**2.1 Indications of SBRT in hepatocellular carcinoma (HCC)**

SBRT is indicated in hepatocellular carcinoma that is not a candidate for other therapies, including surgery, radiofrequency, or transarterial chemoembolization (TACE) due to tumor location, proximity to vessels or biliary tract, and/or size. Its use in combination with the aforementioned techniques is also postulated. More evidence is needed for it to become a therapeutic modality of first choice. Data on quality of life can help in this process, making the technique not only effective, but also comfortable and with a low impact on patients' quality of life.

SBRT is an effective treatment for hepatocellular carcinoma with acceptable toxicity rates in selected patients. Despite being a procedure intended for patients who are not candidates for other treatments, it has demonstrated excellent local control in prospective and retrospective studies (studies are summarized in **Table 1**). It can be used as an exclusive treatment or in combination with other treatments. Based on the available data, it appears to complement local techniques.

The combination of SBRT and TACE offers theoretical advantages by decreasing tumor size facilitating SBRT with smaller tumors, and chemotherapy can be radiosensitizing. In addition, lipiodol is radiopaque and may aid IGRT [19].

Patients with portal vein invasion by hepatocellular carcinoma have a very poor prognosis. However, they have been included in treatment with SBRT [5–7] with encouraging results. Recanalization after SBRT facilitates treatment with TACE, which is less effective in vascular invasion. Partial and complete responses have been described with SBRT 37–75% with recanalization in 44–76% and low rates of severe toxicities [20, 21]. The maximum response time can be a few months.

Around 25–44% of patients on the transplant waiting list progress to transplantation. SBRT can help reduce this. Between 63% and 100% of patients reach transplantation with low toxicity rates and partial or complete response in 14–27% and 23–64% of lesions [22, 23]. Mohamed et al compared SBRT, TACE, radiofrequency, and Yttrium-90 microspheres as bridging therapy to transplantation in a retrospective series with 60 patients [24]. Mean necrosis was not statistically significant between treatment modalities, and toxicities were lower with SBRT and Yttrium-90. Despite being retrospective studies with few patients, it appears that SBRT is an effective and well-tolerated treatment as a bridge to transplantation and is competitive with other treatments.

Another scenario being explored is the combination with immunotherapy; the antigenic exposure produced by SBRT and the possible potentiating effect of immunotherapy, already demonstrated in other tumors, have been described. Studies are currently underway to explore the usefulness of the combined treatment of SBRT and immunotherapy due to the excellent results of immunotherapy in hepatocellular carcinoma [25].

The comparative studies available in retrospective series suggest that SBRT is a competitive treatment with other more established treatments. Given its potential, prospective comparative studies are needed [26].
