Advanced Primary Hepatocellular Carcinoma Research Articles

Radiotherapy enhances efficacy of PD-1 inhibitors in advanced hepatocellular carcinoma: A propensity-matched real-world study.

To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma (HCC), combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances the efficacy of anti-programmed death receptor-1 (PD-1) inhibitors in advanced HCC in real-world practice. Between August 2018 and June 2021, 172 patients with advanced primary HCC were enrolled in the tertiary center (Zhongshan Hospital of Fudan University); 95 were treated with a combination of RT and the inhibitor of PD-1 (RT-PD1 cohort), and 77 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes. Among 71 propensity-matched pairs, median progression-free survival was 5.7 months in the RT-PD1 cohort vs. 2.9 months in the PD1 cohort ( P <0.001). Median overall survival was 20.9 months in the RT-PD1 cohort vs. 11.2 months in the PD1 cohort ( P =0.018). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had significantly higher objective response rates (40.8%, 29/71 vs. 19.7%, 14/71, P =0.006) and disease control rates (62.0%, 44/71 vs. 31.0%, 22/71, P <0.001). The incidences of toxic effects were not significantly different between the two cohorts. RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.

Analysis of the safety and effectiveness of TACE combined with targeted immunotherapy in the treatment of intermediate and advanced hepatocellular carcinoma.

To evaluate the effectiveness and safety of transarterial chemoembolization (TACE) combined with immune and targeted therapy in unresectable hepatocellular carcinoma (HCC). Prospective analysis of 23 patients with intermediate or advanced primary HCC treated at the Department of Hepatic Surgery, The First Affiliated Hospital of the University of Science and Technology of China from July 2019, including 11 cases treated with TACE alone and 12 cases treated with TACE combined with targeted therapy. The basal indexes of patients in the two groups were compared, and the response during treatment was observed; regular follow-up was performed to assess the efficacy of tumor treatment. Compared with TACE treatment alone, the objective response rate (ORR) was significantly higher in the TACE combined with targeted treatment group (50.0% vs 36.4%), with a higher success rate of surgical conversion (33.3% vs 18.2%) and a significantly longer progression-free survival (PFS) (20.5 ± 2.9months vs 11.6 ± 2.9months). Multifactorial regression analysis identified tumor vascular invasion as an independent prognostic factor affecting HCC. No patient experienced catheter retention-related complications during treatment, and there were no intolerable adverse effects. TACE combined with targeted treatment for intermediate to advanced unresectable HCC was effective, with good tumor responsiveness, high surgical conversion rate, and safe and controllable adverse reactions during treatment.

Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China.

PurposeAnlotinib, a novel multi-target tyrosine kinase inhibitor, has shown encouraging antitumor effects in advanced hepatocellular carcinoma (HCC). This study evaluated the effectiveness and safety of anlotinib with or without programmed death-1 (PD-1) blockades for patients with advanced primary HCC in a real-world setting in China.Patients and MethodsBetween July 2019 and May 2021, 27 patients with advanced primary HCC who received at least 2 cycles of anlotinib were included in this retrospective study. Primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsOf the 27 patients, ORR and DCR were 25.93% and 74.07%, respectively. The median follow-up time was 6.27 months (range: 1.30–17.40) with a median PFS and OS of 3.29 months (95% CI: 1.31–15.47) and 6.21 months (95% CI: 2.23–15.87), respectively. A total of 14 patients received anlotinib and PD-1 blockade combination therapy, and 13 received anlotinib monotherapy. No significant differences were observed in ORR (28.57 vs 23.08%), DCR (71.43 vs 76.92%), PFS (3.38 [95% CI: 2.66–13.14] vs 11.86 months [95% CI: 4.27–15.93]) and OS (4.90 [95% CI: 2.56–13.60] vs 11.04 months [95% CI: 1.31–17.18]) between the two groups (all p>0.05). Treatment-related AEs were reported in 88.89% of patients. Grade 3 AE was bleeding, which occurred in 3 patients (11.11%).ConclusionAnlotinib yielded a promising efficacy and manageable safety in patients with advanced primary HCC irrespective of whether patients received PD-1 blockades, indicating that anlotinib might be a promising treatment option for this patient population.

