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.

Safety and efficacy of Holmium-166 selective internal radiotherapy of primary and secondary liver cancer confirmed by real-world data.

Purpose: Holmium-166 has emerged as a promising option for selective internal radiotherapy (SIRT) for hepatic malignancies, but data on routine clinical use are lacking. The purpose of this study was to describe the safety and effectiveness of Holmium-166 SIRT in real-world practice through retrospective analysis of a multicenter registry. Methods: Retrospective analysis was conducted on Holmium-166 SIRT procedures performed between July 15, 2019, and July 15, 2021, across seven European centers. Treatment planning, treatment realization and post-treatment follow-up were conducted according to routine local practice. Safety and effectiveness data were extracted from the patients' health records. Primary endpoint analysis was assessed for the entire study population with separate analysis for subgroups with hepatocellular carcinoma, metastatic colorectal cancer and intrahepatic cholangiocarcinoma. Results: A total of 167 SIRT procedures in 146 patients (mean age 66 ± 11 years, 68% male) were retrospectively evaluated. Most common tumor entities were hepatocellular carcinoma (n=55), metastatic colorectal cancer (n=35), intrahepatic cholangiocarcinoma (n=19) and metastatic neuroendocrine tumors (n=10). Nine adverse events grade ≥ 3 according to Common Terminology Criteria for Adverse Events were recorded, including one fatal case of radioembolization-induced liver disease. Response rates and median overall survival for the above mentioned subgroups were comparable to results from previous Holmium-166 trials as well as to results from Yttrium-90 registries. Conclusion: This study confirms that the safety and effectiveness of Holmium-166 SIRT derived from prospective trials also applies in routine clinical practice, reinforcing its potential as a viable treatment option for primary and secondary liver cancer.

A Retrospective Cohort Analysis of Transarterial Chemoembolization for Hepatocellular Cancer at a Tertiary Center in Switzerland.

Background/Objectives: International guidelines recommend transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC). However, it is used outside these recommendations and has proven beneficial in prolonging survival. Since the role of TACE outside BCLC stage B is unclear, the present study analyzed the results of TACE performed at a tertiary center in Switzerland for different treatment groups, and aims to highlight the treatment outcomes for these groups. Methods: This retrospective cohort study includes 101 HCC patients undergoing TACE at our center. Patients were further subdivided into groups according to therapy combinations (therapies applied before and after index TACE). Kaplan-Meier survival curves were calculated for the Barcelona Center for Liver Cancer (BCLC) subgroups. Results: After TACE, the median survival was 28.1 months for BCLC 0, 31.5 months for BCLC A, 20.5 months for BCLC B, 10.8 for BCLC C, and 7.5 months for BCLC D. A lesion size larger than 55 mm was negatively associated with survival (HR 2.8, 95% CI 1.15-6.78). Complications occurred after TACE procedures: Clavien-Dindo I + II = 30, Clavien-Dindo > 3 = 2. Conclusions: TACE was performed in a substantial part of our cohort outside of routinely used treatment guidelines. The combination of the survival data and complication rate in these patients suggests it was a safe and beneficial strategy. Furthermore, our data show that in our cohort, the survival benefit associated with TACE was restricted to patients with a lesion size smaller than 55 mm.

CT-guided percutaneous marking of small pulmonary nodules with [99mTc]Tc-Macrosalb is very accurate and allows minimally invasive lung-sparing resection: a single-centre quality control.

