Second-Line Treatment after Failure of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Tyrosine Kinase Inhibitor, Retrial of Immunotherapy, or Locoregional Therapy?

Background: Immune checkpoint inhibitor (ICI)-based therapy such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab became mainstream first-line systemic treatment in advanced hepatocellular carcinoma (HCC) patients since remarkably superior efficacy of ICI-based therapy compared to tyrosine kinase inhibitors (TKIs) was reported in two recent randomized controlled trials (RCTs) (IMbrave150, HIMALAYA). However, the optimal second-line therapy after treatment failure of first-line ICI-based therapy remains unknown as no RCT has examined this issue. Summary: Therefore, at present, most clinicians are empirically treating patients with TKIs or retrial of ICI or locoregional treatment (LRT) modality such as transarterial therapy, radiofrequency ablation, and radiation therapy in this clinical setting without solid evidence. In this review, we will discuss current optimal strategies for second-line treatment after the failure of first-line ICI-based therapy by reviewing published studies and ongoing prospective trials. Key Messages: Clinicians should consider carefully whether to treat the patients with TKI, other ICI-based therapy, or LRT in this situation by considering several factors including liver function reserve, performance status, adverse events of previous therapy, and presence of lesion that can consider LRT such as oligoprogression and vascular invasion. In the meantime, we await the results of ongoing prospective trials to elucidate the best management options.

Extensive Unpredictable Pancreas Cancer Inter-fraction Motion: A Case Report.

We present a case of locally advanced pancreatic cancer with duodenal invasion treated with consolidative chemoradiation, where extensive unpredictable interfraction motion was observed. Initially, two attempts were made to treat with volumetric modulated arc therapy technique. However, due to substantial interfractional motion of the pancreatic head mass relative to the regional nodal areas, the patient was eventually replanned and treated with a four-field box technique. This case highlights the difficulty in delivering conformal radiation to the pancreas and quantifies the movement of the target, the adjacent biliary stent, and regional nodes.