Defining textbook outcome for selective internal radiation therapy of hepatocellular carcinoma: an international expert study.

BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.

Non-hypervascular hepatobiliary phase hypointense lesions detected in patients with hepatocellular carcinoma: a post hoc analysis of SORAMIC trial to identify risk factors for progression.

OBJECTIVES: To identify clinical and imaging parameters associated with progression of non-hypervascular hepatobiliary phase hypointense lesions during follow-up in patients who received treatment for hepatocellular carcinoma. METHODS: A total of 67 patients with 106 lesions were identified after screening 538 patients who underwent gadoxetic acid-enhanced MRI within the SORAMIC trial. All patients were allocated to the trial treatment according to the trial scheme, and 61 of 67 patients received systemic treatment with sorafenib (either alone or combined with locoregional therapies) during the trial period. Follow-up images after treatment according to trial scheme were reviewed for subsequent hypervascularization or > 1 cm size increase. The correlation between progression and several imaging and clinical parameters was assessed using univariable and multivariable analyses. RESULTS: On a median 178 (range, 48-1072) days follow-up period, progression was encountered in 18 (16.9%) lesions in 12 (17.9%) patients. In univariable analysis size > 12.6 mm (p = 0.070), ECOG-PS (p = 0.025), hypointensity at T1-weighted imaging (p = 0.028), hyperintensity at T2-weighted imaging (p < 0.001), hyperintensity at DWI images (p = 0.007), and cirrhosis (p = 0.065) were correlated with progression during follow-up. Hyperintensity at T2 images (p = 0.011) was an independent risk factor for progression in multivariable analysis, as well as cirrhosis (p = 0.033) and ECOG-PS (p = 0.030). CONCLUSIONS: Non-hypervascular hepatobiliary phase hypointense lesions are associated with subsequent progression after treatment in patients with HCC. T2 hyperintensity, diffusion restriction, cirrhosis, and higher ECOG-PS could identify lesions with increased risk. These factors should be considered for further diagnostic evaluation or treatment of such lesions. KEY POINTS: • Non-hypervascular hepatobiliary phase hypointense lesions have considerable risk of progression in patients with hepatocellular carcinoma receiving treatment. • T2 hyperintensity, cirrhosis, ECOG-PS, and hyperintensity at DWI are associated with increased risk of progression. • Non-hypervascular hepatobiliary phase hypointense lesions should be considered in the decision-making process of locoregional therapies, especially in the presence of these risk factors.

Prognostic value of baseline imaging and clinical features in patients with advanced hepatocellular carcinoma.

AIMS: To investigate the prognostic value of baseline imaging features for overall survival (OS) and liver decompensation (LD) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with advanced HCC from the SORAMIC trial were evaluated in this post hoc analysis. Several radiological imaging features were collected from baseline computed tomography (CT) and magnetic resonance imaging (MRI) imaging, besides clinical values. The prognostic value of these features for OS and LD (grade 2 bilirubin increase) was quantified with univariate Cox proportional hazard models and multivariate Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS: Three hundred and seventy-six patients were included in this study. The treatment arm was not correlated with OS. LASSO showed satellite lesions, atypical HCC, peritumoral arterial enhancement, larger tumour size, higher albumin-bilirubin (ALBI) score, liver-spleen ratio <1.5, ascites, pleural effusion and higher bilirubin values were predictors of worse OS, and higher relative liver enhancement, smooth margin and capsule were associated with better OS. LASSO analysis for LD showed satellite lesions, peritumoral hypointensity in hepatobiliary phase, high ALBI score, higher bilirubin values and ascites were predictors of LD, while randomisation to sorafenib arm was associated with lower LD. CONCLUSIONS: Imaging features showing aggressive tumour biology and poor liver function, in addition to clinical parameters, can serve as imaging biomarkers for OS and LD in patients receiving sorafenib and selective internal radiation therapy for HCC.

Addition of Y-90 radioembolization increases tumor response and local disease control in hepatocellular carcinoma patients receiving sorafenib.

