Radioembolization vs sorafenib in locally advanced hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score and Bayesian analysis.

OBJECTIVE: In this study we aimed to compare patient outcomes between the use of transarterial radioembolization (TARE) and sorafenib in patients with hepatocellular carcinoma (HCC) and intrahepatic portal vein tumor thrombosis (PVTT). METHODS: A total of 65 patients with HCC and intrahepatic PVTT treated in five Italian hospitals between 2012 and 2018 were included in the analysis. Those with any previous treatment, extension of PVTT to the main portal tract and extrahepatic involvement were excluded. Propensity score matching analysis and Bayesian model averaging analysis were performed. RESULTS: Of the 41 patients treated with TARE and 24 with sorafenib, 11 patients were downstaged to curative-intent surgery (liver transplant in three and hepatectomy in eight), including 10 treated with TARE and one with sorafenib. TARE was more effective than sorafenib in downstaging patients to surgery, achieving a mean survival of 54 months. In the 54 patients without downstaging after treatment, of whom 31 were treated with TARE and 23 with sorafenib, median survival was 20.3 and 9.1 months, respectively (P = 0.001), with different 1-, 2- and 3-year OS rates (64.5%, 42.6% and 37.3% vs 39.1%, 13.0% and 0%). Both propensity score and Bayesian model averaging confirmed an improvement in overall survival in the TARE group compared with sorafenib treatment. CONCLUSIONS: TARE was more effective than sorafenib in downstaging patients with HCC to surgery, providing a significant improvement in survival. Even in patients who were not downstaged to surgery, survival appeared to be superior with TARE over sorafenib.

Downstaging unresectable hepatocellular carcinoma by radioembolization using 90-yttrium resin microspheres: a single center experience.

BACKGROUND: Only one third of patients with hepatocellular carcinoma can benefit from curative treatments at the time of first diagnosis. Tumor downstaging by radioembolization may enable initially unresectable hepatocellular carcinoma (HCC) to be treated with surgery lengthening survival. METHODS: From June 2011 through June 2014, all patients with a first diagnosis of unresectable HCC with intrahepatic portal vein thrombosis were treated in our center with radioembolization using 90-yttrium resin microspheres. A 3-year enrollment period and a 5-year follow-up were planned to adequately investigate survivals. RESULTS: Twenty-four patients were enrolled, five were downstaged to surgery, eight did not reach downstaging but achieved partial response or stable disease, and eleven showed HCC progression despite radioembolization. High tumor absorbed radiation doses (454 vs. 248 and 138 Gy, P=0.005) and low serum AFP levels (53 vs. 1,447 and 4,603 ng/mL, P=0.05) were the variables significantly associated with successful downstaging. Mean and median survivals were 54, 30 and 11 months and 70, 24 and 11 months in the three groups respectively. No severe side effects were registered. CONCLUSIONS: In our center, about 20% of patients with locally advanced unresectable hepatocellular carcinoma were successfully downstaged to surgery after radioembolization. This strategy increases survival and is associated with an excellent safety profile.

PET-CT post therapy dosimetry in radioembolization with resin 90Y microspheres: Comparison with pre-treatment SPECT-CT 99mTc-MAA results.

Resin microspheres radioembolization is an effective treatment for liver tumors when the surgical option is not feasible. Doses delivered to tumor and normal liver can be assess in the pre-therapy phase by means of a 99mTc-MAA SPECT-CT simulation and after the treatment with 90Y PET-CT acquisition. The optimal therapeutic 90Y activity is determined on 99mTc-MAA SPECT-CT dose results in order to avoid healthy parenchyma toxicity and to effectively irradiate the tumor. The assumption of identical radiopharmaceutical distribution between simulation and verification is still under debate and literature data showed controversial results. In this study 10 HCC patient's dosimetry performed on 99mTc SPECT-CT and 90Y PET-CT were compared. Patients were selected when a good agreement between the pre and post-therapy distribution was observed in order to investigate the intrinsic dosimetric variations between the two imaging modalities. Mean doses (MIRD and Voxel approaches) showed a good correlation (Pearson's coefficient r > 0.90) both for tumor and normal liver. Dose Volume Histogram curves were compared with a good agreement particularly for normal liver (D50). Goal doses were achieved for 90% of patients. Bland-Altman analysis indicates lower variations for healthy parenchyma than for tumor (1.96 SD equal to 9.1 Gy and 68 Gy respectively) confirming the robustness of the dose-toxicity approach. PET-CT dosimetry well correlates with SPECT-CT doses (under assumption of same catheter position and 90Y activity). Better agreement was showed for 7/10 and 8/10 patients for T and NL respectively, confirming dosimetry as effective tool to optimize and individualize the treatment.

Short duration treatment in genotype 1 chronic hepatitis C patients with rapid virologic response to pegylated interferon plus ribavirin.

