Appraisal of Long-Term Outcomes of Liver-Directed Concurrent Chemoradiotherapy for Hepatocellular Carcinoma with Major Portal Vein Invasion

Backgrounds and Aims: Molecular-targeted agents are acceptable standards to treat advanced-stage hepatocellular carcinoma (HCC), however, their therapeutic benefit, ie, sorafenib, was significantly offset in case of major vessel invasion. Liver-directed concurrent chemo-radiotherapy (LD-CCRT) provided favorable outcomes in terms of survivals and tumor shrinkage, so, we appraised its long-term therapeutic efficacy. Patients and Methods: Advanced HCC patients with portal vein invasion (main trunk or the 1st order branch) were enrolled. During a 5-week radiotherapy course, concurrent hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and leucovorin was administered through an implanted port on the first and last 5 days. Four weeks after LD-CCRT, a maintenance HAIC using 5-fluorouracil and cisplatin was administered every 4 weeks. Results: Among 152 patients, the objective response rates as the best response by modified Response Evaluation Criteria In Solid Tumors were 48.0% after LD-CCRT and 55.3% during subsequent HAIC maintenance. After LD-CCRT, biological responses in alpha-fetoprotein and protein induced by the absence of vitamin K or antagonist-II levels were achieved in 46.2% and 52.6%, respectively. Sixteen patients (10.5%) underwent curative resection or liver transplantation after down-staging. Median overall survival and progression-free survival were 13.5 and 6.9 months, respectively. Conclusion: LD-CCRT followed by maintenance HAIC yielded favorable survival outcomes in advanced HCC patients with major portal vein invasion. Through initial tumor reduction, LD-CCRT induced down-staging with subsequent curative treatment feasible in 10.5% of patients, resulting in long-term survival. Further prospective trials are warranted to confirm these results.