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; 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 肉瘤代表了可能在整个寿命中发展的罕见且高度异质的亚型。 在美国（美国），每年大约有14,000例新病例，生存率约为65％。 除了儿科癌症幸存者队列研究中包括的那些外，没有肉瘤幸存者队列 要系统地研究复发，器官毒性，功能，生活质量和生存及其 预测指标。我们建议通过建立大约的队列来解决知识中的这些关键差距 2100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计划之一，自1987年以来存在。在这个同类中，我们将 系统地收集有关疾病，治疗，反应，复发，与治疗相关的毒性的重复信息， 社会人口统计学，生活方式，功能状况，生活质量，身体健康成果和生存，一起 带有生物测量（肿瘤组织和外周血样本）。我们假设：1）外部因素，肿瘤 生物学和种系基因组学有助于肿瘤结局和长期器官毒性； 2）健康 生活方式，例如高质量的饮食，运动，吸烟和饮酒的戒酒减轻 不利的健康后果，改善肉瘤幸存者的生存和生活质量； 3）液体活检 通过识别肉瘤的基因组驱动因素而开发的工具将具有预测性和预后效用。我们的 当前赠款期的目的是评估1）疾病，治疗，社会人口统计学和生活方式的影响 对队列中不良肿瘤学和非综合结果和死亡率的贡献者； 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，治疗功效和治疗引起的正常组织毒性； 3）基因组驱动器 肉瘤开发个性化的液体活检测定法，以监测治疗反应，复发和 最小残留疾病。在整个生命周期中建立了一群潜在的肉瘤幸存者 广泛且表征良好的临床和流行病学数据，患者报告的结局，肿瘤组织和 连环血样本为肉瘤后的长期前瞻性调查奠定了基础。这 努力对于提高对影响寿命的罕见肿瘤的理解至关重要，但严重 研究不足。鉴定健康结果及其预测性和预后因素可以 导致精确治疗和生存护理，目前在临床上无法满足。