Integrating plasma IGF-1 into novel classification of hepatocellular carcinoma

将血浆 IGF-1 纳入肝细胞癌的新分类

• 批准号: 8507663
• 负责人: Ahmed Kaseb
• 金额: $ 19.38万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-09 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507663
• 关键词: Affect; Albumins; Amendment; Ascites; Bilirubin; Biological Markers; Cessation of life; Child; Cirrhosis; Classification; Clinic; Clinical; Clinical Data; Clinical Trials; Clinical Trials Design; Consensus; Data; Diagnostic Neoplasm Staging; Disease; Disease Outcome; Diuretics; Enzyme-Linked Immunosorbent Assay; Excision; Functional disorder; Goals; Healthcare; Hepatic; Hepatic Encephalopathy; Incidence; Institution; Insulin-Like Growth Factor I; Laboratories; Lactulose; Lead; Lesion; Liver; Liver Failure; Liver diseases; Local Therapy; Malignant Neoplasms; Malignant neoplasm of liver; Measurement; Measures; Medical; Operative Surgical Procedures; Outcome; Patients; Performance; Plasma; Primary carcinoma of the liver cells; Procedures; Prognostic Factor; Prognostic Marker; Prothrombin time assay; Publishing; Reporting; Research Personnel; Resources; Sampling; Selection Criteria; Serum; Serum Albumin; Severities; Somatomedins; Staging; Staging System; Stratification; System; Systemic Therapy; Testing; Therapeutic; Therapy Clinical Trials; Tumor stage; United States; Validation; base; chronic liver disease; clinical practice; cohort; improved; liver function; novel; outcome forecast; programs; tool; treatment effect; tumor

DESCRIPTION (provided by applicant): In hepatocellular carcinoma (HCC) management, the Child-Pugh (CP) score is the current standard tool for assessing the underlying chronic liver disease (CLD) status in clinical practice and stratifying patients in HCC therapeutic trials. It alo is an essential parameter in most currently used HCC staging systems, particularly Cancer of the Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC). Multiple experts panels consensus statements reached the consensus that patients with HCC considered for surgical resection or local or systemic therapeutic trials must have a CP score of A [1-3]. This selection criterion facilitates assessment of the effect of treatment without the confounding issues of liver failure and death as a result of underlying cirrhosis. However, the panels also acknowledged the need to refine the CP score since it is relatively quantitative. The score uses five variables: three objective laboratory-based parameters that assess the synthetic function of the liver through serum albumin level and prothrombin time or the elimination function of the liver through measuring serum bilirubin level, in addition to two subjective clinical parameters, hepatic encephalopathy and ascites. The last two parameters are clinically difficult to grade, may be precipitated by other nonliver diseases, and may vary in severity according to treatment with diuretics and lactulose. Thus, major refinement of the CP score is critically needed to optimize HCC management and improve the typically dismal outcome of this disease. Our most recent published reports described the use of the plasma insulin-like growth factor (IGF)-1 level as a tool for assessing the status of the underlying CLD. Integration of measurement of this level into the CLIP and BCLC systems significantly improved their predictive ability and refined HCC patient stratification. Therefore, our overall goal for the proposed study is to develop a noninvasive biomarker-based strategy to personalize HCC classification. Our central hypothesis is that the baseline plasma IGF-1 level is an easily measured surrogate prognostic biomarker of the extent of hepatic dysfunction that can be used instead of assessment of ascites and hepatic encephalopathy to refine the predictive ability of CP and HCC classifications. We will test this hypothesis in three specific aims: 1) To construct a new CP score and new CLIP and BCLC staging systems by integrating plasma IGF-1 measurement into the CP score parameters. 2) To compare the performance of the original CP score and CLIP and BCLC staging systems with that of the IGF-integrated systems. 3) To prospectively validate the performance of the IGF-1-integrated "CP score and CLIP and BCLC staging" systems in an independent cohort of HCC patients. Should we achieve our aims we may be able to develop new strategies in personalized therapy in better designed clinical trials of comparable criteria.

