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

基本信息

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
项目类别：
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

项目摘要

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).

项目概要肝母细胞瘤 (HB) 和肝细胞癌 (HCC) 是最常诊断的肝脏肿瘤儿童中，HBs 最常见于 5 岁以下幼儿，而 HCCs 则更常见 HB 和 HCC 患者的结局和治疗选择差异很大。 HB 患者的 5 年总生存率超过 70%，HCC 患者的 5 年总生存率低于 30%。化疗和手术对于低危 HB 有效，高危 HB 的 3 年总生存率为 50%。大剂量化疗通常对高风险 HBs 无效，并且与显着的发病率相关。完整的手术切除是治愈 HCC 的唯一机会，可以帮助优化分子生物标志物。针对无法从化疗中受益或不需要高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和低的预后生物标志物我们提出并回顾性评估了诊断时的高风险 HBs 来对患者进行分类。基于风险——包括他们对积极治疗的需求，这些模型识别出不需要的患者。积极治疗、将从积极治疗中受益的患者以及患有更严重肿瘤的患者我们开发并认证了分子检测方法。在这里，我们建议前瞻性地分析患者和肿瘤的预测生物标志物。验证这些生物标志物、检测方法和模型，以生成第一个经过验证的分子诊断平台我们将受益于与临床试验数据的密切合作。在美国和欧盟，包括 AHEP1531（美国）、ChILTERN（欧盟）和 iPC（欧盟-美国合作）。