PURPOSE: The detection of small lung nodules in thoracoscopic procedure is difficult when the lesions are not located within the outer border of the lung. In the case of ground-glass opacities, it is often impossible to palpate the lesion. Marking lung nodules using a radiotracer is a known technique. We analysed the accuracy and safety of the technique and the potential benefits of operating in a hybrid operating room. METHODS: 57 patients, including 33 (58%) females with a median age of 67 years (range 21-82) were included. In 27 patients, we marked and resected the lesion in a hybrid room. In 30 patients, the lesion was marked at the department of radiology the day before resection. [99mTc]Tc-Macrosalb (Pulmocis®) was used at an activity of 1 MBq in the hybrid room and at an activity of 3 MBq the day before to get technical feasible results. Radioactivity was detected using the Neoprobe® detection system. RESULTS: Precise detection and resection of the nodules was possible in 95% of the lesions and in 93% of the patients. Complete thoracoscopic resection was possible in 90% of the patients. Total conversion rate was 10%, but conversion due to failure of the marking of the nodule was observed in only 5% of the patients. Histology revealed 28 (37%) primary lung cancers, 24 (32%) metastases and 21 (28%) benign lesions. In 13 (23%) patients, minor complications were observed. None of them required additional interventions. CONCLUSION: The radio-guided detection of small pulmonary nodules is very accurate and safe after CT-guided injection of [99mTc]Tc-Macrosalb. Performing the operation in a hybrid room has several logistic advantages and allows using lower technetium-99m activities. The technique allows minimally invasive lung sparing resection and prevents overtreatment of benign and metastatic lesions.

Prognostic role of radiomics-based body composition analysis for the 1-year survival for hepatocellular carcinoma patients.

BACKGROUND: Parameters of body composition have prognostic potential in patients with oncologic diseases. The aim of the present study was to analyse the prognostic potential of radiomics-based parameters of the skeletal musculature and adipose tissues in patients with advanced hepatocellular carcinoma (HCC). METHODS: Radiomics features were extracted from a cohort of 297 HCC patients as post hoc sub-study of the SORAMIC randomized controlled trial. Patients were treated with selective internal radiation therapy (SIRT) in combination with sorafenib or with sorafenib alone yielding two groups: (1) sorafenib monotherapy (n = 147) and (2) sorafenib and SIRT (n = 150). The main outcome was 1-year survival. Segmentation of muscle tissue and adipose tissue was used to retrieve 881 features. Correlation analysis and feature cleansing yielded 292 features for each patient group and each tissue type. We combined 9 feature selection methods with 10 feature set compositions to build 90 feature sets. We used 11 classifiers to build 990 models. We subdivided the patient groups into a train and validation cohort and a test cohort, that is, one third of the patient groups. RESULTS: We used the train and validation set to identify the best feature selection and classification model and applied it to the test set for each patient group. Classification yields for patients who underwent sorafenib monotherapy an accuracy of 75.51% and area under the curve (AUC) of 0.7576 (95% confidence interval [CI]: 0.6376-0.8776). For patients who underwent treatment with SIRT and sorafenib, results are accuracy = 78.00% and AUC = 0.8032 (95% CI: 0.6930-0.9134). CONCLUSIONS: Parameters of radiomics-based analysis of the skeletal musculature and adipose tissue predict 1-year survival in patients with advanced HCC. The prognostic value of radiomics-based parameters was higher in patients who were treated with SIRT and sorafenib.

Impact of body composition in advanced hepatocellular carcinoma: A subanalysis of the SORAMIC trial.

BACKGROUND: Body composition parameters have been reported to be prognostic factors in patients with oncologic diseases. However, the available data on patients with HCC are conflicting. The aim of this study was to assess the impact of body composition on survival in patients with HCC treated with sorafenib or selective internal radioembolization (SIRT) and sorafenib. METHODS: This is an exploratory subanalysis of the prospective, randomized controlled SORAMIC trial. Within the palliative arm of the study, patients were selected if a baseline abdominal CT was available. A broad set of skeletal muscle and adipose tissue parameters were measured at the L3 level. Low skeletal muscle mass (LSMM) and density parameters were defined using published cutoffs. The parameters were correlated with overall survival. RESULTS: Of 424 patients in the palliative study arm, 369 patients were included in the analysis. There were 192 patients in the combined sorafenib/SIRT and 177 patients in the sorafenib group. Median overall survival was 9.9 months for the entire cohort and 10.8 and 9.2 months for the SIRT/sorafenib and sorafenib groups, respectively. There was no relevant association of either body composition parameter with overall survival in either the overall cohort or in the SIRT/sorafenib or sorafenib subgroups. CONCLUSIONS: This subanalysis of the prospective SORAMIC trial does not suggest a relevant influence of body composition parameters of survival in patients with advanced HCC. Body composition parameters therefore do not serve in patient allocation in this palliative treatment cohort.

