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Page 2 of 4 Zhong. Hepatoma Res. 2026;12:54

Against this rapidly evolving background, we organized this Special Topic entitled “Combining Locoregional
and Systemic Therapies in Liver Cancer: From Strategy to Survival” in Hepatoma Research. The purpose of
this collection is to provide a comprehensive perspective on how different therapeutic modalities can be
integrated to achieve more effective and individualized management of liver cancer. Rather than simply
combining available treatments, the ultimate goal of integrated therapy is to determine the optimal
therapeutic strategy for each patient based on disease characteristics, biological mechanisms, treatment
response, and safety considerations.

A central theme of this Special Topic is the transformation of TACE from a conventional locoregional
treatment into an important component of multimodal therapy. TACE remains a cornerstone treatment for
intermediate-stage HCC; however, repeated TACE procedures may be associated with reduced therapeutic
efficacy and cumulative impairment of liver function. With the emergence of immunotherapy and targeted
therapy, treatment strategies are shifting from repeated local tumor control toward early integration of
systemic therapy to achieve more durable disease management. The article focusing on the relationship
between TACE treatment frequency and prognosis highlights the importance of optimizing TACE intensity,
avoiding unnecessary procedures, and adapting treatment strategies in the era of combination therapy.

Beyond TACE, this Special Topic also explores the expanding role of other locoregional modalities in
combination strategies. Thermal ablation remains a potentially curative treatment for early-stage HCC, but
tumor recurrence after ablation continues to represent an important clinical challenge. The review included
in this collection summarizes the biological mechanisms underlying post-ablation recurrence, including
autophagy activation, epithelial–mesenchymal transition, hypoxic microenvironment formation, and
immune suppression . These findings emphasize that improving local treatment precision and addressing
[3]
residual or recurrent disease through complementary therapies are essential components of future treatment
strategies.

Similarly, Y-90 radioembolization, also known as SIRT, represents an important platform for integrating
local radiation delivery with systemic treatment approaches. By selectively delivering high-dose radiation to
tumor tissue, SIRT provides effective local control while potentially inducing biological changes that may
enhance the efficacy of systemic therapies. Current evidence suggests that combining Y-90 with targeted
therapies or immune-based treatments represents a promising direction; however, further investigation is
needed to define optimal patient selection, treatment sequencing, dosimetry strategies, and clinical
endpoints .
[4]

An important consideration in the era of combination therapy is that increased therapeutic intensity must be
accompanied by improved precision and safety management. As more patients receive locoregional therapy
combined with immune-based treatments, identifying individuals at higher risk of treatment-related toxicity
becomes increasingly important. In this Special Topic, an original study developed a baseline lymphocyte-
subset-based nomogram to predict severe immune-related adverse events in patients receiving TACE plus
immunotherapy, highlighting the potential value of biomarkers in guiding individualized treatment
decisions .
[5]

A global perspective is essential when considering the future development of integrated treatment strategies
for liver cancer. China carries a substantial proportion of the global burden of HCC, and many patients
require multidisciplinary approaches because of advanced disease presentation and complex clinical
conditions. In this context, locoregional therapies, particularly TACE, have accumulated extensive clinical