The 7th Joint Session between JDDW-KDDW-TDDW4(JDDW)
Thu. November 2nd   14:00 - 17:00   Room 10: Portopia Hotel Waraku
JKT4-RS3
 Role of liver-directed therapy for advanced hepatocellular carcinoma in the era of combination immunotherapy
Yung-Yeh Su1, Chiun Hsu2, Li-Tzong Chen3
1National Institute of Cancer Research, National Health Research Institutes, 2National Taiwan University Hospital, 3Kaohsiung Medical University Hospital
Surgery remains the primary method for curing hepatocellular carcinoma (HCC), although determining resectability is a complex issue that depends on tumor factors and the remnant liver function. It is estimated that approximately 60-70% of HCC cases are considered unresectable at the time of diagnosis. In unresectable HCC, systemic therapies such as multikinase inhibitors and immune checkpoint inhibitors (ICIs) are currently the standard treatment, but they primarily provide disease control rather than a cure.
Liver-directed therapy (LDT) can offer potential benefits to patients with advanced HCC in various scenarios. Firstly, the combination of LDT with ICIs may lead to a synergistic effect through the stimulation of systemic immune response by releasing neoantigens into the bloodstream and augmenting the proliferation of tumor-specific T cells. Several pilot studies had demonstrated promising results using the combination of ICIs and LDT, including ablation, Y90-radioembolization, hepatic arterial infusion chemotherapy, transarterial chemoembolization and stereotactic body radiation theray in unresectable HCC.
Combination immunotherapy has shown promising results with higher objective response rates, including anti-VEGF plus ICIs, multikinase inhibitors plus ICIs, or dual ICIs. Following the successful combination ICI treatment, which results in significant tumor shrinkage, applying LDT to the remaining lesion offers the opportunity for cure even in advanced HCC cases.
As combination ICIs have resulted in significantly higher tumor responses, several studies have investigated their application in the neoadjuvant setting, and the results are very promising. Of note, a proportion of patients achieved complete pathological responses after neoadjuvant ICIs, which raises a new question regarding the necessity of adding LDT in such exceptional responders.
In summary, current evidence highlights the importance of combination immunotherapy and LDT in improving treatment outcomes and potentially offering a chance of cure for advanced HCC patients.
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