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Rationale: A prospective longitudinal cohort of individuals at high risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer. Objectives: The goal of this study is to characterize individuals with high risk for lung cancer, accumulating valuable biospecimens and LDCT chest scans longitudinally over 5 years. Methods: Participants 55–80 years of age with a 5-year estimated risk of developing lung cancer >1.5% were recruited and enrolled from clinics at the Vanderbilt University Medical Center, Veteran Affairs Medical Center, and Meharry Medical Center. Individual demographic characteristics were assessed via questionnaire at baseline. Participants underwent an LDCT scan, spirometry, sputum cytology, and research bronchoscopy at the time of enrollment. Participants will be followed yearly for 5 years. Positive LDCT scans are followed-up according to standard of care. The clinical, imaging, and biospecimen data are collected prospectively and stored in a biorepository. Participants are offered smoking cessation counseling at each study visit. Results: A total of 480 participants were enrolled at study baseline and consented to sharing their data and biospecimens for research. Participants are followed with yearly clinic visits to collect imaging data and biospecimens. To date, a total of 19 cancers (13 adenocarcinomas, four squamous cell carcinomas, one large cell neuroendocrine, and one small-cell lung cancer) have been identified. Conclusions: We established a unique prospective cohort of individuals at high risk for lung cancer, enrolled at three institutions, for whom full clinical data, well-annotated LDCT scans, and biospecimens are being collected longitudinally. This repository will allow for the derivation and independent validation of clinical, imaging, and molecular biomarkers of risk for diagnosis of lung cancer. Clinical trial registered with ClinicalTrials.gov (NCT01475500).

Background: alloHCT is offered with curative intent to patients with malignant as well as some nonmalignant hematologic diseases, and conventionally-computed survival estimates are offered for prognosticating outcomes. However, conventionally-computed survival and mortality risk estimates do not account for patients' elapsed survival time which, among other factors, could affect subsequent mortality. Conditional survival overcomes these limitations by calculating the probability of survival after having already survived a certain period of time - such data are unavailable for alloHCT recipients. We describe conditional survival and cause-specific mortality (disease-related [DRM], non-disease-related [NDRM], and GvHD-related) after alloHCT to provide clinically relevant information for patients who have survived 6 mos, 1, 2, 5, and 10y after alloHCT. Methods: From 1976 to 2013, 4,315 consecutive patients underwent alloHCT for hematologic diseases at a single institution. Vital status and cause of death were determined using the National Death Index Plus and medical records. Results: Diagnoses included acute leukemia (54%), chronic leukemia (17%), lymphoma (11%), myelodysplastic syndrome (10%), severe aplastic anemia (5%), and other hematologic diseases (3%); median age at HCT was 38.5y (0.3-75.4). As of December 31, 2014, 1841 patients were still alive in whom the median follow-up was 8.5y (0.2-36.6). Of 2,474 deaths (57% of cohort) for whom causes of deaths are available, 42% was due to primary disease, 30% to graft versus host disease (GvHD), 12% to infection, 5% to cardiopulmonary diseases, 3% to subsequent malignant neoplasm (SMN), and 8% to other causes. Conventionally-computed probabilities of survival at 5, 10, 15, and 20y after alloHCT were 48%, 43%, 40%, and 34%, respectively. On the other hand, for patients who had survived 6 mo, 1, 2, 5, 10y after alloHCT, 5-y conditional survival rates were 62%, 72%, 80%, 88% and 93%, respectively (Figure A). Overall, the cohort was at a 24-fold (Standardized Mortality Ratio [SMR]=24.1, 95%CI=23.1-25.0) risk of any death, compared to the general population; the risk of death from pulmonary complications was 31-fold, that from SMN was 31-fold, and that from cardiovascular complications was 3.5-fold. SMR and cause-specific conditional mortality rates by primary diagnosis are shown in the Table. Significantly elevated risk of all-cause mortality persisted in patients who survived 5 and 10y post alloHCT (SMR=3.7, 2.6, respectively, p1.8, p Disclosures Forman: Mustang Therapeutics: Other: Licensing Agreement, Patents & Royalties, Research Funding.