Abstract

Percutaneous biopsy for the characterization of intermediate and advanced stage hepatocellular carcinoma (HCC) is projected to increase in the era of precision medicine. Given its controversial role in management, the purpose of this study was to profile the safety and efficacy of acquiring high-volume HCC core biopsies. Between April 2016 and September 2019, 30 patients with embolotherapy-naïve advanced HCC, were enrolled in this IRB-approved prospective trial. Multiple co-axial 18G core-biopsies of a targetable HCC were obtained during transarterial chemoembolization (TACE) or radioembolization (TARE). Cores were sent to pathology, the Center for Personalized Diagnostics (CPD) for solid-tumor next generation sequencing, or prepared for custom sequencing using an HCC panel developed in our lab. From 30 patients, 33 LR4 (1) or LR5 (32) HCCs were biopsied. A median of 7 core biopsies were obtained during the initial treatment. Nine tumors were biopsied a second time (post-TACE), and 2 were biopsied a third time (recurrence). Of 44 biopsy encounters, 1 (2.3%) minor (SIR class A or B) and 0 major biopsy-attributable adverse events were reported during the postprocedural period. Three (9.1%) biopsies revealed discordant pathology of cholangiocarcinoma resulting in a change in management. Four (12%) biopsies revealed poorly differentiated carcinoma, ultimately favored to represent HCC over cholangiocarcinoma. Five (15%) biopsies were negative for tumor, only 1 of which was later confirmed as sampling error. Of 12 cores sent to CPD, 9 (75%) were adequate for analysis. In custom sequenced samples, TERT, CTNNB1, and ALB were the most frequent variant alleles in a markedly heterogeneous pool. No changes in genetic mutations were identified in post-TACE samples when compared to pre-TACE biopsies. Obtaining a high-volume of co-axial percutaneous core biopsies during HCC treatment by TACE or TARE is safe, providing desperately needed tissue for the molecular characterization of intermediate and advanced stage HCC. Biopsy results may change management in imaging discordant tumors.

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