Efficacy and safety of anlotinib with or without PD-1 blockades in the treatment of advanced primary hepatocellular carcinoma (HCC): A real-world exploratory study.

432 Background: Half of the new cases and deaths of HCC was observed in China all over the world in 2020. However, the prognosis of traditional treatments for patients (pts) with HCC was dismal currently. Small-molecule anti-angiogenesis targeted drugs and PD-1 blockades were proved to demonstrate potential efficacy in advanced primary HCC. Anlotinib was a novel oral multi-targeted tyrosine kinase inhibitor for tumor angiogenesis and proliferation, which had been licensed for treatment of considerable malignancies in China. However, the real-world evidence of anlotinib and PD-1 blockades in HCC was still scanty currently. Consequently, the aim of this study was to investigate the efficacy and toxicity of anlotinib with or without PD-1 blockades in the treatment of advanced primary HCC in real-world. Methods: Pts with advanced primary HCC who received at least 2 cycles of anlotinib (8̃12mg, po, d1̃14, q3w) were recruited in this study. Clinical efficacy and survival data was summarized, adverse events were documented retrospectively. The tumor response was assessed by investigator according to RECIST version 1.1 using CT scans. The primary endpoint was objective response rate (ORR), secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: From Jul 2019 to May 2021, a total of 28 eligible pts were screened. Among them, 12 pts received anlotinib as first-line treatment, 9 pts as second-line treatment and 7 pts as third-line treatment and above. In best overall response assessment, there were 5 CR (17.8%), 2 PR (7.1%), 13 SD (46.4%), 7 PD (25.0%) and 1 NE (3.5%). ORR was 25.0% (95%CI: 10.7̃44.9%) and DCR was 71.4% (95%CI: 55.3̃86.8%). At the data cut-off date, 15 pts discontinued treatment due to disease progression, the preliminarily prognostic results indicated that the median PFS of the 28 pts was 4.93 months (95%CI: 1.60̃8.26), and the median OS was 13.21 months (95%CI: 10.77̃15.65). Specifically, 14 pts combined with PD-1 blockades treatment, ORR was 28.6% (95%CI: 8.4̃58.1%) and DCR was 71.4% (95%CI: 41.9̃91.6%). The remaining 14 pts failed to receive PD-1 blockade combination therapy with the ORR of 21.4% (95%CI: 4.7̃50.8%) and DCR of 71.4% (95%CI: 41.9̃91.6%). The safety profile suggested that the most common drug-related adverse events were decreased appetite, fatigue, thrombocytopenia, hypertension, diarrhea, anemia, hand-foot syndrome, proteinuria and bleeding. The common grade 3 adverse event was bleeding (10.7%). Conclusions: Present study indicated that anlotinib-related regimens in the treatment of advanced primary HCC exhibited potential efficacy and manageable adverse events in real-world setting. The conclusion should be validated in more pts included subsequently.

Effects of Ginsenosides on Microvascular and Immune Microenvironment and Prognosis of Hepatocellular Carcinoma

To investigate the effects of ginsenosides on the microvascular and immune microenvironment of hepatocellular carcinoma rats and analyzes the relationship on the prognosis of patients with hepatocellular carcinoma. 60 patients with hepatocellular carcinoma were collected and randomly divided into control and treatment group in our hospital from January 2018 to January 2020 and clinical symptoms improvement and adverse reactions were compared and analyzed. 60 rats were randomly divided into ginsenoside, control and model group. The immune cell infiltration and microvascular density were detected and analyzed. In animal studies, the infiltration of cluster of differentiation 3+, cluster of differentiation 4+, cluster of differentiation 8+ and forkhead box P3+ T lymphocytes increased significantly while the transforming growth factor beta 1 value decreased significantly after treatment with ginsenoside. Clinically, the patients in the treatment group showed significant improvement in their conscious symptoms and higher treatment efficiency while the adverse reactions such as decrease of white blood cell, decrease of hemoglobin, decrease of platelet, nausea and vomiting and low fever than that of in control group. In hepatocellular carcinoma model, ginsenosides induced lymphocyte infiltration and inhibited tumor angiogenesis to exert anti-tumor effects. And ginsenoside has both anti-tumor and quality of life effects and has good efficacy in the treatment of advanced primary hepatocellular carcinoma.

