Associations Between Single Nucleotide Polymorphisms of Hypoxia-Related Genes and Capsule Formation in Hepatocellular Carcinoma.

Purpose: Tumor capsule is an independent prognostic factor for patients with hepatocellular carcinoma (HCC) and used increasingly to guide clinical decision-making. Considering the genetic complexity for capsule formation and its potential association with hypoxia, the significance of the polymorphisms of hypoxia-related genes in capsule formation and HCC prognosis remains to be elucidated. Patients and Methods: Peripheral blood samples from HCC patients were collected in this study. Single nucleotide polymorphism (SNP) genotyping was conducted by the iPLEX chemistry on a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (Sequenom, Inc.). The demographic and clinical data for the patients were obtained through medical chart review and/or consultation with the treating physicians. SPSS 25.0, R 4.1.1, and PLINK toolset were used to perform statistical analysis. Results: A total of 183 patients were enrolled, including 88 patients assigned to the capsule group and 95 to the non-capsule group. SLC2A1 rs841858 T allele, SLC2A1 rs2297977 T allele, STAT1 rs1547550 C allele, and STAT1 rs34997637 G allele were associated with significantly increased risk of capsule formation. The genotypes of SLC2A1 rs841858, SLC2A1 rs2297977, STAT1 rs34997637, and STAT1 rs1914408 were significantly associated with the formation of HCC capsule. The polymorphisms of STAT1 rs2066802, STAT1 rs12693591, and HIF1A rs2057482 showed close relationship with the prognosis of HCC patients in the capsule group, while the genotype distributions of CTNNB1 rs4135385, IFNG rs1861494, and SERPINE1 rs2227631 were closely related to the survival of patients in the non-capsule group. Further haplotype analysis suggested that SLC2A1 block 1 and STAT1 block 2 were related to the susceptibility of HCC capsule. Conclusion: The polymorphisms of the hypoxia-related genes (HIF1A, SERPINE1, IFNG, STAT1, CTNNB1, and SLC2A1) were correlated with the formation of HCC capsule. Several SNPs in these genes also showed association with HCC prognosis except SLC2A1. Further functional studies are warranted to explore the underlying mechanisms.

D-dimer for assessment of treatment response, and survival to drug-eluting beads transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: D-dimer exhibits a certain prognostic value in hepatocellular carcinoma (HCC) patients who underwent hepatectomy and microwave ablation, while its value in estimating the clinical benefit of drug-eluting beads transarterial chemoembolization (DEB-TACE) remains unclear. Hence, this study aimed to investigate the correlation of D-dimer with tumor features, response and survival to DEB-TACE in HCC patients. METHODS: Fifty-one HCC patients treated with DEB-TACE were recruited. Their serum samples at baseline and after DEB-TACE were collected and proposed for D-dimer detection by the immunoturbidimetry method. RESULTS: Elevated D-dimer levels were related to a higher Child‒Pugh stage (P = 0.013), tumor nodule number (P = 0.031), largest tumor size (P = 0.004), and portal vein invasion (P = 0.050) in HCC patients. Then, patients were classified by the median value of D-dimer, and it was observed that patients with D-dimer >0.7 mg/L achieved a lower complete response rate (12.0% vs. 46.2%, P = 0.007) but a similar objective response rate (84.0% vs. 84.6%, P = 1.000) compared to those with D-dimer ≤0.7 mg/L. The Kaplan‒Meier curve showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to shorter overall survival (OS) (P = 0.013). Further univariate Cox regression analyses showed that D-dimer >0.7 mg/L (vs. ≤0.7 mg/L) was related to unfavorable OS [hazard ratio (HR): 5.524, 95% confidence interval (CI): 1.209-25.229, P = 0.027], but it failed to independently estimate OS (HR: 10.303, 95%CI: 0.640-165.831, P = 0.100) in multivariate Cox regression analyses. Moreover, D-dimer was elevated during DEB-TACE therapy (P<0.001). CONCLUSION: D-dimer may be helpful for monitoring prognosis to DEB-TACE therapy in HCC, while further large-scale-study validation is warranted.

A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma.

Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the combination therapy of regorafenib and programmed death-1 (PD-1) inhibitors with regorafenib monotherapy as a second-line treatment for patients with advanced HCC. Methods: Our multicenter retrospective study evaluated consecutive patients with advanced HCC who received regorafenib plus PD-1 inhibitors or regorafenib alone as a later-line therapy from May 2019 to January 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and safety was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: A total of 133 patients were included in the study (regardless of first-line treatment), including 94 who received regorafenib plus PD-1 inhibitors and 39 who received regorafenib. The regorafenib plus PD-1 inhibitors group had a significantly higher ORR (25.53% vs. 10.26%, P=0.015), higher DCR (87.23% vs. 66.67%, P=0.006), and longer PFS (median 9.0 vs. 4.0 months, P<0.0001) than the regorafenib group. Meanwhile, the median OS (mOS) did not differ between the regorafenib plus PD-1 and regorafenib monotherapy groups {mOS, 14.0 months [95% confidence interval (CI), 14.0-16.0 months] vs. 12.0 months (95% CI, 10.0-22.0 months)}. There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (71.79% vs. 78.72%, P=0.39) and the incidence of grade 3/4 serious adverse effects (5.13% vs. 18.09%, P=0.19) between the regorafenib monotherapy group and PD-1 inhibitors combination group. Conclusions: Compared with regorafenib alone, regorafenib combined with PD-1 inhibitors therapy increased PFS, ORR but did not improve OS, and can be used an option in second-line HCC therapy, regardless of first-line treatments. Regorafenib combined with PD-1 inhibitors is recommended as early as a second-line therapy to benefit patients. The combination regimen was as safe as regorafenib monotherapy for treatment of HCC in patients with compensated liver disease [Child-Turcotte-Pugh (CTP) A/B].

Comparison of the Efficacy and Safety of Transarterial Chemoembolization Plus Microwave Ablation versus Surgical Resection in Patients with Solitary Large Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

Background: The liver resection for solitary large hepatocellular carcinoma (SLHCC) remains controversial due to the high risk of complications and recurrence after resection. This study aimed to compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) plus microwave ablation (MWA) with resection for SLHCC. Methods: We retrospectively analyzed a total of 148 patients who were treated with either TACE-MWA (n = 94) or resection (n = 54) for SLHCC (≥5 cm). A matched cohort composed of 86 patients was included after propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and safety. Results: The TACE-MWA group was older with higher ALT and AST (all P < 0.05). After PSM, the 1-, 3-, and 5-year OS were 100%, 80.3%, and 51.0% in the TACE-MWA group, and 88.3%, 66.7%, and 39.4% in the liver resection group, respectively. The 1-, 3-, and 5-year PFS were 76.7%, 48.8%, and 19.6% in the TACE-MWA group, and 72%, 40.2%, and 22.6% in the liver resection group, respectively. There was no significant difference in OS and PFS between the two groups (all P > 0.05). For SLHCC patients with tumor size ≥7cm, TACE-MWA showed favorable OS than liver resection. The TACE-MWA group exhibited a lower rate of major complications and shorter hospital stay than the resection group. Conclusion: TACE-MWA showed comparable efficacy to liver resection in patients with SLHCC, but better safety and shorter hospital stay. TACE-MWA might provide a longer OS than liver resection for SLHCC patients with tumor size ≥7cm.

Safety and efficacy of percutaneous microwave ablation using combined computed tomography and ultrasound-guided imaging in patients with hepatocellular carcinoma: A retrospective study.

Background: We retrospectively evaluated the safety and efficacy of percutaneous microwave ablation (MWA) using combined computed tomography (CT) and ultrasound (US)-guided imaging in patients with Barcelona Clinic Liver Cancer (BCLC)-A1-3 hepatocellular carcinoma (HCC). Methods: We included 88 consecutive patients with single HCC who were treated with transcatheter arterial chemoembolization (TACE) using our database. The patients were divided into three groups. The combination group received MWA under the guidance of nonenhanced CT and US, CT group received MWA under the guidance of nonenhanced CT alone and US group received MWA under the guidance of US alone. The study endpoints included the treatment time, number of puncture, local recurrence rate, and adverse events. Results: The median treatment time and mean puncture number were 38.6 (30-45) min, 1.2 (1-2) times (combination group); 45.8 (35-56) min, 4.2 (3-7) times (CT group); and 36.7 (30-47) min, 1.1 (1-2) times (US group), respectively. The median puncture number was significantly less than in the CT group. The local recurrence rate in the combination group was significantly inferior to that in the US group. There was a statistically significant difference between the combination group and CT group in Grade C complication rate. Conclusions: Combining CT-and US-guide MWA in patients with BCLC-A1-3 HCC appeared to be much better than the use of guidance of CT or US alone.

