 AFP 策略量身定制的早期检测策略的有效性使用微观模拟模型根据个体风险和筛查测试定制早期 HCC 检测工作。性能超越了当前的“一刀切”策略，并使 HCC 筛查与原则保持一致我们提出的 HCC 早期检测策略将最大限度地提高筛查效益和最大限度地减少对每位患者的筛查伤害，优化美国 HCC 筛查的价值。

项目成果

期刊论文数量（40）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hepatocellular carcinoma surveillance, early detection and survival in a privately insured US cohort.

美国私人保险队列中的肝细胞癌监测、早期发现和生存。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Chen, Vincent L;Singal, Amit G;Tapper, Elliot B;Parikh, Neehar D
通讯作者：
Parikh, Neehar D

Dynamic Changes in Ultrasound Quality for Hepatocellular Carcinoma Screening in Patients With Cirrhosis.

肝硬化患者肝细胞癌筛查超声质量的动态变化。

DOI：
发表时间：
2022-07
期刊：
影响因子：
0
作者：
Schoenberger, Haley;Chong, Nicolas;Fetzer, David T;Rich, Nicole E;Yokoo, Takeshi;Khatri, Gaurav;Olivares, Jocelyn;Parikh, Neehar D;Yopp, Adam C;Marrero, Jorge A;Singal, Amit G
通讯作者：
Singal, Amit G

HCC surveillance improves early detection, curative treatment receipt, and survival in patients with cirrhosis: A meta-analysis.

HCC 监测可改善肝硬化患者的早期发现、治疗接受和生存：一项荟萃分析。

DOI：
发表时间：
2022-07
期刊：
影响因子：
25.7
作者：
Singal, Amit G;Zhang, Emily;Narasimman, Manasa;Rich, Nicole E;Waljee, Akbar K;Hoshida, Yujin;Yang, Ju Dong;Reig, Maria;Cabibbo, Giuseppe;Nahon, Pierre;Parikh, Neehar D;Marrero, Jorge A
通讯作者：
Marrero, Jorge A

Blood-Based Biomarkers for HCC Surveillance: Ready for the Center Stage?

用于 HCC 监测的血液生物标志物：准备好登上舞台中心了吗？