<b><i>Background:</i></b> Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. <b><i>Methods:</i></b> Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. <b><i>Results:</i></b> Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. <b><i>Conclusions:</i></b> Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.

BackgroundThe long-term survival in hepatocellullar carcinoma (HCC) patients after transarterial chemoembolization (TACE) remains dismal due to local and/or regional recurrence as well as distant metastasis. The efficacy of sorafenib in advanced HCC has been demonstrated and brought great hope. Recently, the use of sorafenib in combination with TACE for BCLC stage B and C HCC patients was recommended. However, data on this dual-modality treatment is little, and its advantage over TACE alone has not been addressed. The present study sought to understand the efficacy of the combination of TACE and sorafenib in the treatment of advanced HCC.MethodsBetween June 2008 and Feb 2011, 45 patients with advanced HCC were enrolled and treated with sorafenib in combination with TACE according to an institutional protocol of the Zhongshan hospital, Fudan University. The control group of 45 other HCC patients with similar characteristics treated with TACE alone in the same period of time in our institute were selected for retrospective comparison of the treatment outcomes especially overall survival time. Adverse reactions induced by sorafenib were observed and recorded.ResultsThe median overall survival time of the combined treatment group was 27 (95% Confidence Interval: 21.9–32.1) months, and that of TACE alone group was 17 months (95% Confidence Interval: 8.9–25.0) months (P = 0.001). Patients required significantly less frequent TACE for their symptomatic treatment after the initiation of sorafenib therapy. The most common adverse events associated with sorafenib were hand-foot skin reaction, rash and diarrhea. Of CTCAE grade IV or V toxicity was observed.ConclusionTACE combined sorafenib significantly prolonged median overall survival time of patients with advanced HCC.

Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may prolong overall survival when compared with TACE alone. (©) RSNA, 2016.