Transarterial interventional therapy combined with tyrosine kinase inhibitors with or without anti-PD-1 antibodies as initial treatment for hepatocellular carcinoma with major portal vein tumor thrombosis: a single-center retrospective study.

Transarterial interventional therapy combined with tyrosine kinase inhibitors (TKIs) and anti-Pd-1 antibodies (triplet regimen) has shown promising results in advanced HCC. However, the clinical utility of the triplet regimen in patients with HCC and major portal vein tumor thrombosis (PVTT) remains unclear. This study compared the efficacy and safety of the triplet regimen versus transarterial interventional therapy combined with TKIs (double regimen) for such patients. Thirty-nine patients treated with the triplet regimen were retrospectively compared with 37 patients treated with the double regimen. The objective response rate (ORR), the response rate of PVTT treatment, and safety were observed; progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan‒Meier method and log-rank test. Predictors of survival were identified using multivariate analysis. Median OS and median PFS were significantly improved in the Triplet Group compared with the Double Group (482 vs. 310 days; 208 vs. 85 days). The ORR and the response rate of PVTT were significantly higher in the Triplet Group than in the Double Group (59% vs. 35%; 62% vs. 35%). There was no significant difference in the incidence of grade 3/4 adverse events between the two groups (33% vs. 21%). The most frequent grade 3/4 adverse events were thrombocytopenia (10%) in the Triplet Group and hand-foot syndrome (14%) in the Double Group. Multivariable analysis showed that treatment method and PVTT treatment response were significant predictors of OS. The triplet regimen showed superiority over the doublet regimen in improving OS and PFS and had acceptable safety in patients with HCC and major PVTT.

Comparison of Arterial Infusion Chemotherapy and Chemoembolization for Locally Advanced Hepatocellular Carcinoma: a Multicenter Retrospective Study.

BACKGROUND: Unresectable hepatocellular carcinoma (HCC) has a poor prognosis. We aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) for locally advanced HCC compared to transcatheter arterial chemoembolization (TACE). METHODS: A propensity score-matched cohort study was performed in patients with locally advanced HCC with ≥ 4 tumors or portal vein tumor thrombosis (PVTT) who underwent either HAIC using oxaliplatin plus raltitrexed or TACE at three institutions between June 2015 and December 2021. Overall survival (OS), progression-free survival (PFS), objective response rates (ORR), and adverse events (AEs) were compared between the groups. RESULTS: After propensity score matching, 62 pairs of patients were evaluated. The HAIC group had longer OS (15.0 [95% CI: 12.1-17.9] vs. 9.0 [95% CI: 5.1-12.9] months; P = 0.034), better PFS (6.7 [95% CI: 5.1-8.3] vs. 4.0 [95% CI: 2.6-5.4] months; P = 0.020), and a higher ORR (RECIST 1.1: 54.8% vs. 11.3%; P < 0.001) than the TACE group in the intention-to-treat population. Compared with the TACE group, Grade 1-2 nausea and vomiting occurred significantly more frequently in the HAIC group. CONCLUSION: Compared to TACE, HAIC significantly increased the ORR of locally advanced HCC with multiple tumors or portal invasion and prolonged survival without causing a significant increase in severe AEs.

Conversion Therapy of Large Unresectable Hepatocellular Carcinoma With Ipsilateral Portal Vein Tumor Thrombus Using Portal Vein Embolization Plus Transcatheter Arterial Chemoembolization.

Background: The study aimed to assess the safety and efficacy of conversion therapy with portal vein embolization (PVE) and transcatheter arterial chemoembolization (TACE) in patients with large unresectable hepatocellular carcinoma (HCC) and ipsilateral portal vein tumor thrombus (PVTT). Methods: This retrospective study evaluated consecutive patients with initially large (≥5 cm) unresectable HCC with ipsilateral PVTT who underwent PVE + TACE at our center between June 2016 and September 2020 (Group A). Clinically equivalent patients from three centers who were receiving tyrosine kinase inhibitors (TKIs) + TACE (Group B) were included. The survival times were evaluated and compared between the two therapeutic groups. Results: In Group A (n = 33), the median tumor diameter was 14 cm (range, 5-18 cm) and 19 (57.6%) patients underwent radical resection 18-95 days after PVE. Radical liver resection was not performed because of inadequate hypertrophy (n = 11), pulmonary metastasis (n = 1), lack of consent for surgery (n = 1), and the rupture of the HCC (n = 1). There were no patients who underwent radical resection in Group B (n = 64) (P = 0.000). The mean and median overall survival (OS) were 736.5 days and 425.0 days in Group A and 424.5 days and 344.0 days in Group B, respectively. Compared with TKIs + TACE, treatment with PVE + TACE prolonged OS (P = 0.023). Conclusions: This study shows that conversion therapy was safe and effective in patients with initially large unresectable HCC with ipsilateral PVTT treated with PVE + TACE. Moreover, PVE + TACE conferred more favorable outcomes than treatment with TKIs + TACE.