Safety and Clinical Efficacy of PD-1 on Advanced Primary Hepatocellular Carcinoma

Safety and Clinical Efficacy of PD-1 on Advanced Primary Hepatocellular Carcinoma

Programmed Cell Death Protein-1 (PD-1)-Targeted Immunotherapy for Advanced Hepatocellular Carcinoma in Real World.

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant solid tumors. Its incidence is increasing worldwide due to the dissemination of hepatitis B infection, HCV infection and nonalcoholic steatohepatitis-related HCC. For patients with advanced HCC, the available treatments are extremely limited and the prognosis is very poor. Therefore, it is urgent to discover new innovative approaches. Programmed cell death protein-1-targeted immunotherapy has shown promising results in multicenter clinical trials.AimTo evaluate the effectiveness and safety of anti-PD-1 agent in patients with advanced primary hepatocellular carcinoma.MethodsA retrospective analysis of 55 patients with advanced primary hepatocellular carcinoma who had been administered anti-PD-1 agent. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors and any adverse events were recorded.ResultsThe median overall survival (OS) was 15 months. The median progression-free survival (PFS) was 10 months. No patient had complete response (CR) and 12 (22%) participants achieved partial response (PR), resulting in an overall response rate (ORR) of 22%. Thirty-seven (67%) patients showed stable disease (SD) and 6 (11%) subjects had progressive disease (PD) at first radiological evaluation. The disease control rate (DCR) was 89%. The total side effect rate was 61.8% and most were relieved after treatment.ConclusionProgrammed cell death protein‐1‐targeted immunotherapy is a safe and effective treatment for advanced primary hepatocellular carcinoma.

Transarterial Chemoembolization and Sorafenib Combined with Microwave Ablation for Advanced Primary Hepatocellular Carcinoma: A Preliminary Investigation of Safety and Efficacy.

PurposeThe aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC).MethodsBetween January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model.ResultsBaseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P<0.001) and a longer TTP (median, 6.0 vs 3.0 months; P<0.001) compared with non-MWA group. Multivariate analyses showed that portal vein tumor thrombosis (PVTT) (P=0.002), duration of sorafenib (P<0.001), and MWA treatment (P=0.011) were independently associated with OS. MWA treatment strategy (P<0.001) was a significant predictor of TTP. There were no treatment-related mortalities in either group. The rates of minor complications (42.9% vs 38.7%, P=0.599) and major complications (1.29% vs 1.33%, P=0.985) in the MWA group were similar to those in the non-MWA group.ConclusionTACE-S-MWA was safe and effective for advanced primary HCC. TACE-S-MWA resulted in better OS and TTP than did TACE-S for treatment of patients with advanced primary HCC.

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

BackgroundThe treatment for advanced primary hepatocellular carcinoma (HCC) is sorafenib (SORA), while HCC has become increasingly drug resistant with enhanced aerobic glycolysis. The present study aimed to examine the chemotherapeutic effects of a flavonoid proanthocyanidin B2 (PB2) on HCC.MethodsFive kinds of HCC cell lines and LO2 were used to test the effect of PB2 on aerobic glycolysis. The proliferation, cell cycle, apoptosis and a xenograft mouse model were analyzed. Lentivirus overexpressed pyruvate kinase M2 (PKM2) or sh-PKM2 was used to verify the target of PB2. The detailed mechanism was investigated by immunofluorescence, co-immunoprecipitation, and western blotting.ResultsPB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro. PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2. In addition, PKM2 inhibited the nuclear translocation of PKM2 and co-localization of PKM2/HIF-1α in the nucleus, leading to the inhibition of aerobic glycolysis. Co-treatment with PB2 was also effective in enhancing the chemosensitivity of SORA.ConclusionsPB2 inhibited the expression and nuclear translocation of PKM2, therefore disrupting the interaction between PKM2/HSP90/HIF-1α, to suppress aerobic glycolysis and proliferation, and trigger apoptosis in HCC via HIF-1α-mediated transcription suppression.

