The Boston Lung Cancer Survival Cohort

波士顿肺癌生存队列

• 批准号: 10415930
• 负责人: David C Christiani
• 金额: $ 125.35万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415930
• 关键词: Archives; Area; Award; Basic Science; Biological; Biological Markers; Boston; Cancer Center; Cancer Patient; Cessation of life; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Cancer Center; Clinical Research; Cohort Studies; Collaborations; Computerized Medical Record; Coupling; DNA; DNA Methylation; Dana-Farber Cancer Institute; Data; Data Management Resources; Databases; Development; Diet; Dimensions; Disease; Enrollment; Environment; Epidemiologic Methods; Epidemiology; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Erlotinib; Evaluation; Factor Analysis; Follow-Up Studies; Future; Gefitinib; General Hospitals; Genetic; Genomics; Grant; Heterogeneity; High Resolution Computed Tomography; Histology; Immunotherapy; Infrastructure; Interdisciplinary Study; International; Laboratories; Leukocytes; Link; Lung; Lung Adenocarcinoma; Malignant Neoplasms; Malignant neoplasm of lung; Massachusetts; Methodology; Methods; Methylation; Molecular; Mutation; Natural History; Occupational; Oncogenic; Outcome; Participant; Patients; Pharmaceutical Preparations; Phenotype; Physical activity; Pilot Projects; Population Heterogeneity; Quality Control; Questionnaires; Recurrence; Research; Research Design; Research Methodology; Research Personnel; Resource Sharing; Resources; Risk Factors; Sampling; Secure; Serum; Smoking; Smoking History; Structure of parenchyma of lung; Survivors; System; Therapeutic; Tissues; Toxic effect; Translational Research; Treatment Efficacy; Treatment outcome; Treatment-related toxicity; Tumor Tissue; U-Series Cooperative Agreements; United States; Update; Urine; Weight; X-Ray Computed Tomography; automated image analysis; biobank; bioinformatics pipeline; cancer epidemiology; cancer survival; cell free DNA; clinical investigation; cohort; data management; data quality; data sharing; dietary; driver mutation; epidemiologic data; follow-up; genetic epidemiology; genome-wide; genotyped patients; indexing; innovation; lung imaging; lung small cell carcinoma; member; method development; microbiome research; mortality; multidisciplinary; mutational status; new technology; next generation sequencing; novel; pathology imaging; predictive marker; prognostic; programs; prospective; pulmonary function; radiomics; recruit; respiratory; response; screening program; survival outcome; survival prediction; targeted treatment; traditional therapy; transcriptomics; translational medicine; treatment response; tumor