Treatment efficacy and safety of drug-eluting beads transarterial chemoembolization versus conventional transarterial chemoembolization in hepatocellular carcinoma patients with arterioportal fistula.

This study aimed to compare the treatment efficacy and tolerance between drug-eluting beads transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) in hepatocellular carcinoma (HCC) patients with arterioportal fistula (APF). A total of 44 HCC patients with APF scheduled for DEB-TACE (N = 24, as DEB-TACE group) or cTACE (N = 20, as cTACE group) were recruited. Treatment response, hepatic function, and adverse events were assessed or recorded. Besides, progression-free survival (PFS) and overall survival (OS) were calculated. Total treatment response was better in the DEB-TACE group compared with the cTACE group (P = .012). Meanwhile, the objective response rate (87.5% versus 60.0%) was higher (P = .013), while the disease control rate (95.8% versus 85.0%) was similar in the DEB-TACE group compared to the cTACE group (P = .213). Besides, PFS (mean value: 12.2 (95%CI: 9.9-14.6) months versus 7.8 (95%CI: 5.6-10.0) months) (P = .037), but not OS (mean value: 20.0 (95%CI: 18.1-21.9) months versus. 18.6 (95%CI: 15.4-21.8) months) (P = .341) was prolonged in DEB-TACE group compared with cTACE group. Regarding the safety, Child-Pugh stage, albumin level, and bilirubin level after treatment were all similar between the DEB-TACE group and cTACE group (all P > .05); moreover, no difference was found in the occurrence of adverse events during or after treatment between the two groups (all P > .05). Moreover, subsequent analyses found that embolic materials for APF (microspheres) in the DEB-TACE group did not affect the treatment efficacy (all P > .05). DEB-TACE promotes treatment response and PFS compared with cTACE and shows good safety in HCC patients with APF.

Effect of microwave ablation on platelet and coagulation function in patients with BCLC-A hepatocellular carcinoma.

AIM: To preliminarily evaluate the effect of microwave ablation (MWA) alone on platelet (PLT) and coagulation function in patients with BCLC-A hepatocellular carcinoma (B-A-HCC) using a retrospective method. MATERIALS AND METHODS: A total of 36 patients with 48 B-A-HCCs were radically treated with MWA alone under the guidance of ultrasound between April and October 2018. PLT coagulation indexes were measured before and after MWA at 1 day, 3 days, 1 week, and 2 weeks, and blood samples (after morning fasting) were collected from cubital veins. Coagulation indexes included prothrombin time (PT), prothrombin activity (PTA), thrombin time (TT), Activated Partial Thromboplastin Time (APTT), international standardized ratio (INR), plasma fibrinogen (FIB), plasma antithrombin III (AT-III), and D dimer (DD). Overall survival (OS), recurrence-free survival (RFS), local tumor progression (LTP), and adverse reactions were also recorded. RESULTS: All patients were radically treated with MWA alone. The median size of the lesion was 2.6 (1.5-7.0) cm3. On the first day after MWA, the level of PLT decreased significantly compared with the values before MWA and gradually returned to preoperative levels one week after MWA. One day after MWA, the levels of PT, INR, and AT-III increased markedly and the level of PTA decreased significantly, all of them gradually returned to baseline after 3 days to a week of time. 1, 3, and 7 days after MWA, the levels of FIB, and DD increased significantly, and the level of TT decreased significantly; all of them gradually returned to baseline at 2 weeks. At 6 months posttreatment, the OS and RFS rates were 100% and 91.7%, the LTP rates was 5.6%, no significant adverse reactions. CONCLUSION: PLT and coagulation indexes were abnormal in patients with B-A-HCC who were radically treated with MWA alone after treatment; without specific treatment, they all gradually returned to baseline within a week or two.

FAM83H-AS1/miR-485-5p/MEF2D axis facilitates proliferation, migration and invasion of hepatocellular carcinoma cells.