描述（由申请人提供）：在肝细胞癌（HCC）管理中，Child-Pugh（CP）评分是目前在临床实践中评估基础慢性肝病（CLD）状态和在HCC治疗试验中对患者进行分层的标准工具。它也是大多数目前使用的HCC分期系统，特别是意大利肝癌计划（CLIP）和巴塞罗那临床肝癌（BCLC）中的重要参数。多个专家小组的共识声明达成共识，即考虑手术切除或局部或全身治疗试验的HCC患者必须具有A的CP评分[1-3]。该选择标准有助于评估治疗效果，而不会出现肝衰竭和潜在肝硬化导致死亡的混杂问题。然而，小组也承认需要完善CP评分，因为它是相对定量的。分数使用五个变量：三个基于实验室的客观参数，通过血清白蛋白水平和凝血酶原时间评估肝脏的合成功能，或通过测量血清胆红素水平评估肝脏的消除功能，以及两个主观临床参数，肝性脑病和腹水。后两个参数在临床上难以分级，可能由其他非肝脏疾病引起，并且严重程度可能因利尿剂和乳果糖治疗而异。因此，CP评分的主要改进是迫切需要的，以优化HCC管理和改善这种疾病的典型的令人沮丧的结果。我们最近发表的报告描述了使用血浆胰岛素样生长因子（IGF）-1水平作为评估潜在CLD状态的工具。将该水平的测量整合到CLIP和BCLC系统中显著提高了其预测能力并细化了HCC患者分层。因此，我们提出的研究的总体目标是开发一种基于生物标志物的非侵入性策略，以个性化HCC分类。我们的中心假设是，基线血浆IGF-1水平是肝功能障碍程度的一种容易测量的替代预后生物标志物，可用于代替腹水和肝性脑病的评估，以改善CP和HCC分类的预测能力。我们将在三个具体目标中检验这一假设：1）通过将血浆IGF-1测量整合到CP评分参数中来构建新的CP评分和新的CLIP和BCLC分期系统。2)比较原始CP评分、CLIP和BCLC分期系统与IGF整合系统的性能。3)在一个独立的HCC患者队列中前瞻性验证IGF-1整合的“CP评分和CLIP和BCLC分期”系统的性能。如果我们实现了我们的目标，我们也许能够在设计更好的临床试验中制定个性化治疗的新策略。

项目成果

Reassessing hepatocellular carcinoma staging in a changing patient population.

重新评估不断变化的患者群体中的肝细胞癌分期。

• DOI: 10.1159/000356573
• 发表时间: 2014
• 期刊: Oncology
• 影响因子: 3.5
• 作者: Kaseb,AhmedO;Shah,NeerajN;Hassabo,HeshamM;Morris,JeffreyS;Xiao,Lianchun;Abaza,YasminM;Soliman,Khalid;Lee,Ju-Seog;Vauthey,Jean-Nicholas;Wallace,Michael;Aloia,ThomasA;Curley,Steven;Abbruzzese,JamesL;Hassan,ManalM
• 通讯作者: Hassan,ManalM

Natural History of T1N0M0 Hepatocellular Carcinoma: Large-Scale Study in the United States.

• DOI: 10.1159/000455957
• 发表时间: 2017
• 期刊: Oncology
• 影响因子: 3.5
• 作者: Al-Shamsi HO;Abdel-Wahab R;Hassan MM;Shalaby AS;Dahbour I;Lacin S;Mahvash A;Odisio BC;Murthy R;Avritscher R;Abdelsalam ME;Rashid A;Vauthey JN;Aloia TA;Conrad C;Chun YS;Krishnan S;Das P;Koay EJ;Amin HM;Yao JC;Kaseb AO
• 通讯作者: Kaseb AO

Refining prognosis in patients with hepatocellular carcinoma through incorporation of metabolic imaging biomarkers.

• DOI: 10.1007/s00259-016-3583-2
• 发表时间: 2017-06
• 期刊: European journal of nuclear medicine and molecular imaging
• 影响因子: 9.1
• 作者: Takeuchi S;Rohren EM;Abdel-Wahab R;Xiao L;Morris JS;Macapinlac HA;Hassan MM;Kaseb AO
• 通讯作者: Kaseb AO

The transcription factors Ik-1 and MZF1 downregulate IGF-IR expression in NPM-ALK⁺ T-cell lymphoma.

• DOI: 10.1186/s12943-015-0324-2
• 发表时间: 2015-02-25
• 期刊: Molecular cancer
• 影响因子: 37.3
• 作者: Vishwamitra D;Curry CV;Alkan S;Song YH;Gallick GE;Kaseb AO;Shi P;Amin HM
• 通讯作者: Amin HM

Validation of an IGF-CTP scoring system for assessing hepatic reserve in Egyptian patients with hepatocellular carcinoma.

• DOI: 10.18632/oncotarget.4176
• 发表时间: 2015-08-28
• 期刊: Oncotarget
• 作者: Abdel-Wahab R;Shehata S;Hassan MM;Xiao L;Lee JS;Cheung S;Essa HH;Hassabo HM;Shalaby AS;Mosad E;Raghav K;Rashid A;Wolff RA;Morris JS;Amin HM;Kaseb AO
• 通讯作者: Kaseb AO