Predicting ocular outcomes, quality of life and survival after proton beam radiotherapy of choroidal melanoma

项目摘要/摘要 我正在申请眼科肿瘤学职业发展奖(K23)。K23将允许我建立一个 加强脉络膜患者预后和改善整体护理的临床研究计划 黑色素瘤。拟议的研究和培训将为R01/UG1提案奠定基础 建立一个国际眼部黑色素瘤登记系统，促进与大型 数据集。 我的长期职业目标是：1)在加州大学领导一个多学科的眼科肿瘤学团队， 旧金山(加州大学旧金山分校)；2)创建临床结果、分子病理学数据和 患者报告的结果(PRO)预测眼睛结果、生存和生活质量(QOL)；3)进步 眼科肿瘤学的随机试验和多中心合作，以促进诊断和治疗。 我的培训目标是：1)掌握先进的生物统计学方法、数据库管理和 通过教学课程和学徒制度进行学习设计，与眼科领域的知名导师合作 肿瘤学、分子病理学和统计学；2)了解葡萄膜黑色素瘤的分子诊断学和 如何通过有指导的实验室在临床实践中评估新的预测和诊断测试 与杰出的分子病理学家合作的经验；3)参与多学科合作研究 与国际同行建立联系，为未来的多中心研究；以及4)熟练掌握 科学写作。 该项目的具体目标是：1)开发和验证预测视力的预测模型 脉络膜质子放射治疗后的预后、局部肿瘤控制和眼球保护 黑色素瘤。我们将测试辐射剂量学比基线更好地预测这种结果的假设。 临床特点。2)：验证有针对性的下一代基因测序(NGS)分析作为预后测试 用于脉络膜黑色素瘤的生存。我们假设脉络膜黑色素瘤的NGS可靠地决定了 肿瘤致命性。3)：建立预测质子放射治疗后PROS和生活质量的预测模型 脉络膜黑色素瘤。我们假设社会因素比眼睛特征更能预测 确定PRO和QOL我们将对现有的接受治疗的患者数据集进行二次分析 利物浦眼科肿瘤学中心，主要由主要导师(BD)创建和验证 预后模型，然后我们将在加州大学旧金山分校的一组患者中对其进行评估。

PROJECT SUMMARY/ABSTRACT I am applying for a Career Development Award (K23) in ocular oncology. A K23 will allow me to establish a clinical research program to enhance prognostication and improve holistic care for patients with choroidal melanoma. The proposed research and training will provide the foundation for an R01/UG1 proposal to develop an international ocular melanoma registry, fostering multi-center comparative studies with large datasets. My long-term career goals are to: 1) lead a multidisciplinary ocular oncology team at University of California, San Francisco (UCSF); 2) create a prospective database of clinical outcomes, molecular pathology data and patient- reported outcomes (PROs) to predict ocular outcomes, survival and quality of life (QOL); 3) advance randomized trials and multicenter collaboration in ocular oncology, to advance diagnostics and therapeutics. My training objectives are to: 1) master advanced biostatistics methodology, database management and study design through didactic courses and apprenticeships, working with renowned mentors in ocular oncology, molecular pathology and statistics; 2) understand molecular diagnostics in uveal melanoma and how to evaluate new prognostic and diagnostic tests in clinical practice, through mentored laboratory experiences with a pre-eminent molecular pathologist; 3) engage in multidisciplinary research, in collaboration with international colleagues, forming connections for future multi-center studies; and 4) become proficient in scientific writing. The specific aims of this project are to: 1) develop and validate prognostic models for predicting visual outcome, local tumor control and ocular conservation after proton beam radiotherapy for choroidal melanoma. We will test the hypothesis that radiation dosimetry predicts such outcomes better than baseline clinical features. 2): validate a targeted next-generation genetic sequencing (NGS) assay as a prognostic test for survival in choroidal melanoma. We hypothesize that NGS of choroidal melanoma reliably determines tumor lethality. 3): develop prognostic models for predicting PROs and QOL after proton beam radiotherapy for choroidal melanoma. We hypothesize that social factors are more predictive than ophthalmic features in determining PROs and QOL We will perform secondary analysis of an existing dataset of patients treated at the Liverpool Ocular Oncology Centre, mostly by the primary mentor (BD), to create and validate the prognostic models, which we will then evaluate in a cohort of patients at UCSF.