Research Into Visual Endpoints and RB Health Outcomes After Treatment: The RIVERBOAT Consortium

视觉终点和 RB 治疗后健康结果的研究：RIVERBOAT 联盟

• 批准号: 10473688
• 负责人: Debra L. Friedman
• 金额: $ 49.5万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-03 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10473688
• 关键词: Acute; Address; Affect; Aftercare; American; Area; Asian; Biological; Biological Assay; Black race; Blindness; Blood; Blood Vessels; Chemotherapy and/or radiation; Child; Classification; Clinical; Counseling; Country; DNA; Data; Deformity; Development; Disease; Equilibrium; Excision; Eye; Face; Failure; Family; Genes; Genetic; Genetic Determinism; Genomics; Genotype; Geography; Goals; Health; Hispanic; Iatrogenesis; Impaired cognition; Income; Institution; International; Intraocular retinoblastoma; Intravenous; Knowledge; Lead; Malignant Neoplasms; Medical Records; Modality; Molecular; Morbidity - disease rate; Mutation; Neurocognitive; Neurocognitive Deficit; Nucleic Acid Regulatory Sequences; Ophthalmology; Outcome; Pathogenesis; Patient Self-Report; Patient-Focused Outcomes; Patients; Pediatric Oncology; Pediatric Oncology Group; Phenotype; Public Health; Questionnaires; RB1 gene; RNA Splicing; Radiation; Radiation therapy; Research; Research Personnel; Retina; Retinoblastoma; Risk; Role; Sampling; Seeds; Selection for Treatments; Shotguns; Siblings; Site; Survivors; Testing; Therapeutic; Time; Tissues; Toxic effect; Translating; Treatment outcome; Treatment-related toxicity; Tumor Tissue; Vision; Vision Screening; Visual; Visual impairment; Work; acute toxicity; advanced disease; adverse outcome; base; biobank; cancer therapy; causal variant; chemotherapy; cohort; ethnic diversity; exome; exome sequencing; eye preservation; gene interaction; genome-wide; improved; innovation; mortality; multi-racial; next generation sequencing; novel therapeutics; patient oriented; preservation; psychosocial; racial and ethnic; racial diversity; success; survivorship; systemic toxicity; targeted treatment; treatment strategy; tumor; virtual

PROJECT SUMMARY The overall goal of this effort is to organize the first and largest international multicenter, multi-racial and ethnic consortium of retinoblastoma (RB) survivors to study health outcomes and interrogate genotype-phenotype correlations of disease presentation. Intraocular RB is virtually 100% curable in high-income countries and treatment thus focuses on globe salvage with preservation of functional vision and minimizing acute and long- term adverse outcomes. RB has been curable for decades with enucleation or radiation therapy. However, the morbidity of eye removal, visual impairment, orbital and facial deformities, psychosocial and neurocognitive impairment and high subsequent malignant neoplasm (SMN) rates prompted in the 1990's the use of intravenous chemotherapy with local ophthalmic therapies (IVC). Failure of globe salvage in up to 40% of eyes with IVC, combined with systemic toxicities led to the increased use of intra-arterial chemotherapy (IAC) since 2008. IVC and IAC are believed to be associated with excellent patient centered outcomes and lower SMN rates than enucleation or radiation. IVC is potentially associated with more systemic toxicities, while IAC with greater local toxicity. Therapeutic options are thus, in part, determined by acute and long-term toxicities. Treatment must also be determined by likelihood of cure with globe and vision savage, which is heavily influenced by disease presentation, and in particular, vitreous and subretinal seeds. However, the biologic basis of seed development remains largely unknown. Such knowledge can inform choice of therapy and lead to development of targeted therapies associated with an improved balance of efficacy and toxicity. No organized systematic approach has been undertaken to assess acute toxicities and long-term outcomes of IVC and IAC or the biologic determinants of aggressive disease presentation, which drives therapeutic decisions, and in turn, health outcomes. We have therefore assembled pediatric oncology and ophthalmology investigators to form the Research Into Visual Endpoints and RB Health Outcomes After Treatment (RIVERBOAT) Consortium to: 1) define acute toxicity and visual outcomes in RB survivors and compare patient-centered psychosocial and neurocognitive outcomes in survivors with normative data and sibling controls; 2) create the first Clinically-Annotated Patient Tissues to Analyze gene INteractions to assess biologic correlates of disease and to facilitate future research: RIVERBOAT- CAPTAIN Biorepository; and 3) using the RIVERBOAT-CAPTAIN biorepository, determine the interplay between specific RB1 mutation type and the role of additional modifier genes in determining tumor phenotypes that drive treatment decisions. We will positively impact survivors of RB by: 1) assessing short and long-term outcomes of contemporary therapy; 2) establishing a clinically-annotated biorepository for genomic research; and 3) examining molecular pathogenesis of disease presentation. This will address the goal of RB management: globe and vision preservation without treatment-related adverse sequelae.

项目概要 这项工作的总体目标是组织第一个也是最大的国际多中心、多种族和民族的活动 视网膜母细胞瘤（RB）幸存者联盟研究健康结果并询问基因型-表型 疾病表现的相关性。在高收入国家，眼内 RB 实际上 100% 可以治愈 因此，治疗的重点是挽救眼球，保留功能性视力并最大限度地减少急性和长期视力障碍。 术语不良后果。几十年来，RB 一直可以通过剜除术或放射疗法治愈。然而， 眼球摘除、视力障碍、眼眶和面部畸形、心理社会和神经认知的发病率 损伤和随后的高恶性肿瘤 (SMN) 发生率促使 20 世纪 90 年代使用静脉注射 局部眼科治疗（IVC）的化疗。高达 40% 的 IVC 眼睛无法挽救眼球， 加上全身毒性导致自 2008 年以来动脉内化疗 (IAC) 的使用增加。 IVC 和 IAC 被认为与以患者为中心的良好结果和较低的 SMN 率相关 摘除或辐射。 IVC 可能与更多的全身毒性相关，而 IAC 则与更大的局部毒性相关。 毒性。因此，治疗选择部分取决于急性和长期毒性。治疗还必须 取决于眼球和视力的治愈可能性，这在很大程度上受疾病的影响 呈现，特别是玻璃体和视网膜下种子。然而，种子发育的生物学基础 仍然很大程度上未知。这些知识可以为治疗选择提供信息，并导致有针对性的开发 与改善功效和毒性平衡相关的疗法。尚无有组织的系统方法 旨在评估 IVC 和 IAC 的急性毒性和长期结果或生物决定因素 侵袭性疾病的表现，推动治疗决策，进而影响健康结果。我们有 因此，聚集了儿科肿瘤学和眼科研究人员，组成了视觉研究 终点和 RB 治疗后健康结果 (RIVERBOAT) 联盟：1) 定义急性毒性和 RB 幸存者的视觉结果，并比较以患者为中心的心理社会和神经认知结果 具有规范数据和兄弟姐妹对照的幸存者； 2) 创建第一个临床注释的患者组织 分析基因相互作用以评估疾病的生物学相关性并促进未来的研究：RIVERBOAT- 船长生物样本库； 3) 使用 RIVERBOAT-CAPTAIN 生物样本库，确定之间的相互作用 特定的 RB1 突变类型以及其他修饰基因在确定驱动肿瘤表型中的作用 治疗决定。我们将通过以下方式对 RB 幸存者产生积极影响：1) 评估 RB 的短期和长期结果 现代疗法； 2）建立用于基因组研究的临床注释生物样本库；和 3) 检查疾病表现的分子发病机制。这将实现 RB 管理的目标：全球 和视力保留，且没有治疗相关的不良后遗症。