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.

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.

Extrahepatic Disease in Hepatocellular Carcinoma: Do We Always Need Whole-Body CT or Is Liver MRI Sufficient? A Subanalysis of the SORAMIC Trial.

Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, multicenter, randomized controlled SORAMIC trial, two blinded readers independently analyzed the whole-body contrast-enhanced CT and gadoxetic acid-enhanced liver MRI data sets of 538 HCC patients. EHD (defined as tumor manifestation outside the liver) detection rates of the two imaging modalities were compared using multiparametric statistical tests. In addition, the most appropriate treatment recommendation was determined by a truth panel. Results: EHD was detected significantly more frequently in patients with portal vein infiltration (21% vs. 10%, p < 0.001), macrovascular infiltration (22% vs. 9%, p < 0.001), and bilobar liver involvement (18% vs. 9%, p = 0.006). Further on, the maximum lesion diameter in patients with EHD was significantly higher (8.2 cm vs. 5.8 cm, p = 0.002). CT detected EHD in significantly more patients compared to MRI in both reader groups (p < 0.001). Higher detection rates of EHD in CT led to a change in management only in one patient since EHD was predominantly present in patients with locally advanced HCC, in whom palliative treatment is the standard of care. Conclusions: Whole-body contrast-enhanced CT shows significantly higher EHD detection rates compared to hepatobiliary contrast liver MRI. However, the higher detection rate did not yield a significant impact on patient management in advanced HCC.

Endovascular embolization techniques in acute thoracic and abdominal bleedings can be technically reproduced and trained in a standardized simulation setting using SLA 3D printing: a 1-year single-center study.

BACKGROUND: Endovascular embolization techniques are nowadays well established in the management of acute arterial bleedings. However, the education and training of the next generation of interventionalists are still based on the traditional apprenticeship model, where the trainee learns and practices directly at the patient, which potentially affects the patient's safety. The objective of this study was to design and develop a standardized endovascular simulation concept for the training of acute bleeding embolizations, based on real-life cases. RESULTS: An adaptable and cost-effective endovascular simulator was developed using an in-house 3D print laboratory. All thoracic and abdominal acute bleeding embolizations over more than a year with appropriate pre-interventional computed tomography scans were included to manufacture 3D printed vascular models. A peristaltic pump was used to generate pulsatile flow curves. Forty embolization cases were engaged in this study, and 27 cases were fully reproduced in the simulation setting (69.23%). The simulation success was significantly lower in pulmonary embolizations (p = 0.031) and significantly higher in soft tissue (p = 0.032) and coil embolizations (p = 0.045). The overall simulation success was 7.8 out of 10 available points. CONCLUSIONS: Using stereolithography 3D printing in a standardized simulation concept, endovascular embolization techniques for treating acute internal hemorrhages in the chest and abdomen can be simulated and trained based on the patient-specific anatomy in a majority of the cases and at a broad spectrum of different causes.

Gadoxetic Acid-Based MRI for Decision-Making in Hepatocellular Carcinoma Employing Perfusion Criteria Only-A Post Hoc Analysis from the SORAMIC Trial Diagnostic Cohort.