BACKGROUND: Abundant evidence has manifested that long noncoding RNAs (lncRNAs) are closely implicated in human cancers, including hepatocellular carcinoma (HCC). Remarkably, lncRNA FAM83H antisense RNA 1 (FAM83H-AS1) has been reported to be a tumor-propeller in multiple cancers. However, its effect on HCC progression remains unknown. METHODS: FAM83H-AS1 expression was analyzed by RT-qPCR. Colony formation, EdU, and flow cytometry as well as transwell assays were implemented to analyze the biological functions of FAM83H-AS1 on HCC progression. Luciferase reporter, RIP and RNA pull-down assays were implemented to detect the interaction among FAM83H-AS1, microRNA-485-5p (miR-485-5p), and myocyte enhancer factor 2D (MEF2D) in HCC cells. RESULTS: FAM83H-AS1 expression in HCC cells was markedly elevated. FAM83H-AS1 accelerated cell proliferation, migration and invasion whereas inhibiting cell apoptosis in HCC. Besides, we confirmed that FAM83H-AS1 acts as a miR-485-5p sponge in HCC cells. Additionally, MEF2D was verified to be a direct target of miR-485-5p. FAM83H-AS1 could upregulate MEF2D expression via sponging miR-485-5p. Further, rescue experiments testified that MEF2D upregulation or miR-485-5p downregulation offset the repressive effect of FAM83H-AS1 depletion on HCC cell progression. CONCLUSIONS: FAM83H-AS1 facilitates HCC malignant progression via targeting miR-485-5p/MEF2D axis, suggesting that FAM83H-AS1 may be a promising biomarker for HCC treatment in the future.

Drug-eluting beads-transarterial chemoembolization plus microwave ablation is an effective and safe treatment strategy in treating hepatocellular carcinoma adjacent to gallbladder.

The present study aimed to compare the efficacy and safety of drug-eluting beads-transarterial chemoembolization (DEB-TACE) plus microwave ablation (MWA) versus (vs.) surgery in treating patients with hepatocellular carcinoma (HCC) adjacent to gallbladder. Totally 54 patients with HCC adjacent to gallbladder were included and divided into two groups: DEB-TACE plus MWA group (n = 24) and surgery group (n = 30). Treatment response, relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and adverse events were assessed and documented. For DEB-TACE plus MWA group, complete response rate, objective response rate and disease control rate were 79.2%, 95.8% and 100.0% after one-month post treatment, respectively. In terms of survival profiles, DEB-TACE plus MWA group presented similar RFS (28.2 (95% CI: 12.5-43.9) months vs. 26.6 (95% CI: 19.2-34.1) months) (P = 0.930), PFS (21.2 (95% CI: 1.6-40.8) months vs. 26.6 (95% CI: 19.2-34.1) months) (P = 0.541), and OS (41.4 (95% CI: 35.0-47.9) months vs. 59.7 (95% CI: 51.7-67.7) months) (P = 0.138) compared with surgery group, and further multivariate Cox's regression analysis validated that, after adjustment of confounding factors, DEB-TACE plus MWA group exhibited no difference of RPS, PFS or OS compared with surgery group. Regarding safety, the intraoperative adverse event incidence was higher in DEB-TACE plus MWA group compared with surgery group (P = 0.008), while two groups exhibited no difference of postoperative adverse event incidence (P = 0.618). In conclusion, DEB-TACE plus MWA presents to be an optional treatment strategy in patients with HCC adjacent to gallbladder.

Gene Polymorphism of MUC15, MMP14, BRAF, and COL1A1 Is Associated with Capsule Formation in Hepatocellular Carcinoma.

Background: The presence of a capsule is an important prognostic factor in hepatocellular carcinoma (HCC). Capsule formation is affected by tumor-host interaction, which may include collagen deposition and extracellular matrix (ECM) degradation. Purpose: This study aimed to examine whether single-nucleotide polymorphisms (SNPs) in the genes for COL1A1 MUC15, MMP14, CD97, SMYD3, BRAF, and transforming growth factor beta 1 (TGF-ß) are related to capsule formation. Methods: We prospectively recruited and analyzed 185 patients with HCC with or without a capsule between 2019 and 2020. The SNPs involved were analyzed by polymerase chain reaction. Differences in the allele and genotype frequency between the cases and controls were evaluated using the chi-square test. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis with adjustment for age and sex. Stratification analyses were also performed with preselected variables. Results: The single-locus analysis showed that the presence of a capsule was significantly associated with five SNPs : MUC15 rs17309195 (P=0.01), rs12271124 (P= 0.02), rs10430847 (P=0.04), MMP14 rs17884816 (P=0.01), and BRAF rs74512895 (P=0.03). Adjusted logistic regression revealed that the decreased capsule formation was statistically significantly associated with BRAF rs76603725, COL1A1 rs2269336, and MUC15 rs17309195, while MMP14 rs17884816 and MUC15 rs10430847, rs2063278, and rs967490 were associated with increased capsule formation. The MUC15 block 2 haplotype was associated with increased capsule formation. Conclusions: MUC15, MMP14, BRAF, and COL1A1 gene polymorphisms are associated with capsule formation in HCC. Studies involving larger samples are needed to confirm our results.

