**4. Evaluation of response**

The Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria take into account changes in tumor size, underestimating the detection of complete response and overestimating partial responses. Disappearance of arterial hyperenhancement

#### *SBRT in Hepatocellular Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.109622*

is considered a complete response, while a 30% reduction is a partial response and a 20% increase is progression [43, 44]. If none of these changes is present, it is considered stable disease. Different criteria may be useful for ablation, embolization, or systemic treatment, but their application in SBRT is unclear. Most clinical trials of SBRT in hepatocellular carcinoma use these criteria for response assessment, and there is a need to standardize the response by unifying the imaging changes observed after SBRT in hepatocellular carcinoma. Facciuto et al showed correlation of RECIST v1.1 with complete response in 14% of patients at 3 months [23]. Mannina et al retrospectively evaluated 38 patients with hepatocellular carcinoma (Child Pugh A 45%) treated with SBRT prior to transplantation and demonstrated low concordance of complete responses or partial response with RECIST (sensitivity 90% and specificity 17%), mRECIST (sensitivity 54% and specificity 50%), and European Association for the Study of the Liver (EASL) (sensitivity 83% and specificity 18%); however, no patient was incorrectly categorized to progression [42].

The timing of imaging response assessment is crucial. Sanuki et al demonstrated median time to complete response of 5.9 months (1.2–34.2 months) [45]. Complete response increased from 24% at 3 months to 67% at 6 months and 71% at 12 months. Kimura et al demonstrated that 25.3% had residual arterial hyperenhancement at 3 months, which decreased significantly to 2% at 6 months [46]. Price et al demonstrated discordance between response assessment by EASL and RECIST [47]. Evaluating the mean decrease in tumor size (RECIST), they found 35, 37, 48, and 55% reduction at 3, 6, 9, and 12 months, respectively. However, a decrease in arterial enhancement of 50% (partial response by EASL) was more predictive of response in the first 6 to 12 months.

After SBRT, there are changes in the surrounding liver tissue. According to these changes, some authors have described temporal changes in hyperenhancement, corresponding to areas of high dose, finding an increase in hyperenhancement from 12% at 1 month to 54% at 6 months. The delay in image acquisition shows isoattenuation in most patients, being rare in the late phase, which may help to distinguish the response to treatment. In addition, the degree of cirrhosis may predict different behavior [45]. Kimura et al found that the majority of tumors in Child Pugh A patients went from hypo- or isoattenuation to hyperattenuation within 6 months of treatment; however, no such changes were seen in Child Pugh B patients. It should be noted that the optimal response time is at least 6 to 12 months after SBRT, lesion stability, or shrinkage is associated with local treatment success, arterial phase hyperenhancement may persist despite complete pathologic response, and late washout may persist after SBRT [48]. Some of these lesions may be incorrectly categorized as treatment failures by administering unnecessary additional treatments.