The value of gadoxetic acid in the diagnosis of hepatocellular carcinoma (HCC), based on perfusion criteria, is under dispute. This post-hoc analysis of the prospective, phase II, randomized, controlled SORAMIC study compared the accuracy of gadoxetic acid-enhanced dynamic magnetic resonance imaging (MRI) (arterial, portovenous, and venous phase only) versus contrast-enhanced computed tomography (CT) for stratifying patients with HCC to curative ablation or palliative treatment. Two reader groups (radiologists, R1 and R2) performed blind reads of CT and gadoxetic acid-enhanced MRI (contrast dynamics only). A truth panel, with access to clinical and imaging follow-up data, served as reference. Primary endpoint was non-inferiority (margin: 5% points) of MRI vs. CT (lower 95% confidence interval [CI] > 0.75) in a first step and superiority (complete 95% CI > 1) in a second step. The intent-to-treat population comprised 538 patients. Accuracy of treatment decisions was 73.4% and 70.8% for CT (R1 and R2, respectively) and 75.1% and 70.3% for gadoxetic acid-enhanced dynamic MRI. Non-inferiority but not superiority of gadoxetic acid-enhanced dynamic MRI versus CT was demonstrated (odds ratio 1.01; CI 0.97-1.05). Despite a theoretical disadvantage in wash-out depiction, gadoxetic acid-enhanced dynamic MRI is non-inferior to CT in accuracy of treatment decisions for curative ablation versus palliative strategies. This outcome was not subject to the use of additional MR standard sequences.

Stimulatory MAIT cell antigens reach the circulation and are efficiently metabolised and presented by human liver cells.

OBJECTIVE: Mucosal-associated invariant T (MAIT) cells are the most abundant T cells in human liver. They respond to bacterial metabolites presented by major histocompatibility complex-like molecule MR1. MAIT cells exert regulatory and antimicrobial functions and are implicated in liver fibrogenesis. It is not well understood which liver cells function as antigen (Ag)-presenting cells for MAIT cells, and under which conditions stimulatory Ags reach the circulation. DESIGN: We used different types of primary human liver cells in Ag-presentation assays to blood-derived and liver-derived MAIT cells. We assessed MAIT cell stimulatory potential of serum from healthy subjects and patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt stent, and patients with inflammatory bowel disease (IBD). RESULTS: MAIT cells were dispersed throughout healthy human liver and all tested liver cell types stimulated MAIT cells, hepatocytes being most efficient. MAIT cell activation by liver cells occurred in response to bacterial lysate and pure Ag, and was prevented by non-activating MR1 ligands. Serum derived from peripheral and portal blood, and from patients with IBD stimulated MAIT cells in MR1-dependent manner. CONCLUSION: Our findings reveal previously unrecognised roles of liver cells in Ag metabolism and activation of MAIT cells, repression of which creates an opportunity to design antifibrotic therapies. The presence of MAIT cell stimulatory Ags in serum rationalises the observed activated MAIT cell phenotype in liver. Increased serum levels of gut-derived MAIT cell stimulatory ligands in patients with impaired intestinal barrier function indicate that intrahepatic Ag-presentation may represent an important step in the development of liver disease.

Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib.

BACKGROUND: The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. METHODS: Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. RESULTS: The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22-0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. CONCLUSION: OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.

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.

Persistent acute cholecystitis after cholecystostomy - increased mortality due to treatment approach?

BACKGROUND: Percutaneous cholecystostomy (PC) is a treatment option for acute cholecystitis (AC) in cases where cholecystectomy (CCY) is not feasible due to limited health conditions. The use of PC remains questionable. The aim was to retrospectively analyse the outcome of patients after PC. METHODS: All patients who underwent PC for AC at a tertiary referral hospital over 10 years were included. Descriptive statistics, analysed mortality with and without CCY after PC, and a multivariable logistic regression for potential confounder and a landmark sensitivity analysis for immortal time bias were used. RESULTS: Of 158 patients, 79 were treated with PC alone and 79 had PC with subsequent CCY. Without CCY, 48% (38 patients) died compared to 9% with CCY. In the multivariable analysis CCY was associated with 85% lower risk of mortality. The landmark analysis was compatible with the main analyses. Direct PC-complications occurred in 17% patients. Histologically, 22/75 (29%) specimens showed chronic cholecystitis, and 76% AC. CONCLUSION: Due to the high mortality rate of PC alone, performing up-front CCY is proposed. PC represents no definitive treatment for AC and should remain a short-term solution because of the persistent inflammatory focus. According to these findings, almost all specimens showed persistent inflammation.

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.

