Response and Survival in Patients of BCLC Stage C Hepatocellular Carcinoma Receiving SBRT and Immunotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Immune checkpoint inhibitors (ICI) demonstrated antitumor activity has been increasingly used as first-line or second-line treatments for patients with advanced hepatocellular carcinoma (HCC). In the meanwhile, radiotherapy is turning into a crucial component of multidisciplinary treatment for HCC. Mounting evidence suggests local radiotherapy including SBRT might promote immunogenic tumor cell death and could enhance immunotherapeutic effects in several cancers. However, evidence on advanced HCC is few. Here we report the efficacy and safety of combined SBRT and immunotherapy in patients of BCLC stage C HCC in our center. <h3>Materials/Methods</h3> This is a retrospective analysis of twenty-nine patients with advanced HCC, previously treated with sorafenib or lenvatinib, who received SBRT and anti-PD1 antibody concomitantly or sequentially. Here we report their treatment responses both in-field and outside the radiation field according to RECIST1.1 criteria, progression-free survival (PFS), overall survival (OS), and toxicities. <h3>Results</h3> The median age was 55.1 years (range, 25-75), 90% of patients were male, eighty percent had hepatitis B virus and all patients' Child-Pugh score ≤ B7. Among these patients, twenty-one (70%) had portal vein tumor thrombosis (PVTT), four (13.3%) had inferior vena cava tumor thrombosis and nineteen (63.3%) had extrahepatic metastasis. Eight patients had both extrahepatic metastases and PVTT. 86.2% of patients were also treated with second-line targeted therapy. Tumors treated with SBRT located in liver (52.7%), lung (33.3%), bone (11.2%) and retroperitoneal lymph nodes (2.8%). SBRT administration was a median of 40Gy (range, 25-60) and 5 fractions (range, 3-6). The median follow-up was 16.5 months (range, 6-58). The in-field ORRs were 82.8% and the DCR were 100% (CR 20.7%, PR 62.1%, four bone lesions and one lymph nodes were SD). The out-field ORRs were 27.6% and the DCR were 86.2%. The median PFS was 7 months (95% CI, 1-24 months). Six months PFS rate was 53.3% and 1-year PFS rate was 32.6%. At the time of data cutoff, the median duration of OS has not reached. 1-year OS rate was 62.1% and 2-years OS rate was 50.5%. The prognosis of patients with PVTT was worse than those patients without PVTT (2-years OS rate 35.07% vs 88.89%; p=0.04). Treatment-related AEs consisted of platelet count decrease in four patients, alanine/aspartate aminotransferase increase in five patients and myocarditis in one patient. No SBRT-related grade 3 or higher adverse events occurred. <h3>Conclusion</h3> Our experience suggests that combined SBRT and second line ICI with or without targeted drug can be a safe and effective therapy for BCLC stage C HCC. Further prospective trials are warranted.