Early Detection of Hepatocellular Carcinoma

肝细胞癌的早期发现

• 批准号: 9926812
• 负责人: LAURA BERETTA
• 金额: $ 64.42万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-03 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926812
• 关键词: AFP gene; Address; Adopted; Alcohol abuse; Behavior; Biological Assay; Biological Markers; Biological Specimen Banks; Blood specimen; Caliber; Cancer Center; Cancer Etiology; Cessation of life; Characteristics; Chemoprevention; Chronic Hepatitis B; Cirrhosis; Clinical; Cohort Studies; Collection; Data; Development; Diagnosis; Diagnostic; Disease; Early Diagnosis; Enrollment; Evaluation Studies; FDA approved; Fatty Acids; Foundations; Goals; Hepatitis B Virus; Hepatitis C; Hospitals; Image; Incidence; Individual; Institutes; Lesion; Liver; Liver Cirrhosis; Magnetic Resonance Imaging; Measures; Medical center; Methodist Church; Modality; Molecular; Newly Diagnosed; Patients; Performance; Primary carcinoma of the liver cells; Prospective cohort; Risk; Risk Assessment; Risk Factors; Sampling; Sensitivity and Specificity; Testing; Time; Ultrasonography; United States; alpha-Fetoproteins; biomarker panel; clinical application; clinical material; cohort; contrast enhanced; cost; curative treatments; data management; early detection biomarkers; follow-up; high risk; improved; member; nonalcoholic steatohepatitis; novel; novel marker; patient subsets; pre-clinical; prediction algorithm; predictive marker; predictive modeling; prospective; protein biomarkers; public health relevance; screening; surveillance strategy; translational impact; tumor; validation studies

 DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related death in the United States. It is critically important to identify those at high risk for HCC and institute effective surveillance strategies for early diagnosis. Livr cirrhosis is the main risk factor for HCC. Ultrasound and α-fetoprotein (AFP) every 6 months remains the surveillance modality most frequently used on cirrhosis patients but the sensitivity and specificity of the tests are low. Our extensive prior biomarker studies in HCC cases, cirrhosis controls and HCC pre-diagnosis samples identified novel markers for HCC risk prediction and surveillance. In this proposal, we will further evaluate the performance of these novel markers together with FDA-approved markers. The validation study will be performed in a large contrast MRI surveillance cohort that provides a unique opportunity to study biomarkers on clinical material from patients rigorously classified as having a very early disease in a surveillance setting. Longitudinal collection of blood samples will be particularly valuable in assessing how early biomarkers become positive during the period when lesions are observed to a confirmed diagnosis of HCC. Cirrhotic patients under contrast MRI surveillance (n=3500 patients) will be enrolled at Baylor-St. Luke's Medical Center and Houston Methodist Hospital. Data management, specimen repository and molecular assays will be performed at MD Anderson Cancer Center. It is anticipated that at least 150 HCCs will be detected during the study with most of them detected at an early stage. We will identify the panel of biomarkers that best distinguishes between early HCC and cirrhosis and that could therefore have utility in HCC surveillance. We will evaluate the capacity of the novel marker panel to detect preclinical disease and determine longitudinal changes in these biomarkers predictive of HCC development. Our prior studies also identified specific fatty acids that discriminate between patients with cirrhosis who developed HCC within 5 years and those who didn't progress to HCC. These fatty acids may therefore have utility in HCC risk assessment. We will determine using the same MRI surveillance cohort the fatty acid panel that best predicts HCC development. Finally, this study will evaluate the complementarity performance of ultrasound and the novel biomarker panel and determine whether contrast-enhanced ultrasound results in any significant improvement in the ability of ultrasound to detect small tumor foci. This proposal achieves in one study two major goals: early detection and characteristics of tumors when biomarker becomes positive. This study has a number of high-impact translational applications: spare patients from unnecessary imaging tests; identify at-risk patients and trigger the decision to perform MRI instead of ultrasound in patients under surveillance; detect lesions at an early stage allowing for curative treatment. Such clinical applications would significantly reduce the cost of HCC surveillance and improve survival of HCC patients.

 描述（由适用提供）：肝细胞癌（HCC）是美国与癌症相关死亡增长最快的原因。确定HCC高风险的人并制定有效的早期诊断监视策略非常重要。 LIVR肝硬化是HCC的主要危险因素。超声和α-毒素蛋白（AFP）每6个月仍然是最常用于肝硬化患者的监视方式，但测试的敏感性和特异性较低。我们在HCC病例，肝硬化控制和HCC前诊断样本中进行的大量生物标志物研究确定了HCC风险预测和监视的新标记。在此提案中，我们将进一步评估这些新颖标记的性能以及FDA批准的标记。验证研究将在大型的对比度MRI监视队列中进行，该研究提供了一个独特的机会，可以从严格归类为在监视环境中患有非常早期疾病的患者的临床材料上研究生物标志物。血液样本的纵向收集对于评估在观察到已确认的HCC诊断的病变期间的早期生物标志物的阳性方面将特别有价值。在贝勒-ST中将招募对比度MRI监测（n = 3500名患者）进行的肝硬化患者（n = 3500例）。卢克医疗中心和休斯顿卫理公会医院。数据管理，标本存储库和分子阿萨斯将在MD Anderson癌症中心进行。预计在研究期间将至少检测到150个HCC，大多数在早期都检测到。我们将确定最能区分早期HCC和肝硬化的生物标志物小组，因此可以在HCC监视中有用。我们将评估新标记面板检测临床前疾病并确定这些生物标志物预测HCC发育的纵向变化的能力。我们先前的研究还确定了特定的脂肪酸，这些脂肪酸会区分肝硬化患者，这些患者在5年内发展了HCC，以及那些未发展为HCC的患者。因此，这些脂肪酸可能在HCC风险评估中具有效用。我们将确定使用最能预测的脂肪酸面板相同的MRI监视队列。 HCC开发。最后，这项研究将评估超声和新型生物标志物面板的完成性能，并确定对比增强的超声是否会导致超声检测小肿瘤焦点的能力有显着提高。该提议在一个研究中实现了两个主要目标：生物标志物变为阳性时的早期检测和肿瘤的特征。这项研究有许多高影响的翻译应用：不必要的成像测试的备用患者；确定高危患者，并触发在监视的患者中进行MRI而不是超声检查的决定；在早期阶段检测病变，允许治疗治疗。这种临床应用将大大降低HCC监视的成本并改善HCC患者的存活率。