Hepatic arterial infusion oxaliplatin plus raltitrexed and chemoembolization in hepatocellular carcinoma with portal vein invasion: A propensity score-matching cohort study.

BACKGROUND: About 55% of hepatocellular carcinoma (HCC) cases in China are advanced HCC at the initial diagnosis. We aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) for HCC with portal vein tumor thrombosis (PVTT) compared to transcatheter arterial chemoembolization (TACE) after propensity score matching (PSM). METHODS: A propensity score-matched cohort study was performed in patients with advanced HCC with PVTT who underwent either HAIC using oxaliplatin plus raltitrexed or TACE at three institutions between January 2016 and January 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events were compared between the groups. RESULTS: After PSM, 44 pairs of patients were assessed. The HAIC group had longer OS (11.2 [95% confidence interval [CI]: 9.9-12.5] vs. 9.0 [95% CI: 5.3-12.7] months; p = 0.010), better PFS (5.6 [95% CI: 3.7-7.9] vs. 2.0 [95% CI: 1.3-2.7] months; p = 0.006), and a higher ORR (Response Evaluation Criteria in Solid Tumors [version 1.1]: 56.8% vs. 18.2%; p < 0.001) than the TACE group. In multivariate analysis, HAIC was identified as an independent favorable prognostic factor for survival. CONCLUSIONS: Compared to TACE, HAIC significantly increased the ORR of HCC with portal invasion and prolonged survival without causing a significant increase in severe adverse events.

Hepatic arterial infusion of oxaliplatin plus raltitrexed in unresectable hepatocellular carcinoma with or without portal vein tumour thrombosis.

Background: Unresectable hepatocellular carcinoma (HCC) has a poor prognosis. According to the HCC management guidelines in China, the standard treatment of Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC with portal vein tumour thrombosis (PVTT) is chemoembolization. However, some patients with BCLC stage B or C HCC with PVTT respond poorly to chemoembolization. We aimed to compare tumour responses and survival benefits between patients with unresectable HCC with or without PVTT. Methods: We reviewed 119 consecutive patients with unresectable HCC with PVTT (n = 67) and without PVTT (n = 52) who underwent hepatic arterial infusion of oxaliplatin plus raltitrexed between January 2018 and April 2021. Overall survival, progression-free survival, tumour responses, and adverse events were compared between the groups. Results: There were no significant between-group differences in the objective response rates and median progression-free survival. The median overall survival was significantly longer in the group without PVTT than in that with PVTT (17.0 vs 10.4 months, respectively; P = 0.024). Conclusion: Hepatic arterial infusion of oxaliplatin plus raltitrexed may be efficacious in patients with unresectable HCC with or without PVTT.

Comparison of the efficacy and safety of conventional transarterial chemoembolization with and without drug-eluting beads embolization for the treatment of unresectable large hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) has a poor prognosis. Moreover, large HCCs have been commonly observed. We aimed to evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) combined with conventional TACE (cTACE) for the treatment of patients with unresectable large HCCs (main tumor ≥5 cm in diameter) compared with cTACE alone. METHODS: A retrospective matched cohort study was performed on consecutive patients with unresectable large HCCs who underwent TACE as the initial treatment at the Fujian Medical University Cancer Hospital from May 2017 and March 2019. Fifty-five patients who underwent DEB-TACE combined with cTACE were compared with a case-matched control group of 110 patients who received cTACE alone. We compared the tumor response at 1 and 3 months after TACE, time to progression (TTP), and adverse events between the groups. RESULTS: The objective response rate was higher for the DEB-TACE combined with cTACE group than for the cTACE alone group at 1 (39 of 55 [70.9%] vs. 57 of 110 [51.8%], p = 0.019) and 3 months (27 of 43 [62.8%] vs. 31 of 71 [43.7%], p = 0.048) post-treatment. The DEB-TACE combined with cTACE group also had a significantly longer median TTP than that of the cTACE group (7.2 vs. 5.3 months, p = 0.039). Compared with the cTACE group, occurrences of abdominal pain, nausea/vomiting, and constipation were significantly more frequent in the DEB-TACE combined with cTACE group (p < 0.05). CONCLUSION: Compared with cTACE alone, DEB-TACE combined with cTACE significantly increased the objective response rate at 1 and 3 months after the treatment of unresectable large HCCs, and had a longer TTP, without any significant increase in the number of severe complications.

Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with intermediate and advanced stage hepatocellular carcinoma: A phase II, single-arm, prospective study.

PURPOSE: To investigate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed in patients with intermediate stage and advanced stage hepatocellular carcinoma (HCC). METHODS: In this phase II, single-arm clinical trial, we enrolled patients aged 18-70 years with intermediate stage and advanced stage HCC, which included patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B who experienced transcatheter arterial chemoembolization failure/refractoriness, and those with BCLC stage C with portal vein invasion. We performed HAI with oxaliplatin and raltitrexed. Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon's two-stage design. The primary end-point was the objective response rate in accordance with the Response Evaluation Criteria in Solid Tumours. RESULTS: Fifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. Treatment-related grade IV adverse events or deaths were not reported, and the observed grade III adverse events were elevated aspartate aminotransferase levels (5 [12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopaenia (1 [2.6%]) and abdominal infection (1 [2.6%]). CONCLUSION: HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients with intermediate and advanced stage HCC, and further evaluation is warranted.

Comparison of the efficacy and safety of Transarterial chemoembolization with and without Apatinib for the treatment of BCLC stage C hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer worldwide, with a poor prognosis. Most patients are diagnosed at advanced stages and are only eligible for palliative therapy. Therefore, this study aimed to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with apatinib (TACE-apatinib) treatment and TACE-alone treatment for Barcelona Clinic Liver Cancer stage C HCC. METHODS: We retrospectively reviewed 80 consecutive patients with BCLC stage C HCC who received TACE-apatinib or TACE-alone as the initial treatment. We compared the clinical and laboratory outcomes, imaging findings at 1 and 3 months after TACE, tumor response, time to progression (TTP), overall survival (OS), and adverse events between both groups. RESULTS: The overall response rate was higher in the TACE-apatinib group than in the TACE-alone group at 1 and 3 months after treatment (66.7% vs 39.6%, respectively, P = 0.020; 45.8% vs 17.6%, respectively, P = 0.021). The median TTP and OS in the TACE-apatinib group were longer than those of the TACE-alone group (TTP: 6.3 months vs 3.5 months, respectively, P = 0.002; OS: 13.0 months vs 9.9 months, respectively, P = 0.041). Apatinib-associated side effects such as hypertension, hand-foot syndrome, oral ulcers, proteinuria, and diarrhea were more prevalent in the TACE-apatinib group than in TACE-alone group (P < 0.05). CONCLUSION: Compared to TACE-alone treatment, TACE-apatinib increased the TTP, OS, and tumor-response rate at 1 and 3 months after treatment of BCLC stage C HCC without any significant increase in severe adverse events.

Transarterial chemoembolization for unresectable hepatocellular carcinoma: A comparison of the efficacy and safety of 2 embolic agents.

The aim of this study was to compare the efficacy and safety of 2 different embolic agents, namely gelatin sponge particle (GSP) and Lipiodol, for transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC).We retrospectively reviewed 87 consecutive patients with unresectable HCC who underwent Lipiodol TACE with lobaplatin and 87 consecutive patients with unresectable HCC who underwent GSP TACE with lobaplatin between January 2013 and June 2017 in our institution as the initial treatment. Both groups were compared considering the clinical and laboratory outcomes and imaging findings before and after TACE. Tumor response and adverse events were also evaluated.There was significant difference in the rate of complete and overall response between the groups (P = .029 and .001, respectively), specifically when the tumor size was >5 cm (P = .001). The disease control rate was significantly better in the GSP group than in the Lipiodol group (94.3% vs. 86.4%, P = .011). The response differences in higher stages were significant between the 2 groups (P = .035 and .007, respectively). The grades of adverse events were also significantly different between the groups (P = .000).GSP-as an embolic agent in TACE for HCC-could significantly increase the rate of tumor response 1 month after treatment, especially in large tumors, without any significant increase in severe adverse events, when compared to Lipiodol.

Efficacy and Safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma: A prospective observation study.

This prospective study aimed to evaluate the efficacy and safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma (HCC).The patients with intermediate/advanced HCC, who met predetermined inclusion and exclusion criteria, underwent oral treatment of apatinib 500 mg daily. The drug-related adverse effects were monitored by regular follow-up and workup including laboratory tests and imaging examinations. Tumor response was assessed by response evaluation criteria in solid tumor criteria. The time to tumor progression (TTP) and overall survival rate (OS) were calculated using the Kaplan-Meier method.A total of 31 patients were enrolled in the study from October 28, 2015 to December 28, 2016. The number of patients with intermediate and advanced HCC was 4 (12.90%) and 27 (87.10%), respectively. The mean tumor size was 9.47 ± 5.48 cm (range: 1.2-19 cm). Vascular invasion was seen in 14 patients (45.16%). A total of 21 (67.74%) patients exhibited extrahepatic metastases. On the basis of first follow-up computed tomography and magnetic resonance imaging at 6 weeks after treatment, 10 (32.26%), 15 (48.39%), and 6 (19.35%) of 31 patients achieved a partial response, stable disease, and progression of disease, respectively. Response rate and disease control rate were 32.26% and 80.65%, respectively. The median TTP was 4.8 months (95% confidence interval: 3.75-5.86 months). Furthermore, 6- and 12-month OS rates were 73.8% and 55.4%, respectively. Grade 3 thrombocytopenia (6.45%) and hypertension (48.39%) were the most common hematologic and nonhematologic toxicities. Grade 3 elevation of either serum total bilirubin or aminotransferase (6.45%) was observed as the top incidence among important indexes of liver function.Our preliminary findings suggest apatinib is a safe and effective therapy in intermediate/advanced HCC patients with high tumor response and survival rates.

Multifunctional nanocomplex for surface-enhanced Raman scattering imaging and near-infrared photodynamic antimicrobial therapy of vancomycin-resistant bacteria.

Since vancomycin (Van)-resistant enterococci (VRE) strains first emerged as a serious threat to public health, extensive studies focused on optical imaging and antimicrobial therapy have been performed for monitoring and microbiological control. In this study, we developed silicon 2,3-naphthalocyanine dihydroxide (Nc) and Van functionalized silica-encapsulated, silver-coated gold nanoparticles (Au@AgNP@SiO2@Nc-Van) as a novel theranostic system for surface-enhanced Raman scattering (SERS) detection and antimicrobial photodynamic therapy (aPDT) of VRE strains. The silver-coated gold nanoparticle, as the SERS-active core, exhibited excellent Raman enhancement efficacy. Results of in vitro bacterial SERS imaging revealed Van-enhanced specific binding affinity toward VRE. Meanwhile, Si(IV) naphthalocyanine, serving as a near-infrared (NIR) photosensitizer, was axially linked to the nanoparticle surface, yielding nanostructured hybrid materials that could photoinactivate VRE. Almost 4-5 logs of bacterial reduction were obtained upon in vitro photodynamic therapy of VRE treated with a nanomolar concentration of the nanocomplex. Mouse infection assays were applied for an in vivo evaluation of VRE lethality. Upon near-infrared light irradiation, this hybrid nanomaterial caused obvious infection regression and even complete eradication compared to the findings in the non-treated groups. Therefore, this novel nanosystem integrating SERS imaging and noninvasive aPDT has huge potential for applications in theranostics with regard to VRE management.

Characterization of a near-infrared fluorescent DCPO-tagged glucose analogue for cancer cell imaging.

Cancer cells are usually characterized with an increase in glucose uptake when compared with normal cells, which is known as Warburg effect. Near-infrared (NIR) fluorescent glucose analogues have been previously synthesized and been applied in cancer cell imaging. However, most NIR dyes usually have one or more charge in their structures, which may cause low cell membrane permeability and hamper their application in cell imaging. Here we reported a novel glucose analogue N2, which was designed and synthesized based on a new type of NIR dye, DCPO. As expected, higher level of N2 uptake was observed in hepatic carcinoma cells (HepG2) and gastric cancer cells (NCI-N87) than their equivalent cells from normal tissues of the same origin, respectively. The accumulation of N2 in cancer cells was in consistent with the overexpression of glucose transporter GLUT-1 in these cells. The cellular uptake of N2 was then confirmed to be dependent on GLUT-1, which was evidenced by the decreased uptake of N2 in the presence of d-glucose or GLUT-1 inhibitor phloretin. Moreover, uptake of N2 in cancer cells was found to be in a concentration- and time-dependent manner. In all, our study demonstrated that N2, as a novel DCPO-conjugated bioprobe, could be used to monitor cellular glucose consumption, and therefore might be applied in cancer cell bioimaging and bioassay in cancer studies.