Supervised learning based on tumor imaging and biopsy transcriptomics predicts response of hepatocellular carcinoma to transarterial chemoembolization.

Although transarterial chemoembolization (TACE) is the most widely used treatment for intermediate-stage, unresectable hepatocellular carcinoma (HCC), it is only effective in a subset of patients. In this study, we combine clinical, radiological, and genomics data in supervised machine-learning models toward the development of a clinically applicable predictive classifier of response to TACE in HCC patients. Our study consists of a discovery cohort of 33 tumors through which we identify predictive biomarkers, which are confirmed in a validation cohort. We find that radiological assessment of tumor area and several transcriptomic signatures, primarily the expression of FAM111B and HPRT1, are most predictive of response to TACE. Logistic regression decision support models consisting of tumor area and RNA-seq gene expression estimates for FAM111B and HPRT1 yield a predictive accuracy of ∼90%. Reverse transcription droplet digital PCR (RT-ddPCR) confirms these genes in combination with tumor area as a predictive classifier for response to TACE.

Investigating difficult to detect pancreatic lesions: Characterization of benign pancreatic islet cell tumors using multiparametric pancreatic 3-T MRI.

INTRODUCTION: Pancreatic islet-cell tumors (PICT) often present with atypical signal-characteristics and are often missed on preoperative imaging. The aim of this study is to provide a multiparametric PICT characterization and investigate factors impeding PICT detection. MATERIAL AND METHODS: This is a detailed MRI analysis of a prospective, monocenter study, including 49 consecutive patients (37 female, 12 male; median age 50) with symptoms due to endogenous hyperinsulinemic hypoglycemia (EHH) and mostly negative prior-imaging. All patients received a 3-T MRI and a 68Ga-DOTA-exendin-4-PET/CT. Pooled accuracy, sensitivity, specificity and inter-reader agreement were calculated. Reference-standard was histopathology and 68Ga-DOTA-Exendin-4-PET/CT in one patient who refused surgery. For PICT analyses, 34 patients with 49 PICTs (48 histologically proven; one 68Ga-DOTA-exendin-4-PET/CT positive) were assessed. Dynamic contrast-enhanced (DCE) Magnetic Resonance Images (MRI) with Golden-Angle-Radial-Sparse-Parallel (GRASP) reconstruction, enabling imaging at high spatial and temporal resolution, was used to assess enhancement-patterns of PICTs. Tumor-to-background (T2B) ratio for each sequence and the employed quantitative threshold for conspicuity of PICTs were analyzed in regard to prediction of true-positive PICTs. RESULTS: Evaluation of 49 patients revealed a pooled lesion-based accuracy, sensitivity and specificity of 70.3%, 72.9% and 62.5%, respectively. Mean PICT size was 12.9±5.3mm for detected, 9.0±2.9mm for undetected PICTs (p-value 0.0112). In-phase T1w detected the most PICT (67.3%). Depending on the sequence, PICTs were isointense and poorly visible in 29-68%. Only 2/41(4.9%) PICTs showed typical signal-characteristics across T1w, T2w, DWI and ceT1w combined. 66.6% of PICTs enhanced simultaneously to the parenchyma, 17.8% early and 15.6% late. Predictor screening analysis showed number of sequences detecting a PICT, lesion size and in-phase T1w T2B ratio had the highest contribution for detecting a true-positive PICT. CONCLUSION: The majority of PICTs enhance simultaneously to surrounding parenchyma, present with atypical signal-characteristics and thus are poorly visible. In non-enhancing PICTs, radiologists should search for small lesions most likely conspicuous on unenhanced T1w or DWI.

Response prediction of hepatocellular carcinoma undergoing transcatheter arterial chemoembolization: unlocking the potential of CT texture analysis through nested decision tree models.

