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: 10228004
• 负责人: Debra L Friedman
• 金额: $ 16.94万
• 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/10228004
• 关键词: Acute; Address; Affect; Aftercare; American; Area; Asians; Biological; Biological Assay; 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; Hispanics; 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.

项目摘要 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，多种族和种族 视网膜母细胞瘤（RB）幸存者研究健康结果并询问基因型 - 表型的财团 疾病表现的相关性。在高收入国家和 因此，治疗的重点是保存功能视觉并最大程度地减少急性和长期 术语不利结果。 RB已可以通过插核或放射治疗几十年来治愈。但是， 眼睛去除眼睛，视觉障碍，轨道和面部畸形，社会心理和神经认知的发病率 1990年代使用的损害和随后的恶性肿瘤（SMN）率 局部眼科疗法（IVC）化学疗法。 IVC多达40％的眼睛中，地球救助的失败， 结合系统性毒性，自2008年以来，动脉内化疗（IAC）的使用增加了。 据信IAC与优秀的以患者为中心的结果和SMN率相关 摘除或辐射。 IVC潜在地与更多的系统性毒性有关，而IAC与更大的局部毒性有关 毒性。因此，治疗选择部分取决于急性和长期毒性。也必须进行治疗 通过与地球和视力野蛮的治愈可能性确定，这受到疾病的严重影响 呈现，特别是玻璃体和视网膜下种子。但是，种子开发的生物基础 仍然是未知的。这种知识可以为治疗的选择提供信息，并导致有针对性的发展 与疗效和毒性平衡有关的疗法。没有有组织的系统方法 进行了评估IVC和IAC或生物决定因素的急性毒性和长期结局 侵略性疾病表现，推动治疗决定，然后是健康结果。我们有 因此，组装的小儿肿瘤学和眼科研究人员构成了视觉研究 治疗后的终点和RB健康结果（河船）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 具有规范数据和同胞控制的幸存者； 2）创建第一个临床上注销的患者组织 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：河船 Biorepository上尉； 3）使用河船船长生物座位，确定 特定的RB1突变类型以及其他修饰符基因在确定驱动肿瘤表型中的作用 治疗决定。我们将对RB的幸存者产生积极影响：1）评估短期和长期结局 当代疗法； 2）建立一个临床上注销的生物措施进行基因组研究； 3） 检查疾病表现的分子发病机理。这将解决RB管理的目标：Globe 和视力保存，而无需治疗相关的不良后遗症。