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

Sojung Han,1,2 Hye Won Lee,1– 3 Jun Yong Park,1– 3 Seung Up Kim,1– 3 Do Young Kim,1– 3 Sang Hoon Ahn,1– 3 Kwang-Hyub Han,1 Jinsil Seong,4 Jong Yun Won,5 Dai Hoon Han,2,6,7,* Beom Kyung Kim1– 3,* 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea; 3Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; 4Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea; 6Liver Cancer Center, Yonsei Cancer Center, Yonsei University Health System, Seoul, Republic of Korea; 7Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea*These authors contributed equally to this work.Correspondence: Dai Hoon HanDepartment of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun–Gu, Seoul 03722, Republic of KoreaTel +82-2-2228-2139Fax +82-2-313-8289Email dhhan@yuhs.acBeom Kyung KimDepartment of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun–gu, Seoul 03722, Republic of KoreaTel +82-2-2228-1930Fax +82-2-393-6884Email beomkkim@yuhs.acBackgrounds 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.Keywords: hepatocellular carcinoma, portal vein invasion, concurrent chemoradiotherapy, prognosis, response