CAUSAL: Cohort to Augment the Understanding of Sarcoma Survivorship Across the Lifespan

因果关系：增强对整个生命周期肉瘤幸存者的理解的队列

• 批准号: 10212723
• 负责人: Debra L. Friedman
• 金额: $ 107.61万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212723
• 关键词: 15 year old; Abstinence; Academic Medical Centers; Address; Adjuvant Chemotherapy; Affect; Alcohol consumption; Biological Assay; Biology; Blood specimen; Cancer Survivor; Caring; Cessation of life; Chemotherapy and/or radiation; Clinical; Clinical Data; Cohort Studies; Connective Tissue; DNA Repair Gene; DNA analysis; Data; Diagnosis; Disease; Electronic Health Record; Equilibrium; Foundations; Future; Gene Expression; Genetic Polymorphism; Genetic Predisposition to Disease; Genomics; Goals; Grant; Health; Heart Diseases; Incidence; Individual; Infrastructure; Investigation; Kidney Diseases; Knowledge; Lead; Life; Life Style; Liver diseases; Longevity; Lung diseases; Medical Oncologist; Mesenchymal; Micrometastasis; Monitor; Neoadjuvant Therapy; Newly Diagnosed; Normal tissue morphology; Oncogenes; Organ; Orthopedics; Outcome; Participant; Patient Outcomes Assessments; Patients; Pediatric Oncologist; Population; Precision therapeutics; Predictive Factor; Prevalence; Prognostic Factor; Prognostic Marker; Prospective cohort; Quality of life; Radiation Oncologist; Radiation therapy; Recurrence; Relapse; Research; Residual Neoplasm; Risk Factors; Role; Sampling; Severities; Somatic Mutation; Specialist; Surveys; Survivors; Tennessee; Therapeutic Intervention; Time; Toxic effect; Treatment Efficacy; Treatment-Related Cancer; Treatment-related toxicity; Tumor Biology; Tumor Subtype; Tumor Tissue; United States; Variant; cancer diagnosis; cancer therapy; childhood cancer survivor; cigarette smoking; circulating biomarkers; cohort; design; diet and exercise; drug metabolism; epidemiologic data; financial toxicity; follow-up; functional status; genetic risk factor; genome sequencing; healthy lifestyle; improved; improved outcome; indexing; lifestyle factors; liquid biopsy; molecular marker; mortality; next generation sequencing; peripheral blood; physical conditioning; polygenic risk score; predictive marker; prognostic value; programs; prospective; psychologic; psychosocial; rare cancer; recruit; response; sarcoma; social; sociodemographics; surveillance strategy; survivorship; tool; transcriptomics; treatment center; treatment response; tumor; tumor DNA; whole genome

PROJECT SUMMARY Sarcomas represent a rare and highly heterogeneous subtype of tumors that may develop across the lifespan. In the United States (US), there are approximately 14,000 new cases annually, with approximately 65% survival. Aside from those included in pediatric cancer survivor cohort studies, there are no sarcoma survivor cohorts in which to systematically study recurrence, organ toxicity, function, quality of life, and survival as well as their predictors. We propose to address these critical gaps in knowledge by establishing a cohort of approximately 2100 sarcoma survivors through the Vanderbilt University Medical Center (VUMC) Sarcoma Treatment Center, which is amongst the largest sarcoma programs in the US, in existence since 1987. In this cohort, we will systematically collect repeated information on disease, treatment, response, relapse, treatment-related toxicity, sociodemographics, lifestyle, functional status, quality of life, physical health outcomes, and survival, together with biospecimens (tumor tissue and peripheral blood samples). We hypothesize that: 1) extrinsic factors, tumor biology, and germline genomics contribute to oncologic outcomes and long-term organ toxicity; 2) healthy lifestyle, e.g., high quality of diet, exercise, abstinence from cigarette smoking and alcohol drinking mitigate the adverse health consequences, improve survival and quality of life among sarcoma survivors; and 3) liquid biopsy tools, developed through identifying genomic drivers of sarcoma, will be of predictive and prognostic utility. Our aims for current grant period are to evaluate1) the impact of disease, treatment, sociodemographic and lifestyle contributors on adverse oncologic and non-oncologic outcomes and mortality in the cohort; 2) the role of drug metabolism and DNA repair gene functional polymorphisms, genetically predicted gene expression levels, and polygenic risk scores, on treatment efficacy and therapy-induced normal tissue toxicity; and 3) genomic drivers of sarcoma to develop personalized liquid biopsy assays for monitoring treatment response, recurrence, and minimal residual disease. Establishment of a prospective cohort of sarcoma survivors across the lifespan, with extensive and well characterized clinical and epidemiologic data, patient reported outcomes, tumor tissue and serial blood samples builds a foundation for a long-term prospective investigation on life after sarcoma. This effort is critically important to improve the understanding of a rare tumor affecting the lifespan but seriously underrepresented in research. Identification of health outcomes and their predictive and prognostic factors can lead to precision treatment and survivorship care, which are currently clinically unmet needs.

项目摘要 肉瘤是一种罕见的高度异质性的肿瘤亚型，可能在整个生命周期中发展。 在美国，每年约有14，000例新发病例，存活率约为65%。 除了那些包括在儿科癌症幸存者队列研究，没有肉瘤幸存者队列， 系统地研究复发、器官毒性、功能、生活质量和生存率以及它们的 预测器我们建议通过建立一个大约有100名学生的队列来解决这些关键的知识缺口。 2100名肉瘤幸存者通过范德比尔特大学医学中心（VUMC）肉瘤治疗中心， 这是美国最大的肉瘤项目之一，自1987年以来一直存在。在这一组中，我们将 系统地收集关于疾病、治疗、反应、复发、治疗相关毒性 社会人口统计学、生活方式、功能状态、生活质量、身体健康结果和生存率， 生物样本（肿瘤组织和外周血样本）。我们假设：1）外在因素，肿瘤 生物学和生殖系基因组学有助于肿瘤学结果和长期器官毒性; 2）健康 生活方式，例如，高质量的饮食、锻炼、戒烟和戒酒可以减轻 不良健康后果，提高肉瘤幸存者的生存率和生活质量; 3）液体活检 通过鉴定肉瘤的基因组驱动因素而开发的工具将具有预测和预后效用。我们 目前资助期的目标是评估1）疾病、治疗、社会人口和生活方式的影响 队列中不良肿瘤学和非肿瘤学结局和死亡率的影响因素; 2）药物的作用 代谢和DNA修复基因功能多态性，遗传预测的基因表达水平，和 多基因风险评分，关于治疗功效和治疗诱导的正常组织毒性;和3）基因组驱动因素 开发个性化的液体活检检测，用于监测治疗反应，复发， 微小残留病建立一个贯穿整个生命周期的肉瘤存活者前瞻性队列， 广泛且充分表征的临床和流行病学数据、患者报告的结局、肿瘤组织和 系列血液样本为肉瘤后生活的长期前瞻性研究奠定了基础。这 努力提高对影响寿命的罕见肿瘤的理解至关重要， 在研究中代表性不足。确定健康结果及其预测和预后因素， 实现精确治疗和生存护理，而这些是目前临床上未满足的需求。