Liver-Directed Concurrent Chemoradiotherapy vs. Sorafenib for BCLC Stage C Hepatocellular Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Current guideline recommends administration of systemic targeting agent in BCLC stage C hepatocellular carcinoma (HCC). BCLC C involves a wide scope of disease including portal vein tumor thrombosis (PVTT), a significant prognostic factor. Previous studies have revealed the efficacy of radiotherapy in the tumor control of HCC with PVTT. In this study, we investigated the efficacy of concurrent chemoradiotherapy (CCRT) compared to Sorafenib in liver-confined BCLC C HCC patients presenting PVTT. <h3>Materials/Methods</h3> We retrospectively reviewed 409 patients treated with Sorafenib and 637 patients treated with CCRT between January 2005 and October 2016. Patients who had extrahepatic disease or did not have PVTT at diagnosis were excluded, resulting in 28 patients in the Sorafenib group and 448 patients in the CCRT group. Patient and tumor characteristics such as age at diagnosis, initial tumor size, disease extent, PVTT type according to Cheng's classification, pre-treatment Child-Turcotte-Pugh score, ECOG performance score, and response to initial treatment were recorded. Propensity score matching (PSM) was performed to minimize the difference between treatment groups. Overall survival (OS), progression-free survival (PFS), loco-regional failure free survival (LRFFS), and distant metastasis free survival (DMFS) rates were estimated using the Kaplan-Meier method with the log-rank test, and Cox proportional hazard model was utilized for multivariate analysis. <h3>Results</h3> Median follow-up duration of alive patients was 73 months (ranges, 11-110). There were significant differences in PVTT type and disease extent between treatment groups. PSM was performed according to the following factors: age, tumor size, PVTT type, and disease extent. A total of 27 patients from the Sorafenib group and 52 patients from the CCRT group were matched. After PSM, median OS was 4.0 and 8.7 months for the Sorafenib group and for the CCRT group, respectively (<i>P</i> = 0.001). Median PFS and LRFFS were significantly higher in the CCRT group compared to the Sorafenib group (PFS 2.2 vs. 3.8 mo, <i>P</i> = 0.009, LRFFS 2.2 vs. 4.4 mo, <i>P</i> = 0.002), while no difference was observed for DMFS (3.7 vs. 5.0 mo, <i>P</i> = 0.059). In univariate analysis, patients with lower Child-Turcotte-Pugh score and receiving CCRT showed significantly improved OS. In multivariate analysis, CCRT was a significant prognostic factor. One patient from the Sorafenib group and 4 patients from the CCRT group were long term survivors (median OS 79.0 mo), and all of them received surgical treatment of either liver transplantation or liver resection. Of the 4 patients who received CCRT followed by surgical treatment, 2 patients showed total necrotic tumor and the other 2 patients showed 95% tumor necrosis on surgical pathology. <h3>Conclusion</h3> This study showed CCRT as an effective treatment option for HCC patients with PVTT. CCRT can serve as a bridge to surgical treatment, leading to prolonged survival.