The Boston Lung Cancer Survival Cohort

波士顿肺癌生存队列

基本信息

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
项目类别：
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

项目摘要

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，也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) 是在马萨诸塞州登记的超过 11,000 例肺癌病例的癌症流行病学队列 1992 年至今，总医院和丹娜法伯癌症研究所。这是第一篇也是最全面的随访期最长的幸存者队列，到本提议周期结束时将增长到超过 14,000 人通过额外的招募来增强具有致癌驱动突变状态的样本。通过识别通过 Dana 内部的合作，相关患者并提供关键的存档肿瘤组织 Farber/哈佛大学癌症中心 (DF/HCC) 肺癌项目，BLCS 支持首次发现 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。我们现在正在申请对现有队列基础设施的支持，并恢复招募通过合作协议新案件。总体目标有三重：1) 维持肺癌核心队列并最大限度地发挥其潜力，以满足肺癌生存研究的未来科学需求； 2) 启用切割- 流行病学方法开发方法和试点方法的边缘研究问题转化为富有成效的多学科项目赠款，旨在研究生存的各个方面，以及治疗毒性； 3) 利用 DF/HCC 肺项目资源进行创造性的多学科研究合作的重点是治疗结果。将新病例纳入大队列的理由包括： 1）促进新疗法与传统疗法之间的评价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) 收集适合预后/预测的重复生物样本生物标志物； 5) 可以更好地评估研究较少的小细胞肺癌 (SCLC)。这个应用程序还将支持我们通过高通量图像的自动图像分析建立一个创新的慢性阻塞性肺病表型数据库。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在来自电子病历 (EMR) 的支持下将遗传流行病学数据和信息联系起来正在进行的 R35 奖（Xihong Lin 博士）。 BLCS 队列是为数不多的做出重大贡献的存活队列之一有关生存状态的数据，以及可用的肿瘤突变数据和组织。生物标志物数据、肿瘤数据的结合分子表征、CT 成像和传统流行病学危险因素数据将提供强大的支持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，并开发将为研究人员提供新机会的方法。