P171. Genomic Coalteration Patterns in NSCLC and Their Impact on Overall Survival After Surgical Resection
Ohio State Wexner Medical Center
COLUMBUS, OH
United States - Contact Me
Hunter Stecko is a medical student at the Ohio State University College of Medicine and a National Institutes of Health Medical Research Scholars Program (NIH MRSP) Fellow for 2024-2025 academic year. Prior to entering medical school, he earned a BSE in Electrical and Computer Engineering and a BA in Computer Science from Case Western Reserve University and worked as a Research and Development Engineer for Procter and Gamble. As an undergraduate and medical student, he has pursued research in diverse fields ranging from the use of computer vision in medical diagnostics to brain-computer interfacing to cancer genomics to the intersection of medicine with religious faith. His research has been recognized with awards from the Ohio State University Plastic Surgery Department and Neuroimaging Research Institute. He previously served as the Student Body President at the OSU College of Medicine, is a member of the Gold Humanism Honors Society, and is an American Medical Association Physicians of Tomorrow award recipient. Presently, Hunter is working in the Molecular Imaging Branch of the National Cancer Institue in Bethesda, MD, where he studies the application of artificial intelligence and computer vision to abdominal, thoracic, and urologic malignancies under the mentorship of Drs. Baris Turkbey and Peter Choyke. He hopes to pursue a career in general Thoracic Surgery. In his free time, Hunter is a freelance musician, Catholic liturgical music director, and composer of music for choir, string instruments, piano, and pipe organ. He also enjoys cooking, Pittsburgh sports, current events, and staying active.
Description
Methods: The Memorial Sloan Kettering CHORD database was queried for patients with Stage 0-III NSCLC who underwent surgical resection, accessed via cBioPortal. Patients were stratified by disease stage and race. Coalteration patterns among the 55 most frequently altered genomic loci were analyzed using log odds ratios and false discovery rates for both the entire cohort and racial subgroups. OS was assessed using Cox regression analysis, with mortality hazard ratios (MHRs) adjusted for age, stage, and race.
Results: A total of 4,067 patients with Stage 0-III NSCLC who underwent surgical resection were identified. The median age was 73 years (IQR:60-86). The majority were White (82.4%), with smaller proportions identifying as Asian (7.5%) and Black (4.6%). Most patients had Stage I disease (54.2%), followed by Stage II (29.4%) and III (16.1%). Among the cohort, coalterations were common (Figure A). Fewer significant coalterations were observed in Asian and Black patients (Figure B-D). Coalterations between TP53 and CDKN2A [MHR:1.2 (95CI: 1.02-1.4); p=0.026], KEAP1 [MHR:1.21 (95CI: 1.01-1.46); p=0.037], or MYC [MHR:1.63 (95CI: 1.27-2.1); p=<0.001] were associated with worse overall survival in surgically resected NSCLC compared to TP53 alteration alone. Likewise, STK11 and MYC coalteration was associated with poorer OS compared to STK11 alteration alone [MHR:1.53 (95CI: 1.04-2.26); p=0.032]. Conversely, co-occurrent EGFR alteration was associated with better OS compared to TP53 [MHR:0.79 (95CI: 0.67-0.94); p=0.007] or NOTCH4 [MHR:0.28 (95CI: 0.09-0.9); p=0.032] alteration alone. ALK coalterations showed no significant impact on OS.
Conclusions: Genomic coalterations are common in resected NSCLC and vary by racial group. Even after adjusting for clinicodemographic and sociocultural factors known to impact NSCLC outcomes, coalterations have varying associations with survival. These findings highlight the need to consider genomic profile as part of treatment planning, even for patients for whom primary operative management is indicated.
Authors
HUNTER STECKO (1), Jenna Aziz (2), Aaron Guo (2), Robert Merritt (2)
Institutions
(1) Ohio State Wexner Medical Center, COLUMBUS, OH, (2) Ohio State Wexner Medical Center, Columbus, OH