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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.

项目摘要/摘要肝细胞癌的死亡率正在上升，预计它将成为世界上第三大致癌原因。到2030年，美国的癌症死亡人数。考虑到早期肿瘤检测和提高存活率之间的关联，多个国家专业协会建议使用腹部超声进行筛查，无论有没有高危个体每6个月检测一次血清生物标记物甲胎蛋白(AFP)，包括所有患有肝硬变。然而，由于我们目前早期的局限性，大多数肝细胞癌患者的诊断都是在晚期。检测策略。对于所有的肝硬变患者，超声和甲胎蛋白的策略是不够的，原因有三：1) 它忽略了肝硬变患者之间肝癌风险的异质性；2)它忽略了当前较差的准确性筛查试验；3)它忽略了患者之间筛查试验表现的低可靠性。我们的建议的目标是开发和评估一种用于肝癌早期检测的精确医学策略与个体风险和筛查测试表现相匹配的最佳筛查测试的肝硬变患者。我们将利用2000名肝硬变患者的前瞻性队列研究来评估结合新生物标志物的风险分层和早期检测模型。具体来说，我们建议：目标1：开发和验证包含以血液为基础的风险分层模型的性能分子标志物小组对肝硬变患者发生肝细胞癌的风险分层目的2：比较两种基于生物标志物的肝细胞癌早期检测策略的性能。 Doylestown Plus和纵向生物标记物算法在不同的肝硬变患者队列中的应用目标3：使用微观模拟建模，比较定制早期检测策略的成本效益基于个体肝癌风险和预期筛查检测性能，以当前的标准策略所有肝硬变患者的超声和甲胎蛋白检测我们的建议利用两项前瞻性队列研究，对2000名肝硬变患者进行评估基于生物标记物的肝细胞癌风险分层和早期检测模型。我们使用这些数据来比较为所有患者量身定制的早期检测策略与目前的超声和甲胎蛋白检测策略的有效性采用微观仿真建模。根据个体风险和筛查测试量身定做早期肝癌检测工作 Performance超越了目前的“一刀切”策略，使肝细胞癌筛查符合原则精准医学。我们建议的肝细胞癌早期检测策略将最大限度地提高筛查效益和将每个患者的筛查危害降至最低，从而优化美国的肝细胞癌筛查价值。

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）

Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era?

DOI：
10.1016/j.jhep.2022.08.036
发表时间：
2023-01
期刊：
JOURNAL OF HEPATOLOGY
影响因子：
25.7
作者：
Parikh, Neehar D.;Tayob, Nabihah;Singal, Amit G.
通讯作者：
Singal, Amit G.

Author response to Letter to the Editor: 'Chronological change in alpha-foetoprotein levels in hepatocellular carcinoma after eradication of hepatitis C virus'.

作者对给编辑的信的回应：“根除丙型肝炎病毒后肝细胞癌中甲胎蛋白水平的时间变化”。

DOI：
10.1111/liv.14612
发表时间：
2020
期刊：
Liver international : official journal of the International Association for the Study of the Liver
影响因子：
0
作者：
Chen,VincentL;Parikh,NeeharD
通讯作者：
Parikh,NeeharD

Lipidomic Profiles of Plasma Exosomes Identify Candidate Biomarkers for Early Detection of Hepatocellular Carcinoma in Patients with Cirrhosis.

DOI：
10.1158/1940-6207.capr-20-0612
发表时间：
2021-10
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
0
作者：
Sanchez JI;Jiao J;Kwan SY;Veillon L;Warmoes MO;Tan L;Odewole M;Rich NE;Wei P;Lorenzi PL;Singal AG;Beretta L
通讯作者：
Beretta L

GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis.

DOI：
10.1002/hep.32185
发表时间：
2022-03
期刊：
Hepatology (Baltimore, Md.)
影响因子：
0
作者：
Singal AG;Tayob N;Mehta A;Marrero JA;El-Serag H;Jin Q;Saenz de Viteri C;Fobar A;Parikh ND
通讯作者：
Parikh ND

For Whom is Hepatocellular Carcinoma Surveillance After Sustained Virologic Response Cost-Effective?

持续病毒学应答后的肝细胞癌监测对谁来说具有成本效益？