Impact of Bridging Locoregional Therapies for Hepatocellular Carcinoma on Post-transplant Clinical Outcome

Abstract

Long waiting times due to ongoing organ shortage have led to increased utilization of locoregional therapies (LRTs) to bridge patients with hepatocellular carcinoma (HCC) to liver transplantation (LT). We performed this study to evaluate the impact of LRTs on post-LT outcomes. We conducted a retrospective study of patients who were transplanted for HCC at Stanford University Hospital between 2008 and 2018 (n = 302). We found that receipt of ≥5 LRTs was an independent and significant predictor of poor overall 5-year survival (58.3% vs. 83.3%; HR 2.26, p = .03), poor recurrence-free 5-year survival (51.9% vs. 80.4%; HR 2.12, p = .03), and was associated with higher rates of recurrence (25.0% vs. 7.4%, p = .001). Moreover, recurrent HCC was more likely to be the cause of death (58.3% vs. 41.7%, p = .04) in patients who received ≥5 LRTs. Also, patients who required ≥5 LRTs showed an overall lower rate of radiological complete response (46.9% vs. 97.8%, p = .001) and were more likely to have more advanced pathological stage tumors in the explant (65.6% vs. 29.6%, p < .001). In conclusion, receipt of ≥5 bridging LRTs prior to LT is associated with worse post-transplant clinical outcomes.

Keywords: Hepatocellular carcinoma; Liver cancer; Locoregional therapy; Transarterial chemoembolization; Transplant.

FIGURE 1

Higher number of locoregional therapies (LRTs) prior to transplantation for hepatocellular carcinoma (HCC) predicts poor post-transplant survival. (A) Distribution of patients receiving 0 through 8 LRTs. Observed counts are: 0 LRT n = 15, 1 LRT n = 100, 2 LRT n = 54, 3 LRT n = 65, 4 LRT n = 36, 5 LRT n = 18, 6 LRT n = 12, 7 LRT n = 1, 8 LRT n = 1. (B) A comparison of the overall survival in patients receiving <5 (n = 270) or ≥5 LRTs (n = 32. (C) A comparison of the recurrence-free survival in patients receiving < 5 (n = 270) or ≥ 5 LRTs (n = 32)

FIGURE 2

Receiving five or more locoregional therapies (LRTs) has a higher incidence of recurrence. (A) Overall hepatocellular carcinoma (HCC) recurrence rate stratified by <5 LRT and ≥5 LRTs. (B) A comparison of the sites of recurrence in patients with extrahepatic recurrence, stratified by <5 or ≥5 LRTs. Observed counts for each organ are: lung (n = 8 vs. n = 5), bone (n = 6 vs. n = 4), lymph (n = 5 vs. n = 3), and serosa (n = 2 vs. n = 3) for patient receiving <5 or ≥5 LRTs, respectively. Serosal includes pleura and peritoneum. (C) A comparison of the cause of death in patients receiving <5 or ≥5 LRTs. Includes HCC (n = 11 vs. n = 7), respiratory failure (n = 16 vs n = 6), infection (n = 9 vs. n = 1), other cancer (n = 7 vs. n = 3), and liver failure (n = 8 vs. n = 1), respectively. Death by respiratory failure includes causes attributed to cancer and infection. Other cancers causing death in this study include squamous cell carcinoma, lung adenocarcinoma, pancreatic cancer, lymphoma/leukemia, and prostate cancer. * p < .05, ** p < .01

FIGURE 3

Receiving five or more locoregional therapies (LRTs) is associated with worse radiological responses. Comparison of radiologic responses, as determined by mRECIST criteria, after LRT treatments, stratified by <5 or ≥5 LRTs. * p < .05, ** p < .01, *** p < .001