<i>In vitro</i> properties of patient serum predict clinical outcome after high dose rate brachytherapy of hepatocellular carcinoma

Tumor recurrence after local tumor ablation, including high dose rate brachytherapy (HDR-BT), represents a substantial challenge in hepatocellular carcinoma (HCC) treatment. This study aimed to investigate whether induced factors that appear in patient serum after HDR-BT alter HCC growth in vitro, and whether this correlates with outcome. In total, 23 HCC patients [Barcelona clinic liver cancer (BCLC) stage A or B] were treated by HDR-BT (1 × 15 Gy) and classified as responders in case of no progression within 6 months and no diffuse systemic progression within 2 years (n = 12), or nonresponders with recurrence within 6 months and/or diffuse systemic tumor progression or extrahepatic disease within 2 years (n = 11). Patient serum was obtained at baseline and 48 h postprocedure. Two hepatoma cell lines (Huh7, HepG2) were incubated for 72 h in the presence of 20% serum. BrdU incorporation was assessed for serum incubation at baseline and 48 h post-HDR-BT. BrdU incorporation post-HDR-BT compared to baseline was significantly elevated in nonresponders compared to responders for both Huh7 and HepG2. Likewise, confirmatory Cyclin E studies revealed different induction kinetics between a subset of representative responders and nonresponders in HepG2. Time to systemic progression (TTSP) in patients with increased BrdU incorporation was significantly shorter compared to patients with decreased BrdU incorporation after serum incubation. These data indicate that poor outcome following HDR-BT is associated with increased measurable proliferation parameters of hepatoma cell lines in vitro after exposure to patient serum, offering insights into post-treatment tumor biology and a potential biomarker of clinical outcome.