Fuqua, Jacob

Objective: In this study, we evaluate the utility of ctDNA analysis in a large cohort of patients for whom ctDNA testing was ordered commercially with real-world application. Summary Background Data: Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for assessing post-surgical molecular residual disease (MRD) and response to treatment. Methods: A real-world data analysis was performed using commercial ctDNA testing (SignateraTM) from patients (N=795, n=5,971 plasma samples) with stage I-III colon cancer treated at multiple US institutions. The association of ctDNA detection within the MRD window, during surveillance, and the impact of ACT was correlated with patient outcomes. Results: ctDNA-positive patients during the MRD window and surveillance showed significantly shorter DFS compared to ctDNA-negative patients (hazard ratio (HR): 9.85, P<0.0001; HR: 26.91, P<0.0001). Multivariate analysis of the MRD window revealed ctDNA-positivity as the most significant factor associated with inferior DFS (adjHR: 7.7, P<0.001). MRD-positive patients who received ACT showed improved DFS compared to patients observed post-surgery (adjHR: 6.1, FDR adj P=0.0007). No ACT benefit was observed in MRD-negative patients (adj HR: 1.20, FDR adj P=0.768). On evaluating ctDNA dynamics from MRD to surveillance, patients who remained ctDNA-positive or converted from negative to positive showed a significantly inferior DFS (HR: 34.40, P<0.0001; HR: 13.65, P<0.0001) compared to persistently ctDNA-negative patients. Conclusions: Postsurgical ctDNA detection is prognostic of relapse and potentially predictive of ACT benefit in patients with resectable colon cancer, which may enable personalized surveillance, intervention, and/or trial options, ultimately improving patient outcomes.

Abstract Introduction: The development of hepatocellular carcinoma (HCC) is associated with underlying chronic liver disease from viral hepatitis or nonviral etiologies, such as nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease. An area of current research interest is the relationship between etiology of chronic liver disease in HCC patients and the response to specific treatment modalities. The purpose of this study is to identify prognostic indicators and compare survival outcomes among HCC patients within an Appalachian patient population. Methods: A single-institution, retrospective chart review was conducted for all patients diagnosed with HCC between August 2009 and March 2017 at West Virginia University Hospital. Patient demographics, tumor characteristics, laboratory data and treatment information were obtained from the electronic medical record (EMR). Survival analyses were performed using Kaplan-Meier method and multivariable Cox regression analysis. Results: The study sample (n=100) had a mean age of 62 years and was comprised of 82% males and 18% females. Nonviral etiologies of chronic liver disease were predominant (55%) over chronic viral hepatitis (45%). Significant adverse prognostic indicators of overall survival (OS) were Child-Pugh class C and tumor size &gt;5 cm at diagnosis (p&lt;0.0001, log-rank test). Patients who received liver-directed therapy (LDT) or liver resection had greater OS compared to those not treated with either modality (15.5 vs. 2.0 months, p&lt;0.0001). Liver ablation or resection as initial modes of treatment had greater OS compared to those who initially received transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) (17.2 vs 14.9 months, p&lt;0.05). Patients who received TACE or TARE (n=60) as initial treatment had characteristics of advanced disease, with 45% having a tumor greater than 5 cm in size and 77% having multifocal unilobar or bilobar tumors. Among all patients who received LDT or resection, post-treatment albumin-bilirubin grade (ALBI) of 1 or 2 correlated with greater OS than grade 3 (22.5 vs 6.2 months, p&lt;0.0001). In the multivariate Cox analysis, tumor size, Child-Pugh class and mode of initial treatment (resection/ablation vs. TACE/TARE) were independent predictors of OS (p&lt;0.05). Conclusions: Treatment with LDT or liver resection correlated with greater overall survival in this predominantly nonviral cohort of HCC patients. Post-treatment ALBI grade correlated with overall survival and may have prognostic value in guiding clinical management. Mode of initial treatment was a predictor of overall survival, but further studies are needed to compare tumor characteristics between groups. Research is ongoing to evaluate the relationship between chronic liver disease etiology and survival among HCC patients treated with LDT, immunotherapy or a combination of both. Citation Format: Michelle Hartzell, Gary Monroe, Jon Shakesprere, Sijin Wen, J. Wallis Marsh, Jacob Fuqua, Robert Grammer, Beau Toskich, Midhun Malla. Prognostic indicators and outcomes of hepatocellular carcinoma (HCC) in an Appalachian population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6745.