# Unexpected Therapeutic Implications: The Abscopal Effect in the Management of Hepatocellular Carcinoma

## TL;DR

This paper reviews the abscopal effect, a phenomenon where radiation therapy can improve outcomes in hepatocellular carcinoma by boosting the immune response against distant tumors.

## Contribution

The paper provides a comprehensive review of the abscopal effect's mechanisms and therapeutic potential in hepatocellular carcinoma.

## Key findings

- The abscopal effect can lead to systemic tumor shrinkage through enhanced immune response.
- Understanding the abscopal effect could improve treatment options for advanced hepatocellular carcinoma.
- Ionizing radiation may trigger the abscopal effect in locally advanced or metastatic cancer.

## Abstract

Hepatocellular carcinoma is estimated to be the second cause of cancer-related death worldwide and its prognosis is strictly related to both neoplastic stage and liver function. Several treatments are involved in the management of hepatocellular carcinoma. The abscopal effect is a particular phenomenon taking place in locally advanced or metastatic cancer as a positive off-target result of ionizing radiation at a certain distance from the irradiated zone, determining a systemic effect due to the increase in tumor immune response and resulting in the shrinkage of neoplastic lesions with a subsequent increase in tumor prognosis. The progressive understanding of the mechanisms underlying the abscopal effect could lead to important progress in terms of therapeutic solutions for the hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most diagnosed cancer worldwide and represents the second cause of cancer-related death worldwide, according to the estimates by Global Cancer Observatory in 2020. Its prognosis is strictly associated with neoplastic stage and liver function. Several treatments are involved in the management of HCC, according to its stage and the patients’ performance status. The abscopal effect is a particular phenomenon taking place in locally advanced or in metastatic cancer, as a positive off-target result of ionizing radiation at a certain distance from the irradiated zone determining a systemic effect due to the increase in tumor immune response, and resulting in the shrinkage of neoplastic lesions with a subsequent increase in tumor prognosis. If future studies will allow one to master its etiological mechanisms and deliberately trigger them, it could represent a notable weapon in the treatment of hepatocellular carcinoma, particularly at advanced stages, in which sometimes it is able to positively modify the patients’ prognosis. The aim of this review is to evaluate the literature available on this intriguing topic and the characteristics of the mechanisms that originate the abscopal effect, the treatments that can elicit this phenomenon, and the possible relevant therapeutic implications.