Browsing by Author "Choi, Ariel R."

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    Genomic Signature for Initial Brain Metastasis Velocity (iBMV) in Non-Small-Cell Lung Cancer Patients: The Elusive Biomarker to Predict the Development of Brain Metastases?
    (MDPI, 2025-03-15) Glynn, Sarah E.; Lanier, Claire M.; Choi, Ariel R.; D'Agostino, Ralph, Jr.; Farris, Michael; Abdulhaleem, Mohammed; Wang, Yuezhu; Smith, Margaret; Ruiz, Jimmy; Lycan, Thomas; Petty, William Jeffrey; Cramer, Christina K.; Tatter, Stephen B.; Laxton, Adrian W.; White, Jaclyn J.; Su, Jing; Whitlow, Christopher T.; Soto-Pantoja, David R.; Xing, Fei; Jiang, Yuming; Chan, Michael; Helis, Corbin A.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Background/Objectives: No prior studies have attempted to identify a biomarker for initial brain metastasis velocity (iBMV), with limited studies attempting to correlate genomic data with the development of brain metastases. Methods: Patients with non-small-cell lung cancer (NSCLC) who underwent next-generation sequencing (NGS) were identified in our departmental database. iBMV was calculated by dividing the number of BMs by the interval of time between primary cancer and BM diagnosis. Two-sample t-testing was used to identify mutations statistically associated with iBMV (p < 0.1). A value of +1 was assigned to each mutation with a positive association ("deleterious genes"), and a value of -1 to each with an inverse association ("protective genes"). The sum of these values was calculated to define iBMV risk scores of -1, 0 and 1. Pearson correlation test was used to determine the association between iBMV risk score and calculated iBMV, and a competing risk analysis assessed for death as a competing risk to the development of BMs. Results: A total of 312 patients were included in the analysis, 218 of whom (70%) developed brain metastases. "Deleterious genes" included ARID1A, BRAF, CDK4, GNAQ, MLH1, MSH6, PALB2, RAD51D, RB1 and TSC1; "protective genes" included ARAF, IDH1, MYC, and PTPN11. iBMV risk scores of 1, 0 and -1, predicted an 88%, 61% and 65% likelihood of developing a BM (p < 0.01). A competing risk analysis found a significant association between iBMV risk scores of 1 vs. 0 and 1 vs. -1, and the likelihood of developing a BM using death as a competing risk. Overall survival (OS) at 1 and 2 years for patients with iBMV risk scores of 1, 0 and -1 was 72% vs. 84% vs. 85% and 46% vs. 69% vs. 70% (p < 0.02). Conclusions: Development of a genomic signature for iBMV via non-invasive liquid biopsy appears feasible in NSCLC patients. Patients with a positive iBMV risk score were more likely to develop brain metastases. Validation of this signature could lead to a biomarker with the potential to guide treatment recommendations and surveillance schedules.
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    Genomic signature for oligometastatic disease in non-small cell lung cancer patients with brain metastases
    (Frontiers Media, 2024-09-17) Choi, Ariel R.; D’Agostino, Ralph B., Jr.; Farris, Michael K.; Abdulhaleem, Mohammed; Hunting, John C.; Wang, Yuezhu; Smith, Margaret R.; Ruiz, Jimmy; Lycan, Thomas W.; Petty, W. Jeffrey; Cramer, Christina K.; Tatter, Stephen B.; Laxton, Adrian W.; White, Jaclyn J.; Li, Wencheng; Su, Jing; Whitlow, Christopher; Xing, Fei; Chan, Michael D.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Purpose/objectives: Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease. Methods: Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Extracranial oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher's exact tests were used to screen for mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A risk score for the likelihood of oligometastatic disease was generated and correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression. Cox regression was used to determine association between oligometastatic risk score and oligoprogression. Results: 130 patients met study criteria and were included in the analysis. 51 patients (39%) had extracranial oligometastatic disease. Genetic mutations included in the Guardant panel that were associated (p<0.1) with the presence of oligometastatic disease included ATM, JAK2, MAP2K2, and NTRK1, while ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p=0.2). Oligometastatic risk score was significantly associated with the likelihood of oligoprogression based on the Wald chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p=0.03). Conclusions: Elucidation of a genomic signature for extracranial oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients.