Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial.

BACKGROUND: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. METHODS: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. DISCUSSION: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.

Underlying liver disease influences volumetric changes in the spared hemiliver after selective internal radiation therapy with 90Y in patients with hepatocellular carcinoma.

OBJECTIVE: Hypertrophy of the contralateral liver lobe after treatment with yttrium-90 ((90)Y) microspheres has recently been reported. This study aimed to quantify left hepatic lobe hypertrophy after right-sided radioembolization for hepatocellular carcinoma (HCC) and to identify pretreatment predictive factors of hypertrophy in an Asian population. METHODS: A retrospective review of patients with inoperable HCC undergoing selective internal radiation treatment (SIRT) with (90)Y microspheres at a single institution from January 2008 to January 2012 was performed. Only patients who had treatment delivered via the right hepatic artery alone were included. RESULTS: In all, 17 patients fulfilling the study criteria were identified. The mean percentage of left-lobe hypertrophy was 34.2% ± 34.9% (range 19.0-106.5%) during a median of 5-month follow-up. Patients with hepatitis B were found to experience a significantly greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis. There were no cases of acute liver failure after the administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. CONCLUSIONS: Administration of unilobar SIRT to the right liver lobe in patients with HCC resulted in a significant degree of contralateral left lobe hypertrophy. Patients with hepatitis B experienced a greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis.

Survival and pattern of tumor progression with yttrium-90 microsphere radioembolization in predominantly hepatitis B Asian patients with hepatocellular carcinoma.

PURPOSE: Intra-arterial yttrium-90 ((90)Y) microsphere radioembolization (RE) is an emerging treatment option with good outcomes reported predominantly in hepatitis C Western populations with hepatocellular carcinoma (HCC). We report outcomes in predominantly hepatitis B Asian patients treated with (90)Y-RE focusing on overall survival (OS), time to progression (TTP), tumor response, pattern of tumor recurrence and adverse events. Prognostic factors for survival were also identified. METHODS: A retrospective cohort study was conducted in a single tertiary institution. All non-trial patients treated with (90)Y-RE at our institution from 1 January 2008 to 30 June 2012 were included. RESULTS: Data from 103 consecutive patients were analyzed. The majority of patients were Child-Pugh class A (59.2 %) and Barcelona Clinic Liver Cancer (BCLC) stage C (68.9 %). Median OS was 14.4 months (95 % CI 11.0-22.2), which varied by disease stage: Child-Pugh A, 21.7 months; Child-Pugh B, 7.1 months; BCLC B, 23.8 months; BCLC C, 11.8 months. Response and disease control rates by RECIST 1.1 were 21.2 and 59.6 %, respectively, while disease control for index lesions treated with (90)Y-RE was 100 %. Development of new intrahepatic lesions was the main reason for eventual disease progression. Median overall TTP was 5.3 months (95 % CI 4.1-10.0). Pretreatment vascular invasion, low serum albumin and elevated total bilirubin levels predicted poorer survival. CONCLUSIONS: Survival outcomes in hepatitis B Asian patients treated with (90)Y-RE for HCC are comparable to hepatitis C Western populations. While disease control for lesions treated with (90)Y-RE is excellent, the development of new lesions suggests a role for concomitant systemic therapy.

Radioembolization with infusion of yttrium-90 microspheres into a right inferior phrenic artery with hepatic tumor supply is feasible and safe.

PURPOSE: To evaluate the feasibility and safety of yttrium-90 ((90)Y) radioembolization through the inferior phrenic arteries (IPAs). MATERIALS AND METHODS: Retrospective analysis of 108 patients referred for radioembolization to treat primary (n = 103) or secondary (n = 5) liver malignancy was performed. Five patients had malignant hepatic tumors supplied by the IPA and met criteria for infusion of (90)Y spheres into the IPA. Digital subtraction angiography (DSA), catheter-directed computed tomographic (CT) angiography, and technetium-99m ((99m)Tc) macroaggregated albumin (MAA) single photon emission CT (SPECT)/CT were used to plan treatment. Bremsstrahlung SPECT/CT was performed 1 day after radioembolization. Follow-up included clinical and biochemical tests and cross-sectional CT or magnetic resonance imaging. RESULTS: Parasitized extrahepatic arteries were detected in 37% of patients (n = 40). Of these, 62.5% (n = 25) had tumor supply through an IPA. Of the patients with IPA supply, 20% (n = 5) underwent infusion of (90)Y into the right IPA. Reasons for disqualifying patients from infusion into the IPA were less than 10% tumor supply (n = 11), failed catheterization of IPA (n = 3), arterioportovenous shunt (n = 2), failed identification of IPA on pretreatment angiography (n = 1), and gastric or esophageal enhancement on catheter-directed CT angiography (n = 3). In all five patients, technical success was demonstrated on (90)Y imaging, with no significant extrahepatic radionuclide activity. No adverse events related to IPA radioembolization occurred at mean follow-up of 4.5 months (range, 2.2-10.1 mo). CONCLUSIONS: Delivery of (90)Y microspheres through the right IPA is feasible and safe with the use of catheter-directed CT angiography in addition to DSA and (99m)Tc MAA SPECT/CT in patients with tumors with greater than 10% IPA supply.

A novel approach to brachytherapy in hepatocellular carcinoma using a phosphorous32 (32P) brachytherapy delivery device--a first-in-man study.

PURPOSE: While potentially very useful, percutaneously delivered brachytherapy of inoperable intra-abdominal solid tumors faces significant technical challenges. This first-in-man study is designed to determine the safety profile and therapeutic efficacy of a novel phosphorous (32P) brachytherapy device (BrachySil) in patients with unresectable hepatocellular carcinoma. METHODS AND MATERIALS: Patients received single percutaneous and transperitoneal implantations of BrachySil under local anesthesia directly into liver tumors under ultrasound or computed tomographic guidance, at an activity level of 4 MBq/cc of tumor. Toxicity was assessed by the nature, incidence, and severity of adverse events (Common Toxicity Criteria scores) and by hematology and clinical chemistry parameters. Target tumor response was assessed with computed tomographic scans at 12 and 24 weeks postimplantation using World Health Organization criteria. RESULTS: Implantations were successfully carried out in 8 patients (13-74 MBq, mean 40 MBq per tumor) awake and under local anesthesia. Six of the 8 patients reported 19 adverse events, but no serious events were attributable to the study device. Changes in hematology and clinical chemistry were similarly minimal and reflected progressive underlying hepatic disease. All targeted tumors were responding at 12 weeks, with complete response (100% regression) in three lesions. At the end of the study, there were two complete responses, two partial responses, three stable diseases, and one progressive disease. CONCLUSION: Percutaneous implantation of this novel 32P brachytherapy device into hepatocellular carcinoma is safe and well tolerated. A significant degree of antitumor efficacy was demonstrated at this low dose that warrants further investigation.