Establishing a Cohort and a Biorepository to Identify Biomarkers for Early Detection of Lung Cancer: The Nashville Lung Cancer Screening Trial Cohort

Dhairya A Lakhani, Sheau-Chiann Chen, Sanja Antic, Anel Muterspaugh, Christine Cook, Nancy Liu, Hina Shujat, Sophie Jouan, Brandon Winston, Kim Fields, Janelle Wenstrup, Sara L Block, Amy Hinton, Alexandra Miller, Sarah Atmajoana, John T Helton, Khushbu Patel, Aneri B Balar, Katrina Brewer, Subodh Nag, Rajbir Singh, Anthony Disher, Luis Huerta, Richard Fremont, Otis Rickman, Heidi Chen, Rosana Eisenberg, Kim L Sandler, Alexis Paulson, Ronald C Walker, Chirayu Shah, Gary T Smith, Bennett Landman, Stephen Deppen, Eric L Grogan, Melinda C Aldrich, Pierre P Massion, Dhairya A Lakhani, Sheau-Chiann Chen, Sanja Antic, Anel Muterspaugh, Christine Cook, Nancy Liu, Hina Shujat, Sophie Jouan, Brandon Winston, Kim Fields, Janelle Wenstrup, Sara L Block, Amy Hinton, Alexandra Miller, Sarah Atmajoana, John T Helton, Khushbu Patel, Aneri B Balar, Katrina Brewer, Subodh Nag, Rajbir Singh, Anthony Disher, Luis Huerta, Richard Fremont, Otis Rickman, Heidi Chen, Rosana Eisenberg, Kim L Sandler, Alexis Paulson, Ronald C Walker, Chirayu Shah, Gary T Smith, Bennett Landman, Stephen Deppen, Eric L Grogan, Melinda C Aldrich, Pierre P Massion

Abstract

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).

Keywords: biomarkers; biorepository; cancer screening; lung malignancy; pulmonary nodules.

Figures

Figure 1.
Figure 1.
Observational cohort study design. CT = computed tomography.
Figure 2.
Figure 2.
Distribution of Tammemägi 2012 (PLCOm2012) risk assessment models at baseline: violin plot. The score could be calculated for 445 individuals. The figure represents the distribution of PLCOm2012 risk score across these participants with no cancer (n = 426, in blue) and participants with malignant disease (n = 19, in red).

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