Evaluation of Eosinophilic Cationic Protein as a Marker of Alveolar and Cystic Echinococcosis.

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus Echinococcus. In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein of eosinophilic granulocytes, against E. granulosus. Therefore, the main objective of this study was to evaluate ECP as a biomarker in the treatment of alveolar echinococcosis (AE) and cystic echinococcosis (CE). Data were collected retrospectively from the Vienna Echinococcosis Cohort over 7 years until December 2020. Altogether, 32 patients (16 AE and 16 CE) were included. In the selected patients, serum ECP values were compared before and after the beginning of an operative and/or benzimidazole (BMZ) therapy. Mean ECP serum levels before intervention were significantly (p < 0.05) elevated at 34.0 ± 22.9 µg/L in AE patients and at 38.6 ± 19.9 µg/L in CE patients compared to the control group. After the intervention, mean ECP levels decreased significantly (p < 0.05) to 20.4 ± 14.6 µg/L in AE patients and to 22.4 ± 8.3 µg/L in CE patients. Furthermore, ECP showed a significant (p < 0.05) correlation of k = 0.56 with PET-CTI. Based on the significant decrease after operative and/or BMZ treatment and the correlation with clinical markers such as PET-CTI, it is recommended to investigate ECP more intensively as a marker of AE and CE in prospective studies with larger cohorts.

Interim analysis of a real-world precision medicine platform for molecular profiling of metastatic or advanced cancers: MONDTI.

BACKGROUND: High-throughput genomic profiling of tumour specimens facilitates the identification of individual actionable mutations which could be used for individualised targeted therapy. This approach is becoming increasingly more common in the clinic; however, the interpretation of results from molecular profiling tests and efficient guiding of molecular therapies to patients with advanced cancer offer a significant challenge to the oncology community. EXPERIMENTAL DESIGN: MONDTI is a precision medicine platform for molecular characterisation of metastatic solid tumours to identify actionable genomic alterations. From 2013 to 2016, comprehensive molecular profiles derived from real-time biopsy specimens and archived tumour tissue samples of 295 patients were performed. Results and treatment suggestions were discussed within multidisciplinary tumour board meetings. RESULTS: The mutational profile was obtained from 293 (99%) patients and a complete immunohistochemical (IHC) and cytogenetic profile was obtained in 181 (61%) and 188 (64%) patients. The most frequent cancer types were colorectal cancer (12%), non-Hodgkin's lymphomas (9.8%) and head and neck cancers (7.8%). The most commonly detected mutations were TP53 (39%), KRAS (19%) and PIK3CA (9.5%), whereas ≥1 mutation were identified in 217 (74%) samples. Regarding the results for IHC testing, samples were positive for phospho-mammalian target of rapamycin (phospho-mTOR) (71%), epidermal growth factor receptor (EGFR) (68%), mesenchymal epithelial transition (MET) (56%) and/or platelet-derived growth factor alpha (PDGFRα)-expression (48%). Of the 288 tumour samples with one or more genetic alteration detected, 160 (55.6%) targeted therapy recommendations through 67 multidisciplinary tumour board meetings were made; in 69 (24%) cases, an individual treatment concept was initiated. CONCLUSIONS: The results reveal that the open concept for all solid tumours characterised for molecular profile and immunotherapy could not only match individualised treatment concepts at a high rate but also underscores the challenges encountered when offering molecularly matched therapies to a patient population with an advanced stage cancer.

Short- and long-term effects of transarterial chemoembolization on portal hypertension in patients with hepatocellular carcinoma.

Background: Transarterial chemoembolization (TACE) affects hepatic perfusion, and might have an impact on portal pressure in patients with hepatocellular carcinoma (HCC). Objective: The objective of this article is to report the secondary outcome "hepatic hemodynamics" from the AVATACE trial, a prospective randomized, placebo-controlled trial on the efficacy of conventional TACE in combination with bevacizumab or placebo. Methods: Hepatic venous pressure gradient (HVPG) was measured at baseline (prior to first TACE), within nine days ("acute effects"), two months ("intermediate effects") and six months ("long-term effects") after the first TACE. Results: Of 28 patients with early-intermediate stage HCC, n = 20 (71%) had clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) at baseline (median, 12 (interquartile range (IQR): 9-19) mmHg). TACE had neither "acute effects" nor "intermediate effects" on HVPG. However, in 13 patients with available HVPG measurement at month 6, there was a significant increase in HVPG (median, 16 (IQR: 11-19) mmHg) compared with baseline (median, 10 (IQR: 5-12) mmHg; p = 0.007). Portal hypertension-related complications occurred exclusively in patients with CSPH (8 (40%) vs 0). Conclusions: Repeated TACE was associated with a significant long-term increase in HVPG. This should be considered when deciding whether to continue with TACE or switch to systemic treatment, since CSPH drives the development of complications.

Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort.

BACKGROUND: Programmed cell death protein-1-targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. AIM: To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real-world cohort of patients with advanced hepatocellular carcinoma. METHODS: Sixty-five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut-off) across six centres in Austria and Germany were retrospectively analysed. RESULTS: Child-Pugh class A/B/C was 32 (49%)/28 (43%)/5 (8%). Immunotherapy was used as systemic first-/second-/third-/fourth-line treatment in 9 (14%)/27 (42%)/26 (40%)/3 (5%) patients. Fifty-four patients had at least one follow-up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12% and 49% respectively. Of 52 evaluable patients, four (8%) had hyperprogressive disease. Median time to progression was 5.5 (95% CI, 3.5-7.4) months, median progression-free survival was 4.6 (95% CI, 3.0-6.2) months, and median overall survival was 11.0 (95% CI, 8.2-13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child-Pugh A and B patients; however, median overall survival (OS) was shorter in Child-Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first-/second-line and third-/fourth-line respectively. CONCLUSIONS: Programmed cell death protein-1-targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child-Pugh stage B and patients with intensive pretreatment.

Results of the extended analysis for cancer treatment (EXACT) trial: a prospective translational study evaluating individualized treatment regimens in oncology.

BACKGROUND: The concept of personalized medicine defines a promising approach in cancer care. High-throughput genomic profiling of tumor specimens allows the identification of actionable mutations that potentially lead to tailored treatment for individuals' benefit. The aim of this study was to prove efficacy of a personalized treatment option in solid tumor patients after failure of standard treatment concepts. RESULTS: Final analysis demonstrates that 34 patients (62%) had a longer PFS upon experimental treatment (PFS1) when compared to previous therapy (PFS0); PFS ratio > 1.0 (p = 0.002). The median PFS under targeted therapy based on molecular profiling (PFS1) was 112 days (quartiles 66/201) and PFS0 = 61 days (quartiles 51/92; p = 0.002). Of the 55 patients, 31 (56%) showed disease control (DCR), consisting of 2 (4%) patients which achieved a complete remission, 14 (25%) patients with a partial remission and 15 (27%) patients who had a stabilization of disease. Median OS from start of experimental therapy was 348 days (quartiles 177/664). CONCLUSION: The prospective trial EXACT suggests that treatment based on real-time molecular tumor profiling leads to superior clinical benefit. MATERIALS AND METHODS: In this prospective clinical phase II trial, 55 cancer patients, after failure of standard treatment options, aimed to achieve a longer progression-free survival on the experimental treatment based on the individual's molecular profile (PFS1) when compared to the last treatment given before (PFS0). The personalized medicine approach was conceived to be clinical beneficial for patients who show a PFS ratio (PFS 1/PFS0) of > 1.0.

FDG-PET/MRI imaging for the management of alveolar echinococcosis: initial clinical experience at a reference centre in Austria.

BACKGROUND: [18 F]-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (FDG-PET/CT) imaging provides important information about the size and metabolic activity of lesions caused by Echinococcus multilocularis and is therefore recommended for the initial assessment and follow-up of human alveolar echinococcosis (AE). The introduction of positron emission tomography/magnetic resonance imaging (PET/MRI) into clinical practice in affluent health care systems provides an alternative dual imaging modality, which has not yet been evaluated for AE. OBJECTIVE: Here, we describe the initial clinical experience with comparative PET/CT and PET/MR imaging in four human AE patients at an Austrian reference centre. RESULTS: PET/MR imaging showed comparable diagnostic capacity for liver lesions attributable to E. multilocularis infection, with a discrepancy only in the assessment of calcifications in one patient. Effective doses of radiation were 30.4-31 mSV for PET/CT, which were reduced in PET/MRI to the exposure of 18 F-FDG only (4.9-5.5 mSv). CONCLUSIONS: PET/MRI provides comparable diagnostic information for AE management. The reduction in radiation exposure compared to PET/CT may be of particular importance for children and young patients not amenable for curative surgery requiring repeated long-term follow-up with dual imaging modalities. Further studies are warranted to prospectively evaluate the potential of PET/MRI in the management of AE.