PURPOSE: To compare the treatment response and progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients who received sorafenib treatment either alone or combined with radioembolization (RE). METHODS: Follow-up images of the patients treated within a multicenter phase II trial (SORAMIC) were assessed by mRECIST. A total of 177 patients (73 combination arm [RE + sorafenib] and 104 sorafenib arm) were included in this post-hoc analysis. Response and progression characteristics were compared between treatment arms. Survival analyses were done to compare PFS and post-progression survival between treatment arms. Multivariate Cox regression analysis was used to compare survival with factors known to influence PFS in patients with HCC. RESULTS: The combination arm had significantly higher objective response rate (61.6% vs. 29.8%, p < 0.001), complete response rate (13.7% vs. 3.8%, p = 0.022), and a trend for higher disease control rate (79.2% vs. 72.1%, p = 0.075). Progression was encountered in 116 (65.5%) patients and was more common in the sorafenib arm (75% vs. 52.0%, p = 0.001). PFS (median 8.9 vs. 5.4 months, p = 0.022) and hepatic PFS were significantly better in the combination arm (9.0 vs. 5.7 months, p = 0.014). Multivariate analysis confirmed the treatment arm as an independent predictor of PFS. CONCLUSION: In advanced HCC patients receiving sorafenib, combination with RE has an additive anticancer effect on sorafenib treatment resulting in a higher and longer tumor response. However, the enhanced response did not translate into prolonged survival. Better patient selection and superselective treatment could improve outcomes after combination therapy.

Correlation of liver enhancement in gadoxetic acid-enhanced MRI with liver functions: a multicenter-multivendor analysis of hepatocellular carcinoma patients from SORAMIC trial.

OBJECTIVES: To evaluate the correlation between liver enhancement on hepatobiliary phase and liver function parameters in a multicenter, multivendor study. METHODS: A total of 359 patients who underwent gadoxetic acid-enhanced MRI using a standardized protocol with various scanners within a prospective multicenter phase II trial (SORAMIC) were evaluated. The correlation between liver enhancement on hepatobiliary phase normalized to the spleen (liver-to-spleen ratio, LSR) and biochemical laboratory parameters, clinical findings related to liver functions, liver function grading systems (Child-Pugh and Albumin-Bilirubin [ALBI]), and scanner characteristics were analyzed using uni- and multivariate analyses. RESULTS: There was a significant positive correlation between LSR and albumin (rho = 0.193; p < 0.001), platelet counts (rho = 0.148; p = 0.004), and sodium (rho = 0.161; p = 0.002); and a negative correlation between LSR and total bilirubin (rho = -0.215; p < 0.001) and AST (rho = -0.191; p < 0.001). Multivariate analysis confirmed independent significance for each of albumin (p = 0.022), total bilirubin (p = 0.045), AST (p = 0.031), platelet counts (p = 0.012), and sodium (p = 0.006). The presence of ascites (1.47 vs. 1.69, p < 0.001) and varices (1.55 vs. 1.69, p = 0.006) was related to significantly lower LSR. Similarly, patients with ALBI grade 1 had significantly higher LSR than patients with grade 2 (1.74 ± 0.447 vs. 1.56 ± 0.408, p < 0.001); and Child-Pugh A patients had a significantly higher LSR than Child-Pugh B (1.67 ± 0.44 vs. 1.49 ± 0.33, p = 0.021). Also, LSR was negatively correlated with MELD-Na scores (rho = -0.137; p = 0.013). However, one scanner brand was significantly associated with lower LSR (p < 0.001). CONCLUSIONS: The liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI is correlated with biomarkers of liver functions in a multicenter cohort. However, this correlation shows variations between scanner brands. KEY POINTS: • The correlation between liver enhancement on the hepatobiliary phase of gadoxetic acid-enhanced MRI and liver function is consistent in a multicenter-multivendor cohort. • Signal intensity-based indices (liver-to-spleen ratio) can be used as an imaging biomarker of liver function. • However, absolute values might change between vendors.

Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma.

BACKGROUND & AIMS: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function. METHODS: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up. RESULTS: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08). CONCLUSION: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy. CLINICAL TRIAL NUMBER: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.

Duration of response after DEB-TACE compared to lipiodol-TACE in HCC-naïve patients: a propensity score matching analysis.

OBJECTIVES: To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC). METHODS: We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated. RESULTS: Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01). CONCLUSION: Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR. KEY POINTS: • Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.

Radiomics of cholangiocarcinoma on pretreatment CT can identify patients who would best respond to radioembolisation.

