Radiation and Checkpoint Inhibition Amongst HCC Patients With Portal Vein Invasion

Abstract

<h3>Purpose/Objective(s)</h3> Recent studies established atezolizumab and bevacizumab as a new standard of care for Barcelona Clinic Liver Cancer (BCLC) hepatocellular carcinoma (HCC) stage C patients. However, many patients are not candidates for this combination and progression-free survival was only 6.8 months, suggesting that local therapy might be beneficial. This study explores combination radiotherapy and nivolumab for HCC with portal vein thrombus (PVT). <h3>Materials/Methods</h3> We retrospectively reviewed charts of patients with HCC and PVT treated with nivolumab and radiation at a single institution from 2016-2020. Patients were eligible if they had at least one follow up imaging scan to assess response. Progression-free survival (PFS) and overall survival (OS) were assessed. Baseline characteristics were used to predict for outcomes. <h3>Results</h3> 64 patients met inclusion criteria with a median follow up of 7 months (0.13-39.0 months). 42 (65.6%) patients were <b>de novo</b> diagnoses of HCC with PVT, and the remainder had prior therapy. 37 (57.8%) patients received nivolumab prior or concurrent with start of RT, while 27 (42.2%) received the first dose of nivolumab > 1 month post RT. Median radiation dose was 40 Gy (range: 30-50 Gy) with 44 (68.8%) patients being treated with SBRT<b>.</b> Median PFS was 3.8 months (95% confidence interval: 2.3–5.4). Median OS was 9.6 months (95% confidence interval: 5.2–14.0). On log-rank analysis, median OS and PFS did not differ between patients receiving therapy for a <b>de novo</b> diagnosis vs. previous therapy (OS: 12.9 vs 8.7 months, <i>P</i> = 0.46; PFS: 4.9 vs 2.9 months, <i>P</i> = 0.99), between patients with VP1-2 vs. VP3+ PVT (OS: 18.3 vs 9.4 months, <i>P</i> = 0.53; PFS: 3.3 vs 3.8 months, <i>P</i> = 0.44), between patients receiving SBRT vs. fractionated RT (OS: 9.2 vs 14.5 months, <i>P</i> = 0.69; PFS: 4.2 vs 3.2 months, <i>P</i> = 0.30), and between patients receiving nivolumab before/concurrent with RT vs. patients receiving nivolumab after RT (OS: 10.7 vs 9.6 months <i>P</i> = 0.41; PFS: 4.2 vs 2.9 months, <i>P</i> = 0.73). Patients with HCV trended for better OS than those with other etiologies but PFS was not improved (OS: 33.3 vs 8.7 months, <i>P</i> = 0.064; PFS: 4.8 vs 2.8 months, <i>P</i> = 0.16). 8 (12.5%) of the patients had OS times > 2 years. <h3>Conclusion</h3> In this retrospective series, combination nivolumab and radiation produced promising OS and PFS for HCC patients with PVT. Prospective studies are needed to know when this approach might be beneficial in the evolving landscape of immunotherapy in HCC.