Short-term efficacy of 125I seed implantation combined with transcatheter arterial chemoembolization in the treatment of advanced primary hepatocellular carcinoma

Objective To evaluate the efficacy and safety of 125I seed implantation combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary hepatocellular carcinoma (PHC). Methods 156 patients who had unresectable PHC seen from January 2012 to December 2015 in our unit were randomly assigned into the study group (76 patients) and the control group (80 patients). The study group of patients were treated with intra-hepatic implantation of 125I seed + TACE, and the control group of patients were treated with three dimensional conformal radiotherapy (3DCRT) + TACE. After radiotherapy the two groups of patients underwent 2 to 3 times TACE treatment. The biomarker levels were compared between the two groups before and after treatment, and the short-term efficacy, clinical safety and 1 year survival rates were assessed. Results The success rates of the treatment for the two groups were both 100%. Patients in the study group were implanted with 1 016 125I seeds, with an average of (13.7±2.5) seeds per patient. The two groups had no significant difference on short-term efficacy (P>0.05). The DCR, ORR and 1 year survival rates in the study group were 63.2%, 92.1%, 55.5%, and they were 61.3%, 90.0%, 58.1% in the control group, respectively. There were no significant differences between these 2 groups (P>0.05). At 1 month after treatment, the two groups had no significant differences on AFP, IGF-II and IGFBP-2 [(5.08±0.85) μg/L vs. (5.12±0.79) μg/L, (4.77±0.58) μg/L vs. (4.86±0.53) μg/L, (4.98±0.67) μg/L vs. (5.04±0.71) μg/L] (P>0.05). There were no significant differences on chemotherapy drug toxicities between the two groups (P>0.05). The incidence of radiation hepatitis in the study group was 1.3%, while the incidences of radiation dermatitis, hepatitis, gastric ulcer in the control group were 5.0%, 8.8%, 2.5%, respectively. The radiation dermatitis incidence in the study group was significantly lower than that of the control group (P<0.05). In the study group, 2 patients (2.6%) had their 125I seed slightly moved. Conclusion The short-term efficacy of 125I seed implantation plus TACE in the treatment of PHC is no less than the 3DCRT + TACE regimen, but with less radiation side effects. Key words: Primary hepatocellular carcinoma; Tumor thrombus; Transcatheter hepatic arterial chemoembolization; 125I seed implantation; Three dimensional conformal radiotherapy; Clinical efficacy

Efficacy and safety of the oxaliplatin-based chemotherapy in the treatment of advanced primary hepatocellular carcinoma: A meta-analysis of prospective studies.

