Sorafenib and a novel immune therapy in lung metastasis from hepatocellular carcinoma following hepatectomy: A case report

Abstract

Abstract. Sorafenib is the standard therapeutic strategy for recurrent hepatocellular carcinoma (HCC) following hepatectomy. However, only few patients truly benefit from this therapy. Thus, new strategies combined with sorafenib are urgently required. We herein present the case of a patient with hepatic and extrahepatic HCC recurrence following hepatectomy, who was treated by combined sorafenib, focused ultrasound knife and DRibbles-pulsed dendritic cell (DC) vaccine. Enzyme-Linked ImmunoSpot assay (ELISPOT) and intracellular staining (ICS) analysis were used to detect the secretion of interferon (IFN)-γ by T cells at different timepoints of the vaccine in order to evaluate the patient's specific T-cell response to SMMC-7721-derived DRibbles vaccine. The α-fetoprotein level decreased from 103,295 to 5 ng̸ml and the patient displayed improved liver function, an Eastern Cooperative Oncology Group performance status score of 0, remission of liver metastases and disappearance of the lung metastases 8 months post-combination therapy. The computed tomography scan revealed the disappearance of liver metastases 2 years post-combination therapy. The ELISPOT data revealed a low antigen-specific T-cell response 4 weeks after the first vaccine cycle and the response decreased to nearly zero prior to the second cycle. However, high antigen-specific T-cell response was observed 2 weeks after the second vaccine cycle and did not decrease, even after 10 months, which was consistent with the result of the ICS analysis, which demonstrated that most of the secreted IFN-γ was produced by CD4 + T cells, whereas a low CD8 + T-cell response was observed (0.429 vs. 0.0665%, respectively). Our results demonstrated that antigen-specific T-cell response aimed to treat recurrent HCC may be induced through stimulation by the DC-DRibbles vaccine. The success of the treatment supports the combination of sorafenib, focused ultrasound knife and DC-DRibbles vaccine as a therapeutic strategy for patients with HCC recurrence following hepatectomy. IntroductionHepatocellular carcinoma (HCC) is the fifth most common type of cancer and the second most common cause of cancer-related mortality worldwide (1). Curative resection or liver transplantation is recommended for early-stage HCC, with a reported 5-year survival of >50% (2). However, a considerable proportion of patients may develop HCC recurrence and the survival of such patients is very poor, as recurrent tumors are usually aggressive and unresectable (3). Moreover, HCC is significantly resistant to radio-or chemotherapy, the standard of care in the majority of advanced tumors (2).Although the multikinase inhibitor sorafenib was approved for the treatment of advanced HCC in 2008, there remain issues regarding the management of this disease (4,5). In particular, this therapy exhibits wide variability in terms of prolongation of patient survival, and only few patients truly benefit from this therapy. Combination therapy with sorafenib and other modalities, such as transarterial chemoembolization...

Lung metastases from hepatocellular carcinoma: multidisciplinary approach—narrative review

“…Recently, multimodal therapies merging sorafenib and other treatments, like transarterial chemoembolization or everolimus have been evaluated (67,68). Apparent profits seem promising, but it is auspicable that the future advent of new effective systemic therapy will further improve the survival of the patients (71,72).…”