# Hepatic Reirradiation for Patients with Recurrent Hepatocellular Carcinoma
## 4 Discussion  
Previous studies had discussed the feasibility of using photon reirradiation to treat recurrent HCCs, but to the best of our knowledge, this was the first study to investigate the treatment outcome considering the use of systemic therapy. Target therapies, including sorafenib, lenvatinib and regrofenib, were proved to have survival benefit after local therapy for unresectable HCC [4]. Systemic therapy, including target therapy, may be added after local RT in real-world practice. Therefore, it is crucial to consider the effect of systemic therapy while evaluating the outcome of reirradiation for recurrent HCC. Two Korean studies did not provide any information about whether they were using systemic therapy or not, while another study from MGH only listed how many patients used it but with no further analysis. Despite the lack of analysis of the use of systemic therapy, 1-yr OS was about 50%, ranging from 57% in [PERSON]'s study to 44.9% in [PERSON]'s study [6; 8; 10]. Moreover, for tumors regressing after reRT, our study revealed a better survival with 1-yr OS up to 74.1% and the mean OS as 30.0 months. For treatment response, [PERSON] shared a total of 62.8% with 18.6% CR and 44.2% PR, using 3D-CRT for reRT, compared with which our total response was 84.4% with 25.0% CR and 59.4% PR [6]. Advances of RT techniques, as well as the use of IGRT and respiratory motion management, are believed to deliver more accurate and precise treatment. The evidence suggests that RT could reactivate the hepatitis B virus, causing fulminant hepatitis with lethal liver failure. For more than half of the patients with chronic hepatitis B, more accurate and precise RT could minimize damage to the normal liver tissue, contributing no lethal liver failure in hepatic reirradiation [11]. Hepatitis, inducing liver cirrhosis, is the major cause of HCC; given that Child-Pugh classification is designed for predicting cirrhosis mortality, our study compiled with the principle [7; 12]. Similar to [PERSON] el al., whose study suggested Child-Pugh A (score 5 and 6) had better survival than Child-Pugh B (score 7-9) after reirradiation [6; 7], our study further analyzed these scores. The result suggested even minorly impaired liver function could still have a negative impact on survival after reirradiation, though Child-Pugh scores 5 and 6 are categorized in the same class A. Moreover, the multivariate analysis suggested LC was an independent contributor to the OS. This is the first study suggesting reirradiation with good LC could prolong survival over previous research. Similarly, repeated RFA for smaller HCC was established to benefit survival rates despite its well-discussed limitations [13; 14]. TACE also shared the similar benefits to OS, as well as the same concern regarding its limitations [15]. SABR for HCC was suggested to have better LC over RFA for larger tumor and subphrenic locations [16]. Therefore, repeated RT was eventually proved to contribute to the OS. Additionally, this study discovered that outfield and DM had no effect on OS. Although it might be limited to small recruitment, this finding also corresponded to the studies suggesting better LC contributes to better OS in spite of extrahepatic condition [16]. For subgroup analysis, CR or PR after reirradiation had no difference in either OS or IF-PFS. This may indicate certain limitations of our evaluation. First, we evaluated treatment outcomes through image study 4-6 weeks after treatment, which might not be the best response. From [PERSON]'s retrospective study, some tumors may have delayed treatment response and thus, continuous observation for at least 9 months after RT is recommended [17]. For remarkable PR, it might regress to CR for longer evaluation. Second, MRI with newly developed liver-specific contrast is superior to MRI with the traditional contrast in HCC evaluation, while MRI is already better than CT scan [18]. Most our post-RT evaluation is based on CT scan due to inconvenience of MRI.