Genomic Coalteration Patterns in NSCLC and Their Impact on Overall Survival After Surgical Resection
Presented During:
Sunday, May 4, 2025: 9:00AM - 4:00PM
Seattle Convention Center | Summit
Posted Room Name:
Poster Area, Exhibit Hall
Abstract No:
P0171
Submission Type:
Abstract Submission
Authors:
HUNTER STECKO (1), Jenna Aziz (1), Aaron Guo (1), Robert Merritt (1), Desmond D'Souza (1), Peter Kneuertz (1)
Institutions:
(1) Ohio State Wexner Medical Center, Columbus, OH
Submitting Author:
HUNTER STECKO
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
Co-Author(s):
Jenna Aziz
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
Aaron Guo
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
*Robert Merritt
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
Desmond D'Souza
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
*Peter Kneuertz
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
Presenting Author:
HUNTER STECKO
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Ohio State Wexner Medical Center
Ohio State Wexner Medical Center
Abstract:
Introduction: Coalterations in key oncogenic pathways significantly influence the progression and prognosis of non-small cell lung cancer (NSCLC). However, the impact of a tumor's genomic profile on overall survival (OS) in resected NSCLC remains understudied. To that end, this study aimed to assess the prevalence of genomic coalterations and their association with OS in resected NSCLC.
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.
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.
THORACIC:
Lung Cancer
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