The Landscape of Comprehensive Therapy Based on Systemic Therapy for Unresectable Hepatocellular Carcinoma (uHCC) in China

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Background

The incidence of Hepatocellular Carcinoma (HCC) in China is the highest in the world, accounting for nearly half of the annual global incidence and mortality associated with this disease. The majority of patients with HCC are diagnosed with advanced cancer and are therefore not suitable for surgical treatment. Treatment of advanced HCC usually comprises locoregional or systemic treatment, and the efficacy and survival benefits are limited. However, over the past 3 years, the number of approved systemic therapies for patients with HCC has expanded greatly, progress has also been made through the exploration of novel therapeutic strategies such as using comprehensive therapy (drug plus drug/drug plus loco-regional therapy) for neoadjuvant therapy or adjuvant therapy. In addition, in China, several locally developed and produced systemic therapies have become available including TKIs and anti-programmed death 1 (PD-1) inhibitors. The preliminary data of conversion therapy has also become a new academic hot spot. Conversion therapy represents the conversion of unresectable liver cancer into resectable liver cancer for excision. There have been several retrospective studies focusing on conversion therapy, the highest section rate up to 42.4%. And many Chinese doctors are trying new combinations of drugs or locoregional treatment to unresectable HCC. In May 9th 2021, the release of “Chinese Expert Consensus on Conversion therapy in Hepatocellular Carcinoma” made conversion therapy to a new stage, which gave a standardization to Surgeons in China in how to do their trails in conversion therapy better.

This Research Topic will invite leading Chinese experts in the field of HCC treatment to share their clinical experience and real-word data on the treatment of patients with advanced HCC, especially in the perioperative period of HCC patients. This will provide valuable insights and data to help inform the development of future treatment strategies for advanced HCC.

Why is this Research Topic specifically focusing on the treatment landscape in China?

The HCC treatment landscape in China is different from other regions for three key reasons. Firstly, doctors in China utilize a unique clinical staging system for HCC (The Chinese National Liver Cancer system [CNLC]) that is adapted to Chinese clinical practice. In addition, compared with many regions, a higher proportion of Chinese patients with HCC have advanced stage disease. The CNLC staging system leads to different treatment recommendations compared with the widely utilized Barcelona Liver Clinic (BCLC) staging system, particularly for patients with advanced disease. For example, the CLNC staging system recommends surgery for a proportion of patients with portal vein tumor thrombosis, and transarterial chemoembolization (TACE) is not the only treatment recommendation for patients with CLNC stage II (equal to BCLC stage B) HCC. Therefore, due to the high incidence rate of HCC in China and also the use of the CNLC staging system, Chinese doctors often have unique experience of utilizing systemic treatment in novel ways and have also accumulated a lot of practical knowledge for treating advanced HCC. Indeed, multiple real-world studies investigating adjuvant and neoadjuvant therapy using systemic therapy have been published by Chinese researchers in recent years. Secondly, the etiology of HCC in China is different to many western countries, with hepatitis B virus (HBV)-related liver cancer accounting for around 77% of cases. Chinese doctors therefore have unique treatment experience in the management of HBV-related HCC. Finally, China has a unique landscape of approved first-line systemic therapies for HCC including lenvatinib, sorafenib, FOLFOX4, apatinib, camrelizumab and atelizumab + bevacizumab. In addition, donafenib and a variety of domestic PD-1 inhibitors are being investigated and preliminary data have been reported. We believe that summarizing clinical trial data for Chinese domestic systemic HCC therapies is both interesting and helpful for non-Chinese researchers to better understand the efficacy and safety of these drugs in liver cancer.

We welcome submissions of Original Research, Review, and Mini Review articles，Methods, Systematic Review in the following subtopics, but not limited to:

1. New advances in down-staging (conversion) / neoadjuvant treatment strategies for HCC based on novel systemic therapies

2. New advances in adjuvant therapy in HCC patients utilizing novel systemic therapies

3. The exploration of sequential second line treatments following standard first-line treatments

4. Predictive markers of efficacy for combination therapy which helps to explain when is better to do surgery after successful down-staging treatment.

5. Advances in combination treatment strategies including systemic and locoregional therapies with high objective response rate (ORR).

6. Other innovative comprehensive treatment strategies based on novel systemic therapies

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: HCC, systemic therapies, comprehensive treatment, down-staging treatment, neoadjuvant treatment, adjuvant treatment, HBV-HCC

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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