Background:Many clinical studies have demonstrated the survival benefits of oxaliplatin-based chemotherapy for advanced hepatocellular carcinoma patients. Therefore, we aim to evaluate the efficacy and safety of oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma by conducting a meta-analysis of prospective studies.Methods:A comprehensive literature search was performed using the PubMed, Cochrane Library, EMBASE, and Web of Science databases from their inception to June 2016. Only prospective studies evaluating oxaliplatin-based chemotherapy in patients with advanced hepatocellular carcinoma were selected. The main outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and main adverse events.Results:Ten prospective studies involving 525 patients were included. The pooled ORR, 1-year PFS, and OS were 14.4% (95% confidence interval [CI] 9.2–19.6%), 9.3% (95%CI 10–28%), and 35.7% (95%CI 27–44%), respectively, for oxaliplatin-based chemotherapy. The median PFS and OS were 4.7 and 9.4 months, respectively. The incidences of grade 3/4 toxicities of neutropenia, thrombopenia, anemia, neurotoxicity, diarrhea, and nausea/vomiting were 17.2%, 9.2%, 6.0%, 4.8%, 3.1%, and 1.8%, respectively. Subgroup analysis revealed that the pooled ORR was 13.9% (95%CI 6.8–21%) in Asian patients and 12.8% (95%CI 6.8–18.7%) in Western patients. For Asian patients, the median PFS and OS were 4.2 and 9.2 months, and the 1-year PFS and OS were 12.5% and 30.5%, respectively. For Western patients, the median PFS and OS were 4.7 and 9.5 months, and the 1-year PFS and OS were 19.6% and 42.4%, respectively. There were no significant differences in the ORR, 1-year PFS, and OS (P > 0.05) between Asian and Western patients.Conclusions:Oxaliplatin-based chemotherapy appears to be effective and safe for the treatment of advanced hepatocellular carcinoma.

RM-047 Role of CT guided celiac neurolysis in treating intractable pain from advanced primary hepatocellular carcinoma

RM-047 Role of CT guided celiac neurolysis in treating intractable pain from advanced primary hepatocellular carcinoma

索拉非尼联合TACE术治疗中晚期原发性肝癌不良反应的观察及护理

Objective: To observe the adverse reactions induced by sorafenib plus TACE for the treatment of advanced primary hepatocellular carcinoma (HCC) adverse reactions, and related nursing countermeasures. Methods : Advanced HCC patients in the South Hospital, from January 2014 to December 2014, were selected and treated with sorafenib plus TACE. Liver functions in all patients were Class A or B grade, and accept TACE and sorafenib therapy. Observe the adverse reactions, take corresponding nursing measures according to its characteristics and examine the treatment effect. Results: We found that all patients can appear different degrees of adverse reactions in the treatment process. The most common is hand foot skin reaction, fever, pain, the occurrence probability more than 70%, and some patients may have nausea, vomiting, rash, fatigue and other adverse reactions. The corresponding nursing measures and preventive measures achieved good treatment effect. Conclusion: A full assessment of the data of advanced primary hepatocellular carcinoma patients is needed prior to sorafenib plus TACE treatment. Moreover, close observation of the side reaction and timely effective nursing measures, can help patients complete the combined treatment and achieve a better therapeutic effect.

Sorafenib-induced pemphigus vulgaris

Sorafenib is a tyrosine kinase inhibitor approved for the treatment of primary kidney cancer, advanced primary hepatocellular carcinoma and radioactive iodine-resistant advanced thyroid carcinoma. Sorafenib is known to cause milder cutaneous side effects such as maculopapular rash and serious cutaneous drug reactions such as desquamation of the skin, hand-foot syndrome Stevens-Johnsons syndrome and toxic epidermal necrolysis. We report a histopathologicaly proved case of pemphigus vulgaris caused by sorafenib.

Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

TACE combined with sorafenib in treatment of advanced primary hepatocellular carcinoma: a report of one case achieving complete response

TACE combined with sorafenib in treatment of advanced primary hepatocellular carcinoma: a report of one case achieving complete response

RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis.

Sorafenib is one of the preferred drugs for the treatment of advanced primary hepatocellular carcinoma (HCC). However, its side-effects and acquired resistance limit its use. The unfolded protein response (UPR) induced by chemotherapeutics has been demonstrated to be required for tumor cells to maintain malignancy and therapy resistance. Activation of the IRE1/XBP1 pathway during the UPR is important for tumor survival under pathophysiological conditions. In the present study, we found that the UPR was activated and RACK1 was overexpressed in three human HCC cell lines and in HCC samples. Activation of the IRE1/XBP1 signaling pathway plays a protective role when HCC cells encounter endoplasmic reticulum (ER) stress due to in vitro sorafenib treatment. We then found that the interaction between IRE1 and RACK1 was essential for the activation of IRE1 signaling in sorafenib-treated cells. Exogenous overexpression of RACK1 enhanced the phosphorylation level of IRE1 and increased XBP1 mRNA splicing activity, which protected the HCC cells from sorafenib-induced apoptosis. However, the re-expression of RACK1 led HCC cells to regain susceptibility to sorafenib-induced apoptosis. Taken together, the present study suggests that the RACK1/IRE1 complex may contribute to activation of the UPR in HCC cells. Targeting RACK1 in combination with sorafenib administration is a potential strategy for clinical trials of advanced HCC treatment.

