Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination

SIMPLE SUMMARY: Radiotherapy is rapidly turning into a crucial component of multidisciplinary treatment for liver cancer because many patients are not surgical treatment candidates. Thanks to technical developments, radiotherapy have achieved high precision treatments, making it possible to eliminate tumor cells without severe damage to the liver and other organs. Stereotactic Body Radiation Therapy is an advanced radiotherapy technique able to eradicate malignant tumors wherever they are located in properly selected patients. The best use of radiotherapy, the most fruitful radiotherapy strategy, and the best way to combine it with other treatments for liver cancer are largely unknown. Radiosensitizers, agents that can potentiate radiotherapy, could broaden the radiotherapeutic landscape. Radiotherapy potentiation can be achieved with diverse treatments, not only drugs but also nanoparticles. In order to clear up the performance of radiotherapy in liver cancer management in the future and the best ways to potentiate its effects, considerable medical research is needed. ABSTRACT: Stereotactic body radiotherapy (SBRT) is an emerging ablative modality for hepatocellular carcinoma (HCC). Most patients with HCC have advanced disease at the time of diagnosis, and therefore, are not candidates for definitive-intent therapies such as resection or transplantation. For this reason, various alternative local and regional therapies have been used to prevent disease progression, palliate symptoms, and delay liver failure. Stereotactic body radiation therapy is a non-invasive technique of delivering ablative doses of radiation to tumors while sparing normal or non-tumor hepatic tissue. Incorporation of SBRT in multidisciplinary HCC management is gradual, initially applied when other liver-directed therapies have failed or are contraindicated, and tried in combination with other locoregional or systemic therapies for more unfavorable conditions by more experienced teams. In order to improve SBRT therapeutic ratio, there has been much interest in augmenting the effect of radiation on tumors by combining it with chemotherapy, molecularly targeted therapeutics, nanoparticles, and immunotherapy. This review aims to synthesize available evidence to evaluate the clinical feasibility and efficacy of SBRT for HCC, and to explore novel radio-potentiation concepts by combining SBRT with novel therapeutics. It is expected that those approaches would result in improved therapeutic outcomes, even though many questions remain with regard to the optimal way to assemble treatments. Further trials are needed to evaluate and consolidate these promising therapies for HCC.