OBJECTIVES: Results after trans-arterial radioembolisation (TARE) for intrahepatic cholangiocarcinoma (iCC) depend on the architecture of the tumour. This latter can be quantified through computed tomography (CT) texture analysis. The aims of the present study were to analyse relationships between CT textural features prior to TARE and objective response (OR), progression-free survival (PFS), and overall survival (OS). METHODS: Texture analysis was retrospectively applied to 55 pre-TARE CT scans of iCCs, focusing attention on the histogram-based features and the grey-level co-occurrence matrix (GLCM). Texture features were harmonised using the ComBat procedure. Objective response was assessed using the Response Evaluation Criteria In Solid Tumours 1.1. The least absolute shrinkage and selection operator (LASSO) method was applied to select the most useful textural features related to OR. RESULTS: Of the 55 patients, 53 had post-TARE imaging available, showing OR in 56.6% of cases. Texture analysis showed that iCCs showing OR after TARE had a higher uptake of iodine contrast in the arterial phase (higher mean histogram values, p < 0.001) and more homogeneous distribution (lower kurtosis, p = 0.043; GLCM contrast, p = 0.004; GLCM dissimilarity, p = 0.005, and higher GLCM homogeneity, p = 0.005; and GLCM correlation p = 0.030) at the pre-TARE CT scan. A favourable radiomic signature was calculated and observed in 15 of the 55 patients. The median PFS of these 15 patients was 12.1 months and that of the remaining 40 patients was 5.1 months (p = 0.008). CONCLUSIONS: Texture analysis of pre-TARE CT scans can quantify vascularisation and homogeneity of iCC architecture, providing clinical information useful in identifying ideal TARE candidates. KEY POINTS: • Hypervascular tumours with a more homogeneous uptake of iodine contrast in the arterial phase were those most likely to be effectively treated by TARE. • The arterial phase was observed to be the best acquisition phase for providing information regarding the "sensitivity" of the tumour to TARE. • Patients with favourable radiomic signature showed a median progression-free survival of 12.1 months versus 5.1 months of patients with an unfavourable signature (p = 0.008).

Yttrium-90 Radioembolization for Hepatocellular Carcinoma with Portal Vein Invasion: Validation of the Milan Prognostic Score.

The aim of the present study was to retrospectively analyze clinical outcomes of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) treated with yttrium-90 radioembolization stratified by Milan PVTT score according to PVTT extension, tumor burden, and bilirubin levels. Seventy patients were included and classified into good (n = 15; 21.4%), intermediate (n = 33; 47.1%), and dismal (n = 22; 31.4%) prognostic groups. Median overall survival durations were 24.6 mo, 13 mo (hazard ratio = 3.2; 95% confidence interval [CI], 1.2-9.7; P = .016), and 5.9 mo (hazard ratio = 4.1; 95% CI, 1.4-13.4; P = .0096), respectively. The Milan score represents an easy tool to select patients with HCC with PVTT who may benefit from radioembolization.

Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of sorafenib and selective internal radiation therapy (SIRT) - with yttrium-90 (90Y) resin microspheres - to sorafenib alone in patients with advanced HCC. METHODS: SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results, patients were assigned to local ablation or palliative cohorts. In the palliative cohort, patients not eligible for TACE were randomised 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. The primary endpoint was overall survival (OS; Kaplan-Meier analysis) in the intention-to-treat (ITT) population. RESULTS: In the ITT cohort, 216 patients were randomised to SIRT + sorafenib and 208 to sorafenib alone. Median OS was 12.1 months in the SIRT + sorafenib arm, and 11.4 months in the sorafenib arm (hazard ratio [HR] 1.01; 95% CI 0.81-1.25; p = 0.9529). Median OS in the per protocol population was 14.0 months in the SIRT + sorafenib arm (n = 114), and 11.1 months in the sorafenib arm (n = 174; HR 0.86; p = 0.2515). Subgroup analyses of the per protocol population indicated a survival benefit of SIRT + sorafenib for patients without cirrhosis (HR 0.46; 0.25-0.86; p = 0.02); cirrhosis of non-alcoholic aetiology (HR 0.63; p = 0.012); or patients ≤65 years old (HR 0.65; p = 0.05). Adverse events (AEs) of Common Terminology Criteria for AE Grades 3-4 were reported in 103/159 (64.8%) patients who received SIRT + sorafenib, 106/197 (53.8%) patients who received sorafenib alone (p = 0.04), and 8/24 (33.3%) patients who only received SIRT. CONCLUSION: Addition of SIRT to sorafenib did not result in a significant improvement in OS compared with sorafenib alone. Subgroup analyses led to hypothesis-generating results that will support the design of future studies. LAY SUMMARY: Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). In selective internal radiation therapy (SIRT), also known as radioembolisation, microscopic, radioactive resin or glass spheres are introduced into the blood vessels that feed the tumours in the liver. This study found that the addition of SIRT with 90yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafenib treatment alone. However, the results give an indication of how future studies using this combination therapy in people with advanced HCC could be designed. STUDY REGISTRATION: EudraCT 2009-012576-27, NCT0112 6645.

Ruptured Mycotic Aneurysm After Intravesical Instillation for Bladder Tumor.

BACKGROUND: Intravesical instillation of Bacillus Calmette-Guérin (BCG) is an effective and widely used treatment for patients with in situ bladder cancer. Major complications are quite uncommon, but a systemic dissemination of the attenuated strain of Mycobacterium bovis is possible. Few cases of aortic rupture caused by M bovis infection are described in literature. METHODS: A 70-year-old male, treated 3 months before with BCG instillation, presented to the emergency department because of a ruptured abdominal aortic aneurysm. The patient was hemodynamically stable, with a "hostile" abdomen. Therefore, an Endologix AFX endograft was deployed. During the postoperative period, his blood inflammatory markers increased, suspicious of a graft infection. Single-photon emission computed tomography (CT)/CT scan showed aortic increased uptake. Antibiotic therapy was continued, but after some days, the patient presented with hematemesis, and the CT scan showed an aortoenteric fistula. In emergency, the infected graft and aneurysm were removed, enteric fistula was closed, and an axillobifemoral bypass was performed. The patient died 25 days after endovascular aneurysm repair explantation. RESULTS: Despite the high suspicion of mycotic aortic aneurysm and graft infection by M bovis, there is no proof of this theory because of the absence of any positive culture test. M bovis is a slow-growing bacteria, and specific culture tests are required to identify it; indeed, all our blood and intraoperative samples were positive to other bacteria, probably the contaminant ones. CONCLUSIONS: Mycotic aneurysm is an extremely rare complication of intravesical BCG therapy, but it must be taken into consideration in patients with rapidly growing aortic aneurysms or rupture of a normal aorta, who have been previously submitted to this kind of instillation.

Trans-arterial radioembolization for intermediate-advanced hepatocellular carcinoma: a budget impact analysis.

BACKGROUND: Trans-arterial radio-embolization (TARE) is an emerging treatment for the management of hepatocellular carcinoma (HCC). TARE may compete with systemic chemotherapy, sorafenib, in intermediate stage patients with prior chemoembolization failure or advanced patients with tumoral macrovascular invasion with no extra-hepatic spread and good liver function. We performed a budget impact analysis (BIA) evaluating the expected changes in the expenditure for the Italian Healthcare Service within scenarios of increased utilization of TARE in place of sorafenib over the next five years. METHODS: Starting from patient level data from three oncology centres in Italy, a Markov model was developed to project on a lifetime horizon survivals and costs associated to matched cohorts of intermediate-advanced HCC patients treated with TARE or sorafenib. The initial model has been integrated with epidemiological data to perform a BIA comparing the current scenario with 20 and 80% utilization rates for TARE and sorafenib, respectively, with increasing utilization rates of TARE of 30, 40 and 50% over the next 1, 3 and 5 years. RESULTS: Compared to the current scenario, progressively increasing utilization rates of TARE over sorafenib in the next 5 years is expected to save globally about 7 million Euros. CONCLUSIONS: Radioembolization can be considered a valuable treatment option for patients with intermediate-advanced HCC. These findings enrich the evidence about the economic sustainability of TARE in comparison to standard systemic chemotherapy within the context of a national healthcare service.

Clinical outcomes with long-term sorafenib treatment of patients with hepatocellular carcinoma: a multicenter real-life study.

AIM: This multicenter field-practice study evaluates outcomes of long-term sorafenib in hepatocellular carcinoma (HCC) patients. METHODS: Consecutive HCC patients on sorafenib were enrolled. We evaluated those receiving sorafenib for ≥12 months. RESULTS: Out of 800 patients on sorafenib, 81 (10%) received long-term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6). Only 21 (26%) reported grade 3/4 adverse events. Complete response was reported in 11 patients (14%). Median overall survival was 34.8 months (95% CI: 29.9-44.3). Only baseline Child-Pugh class was associated with survival. CONCLUSION: Sorafenib could result in long-term control of HCC in a relevant proportion of patients. Given the availability of regorafenib in the second-line setting, an earlier introduction of systemic therapy may be considered according to clinical indications.

Trans-Arterial Radioembolization for Hepatocellular Carcinoma.