OBJECTIVES: To investigate if nested multiparametric decision tree models based on tumor size and CT texture parameters from pre-therapeutic imaging can accurately predict hepatocellular carcinoma (HCC) lesion response to transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: This retrospective study (January 2011-September 2017) included consecutive pre- and post-therapeutic dynamic CT scans of 37 patients with 92 biopsy-proven HCC lesions treated with drug-eluting bead TACE. Following manual segmentation of lesions according to modified Response Evaluation Criteria in Solid Tumors criteria on baseline arterial phase CT images, tumor size and quantitative texture parameters were extracted. HCCs were grouped into lesions undergoing primary TACE (VT-lesions) or repeated TACE (RT-lesions). Distinct multiparametric decision tree models to predict complete response (CR) and progressive disease (PD) for the two groups were generated. AUC and model accuracy were assessed. RESULTS: Thirty-eight of 72 VT-lesions (52.8%) and 8 of 20 RT-lesions (40%) achieved CR. Sixteen VT-lesions (22.2%) and 8 RT-lesions (40%) showed PD on follow-up imaging despite TACE treatment. Mean of positive pixels (MPP) was significantly higher in VT-lesions compared to RT-lesions (180.5 vs 92.8, p = 0.001). The highest AUC in ROC curve analysis and accuracy was observed for the prediction of CR in VT-lesions (AUC 0.96, positive predictive value 96.9%, accuracy 88.9%). Prediction of PD in VT-lesions (AUC 0.88, accuracy 80.6%), CR in RT-lesions (AUC 0.83, accuracy 75.0%), and PD in RT-lesions (AUC 0.86, accuracy 80.0%) was slightly inferior. CONCLUSIONS: Nested multiparametric decision tree models based on tumor heterogeneity and size can predict HCC lesion response to TACE treatment with high accuracy. They may be used as an additional criterion in the multidisciplinary treatment decision-making process. KEY POINTS: • HCC lesion response to TACE treatment can be predicted with high accuracy based on baseline tumor heterogeneity and size. • Complete response of HCC lesions undergoing primary TACE was correctly predicted with 88.9% accuracy and a positive predictive value of 96.9%. • Progressive disease was correctly predicted with 80.6% accuracy for lesions undergoing primary TACE and 80.0% accuracy for lesions undergoing repeated TACE.

Gadoxetic acid-based hepatobiliary MRI in hepatocellular carcinoma.

BACKGROUND & AIMS: SORAMIC is a prospective phase II randomised controlled trial in hepatocellular carcinoma (HCC). It consists of 3 parts: a diagnostic study and 2 therapeutic studies with either curative ablation or palliative Yttrium-90 radioembolisation combined with sorafenib. We report the diagnostic cohort study aimed to determine the accuracy of gadoxetic acid-enhanced magnetic resonance imaging (MRI), including hepatobiliary phase (HBP) imaging features compared with contrast-enhanced computed tomography (CT). The primary objective was the accuracy of treatment decisions stratifying patients for curative or palliative (non-ablation) treatment. METHODS: Patients with clinically suspected HCC underwent gadoxetic acid-enhanced MRI (HBP MRI, including dynamic MRI) and contrast-enhanced CT. Blinded read of the image data was performed by 2 reader groups (radiologists, R1 and R2). A truth panel with access to all clinical data and follow-up imaging served as reference. Imaging criteria for curative ablation were defined as up to 4 lesions <5 cm and absence of macrovascular invasion. The primary endpoint was non-inferiority of HBP MRI vs. CT in a first step and superiority in a second step. RESULTS: The intent-to-treat population comprised 538 patients. Treatment decisions matched the truth panel assessment in 83.3% and 81.2% for HBP MRI (R1 and R2), and 73.4% and 70.8% for CT. Non-inferiority and superiority (second step) of HBP MRI vs. CT were demonstrated (odds ratio 1.14 [1.09-1.19]). HBP MRI identified patients with >4 lesions significantly more frequently than CT. CONCLUSIONS: In HCC, HBP MRI provided a more accurate decision than CT for a curative vs. palliative treatment strategy. LAY SUMMARY: Patients with hepatocellular carcinoma are allocated to curative or palliative treatment according to the stage of their disease. Hepatobiliary imaging using gadoxetic acid-enhanced MRI is more accurate than CT for treatment decision-making.