BACKGROUND: In patients with chronic hepatitis C, rapid HCV-RNA clearance under treatment might allow shorter treatment duration without modifying the sustained virological response (SVR) rate. This study evaluated the impact of rapid virological response (RVR) in HCV genotype 1b infection management. METHODS: In an open-label trial, 180 patients received standard doses of peginterferon alfa-2a plus ribavirin. Those with undetectable serum HCV-RNA at week 6 (RVR) received 24-week short-course treatment; patients with undetectable HCV-RNA at week 12 (early responders [ER]) received 48-week "standard of care" treatment; patients with positive HCV-RNA at week 12 (non-responders [NR]) stopped the treatment. Study end-point was to determine SVR rate at week 24. RESULTS: The following responses were observed: 24% RVR, 44% ER, 32% NR. Among RVR subjects, HCV-RNA baseline levels and age were significantly lower (P=0.038 and 0.035 respectively) than in non-RVR patients. At follow-up, 91% of RVR and 33% of ER patients achieved SVR. Among those with RVR, patients experiencing post-therapy relapse were older than those who achieved a SVR (P=0.028). CONCLUSIONS: Chronic HCV-1b patients, achieving RVR with a 24-week treatment regimen, attained excellent SVR rates. In a cost-effective therapeutic approach, all HCV-1b patients eligible for therapy may have a short duration therapy on the basis of RVR.

Combination therapy with amantadine and interferon in naïve patients with chronic hepatitis C: meta-analysis of individual patient data from six clinical trials.

BACKGROUND/AIMS: In chronic hepatitis C, clinical trials evaluating the efficacy of amantadine (AMA) and interferon (INF) compared to INF monotherapy, have produced conflicting results. We performed a meta-analysis of the individual patient's data from previous studies. METHODS: Nine hundred and seventy-two patients from six European centres were evaluated by means of individual patient meta-analysis, using mixed models with centres and the centre-treatment interaction fitted as random variables. RESULTS: At the end of therapy, virological responses were 38.5% (95% CI 34.1-42.8) after INF and AMA, and 29.5% (95% CI 25.5-33.6) after INF alone (P = 0.003). Sustained response occurred in 111 (23.1%; 95% CI 19.3-20.2) and 85 patients (17.3%; 95% CI 14.0-20.7), respectively (P = 0.03). Even accounting for the centre effect, therapy with AMA and INF was more effective than IFN alone (P = 0.029). When genotypes and viraemia levels were combined, the response rate after combination therapy doubled that observed with IFN alone in all subgroups, except those with low viraemia and genotypes 2 or 3. CONCLUSIONS: In chronic hepatitis C, therapy with AMA and INF is effective and may be an alternative to INF and ribavirin in patients who cannot tolerate ribavirin.

Re-treatment with interferon-beta of patients with chronic hepatitis C virus infection.

OBJECTIVE: To evaluate the efficacy of interferon-beta (IFN-beta) in the re-treatment of patients with chronic hepatitis C who did not respond to IFN-alpha monotherapy. PATIENTS AND METHODS: Thirty patients (24 men and six women; mean age, 41 +/- 13 (SD) years; range, 23-62 years), with chronic hepatitis C that was non-responsive to a standard course of IFN-alpha therapy, were re-treated with recombinant human IFN-beta-1a. All patients received IFN-beta, 12 MIU subcutaneously, three times weekly for 3 months, after which time patients' responses were evaluated. Responders (normal alanine aminotransferase, and negative for serum hepatitis C virus RNA) continued to receive IFN-beta, 12 MIU, for a further 3 months. Non-responders had their dose increased to 18 MIU for the remaining 3 months of treatment. After 6 months of treatment, therapy was stopped and patients were followed-up for a further 6 months. RESULTS: Overall, six (20%) of the 30 patients exhibited a response at the end of treatment. One patient (3.3%) maintained a sustained virological response at the end of post-treatment follow-up. CONCLUSIONS: Treatment with recombinant IFN-beta, at doses of up to 18 MIU for 6 months, is safe and well tolerated. However, the results of the trial do not support the use of IFN-beta monotherapy in patients with chronic hepatitis C that is resistant to IFN-alpha.

A randomized 4-arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C relapsing after interferon monotherapy.

To determine whether a higher dosage of interferon (IFN) and/or a prolonged time of administration may improve the efficacy of combination therapy, we conducted a 4-arm randomized trial on patients with chronic hepatitis C relapsing after 1 or more previous treatment courses with IFN monotherapy. Group A (n = 70) received 3 MU IFN alfa-2b 3 times per week plus ribavirin 1,000 mg/d for 12 months; group B (n = 70) received 5 MU 3 times per week plus ribavirin for 12 months; group C (n = 82) received 3 MU 3 times per week plus ribavirin for 6 months, and group D (n = 73) received 5 MU 3 times per week plus ribavirin for 6 months. The primary end point was the clearance of viremia at the end of 6-month follow-up: test results for hepatitis C virus (HCV)-RNA were negative in 54% of group A, 56% of group B, 40% of group C, and 49% of group D patients (P = NS). Among patients with genotype 1 and 4, the sustained response was significantly higher in groups A and B than in group C (45%, 49% vs. 22%, P =.03; group D = 33%, P = NS). In patients with genotype 2 and 3, the sustained virologic response was not affected by the different regimens (group A = 69%, group B = 68%, group C = 62%, group D = 71%, P = NS). In conclusion, duration of therapy rather than IFN dosage is more important in increasing the sustained virologic rate among HCV-positive patients with genotype 1 and 4 relapsing after IFN monotherapy; patients with genotypes 2 and 3 can be effectively retreated with a 6-month course of combination therapy, avoiding unnecessary side effects and waste of resources.