DONNÉES DE BASE: L'imagerie par la tomographie par émission de positrons au [18F]-2-fluoro-2-désoxy-D-glucose (18F-FDG)/tomodensitométrie (TEP/TDM) fournit des informations importantes sur la taille et l'activité métabolique des lésions causées par Echinococcus multilocularis et est donc recommandée pour l'évaluation initiale et le suivi de l'échinococcose alvéolaire (EA) humaine. L'introduction de la tomographie par émission de positons/imagerie par résonance magnétique (TEP/IRM) dans la pratique clinique des systèmes de soins de santé aisés offre une alternative de modalité d'imagerie double, qui n'a pas encore été évaluée pour l'EA. OBJECTIF: Nous décrivons ici l'expérience clinique initiale comparant les imageries TEP/TDM et TEP/IRM chez quatre patients humains atteints d'EA dans un centre de référence autrichien. RÉSULTATS: L'imagerie TEP/IRM a montré une capacité de diagnostic comparable pour les lésions hépatiques imputables à une infection à E. multilocularis, avec une divergence uniquement lors de l'évaluation des calcifications chez un patient. Les doses efficaces de rayonnement étaient de 30,4 à 31 mSV pour la TEP/TDM, qui ont été réduites dans la TEP/IRM à une exposition au 18 F-FDG uniquement (4,9 à 5,5 mSv). CONCLUSIONS: La TEP/IRM fournit des informations de diagnostic comparables pour la prise en charge de l'EA. La réduction de l'exposition aux rayonnements comparée à la TEP/TDM pourrait avoir une importance particulière pour les enfants et les jeunes patients ne pouvant pas subir de chirurgie curative nécessitant un suivi répété à long terme avec des modalités de double imagerie. Des études supplémentaires sont nécessaires pour évaluer de manière prospective le potentiel de la TEP/IRM dans la prise en charge de l'EA.

Evaluation of direct costs associated with alveolar and cystic echinococcosis in Austria.

BACKGROUND: Cystic echinococcosis (CE) is a globally occurring zoonosis, whereas alveolar echinococcosis (AE) is endemic only in certain parts of the Northern Hemisphere. The socioeconomic impact of human echinococcosis has been shown to be considerable in highly endemic regions. However, detailed data on direct healthcare-related costs associated with CE and AE are scarce for high income countries. The aim of this study was to evaluate direct costs of human disease caused by CE and AE in Austria. METHODS: Clinical data from a registry maintained at a national reference center for echinococcosis at the Medical University of Vienna were obtained for the years 2012-2014. These data were used in conjunction with epidemiological data from Austria's national disease reporting system and diagnostic reference laboratory for echinococcosis to assess nationwide costs attributable to CE and AE. RESULTS: In Austria, total modelled direct costs were 486,598€ (95%CI 341,825€ - 631,372€) per year for CE, and 683,824€ (95%CI 469,161€ - 898,486€) for AE. Median costs per patient with AE from diagnosis until the end of a 10-year follow-up period were 30,832€ (25th- 75th percentile: 23,197€ - 31,220€) and 62,777€ (25th- 75th percentile: 60,806€ - 67,867€) for inoperable and operable patients, respectively. Median costs per patients with CE from diagnosis until end of follow-up after 10 years were 16,253€ (25th- 75th percentile: 8,555€ - 24,832€) and 1,786€ (25th- 75th percentile: 736€ - 2,146€) for patients with active and inactive cyst stages, respectively. The first year after inclusion was the most cost-intense year in the observed period, with hospitalizations and albendazole therapy the main contributors to direct costs. CONCLUSIONS: This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs.

Feasibility of personalized treatment concepts in gastrointestinal malignancies: Sub-group results of prospective clinical phase II trial EXACT.

OBJECTIVE: Advances in high-throughput genomic profiling and the development of new targeted therapies improve patient's survival. In gastrointestinal (GI) malignancies, the concept of personalized medicine (PM) was not investigated so far. The aim of this prospective study was to evaluate the efficacy of a personalized treatment in GI patients who failed standard treatment. METHODS: Out of the original prospective clinical phase II EXACT trial, 21 (38%) GI cancer patients who had no further treatment options were identified. A molecular profile (MP) via a 50 gene next generation sequencing (NGS) panel in combination with immunohistochemistry (IHC) was conducted using real-time biopsy tumor material. Results were discussed by a multidisciplinary team (MDT) to translate the individual MP in an experimental treatment. RESULTS: Of the 55 patients originally included in the EXACT trial, 21 (38%) suffered from GI malignancies. The final analysis showed that 15 (71%) patients had experienced a longer progression-free survival (PFS) upon experimental targeted treatment (124 d, quartiles 70/193 d), when compared with the PFS achieved by the previous conventional therapy (62 d, quartiles 55/83 d) (P=0.014). Thirteen (62%) patients receiving targeted treatment experienced a disease control according to Response Evaluation Criteria in Solid Tumors (RECIST). Median overall survival (OS) from the start of experimental therapy to time of censoring or death was 193 d (quartiles 115/374 d). CONCLUSIONS: PM was not investigated in GI malignancies so far in a prospective trial. This study shows that treatment based on real-time molecular tumor profiling led to a superior clinical benefit, and survival as well as response was significantly improved when compared with previous standard medications.