Imaging features and outcomes in patients with ruptured hepatocellular carcinoma following transcatheter arterial chemoembolization: a retrospective clinical study.

OBJECTIVE: To summarize and analyze the imaging features and outcomes of patients with ruptured hepatocellular carcinoma (HCC) following transcatheter arterial chemoembolization (TACE). METHODS: We investigated all consecutive patients with HCC who received standardized TACE based on our hospital database. Ruptured HCCs were divided into three types according to their relationship with the liver capsule, determined by computed tomography or magnetic resonance imaging scans: Type I, portion of tumor cambered outwards ≤30%; Type II, portion of tumor cambered outwards >30% and <50%; and Type III, portion of tumor cambered outwards ≥50%. RESULTS: There were 54, 40, and 26 patients with Type I, II, and III HCCs, respectively. Among these, eight patients developed ruptured tumors within 2 weeks after TACE, including one, two, and five patients with type I, II, and III ruptured HCCs, respectively. Patients with type III HCCs had a shorter median survival time than patients with type I-II HCCs. CONCLUSIONS: Patients with type III HCCs might have a higher re-rupture rate and benefit less from emergency arterial embolization procedures than patients with type I-II HCCs.

The development of a predictive risk model on post-ablation hemobilia: a multicenter matched case-control study.

OBJECTIVE: This study aimed to develop a predictive risk model for post-ablation hemobilia. METHODS: This was a retrospective, multicenter, matched case-control study. The case group comprised patients with hepatocellular carcinoma who developed post-ablation hemobilia (n = 21); the control group (n = 63) comprised patients with hepatocellular carcinoma but no post-ablation hemobilia; for each case, we included three controls matched for age, sex, platelet count, year of ablation therapy, and center. Univariate and multivariate regression analyses were performed to identify the risk factors for hemobilia. A risk score model was developed based on adjusted odds ratios (ORs). RESULTS: The independent risk factors for occurrence of post-ablation hemobilia were maximum tumor diameter >47 mm [OR = 5.983, 95% CI (1.134-31.551)] and minimum distance from the applicator to the portal trunk ≤8 mm [OR = 4.821, 95% CI (1.225-18.975)]. The risk model was developed using the adjusted ORs; thus a score of 6 was assigned to the former and a score of 5 for the latter. The area under the curve of this risk model was 0.76. Significant hemodynamic instability and inaccurate embolization might increase the risk of recurrence of hemobilia. CONCLUSION: Tumor size >47 mm and distance of the applicator from the portal trunk ≤8 mm are independent risk factors for hemobilia. A predictive risk model for post-ablation hemobilia was developed using these risk factors. ADVANCES IN KNOWLEDGE: This is the first study that developed a risk score model of post-ablation hemobilia. Risk factors of the recurrence of post-ablation hemobilia were also been identified.

Hepatocellular carcinoma with type II-III portal vein tumour thrombosis: treatment using transarterial chemoembolisation and microwave ablation.

