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• W4387164014 abstract "ABSTRACT Background Transarterial chemoembolization (TACE) is the most common treatment in unresectable hepatocellular carcinoma (HCC); however, response rates and durability vary widely, and patients frequently require repeat treatments. With the development of alternative locoregional and systemic therapies for patients with HCC, identifying predictors of response to TACE has become increasingly important for a patient population with minimal hepatic reserve. Preliminary data suggests β-catenin pathway mutations may predict favorable response to liver tumors following bland embolization. We hypothesized that activating β-catenin pathway mutations would lead to improved outcomes following TACE in patients with unresectable HCC. Material and Methods Patients with a clinical diagnosis of HCC planned for TACE were enrolled in a prospective cohort study at two academic medical centers from April 2016 to October 2021. Liver biopsies were taken at time of TACE and mutational profiles determined using a custom next generation sequence panel. Patients with at least one follow-up MRI were included. Primary outcome was objective response rate (ORR) of the targeted tumor at first imaging follow-up. Objective response was defined as complete (CR) or partial response (PR) by mRECIST criteria. Secondary outcomes were CR of targeted tumor at first imaging and at best response, time to target tumor progression (TTP), and overall survival (OS). Results 53 HCC tumors from 50 patients were included in the analysis. Most patients had BCLC stage B disease (28/53, 52.8%) with underlying cirrhosis (42/53, 84.0%) that was well compensated (45/53 Child-Pugh A, 84.9%). Median size of targeted tumor was 4.0 cm (IQR 2.5-6.3 cm). First follow-up imaging was done at a median of 37 days after TACE (IQR 32-63 days) with ORR of 46/53 (86.8%), including 15 tumors with CR (28.3%). At best response, ORR was 49/53 (92.5%), including 19 tumors with CR (35.9%). 19/53 lesions (35.9%) had progression during the study period with a median TTP of 13.7 months and median OS of 23.4 months. Despite similar ORRs (20/22, 90.2% vs 26/31, 83.8%, p=0.46), tumors with activating β-catenin pathway mutations had increased rates of CR at first imaging (9/22, 40.9% vs 6/31, 19.4%, p=0.09) and at best response (12/22, 54.5% vs 7/31, 22.6%, p=0.02) when compared to tumors without these mutations, as well as longer TTP (median not yet reached vs 8.3 months, p=0.02). Conclusions In patients with unresectable HCC, activating mutations in β-catenin pathway have better and more durable response to TACE – a finding that may help guide therapeutic decision making in this heterogeneous population." @default.
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• W4387164014 date "2023-09-29" @default.
• W4387164014 modified "2023-10-05" @default.
• W4387164014 title "Activating B-catenin pathway mutations predict favorable outcomes after transarterial chemoembolization in unresectable hepatocellular carcinoma" @default.
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• W4387164014 doi "https://doi.org/10.1101/2023.09.28.23296283" @default.
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