ABSTRACT Lung cancer is a heterogeneous disease and the leading cancer-related killer in the United States. Understanding the molecular causes of this heterogeneity is the focus of current basic and translational research. The Boston Lung Cancer Study (BLCS) is cancer epidemiology cohort of over 11,000 lung cancer cases enrolled at Massachusetts General Hospital and the Dana-Farber Cancer Institute from 1992-present. This is the first and most comprehensive survivor cohort with the longest follow-up period, and will grow to over 14,000 by the end of this proposed cycle with additional recruitment to enhance the samples with oncogenic driver mutation status. By identifying the relevant patients and providing critical archived tumor tissues, through collaboration within the Dana- Farber/Harvard Cancer Center (DF/HCC) Lung Cancer Program, the BLCS supported the first discovery of the association between EGFR mutations and response to therapy with EGFR-TKIs, initiating the era of targeted therapy in lung cancer. We are now applying for support of the existing cohort infrastructure and resume the recruitment of new cases through a cooperative agreement. The overarching aims are 3-fold: 1) To maintain the lung cancer core cohort and maximize its potential for future scientific needs for lung cancer survival research; 2) To enable cutting- edge research questions by epidemiologic methods development methodologic, and piloting approaches that will turn into productive multidisciplinary project grants aimed at studying various aspects of survival, as well as treatment toxicity; and 3) To leverage the DF/HCC lung program resources for creative multidisciplinary collaborations focused on treatment outcomes. The rationale for recruiting new cases into the large cohort include: 1) facilitating the evaluation between new treatments and traditional therapy and the study design of new clinical investigation in an ever-changing therapeutic environment; 2) collecting more cases with rare oncogenic driver mutations; 3) including patients with accurate histology, smoking histories, and mutational load analyses treated with immunotherapy; 4) collecting repeated biological samples suitable for development of prognostic/predictive biomarkers; and 5) allowing better assessment of the less-studied small-cell lung cancer (SCLC). This application will also support us to establish an innovative COPD phenotyping database via automated image analysis of high- resolution computed tomography, as well as a radiomics data base, as well as to develop a new method of analyzing linked genetic epidemiologic data and information from electronic medical records (EMR) with support from an ongoing R35 award (Dr. Xihong Lin). The BLCS cohort is one of the few survival cohorts contributing substantial data on survival status, with tumor mutation data and tissue available. The combination of biomarker data, tumor molecular characterization, CT imaging and traditional epidemiologic risk factor data will allow powerful translational research and provide unique opportunities to further explore predictors of survival and treatment outcomes. We aim to maintain the quality of the BLCS follow-up and associated data as well as to develop approaches that will provide novel opportunities to investigators.

抽象的 肺癌是一种异质性疾病，是美国与癌症相关的领先杀手。了解 这种异质性的分子原因是当前基本和转化研究的重点。波士顿肺 癌症研究（BLC）是马萨诸塞州招收的11,000例肺癌病例的癌症流行病学队列 综合医院和Dana-Farber癌症研究所从1992年至今。这是第一个也是最全面的 幸存者队列的随访时间最长，到本拟议周期结束时将增长到14,000多个 额外的募集以增强具有致癌驱动器突变状态的样品。通过识别 相关患者并通过DANA内的协作提供关键的存档肿瘤组织 Farber/Harvard Cancer Center（DF/HCC）肺癌计划，BLCS支持了第一次发现 EGFR突变与对EGFR-TKIS治疗的反应之间的关联，启动靶向治疗时代 在肺癌中。我们现在正在申请对现有队列基础设施的支持，并恢复招聘 通过合作协议的新案件。总体目的是3倍：1）维持肺癌核心 队列并最大程度地提高其未来对肺癌生存研究的科学需求的潜力； 2）启用剪裁 - 通过流行病学方法开发方法的边缘研究问题，以及试验方法 变成旨在研究生存的各个方面的生产性多学科项目赠款以及 治疗毒性； 3）利用DF/HCC肺肺活量资源来创造性多学科 合作的重点是治疗结果。将新案件招募到大型队列的基​​本原理包括： 1）促进新疗法与传统疗法之间的评估以及新临床的研究设计 在不断变化的治疗环境中进行调查； 2）收集更多罕见致癌驱动器的病例 突变； 3）包括精确组织学，吸烟史和用治疗的突变负荷分析的患者 免疫疗法； 4）收集重复的生物样品，适合于预后/预测的发展 生物标志物； 5）可以更好地评估较少研究的小细胞肺癌（SCLC）。此应用程序 还将支持我们通过高级的自动图像分析来建立创新的COPD表型数据库 分辨率计算机断层扫描以及放射线数据库，以及开发一种新的分析方法 从电子病历（EMR）中链接的遗传流行病学数据和信息 正在进行的R35奖（Xihong Lin博士）。 BLCS队列是为数不多的生存队列之一 有关生存状况的数据，并提供肿瘤突变数据和组织。生物标志物数据，肿瘤的组合 分子表征，CT成像和传统的流行病学风险因素数据将允许强大 翻译研究并提供了独特的机会来进一步探索生存和治疗的预测指标 结果。我们旨在保持BLCS随访和相关数据的质量以及开发 将为调查人员提供新的机会的方法。