OBJECTIVE: To evaluate the use of transarterial chemoembolisation (TACE) combined with microwave ablation (MWA) to treat patients with hepatocellular carcinoma (HCC) and type Ⅱ-Ⅲ portal vein tumour thrombosis (PVTT) intolerant to targeted drug (TG) therapy. METHODS: A total of 18 patients with HCC and type Ⅱ-Ⅲ PVTT intolerant to TG were enrolled between June 2015 and December 2019, who were treated with TACE + MWA (MWA group). 24 patients were treated with TACE + TG (TG group; control cohort). Time to progression and overall survival (OS) were analysed along with the incidence of adverse events. RESULTS: The median follow-up time was 19.0 months (9.0-32.0 months). The median OS was 17.0 months (8.3-29.3 months; MWA group) and 13.5 months (5.5-22.5 months; TG group) and was not significantly different. The 1- and 2 year OS was also comparable (MWA group: 66.7%, 44.4% vs Target group: 41.7%, 29.2%). Time to progression showed no distinct differences (MWA group: 11.5 months; TG group: 9.0 months) between the two groups. Moreover, the incidence of major Grade 3-4 adverse events in the MWA group (5.6%) was similar to those in the TG group (8.3%). CONCLUSION: TACE + MWA and TACE + TG were comparable in their safety and efficacy in patients with HCC, type Ⅱ-Ⅲ PVTT, and intolerance to TG. ADVANCES IN KNOWLEDGE: TACE + MWA can be used as a palliative treatment alternative for TACE + TG in patients with HCC, type Ⅱ-Ⅲ PVTT, and intolerance to TG.

Drug-eluting bead transarterial chemoembolization is an effective downstaging option for subsequent radical treatments in patients with hepatocellular carcinoma: A cohort study.

BACKGROUND: This study aimed to investigate the potential of drug-eluting bead transarterial chemoembolization (DEB-TACE) as downstaging therapy for subsequent radical treatment in patients with hepatocellular carcinoma (HCC). METHODS: Totally, 32 patients with unresectable HCC were enrolled, then they received DEB-TACE for down-staging therapy followed by radical treatments (surgery, radiofrequency ablation or microwave ablation). The rate of successful down-staging, treatment response (after DEB-TACE and radical therapy), alpha-fetoprotein (AFP), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: After down-staging therapy with DEB-TACE, successful down-staging rate was 59.4%. With the followed radical treatment, the complete response was 81.3%. Subsequent analysis indicated that CNLC stage (IIb vs. IIa) was an independent risk factor for successful down-staging. Furthermore, AFP level presented a declined trend throughout the time points (before DEB-TACE, after DEB-TACE, and after radical treatment). Additionally, 1-year, 2-year and 3-year accumulating PFS were 68.8%, 40.6% and 31.3%, respectively; 1-year, 2-year and 3-year accumulating OS were 84.4%, 71.9% and 53.1%, respectively. Kaplan-Meier curves exhibited that successful down-staging was correlated with longer PFS and OS, then further Cox's regression analysis verified that successful down-staging was an independent factor for predicting increased OS but not PFS. Besides, child-Pugh stage (B vs. A), CNLC stage (IIb vs. IIa) and AFP abnormal after radical treatment were independent factors for decreased PFS or OS. CONCLUSIONS: DEB-TACE has potential as an additionally effective down-staging therapy for radical treatments, and successful down-staging treatment by DEB-TACE associates with favorable survival profiles in patients with unresectable HCC.

Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable Pancreatic Carcinoma.

OBJECTIVE: To assess the safety and efficacy of the combination of recombinant adenovirus-p53 (rAd-p53) with radiochemotherapy for treating unresectable pancreatic carcinoma. METHODS: The eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy. Intratumoral injection of rAd-p53 was guided by B ultrasound. Radiochemotherapy consisted of intensity-modulated radiotherapy (IMRT) at two dose levels and intravenous gemcitabine (Gem). For radiotherapy, gross target volume (GTV) and clinical target volume (CTV) were 55-60 Gy and 45-55 Gy in 25-30 fractions, respectively. Concurrent intravenous gemcitabine was administered at 350 mg/m(2), weekly, for 6 weeks. The primary end points included toxicity, clinical benefit response (CBR) and disease control rate (DCR). The secondary end points included progression-free survival (PFS) and overall survival (OS). RESULTS: Fifteen eligible patients were enrolled. Eight patients (53.3%) were evaluated as CBR and 12 (80%) achieved DCR. The median PFS and OS were 6.7 and 13.8 months, respectively. One-year PFS and OS were 40.0% and 51.1%, respectively. There were 8 (53.3%) patients reported grade 3 toxicities including neutropenia (6 patients, 40%), fever (1 patient, 6.7%) and fatigue (1 patient, 6.7%). There was no grade 4 toxicity reported. CONCLUSION: Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated. Long-term follow-up is needed to confirm the improvement of PFS and OS.