Abstract

The high mortality rate associated with hepatocellular carcinoma (HCC) is partly due to the high proportion of patients who present with advanced stage disease at diagnosis, for whom there are limited treatment options. For selected patients with initially unresectable HCC, locoregional and/or systemic treatments can result in tumor downstaging and consequently provide opportunities for surgical intervention and the potential for long-term survival. Therefore, the key aim of ‘conversion therapy’ is to reduce tumor burden so that patients become amenable to surgical resection. Various therapies have been investigated as candidates for downstaging patients with potentially resectable HCC including transarterial chemoembolization, transarterial radioembolization with yttrium-90 microspheres, radiotherapy, systemic therapies and combination or multimodality treatment approaches. However, downstaging conversion therapy remains controversial and there are several challenges such as defining the criteria used to identify the population of patients who are ‘potentially resectable’, the criteria used to define successful downstaging, and the optimum treatment approach to maximize the success of downstaging therapy. In this review article, we summarize clinical experience and evidence of downstaging conversion treatment in patients identified as having ‘potentially resectable’ HCC.

Highlights

  • Worldwide, liver cancer is the sixth most commonly diagnosed cancer, with an estimated 905,677 new cases and 830,180 deaths in 2020 [1]

  • Interim results from a phase 3 study of neoadjuvant hepatic arterial infusion of chemotherapy (HAIC) with FOLFOX in patients with resectable hepatocellular carcinoma (HCC) (BCLC stage A or B) showed that HAIC monotherapy can reduce the incidence of microvascular tumor thrombi, and this may suggest a role for HAIC monotherapy as part of a conversion therapy strategy [30]

  • A network meta-analysis compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma, and the results showed that lenvatinib is associated with the best overall response rate (ORR) of all systemic therapies included in the analysis [67]

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Summary

Downstaging Conversion Therapy in Patients With

Unresectable Advanced Hepatocellular Carcinoma: An Overview. Front. For selected patients with initially unresectable HCC, locoregional and/or systemic treatments can result in tumor downstaging and provide opportunities for surgical intervention and the potential for long-term survival. Various therapies have been investigated as candidates for downstaging patients with potentially resectable HCC including transarterial chemoembolization, transarterial radioembolization with yttrium-90 microspheres, radiotherapy, systemic therapies and combination or multimodality treatment approaches. Downstaging conversion therapy remains controversial and there are several challenges such as defining the criteria used to identify the population of patients who are ‘potentially resectable’, the criteria used to define successful downstaging, and the optimum treatment approach to maximize the success of downstaging therapy. We summarize clinical experience and evidence of downstaging conversion treatment in patients identified as having ‘potentially resectable’ HCC

INTRODUCTION
Principles of Conversion Therapy
Transarterial Chemoembolization
Study design
Single center retrospective study
Hepatic Artery Infusion Chemotherapy
SYSTEMIC THERAPY
Treatment regimen
MULTIMODAL TREATMENT APPROACHES
Findings
DISCUSSION
Full Text
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