Post-hepatectomy liver failure after major hepatic surgery: not only size matters.

OBJECTIVES: To compare the value of functional future liver remnant (functFLR) to established clinical and imaging variables in prediction of post-hepatectomy liver failure (PHLF) after major liver resection. METHODS: This retrospective, cross-sectional study included 62 patients, who underwent gadoxetic acid enhanced MRI and MDCT within 10 weeks prior to resection of ≥ 4 liver segments. Future liver remnant (FLR) was measured in MDCT using semi-automatic software. Relative liver enhancement for each FLR segment was calculated as the ratio of signal intensity of parenchyma before and 20 min after i.v. administration of gadoxetic acid and given as mean (remnantRLE). Established variables included indocyanine green clearance, FLR, proportion of FLR, weight-adapted FLR and remnantRLE. functFLR was calculated as FLR multiplied by remnantRLE and divided by patient's weight. The association of measured variables and PHLF was tested with univariate and multivariate logistic regression analysis and receiver operator characteristics (ROC) curves compared with the DeLong method. RESULTS: Sixteen patients (25.8%) experienced PHLF. Univariate logistic regression identified FLR (p = 0.015), proportion of FLR (p = 0.004), weight-adapted FLR (p = 0.003), remnantRLE (p = 0.002) and functFLR (p = 0.002) to be significantly related to the probability of PHLF. In multivariate logistic regression analysis, a decreased functFLR was independently associated with the probability of PHLF (0.561; p = 0.002). Comparing ROC curves, functFLR showed a significantly higher area under the curve (0.904; p < 0.001) than established variables. CONCLUSIONS: functFLR seems to be superior to established variables in prediction of PHLF after major liver resection. KEY POINTS: • functFLR is a parameter combining volumetric and functional imaging information, derived from MDCT and gadoxetic acid enhanced MRI. • In comparison to other established methods, functFLR is superior in prediction of post-hepatectomy liver failure. • functFLR could help to improve patient selection prior major hepatic surgery.

Early response evaluation using CT-perfusion one day after transarterial chemoembolization for HCC predicts treatment response and long-term disease control.

PURPOSE: To determine the value of CT perfusion (CTP) for early response assessment after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between April 2013 and April 2015, 41 HCC (16 patients) were included in this study. CT perfusion was performed before and one day after TACE. Blood flow (BF), blood volume (BV), time to start (TTS), arterial liver perfusion (ALP), portal liver perfusion (PVP) and hepatic perfusion index (HPI) were measured. Quantitative perfusion values before and after TACE were compared to the response assessed using mRECIST criteria six weeks after TACE and long-term outcome was assessed. RESULTS: Twenty-one lesions (51%) had complete remission (CR) and five (12%) had partial response (PR) six weeks after TACE. CTP parameters were significantly reduced after TACE in responders (PR, CR, p<0.001) while no difference was observed in non-responders. ALPpost was superior in the prediction of CR compared to BFpost and BVpost (p<0.001) with a sensitivity, specificity, PPV, NPV, and accuracy of 90%, 90%, 91%, 90%, and 91%, respectively. Only 3/21 lesions with CR recurred, with a mean local-recurrence-free survival of 19.6 months. CONCLUSION: CT perfusion detects lesions with complete response one day after TACE, and is a feasible tool for early response assessment.

Intra-cystic concentrations of albendazole-sulphoxide in human cystic echinococcosis: a systematic review and analysis of individual patient data.

Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)-the first-line anthelminthic drug for medical treatment of CE-is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = -0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 µg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 µg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 µg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (ß = -17.2 µg/L/cm; 95th CI, -35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis.

How to STATE suitability and START transarterial chemoembolization in patients with intermediate stage hepatocellular carcinoma.

