In this study of therapy for single, small HCC, SBRT had significantly worse impact on liver function, assessed by ALBI score, but achieved better local control than did RFA. Despite these differences, overall survival was similar between patients treated with the two procedures. To our best knowledge, this is the first study that compared, with propensity-score matching analysis, the long-term effects of SBRT and RFA on liver function.
In studies that have used Child–Pugh score for assessment of liver toxicity, the changes of liver function after treatment were not significantly different between SBRT- and RFA-treated patients [15, 20]. We used ALBI score for assessment of liver function -- which is reportedly a better predictor of the prognosis of HCC than is Child–Pugh score  -- to analyze the liver function as a continuous variable. Thus, we could analyze the delicate changes of liver function, which disclosed the differences between SBRT and RFA treatment.
The increases in ALBI score became noticeable more than 6 months after SBRT. This long interlude can be explained by the fact that, after SBRT, blood flow decreases and the necrotic parenchyma expands over several months [22, 23]. We also found that increase of ALBI scores was associated with abnormal liver function (mALBI grade 2a and 2b) at baseline. This observation is in accordance with reports that worse liver function at baseline was associated with higher risk of RILD [24–26]. Thus, careful follow-up of liver function should be continued for at least 1 year after SBRT, especially in patients with known impaired liver function.
Although liver toxicity, defined by increased ALBI score, was associated with SBRT more than with RFA, the degree was mild and not critical. Moreover, it should be appreciated that the excellent local control rate and the similar overall survival with SBRT was achieved despite the procedure being mostly performed for tumors that were difficult to completely ablate with RFA. Other studies also have found better local control of HCC with SBRT than with RFA, especially for perivascular tumors [6, 15, 20]. Since complete ablation is associated with better prognosis , the excellent local control with SBRT may also be beneficial.In contrast to our findings, an analysis of the National Cancer Database in the United State found SBRT inferior to RFA in survival benefit . However, that study did not include important variables, such as liver function, performance status, and treatment history for HCC, as matching factors. Other studies that balanced baseline liver function and previous treatment history found that survival outcomes with SBRT were similar to [15, 28] or even superior to outcomes with RFA . We also included the numbers of previous treatment and liver function in the propensity-score model and found that overall survival with SBRT was like that with RFA. Taken together, our findings suggest that SBRT is a promising treatment for early-stage HCC, especially for HCCs that are difficult to treat with RFA, despite its modest adverse effect on liver function.
The adverse effect on liver function in our patients treated with SBRT occurred despite our cautious use of that modality. Patients were treated with a total dose of 40Gy, TACE was not combined, and fiducial gold marker was used to compensate for respiratory liver motion. In other institution, doses higher than 40Gy together with TACE have been used [29, 30]. The results of our subgroup analysis stratified by baseline liver function suggest that lower radiation dose (35Gy) may be appropriate for patients with impaired liver function .
Limitations of our study are these: 1) It is a retrospective study, thus inherently flawed by selection and indication bias; though we performed propensity-score matching, unidentified confounding factors could have existed. A prospective study (UMIN000036081) is ongoing in our institution to reassess the present results. 2) Dose and fractions of radiation used for HCC may not have been optimal. Although giving 40 Gy in five fractions is a commonly accepted protocol for treating HCC [15, 30], the issue needs further study.