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.

摘要 肺癌是一种异质性疾病，是美国主要的癌症相关杀手。了解 这种异质性的分子原因是当前基础和转化研究的焦点。波士顿肺 癌症研究（BLCS）是在马萨诸塞州招募的超过11，000例肺癌病例的癌症流行病学队列 从1992年至今，总医院和Dana-Farber癌症研究所。这是第一个也是最全面的 随访期最长的幸存者队列，到本拟议周期结束时将增至14 000多人 并进行额外的补充以增强具有致癌驱动突变状态的样品。通过识别 相关患者，并提供关键的存档肿瘤组织，通过内部合作达纳- 在Farber/哈佛癌症中心（DF/HCC）肺癌项目中，BLCS支持了首次发现 EGFR突变与EGFR-TKI治疗反应之间的关联，开启靶向治疗时代 在肺癌中。我们现正申请支援现有的队列基础设施，并恢复招募 通过合作协议解决新案件。总体目标有三个方面：1）维持肺癌核心 队列，并最大限度地发挥其潜力，为未来的科学需求，肺癌生存研究; 2），使切割- 通过流行病学方法开发方法学和试点方法， 转化为生产性的多学科项目赠款，旨在研究生存的各个方面，以及 治疗毒性;和3）利用DF/HCC肺项目资源进行创造性多学科 合作的重点是治疗结果。大型队列招募新病例的依据包括： 1)促进新疗法与传统疗法之间的评价以及新的临床研究设计， 在不断变化的治疗环境中进行调查; 2）收集更多具有罕见致癌驱动因素的病例 突变; 3）包括具有准确组织学、吸烟史和突变负荷分析的患者， 免疫疗法; 4）收集适合于发展预后/预测性免疫疗法的重复生物样品。 生物标志物;和5）允许更好地评估研究较少的小细胞肺癌（SCLC）。本申请 还将支持我们通过高血压的自动图像分析建立创新的COPD表型数据库， 分辨率计算机断层扫描，以及放射组学数据库，以及开发一种新的分析方法， 将来自电子病历（EMR）的遗传流行病学数据和信息联系起来， 正在进行的R35奖（林锡红博士）。BLCS队列是为数不多的存活队列之一， 生存状态数据，肿瘤突变数据和组织可用。结合生物标志物数据，肿瘤 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的 转化研究并提供独特的机会来进一步探索生存和治疗的预测因素 结果。我们的目标是保持BLCS随访和相关数据的质量， 这些方法将为研究人员提供新的机会。