BACKGROUND & AIMS: We aimed to establish an objective point score to guide the decision for the first treatment with transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). METHODS: 277 patients diagnosed with HCC and treated with transarterial treatments between 1/2002 and 12/2011 at the Medical Universities of Vienna (training cohort) and Innsbruck (validation cohort) were included. We investigated the impact of baseline liver function and tumour load on overall survival (OS, log-rank test) and developed a point score (STATE-score: Selection for TrAnsarterial chemoembolisation TrEatment) in the training-cohort (n=131, Vienna) by using a stepwise Cox regression model. The STATE-score was externally validated in an independent validation cohort (n=146, Innsbruck) and thereafter combined with the Assessment for Retreatment with TACE (ART)-score to identify patients who are (un)suitable for TACE. RESULTS: The STATE-score starts with the serum-albumin level (g/L), which is reduced by 12 points each, if the tumour load exceeds the up-to-7 criteria and/or C-reactive protein (CRP) levels are ⩾1 mg/dl (maximum reduction: 24 points). The STATE-score differentiated 2 groups (<18, ⩾18 points) with distinct prognosis (median OS: 5.3 vs. 19.5 months; p<0.001) and a lower STATE-score was associated with short-term harm and increased mortality after TACE-1 (39% vs. 14% p<0.001). Sequential use of the STATE and the ART-score (START-strategy) identified the most (un)suitable patients for TACE. Results were confirmed in the external validation-cohort and were independent from recently proposed baseline selection tools. CONCLUSION: The STATE-score identifies patients who are (un)suitable for the first TACE. The START-strategy identified the best candidates for multiple TACE sessions.

Characterisation of inflammatory response, coagulation, and radiological findings in Katayama fever: a report of three cases at the Medical University of Vienna, Austria.

BACKGROUND: Katayama fever is an acute clinical condition characterised by high fever, dry cough and general malaise occurring during early Schistosoma spp. infection. It is predominantly reported in travellers from non-endemic regions. Whereas the immunological response to Schistosoma infection is well characterised, alterations in inflammatory markers and coagulation in response to acute infection are poorly understood. METHODS: Here we report the clinical, laboratory and radiological characteristics of three returning travellers with Katayama fever. Inflammatory markers and coagulation status were assessed repeatedly during follow-up to characterise the host response to infection. Radiographic findings were correlated with clinical and laboratory markers. RESULTS: Clinical symptoms were suggestive of a significant inflammatory response in all patients including high fever (>39°C), cough, and general malaise. Classical inflammatory markers including blood sedimentation rate, C-reactive protein, and serum amyloid A were only moderately elevated. Marked eosinophilia (33-42% of white blood cells) was observed and persisted despite anti-inflammatory and anthelminthic treatment for up to 32 weeks. Analysis of blood coagulation markers indicated increased coagulability reflected by elevated D-dimer values (0.57-1.17 µg/ml) and high thrombin generating potentials (peak thrombin activity: 311-384 nM). One patient showed particularly high levels of microparticle-associated tissue factor activity at initial presentation (1.64 pg/ml). Multiple pulmonary and hepatic opacities demonstrated by computed tomography (CT) scanning were associated with raised inflammatory markers in one patient. CONCLUSIONS: The characterisation of the inflammatory response, blood coagulation parameters and radiological findings in three patients adds to our current understanding of Katayama fever and serves as a starting point for further systematic investigations of the pathophysiology of this acute helminthic infection.

The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE.

BACKGROUND & AIMS: Recently, we developed the ART score (assessment for re-treatment with TACE) to guide the decision for a second transarterial chemoembolization (TACE-2) in patients with hepatocellular carcinoma (HCC). Patients with an ART score of 0-1.5 points gained benefit from a second TACE session, while patients with an ART score ≥2.5 points did not. Here, we investigated (1) the prognostic significance of the ART score prior to the third (TACE-3) and fourth TACE (TACE-4), and (2) the feasibility of an ART score guided re-treatment strategy by sequential assessment of the ART score in HCC patients treated with multiple TACE sessions. METHODS: 109 patients, diagnosed with intermediate stage HCC and treated with ≥3 TACE sessions between January 1999 and December 2009 at the Medical Universities of Vienna and Innsbruck, were included. The ART score prior to each TACE session was assessed in comparison to the TACE naïve liver. The prognostic performance of the ART score before TACE-3 and 4 was evaluated with and without stratification based on the ART score prior to the respective last intervention. RESULTS: The pre-TACE-3 ART score discriminated two groups with different prognosis and remained a valid predictor of OS independent of Child-Pugh score (5-7 points), CRP-levels and tumor characteristics. Even in patients with an initially beneficial ART score (0-1.5 points) before TACE-2, repeated ART score assessment before TACE-3 identified a subgroup of patients with dismal prognosis (median OS: 27.8 vs. 10.8 months, p<0.001). Similar results were observed when the ART score was applied before TACE-4. CONCLUSIONS: The sequential assessment of the ART score identifies patients with dismal prognosis prior to each TACE session.