This article offers an overview of a new therapeutic option in hepatocellular carcinoma using trans-arterial radioembolization. In particular, it covers practical aspects of the technique and the currently available preliminary data in terms of disease control. We explore the potentials of radioembolization both in early and advanced stages of the disease, as single treatment and as companion to targeted agents such as sorafenib.

Identification of responders to sorafenib in hepatocellular carcinoma: is tumor volume measurement the way forward?

OBJECTIVES: Early assessment of hepatocellular carcinoma (HCC) response during sorafenib (SO) treatment is challenging, since tumor necrosis, extension and radiological appearance can be inhomogeneous. We evaluated the predictive value of different imaging criteria - such as Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), tumor density and volume variations - in the early follow-up of SO treatment. METHODS: The study included 22 patients. CT images from baseline and 2 months were reviewed to assess response according to RECIST 1.1, mRECIST, EASL, Choi's criteria (decreased tumor density by ≥15%) and arterial-enhancing tumor volume ratio; α-fetoprotein (AFP) variations were expressed as AFP ratio. RESULTS: The response criteria and volume measurements were reproducible (k > 0.80). The overall disease control rate was 40.9% by EASL and mRECIST, and 27.3% by RECIST 1.1; a ≥15% decrease in tumor density was observed in 9 patients (40.9%). The mean volume ratio was 1.73 ± 2.12, the mean AFP ratio 14 ± 37. The 1-year survival rate was 65.9%. Volume ratio was the only predictive factor for survival, with 1-year cumulative survival rates of 90% for volume ratios ≤1.1 and of 45.4% for volume ratios >1.1 (p = 0.04). CONCLUSIONS: Tumor volume measurements are reproducible and might provide an early predictive marker of response in HCC patients treated with SO.

Performance Evaluation of a Miniature and Disposable Endovascular Robotic Device.

PURPOSE: The LIBERTY® Robotic System is a miniature, single-use device designed to facilitate remote-controlled navigation to intravascular targets. We aim to evaluate the robot's performance to manipulate a range of microguidewires and microcatheters during percutaneous endovascular procedures. MATERIALS AND METHODS: Six interventional radiologists performed selective robotic-assisted catheterization of eight pre-determined vascular targets in a pig model. The navigation time from the guiding catheter tip to the target vessel was recorded. Each physician with a clinical experience of 20 years completed a questionnaire to evaluate the ease of use, accuracy, and safety of the robotic operation. RESULTS: Most of the physicians reached the vascular targets in less than one minute. There was no angiographic evidence of vascular injury such as artery laceration or contusion. All physicians reported consensus about the high performance of the robot. CONCLUSION: The miniature disposable robot is effective at reaching a range of vessels in a porcine model. Physicians found the device intuitive and easy to operate remotely.

Skeletal muscle quality predicts overall survival in advanced liver hepatocellular carcinoma treated with SIRT and sorafenib: A subanalysis of the SORAMIC trial.

BACKGROUND AND AIMS: Our purpose was to assess the impact of muscle quality on overall survival (OS) in patients with advanced HCC. METHODS: This is a subanalysis of the SORAMIC trial. Overall, 363 patients were included. The SIRT/Sorafenib treatment group comprised 182 patients and the sorafenib group 181 patients. Myosteatosis was defined as skeletal muscle density (SMD) < 41 HU for patients with a body mass index up to 24.9 kg/m2 and <33 HU for patients with a body mass index ≥25 kg/m2. Albumin-gauge score was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on clinical variables and OS, a Cox regression model was used. Hazard ratios are presented together with 95 % confidence intervals (95 % CI). Kaplan-Meier curves were used for survival analysis. RESULTS: In the SIRT/sorafenib cohort, low albumin-gauge score was an independent predictor of worse OS, HR = 1.74, CI 95% (1.16-2.62), p = 0.01. In the sorafenib cohort, muscle quality parameters did not predict OS. In alcohol-induced HCC (n = 129), myosteatosis independently predicted OS, HR = 1.85, CI 95% (1.10; 3.12), p = 0.02. In viral-induced HCC (n = 99), parameters of muscle quality did not predict OS. In patients with NASH/Non-alcoholic fatty liver disease (NAFLD) induced HCC, albumin-gauge score was a strong independent predictor of worse OS in the subgroup undergoing combined treatment with SIRT and sorafenib, HR = 9.86, CI 95% (1.12; 86.5), p = 0.04. CONCLUSIONS: Myosteatosis predicts independently worse OS in patients with alcohol-induced HCC undergoing combined treatment with SIRT and sorafenib. In patients with NASH/NAFLD induced HCC undergoing treatment with SIRT and sorafenib, albumin-gauge score predicts independently worse OS. IMPACT AND IMPLICATIONS: Associations between parameters of muscle quality and OS are different in accordance to the treatment strategy and etiology of HCC. These findings highlight the prognostic potential of skeletal muscle quality in patients with advanced HCC.

