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.
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