Intraperitoneal perfusion of cytokine-induced killer cells with local hyperthermia for advanced hepatocellular carcinoma

To study the effect and tolerance of intraperitoneal perfusion of cytokine-induced killer (CIK) cells in combination with local radio frequency (RF) hyperthermia in patients with advanced primary hepatocellular carcinoma (HCC). Patients with advanced primary HCC were included in this study. CIK cells were perfused intraperitoneal twice a week, using 3.2 × 10⁹ to 3.6 × 10⁹ cells each session. Local RF hyperthermia was performed 2 h after intraperitoneal perfusion. Following an interval of one month, the next course of treatment was administered. Patients received treatment until disease progression. Tumor size, immune indices (CD3⁺, CD4⁺, CD3⁺CD8⁺, CD3⁺CD56⁺), alpha-fetoprotein (AFP) level, abdominal circumference and adverse events were recorded. Time to progression and overall survival (OS) were calculated. From June 2010 to July 2011, 31 patients diagnosed with advanced primary HCC received intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia in our study. Patients received an average of 4.2 ± 0.6 treatment courses (range, 1-8 courses). Patients were followed up for 8.3 ± 0.7 mo (range, 2-12 mo). Following combination treatment, CD4⁺, CD3⁺CD8⁺ and CD3⁺CD56⁺ cells increased from 35.78% ± 3.51%, 24.61% ± 4.19% and 5.94% ± 0.87% to 45.83% ± 2.48% (P = 0.016), 39.67% ± 3.38% (P = 0.008) and 10.72% ± 0.67% (P = 0.001), respectively. AFP decreased from 167.67 ± 22.44 to 99.89 ± 22.05 ng/mL (P = 0.001) and abdominal circumference decreased from 97.50 ± 3.45 cm to 87.17 ± 4.40 cm (P = 0.002). The disease control rate was 67.7%. The most common adverse events were low fever and slight abdominal erubescence, which resolved without treatment. The median time to progression was 6.1 mo. The 3-, 6- and 9-mo and 1-year survival rates were 93.5%, 77.4%, 41.9% and 17.4%, respectively. The median OS was 8.5 mo. Intraperitoneal perfusion of CIK cells in combination with local RF hyperthermia is safe, can efficiently improve immunological status, and may prolong survival in HCC patients.

Sorafenib combined with TACE in advanced primary hepatocellular carcinoma.

To evaluate the effectiveness and safety of sorafenib combined with transarterial chemoembolization (TACE) in patients with advanced primary hepatocellular carcinoma. A retrospective analysis of 65 patients with advanced primary hepatocellular carcinoma who had been administered sorafenib for more than one month and treated by TACE was performed. The tumor response was evaluated according to the response evaluation criteria in solid tumors and any side effects were recorded. Twelve patients entered a partial remission, 42 entered a stable condition, and the disease progressed in 11 patients. The disease control and objective regression rates were 83.1% and 18.5%, respectively. The one-year survival rate was 63.1%. Among the cases, the median overall survival time was 17 months, and the median time to progression was 9 months. The overall side effects rate was 78.5% and most were relieved after treatment. Sorafenib combined with TACE is a safe and effective treatment of advanced primary hepatocellular carcinoma.

Clinical study of FOLFOX4 regimen for patients of advanced hepatocellular carcinoma

Objective The aim of our study was to observe the efficiency and toxicity of oxaliplatin (L-OHP) combined with CF/5-FU in patients with advanced primary hepatocellular carcinoma.