Predictive value of angiographic scores for the integrated management of the ischemic diabetic foot.

OBJECTIVE: To retrospectively evaluate the agreement between the angiographic scores and the clinical outcomes after endoluminal revascularization in diabetic patients with Fontaine stage IV critical limb ischemia (CLI). METHODS: Clinical and procedural data were retrospectively collected of consecutive diabetic patients with Fontaine stage IV CLI who underwent percutaneous lower limb endoluminal revascularization from January 2009 to June 2011. Pre- and postprocedural angiographic images were retrospectively reviewed to classify lower limb arterial involvement according to four systems: (1) TransAtlantic Inter-Society Consensus [TASC] I; (2) TASC II; (3) Graziani's morphologic classification; and (4) Joint Vascular Society Council calf and foot scores. Foot lesions were graded according to the University of Texas wound classification system. Clinical results (healing, nonhealing, or major amputation) were compared with baseline clinical data and angiographic results. RESULTS: In the study period, 202 percutaneous procedures were performed, with an immediate technical success rate of 94%. Preprocedurally, the mean ± standard deviation calf and foot scores were 7.8 ± 1.6 and 7.3 ± 2.3, respectively; 132 patients (65%) were in Graziani's morphologic classes from 4 to 7; in 112 (55%) cases, TASC II was considered inapplicable, for the absence of femoropopliteal lesions; and finally, 93% of limbs were classified as TASC I type D lesions. After the procedure, mean calf and foot scores were 4.8 ± 2.3 and 5.9 ± 2.6, respectively, and 87% of cases were in Graziani's classes 1 and 2; TASC II was inapplicable in all cases, whereas 80% of cases remained TASC I type D lesions. Healing rate was 67% and major amputation rate was 4%. Among all the clinical and angiographic variables included in the analysis, only pre- and postprocedural foot scores were significantly associated to the clinical outcome (P < .05). CONCLUSIONS: Endoluminal revascularization represents a valuable treatment option in diabetic patients with CLI. TASC classifications are inadequate to describe peripheral arterial involvement in the vast majority of diabetic patients with CLI. Pre- and postprocedural foot scores represent the most significant angiographic parameters to evaluate treatment success.

Contrast-enhanced magnetic resonance imaging of 102 nodules in cirrhosis: correlation with histological findings on explanted livers.

PURPOSE: To analyze Gd-EOB-DTPA-enhanced magnetic resonance (MR) findings of nodules (low-grade dysplastic nodules-LGDNs; high-grade dysplastic nodules-HGDN, and hepatocellular carcinoma-HCC), histologically identified on cirrhotic, explanted livers. METHODS: IRB approval was obtained for this study. Thirty-four patients underwent Gd-EOB-DTPA-enhanced MR examinations (1.5T system), that included 20-min delayed hepatobiliary (HB) phase imaging, before undergoing orthotopic liver transplantation (OLT; mean time MR-OLT: 2.7 months). A total of 102 hepatic nodules were identified and analyzed at histopathological examination, and classified as LGDN, HGDN, and HCC. Two radiologists by consensus performed a quantitative (enhancement ratios, ERs) and a qualitative analyses of signal intensities of identified nodules on vascular dynamic phases (30-35 s after injection-arterial phase; 180-190 s after injection late phase) and on HB phases. Correlation between nodules MR patterns and histological classification was analyzed by means of dedicated statistical software. RESULTS: No differences were appreciable among ERs of HGDN and HCCs on HB phase (P > 0.001). Lesions' enhancement on vascular dynamic and on HB phases significantly correlated to histological classification of nodules (P < 0.0001). Nodular hyperintensity on arterial phase and hypointensity on late phase were highly predictive for HCC (PPV 100%), with a moderate sensitivity (72.5%). Nodular hypointensity on HB phase was detected on 39/40 HCCs (sensitivity 97.5%) and in 21/30 HGDNs, whereas no LGDN showed it. CONCLUSIONS: Hyperenhancement on arterial phase and hypointensity on late phase are the most specific clues for the diagnosis of HCC. Hypointensity on HB phase shows a PPV of 100% in suggesting nodular premalignancy/malignancy, independently from nodular dynamic vascular enhancement.