Screening Criteria Evaluation for Expansion in Pulmonary Neoplasias Using Molecular and Immunologic Markers (SCREEN II).

P0146 

Abstract Submission 

Bright Huo (1), Alison Wallace (2), Katerina-Maria Kontouli (3), Zhaolin Xu (4), Daria Manos (5), John Fris (6), Samuel Chun (7), Daniel French (2)

(1) Dalhousie University, Halifax, Nova Scotia, Canada, (2) Division of Thoracic Surgery, Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada, (3) Department of Primary Education, School of Education University of Ioannina, Ioannina, Epirus, Greece, (4) Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada, (5) Department of Radiology, Dalhousie University, Halifax, Nova Scotia, Canada, (6) Department of Pathology, Dalhousie University, Halifax, Nova Scotia, (7) Department of Urology, Dalhousie University, Halifax, Nova Scotia, Canada

Bright Huo    -  Contact Me
Dalhousie University

Alison Wallace    -  Contact Me
Division of Thoracic Surgery, Department of Surgery, Dalhousie University

Katerina-Maria Kontouli    -  Contact Me
Department of Primary Education, School of Education University of Ioannina

Zhaolin Xu    -  Contact Me
Department of Pathology, Dalhousie University

Daria Manos    -  Contact Me
Department of Radiology, Dalhousie University

John Fris    -  Contact Me
Department of Pathology, Dalhousie University

Samuel Chun    -  Contact Me
Department of Urology, Dalhousie University

Daniel French    -  Contact Me
Division of Thoracic Surgery, Department of Surgery, Dalhousie University

Bright Huo    -  Contact Me
N/A

Objective: The primary objective of SCREEN II was to assess the molecular and immunologic profile of light-or-never-smokers (LONS) and heavy smokers, defined by National Lung Screening Trial (NLST) and by Nederlands–Leuvens Longkanker Screenings Onderzoek (NELSON) criteria, separately. The hypothesis was that molecular and immunologic profiles differ between LONS and heavy smokers.

Methods: A retrospective review of 1,156 lung cancer cases from 2005-2018 at a tertiary Canadian institution was conducted. Multivariable logistic regression was used to compare the rate of KRAS, EGFR, BRAF, PIK3CA, ALK, and PD-L1 (<1%, 1-49%, ≥50%) between LONS and heavy smokers while adjusting for sex, previous cancer history, family history of cancer, symptoms, histological diagnosis, grade, stage, urban or rural environment, and geographic radon levels. Survival differences were assessed between LONS and heavy smokers using multivariate regression while adjusting for clinical, molecular, and immunologic variables.

Results: The cohort was comprised of 45.7% (NLST, n=536) and 63.5% (NELSON, n=745) heavy smokers. LONS had a higher rate of stage I cancer using NELSON criteria [56.3%, (n=240) vs 49.0% (n=365); p = 0.041]. LONS were more likely EGFR-positive in both NLST [OR 0.79, 95% CI 0.21-1.37; p = 0.008] and NELSON [OR 0.79, 95%CI 0.28-1.31; p = 0.002] models. Female LONS were more likely than male LONS to be EGFR-positive in NELSON [OR 0.59, 95% CI = 0.06-1.12; p = 0.031] but not NLST [OR 0.51, 95% CI 0.02-1.05; p = 0.058] models. LONS were more often PIK3CA-positive using NLST [OR 1.33, 95% CI 0.54-2.13; p = 0.001] and NELSON [OR 1.19, 95% CI 0.49-1.90; p = 0.001] models. Heavy smokers were more often KRAS-positive in both NLST [OR 0.35, 95% CI 0.04-0.67; p = 0.029] and NELSON [OR 0.43, 995% CI 0.09-0.76; p = 0.012] models. No differences in ALK, BRAF, and PD-L1 were observed between LONS and heavy smokers using NELSON or NLST models. LONS in the NELSON model were at higher risk for mortality (Figure 1).

Conclusions: When defined by NLST or NELSON criteria, LONS have a higher rate of EGFR and PIK3CA mutations. There was no difference in the rate of ALK, BRAF, or PD-L1 mutations. LONS with non-small-cell lung cancer may be at increased risk for mortality compared to heavy smokers. Molecular profiling, particularly where targeted therapy is available, should be considered in establishing criteria for lung cancer screening.

Lung Cancer