Validation of Clinical Assays for Risk Stratification of Children With Pediatric Liver Neoplasms

小儿肝肿瘤儿童风险分层临床测定的验证

• 批准号: 10663695
• 负责人: Dolores Lopez-Terrada
• 金额: $ 33.3万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663695
• 关键词: 5 year old; 6 year old; Adolescent; Affect; Biological Assay; Biological Markers; Biology; CLIA certified; Cardiotoxicity; Categories; Certification; Cessation of life; Child; Childhood; Cisplatin; Classification; Clinical; Clinical Trials; Collaborations; Combination Drug Therapy; Combined Modality Therapy; Data; Development; Diagnosis; Drug resistance; Enrollment; Europe; European; Excision; Funding; Graft Rejection; Hepatic; Hepatoblastoma; High Dose Chemotherapy; Histology; Immunotherapy; Impairment; International; Intervention; Intervention Studies; Investigational Therapies; Lesion; Liver; Liver neoplasms; Malignant Neoplasms; Medical; Modeling; Molecular; Molecular Diagnosis; Molecular Profiling; Morbidity - disease rate; Neoplasm Metastasis; Neoplasms; Nonmetastatic; Operative Surgical Procedures; Outcome; Patient Recruitments; Patient-Focused Outcomes; Patients; Pediatric Neoplasm; Pediatric Oncology Group; Pediatric cohort; Play; Preparation; Primary carcinoma of the liver cells; Prognosis; Prognostic Marker; Quality of life; Resected; Resistance; Risk; Risk Estimate; Second Primary Cancers; Stratification; Survival Rate; Testing; Therapeutic Trials; Toxic effect; Treatment outcome; Treatment-related toxicity; Tumor Subtype; Unresectable; Validation; Work; aggressive therapy; biomarker validation; chemotherapeutic agent; chemotherapy; cohort; dosage; high risk; improved; improved outcome; liver cancer patient; liver transplantation; molecular marker; molecular modeling; nephrotoxicity; neurotoxicity; ototoxicity; participant enrollment; personalized medicine; predictive marker; predictive modeling; predictive test; profiles in patients; prospective; recruit; research clinical testing; response; risk prediction; risk prediction model; risk stratification; targeted treatment; transplantation therapy; treatment optimization; tumor

Project Summary Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most frequently diagnosed liver tumors in children, with HBs most commonly present in young children less than 5 years of age, and HCCs are more commonly seen in adolescents. HB- and HCC-patient outcomes and treatment options vary dramatically, with 5-year overall survival rates of over 70% for HB and under 30% for HCC patients. While a combination of chemotherapy and surgery is effective for lower-risk HBs, 3-year overall survival for high-risk HBs is 50%. High- dose chemotherapy, which is often ineffective for high-risk HBs, is associated with significant morbidity. Complete surgical resection is the only chance for a cure for HCC. Molecular biomarkers can help optimize treatments for patients that will not benefit from chemotherapy or that do not require high dosage chemotherapy and identify patients that require a combination of aggressive surgery and chemotherapy. In previous work, we, and our collaborators, identified prognostic biomarkers that distinguish between low- and high-risk HBs at diagnosis. We proposed and retrospectively evaluated predictive models to classify patients based on risk—including their need for aggressive therapies. These models identify patients that do not require aggressive therapies, patients that will benefit from aggressive therapies, and patients with tumors that are more likely to metastasize and become resistant to chemotherapy. We developed and certified molecular assays to profile patients and tumors for predictive biomarker used by these models. Here, we propose to prospectively validate these biomarkers, assays, and models to produce the first validated platform for the molecular diagnosis and therapy choice for HBs and HCC. We will benefit from a close collaboration with clinical-trial produced data in the USA and EU, including AHEP1531 (USA), ChILTERN (EU) and iPC (a EU-USA collaboration).

项目摘要 肝母细胞瘤(HB)和肝细胞癌(HCC)是#年最常见的肝脏肿瘤 儿童，其中HBs最常出现在5岁以下的幼儿中，且HCCs 通常见于青少年。乙肝和肝癌患者的预后和治疗选择有很大的不同， 乙肝患者的5年总存活率超过70%，而肝细胞癌患者的总存活率低于30%。而组合在一起 化疗和手术对低风险的HBs有效，高危的HBs的3年总存活率为50%。高- 剂量化疗对高危HBs往往无效，与显著的发病率有关。 彻底手术切除是治愈肝细胞癌的唯一机会。分子生物标记物有助于优化 不会从化疗中受益或不需要大剂量化疗的患者的治疗 并确定需要积极手术和化疗相结合的患者。 在之前的工作中，我们和我们的合作者确定了区分低血压和低血糖的预后生物标记物。 确诊时的高危HBs。我们提出并回顾评估预测模型来对患者进行分类。 基于风险--包括他们对积极治疗的需要。这些模型识别的患者不需要 积极治疗，将从积极治疗中受益的患者，以及患有更多 有可能转移并对化疗产生抗药性。我们开发并认证了分子检测方法来 这些模型所使用的预测生物标记物的患者和肿瘤的概况。在此，我们建议前瞻性地 验证这些生物标记物、分析和模型，以产生第一个经过验证的分子诊断平台 以及对乙肝和肝癌的治疗选择。我们将受益于与临床试验产生的数据的密切合作 在美国和欧盟，包括AHEP1531(美国)、Chiltern(欧盟)和IPC(欧盟-美国合作)。