Analysis of Tumor Burden as a Biomarker for Patient Survival with Neuroendocrine Tumor Liver Metastases Undergoing Intra-Arterial Therapies: A Single-Center Retrospective Analysis.

PURPOSE: To assess the value of quantitative analysis of tumor burden on baseline MRI for prediction of survival in patients with neuroendocrine tumor liver metastases (NELM) undergoing intra-arterial therapies. MATERIALS AND METHODS: This retrospective single-center analysis included 122 patients with NELM who received conventional (n = 74) or drug-eluting beads, (n = 20) chemoembolization and radioembolization (n = 28) from 2000 to 2014. Overall tumor diameter (1D) and area (2D) of up to 3 largest liver lesions were measured on baseline arterially contrast enhanced MR images. Three-dimensional quantitative analysis was performed using the qEASL tool (IntelliSpace Portal Version 8, Philips) to calculate enhancing tumor burden (the ratio between enhancing tumor volume and total liver volume). Based on Q-statistics, patients were stratified into low tumor burden (TB) or high TB. RESULTS: The survival curves were significantly separated between low TB and high TB groups for 1D (p < 0.001), 2D (p < 0.001) and enhancing TB (p = 0.008) measurements, with, respectively, 2.7, 2.6 and 2.2 times longer median overall survival (MOS) in the low TB group (p < 0.001, p < 0.001 and p = 0.008). Multivariate analysis showed that 1D, 2D, and enhancing TB were independent prognostic factors for MOS, with respective hazard ratios of 0.4 (95%CI: 0.2-0.6, p < 0.001), 0.4 (95%CI: 0.3-0.7, p < 0.001) and 0.5 (95%CI: 0.3-0.8, p = 0.003). CONCLUSION: The overall tumor diameter, overall tumor area, and enhancing tumor burden are strong prognostic factors of overall survival in patients with neuroendocrine tumor liver metastases undergoing intra-arterial therapies.

Three-Dimensional Quantitative Tumor Response and Survival Analysis of Hepatocellular Carcinoma Patients Who Failed Initial Transarterial Chemoembolization: Repeat or Switch Treatment?

OBJECTIVES: The purpose of this study was to assess treatment responses and evaluate survival outcomes between responders and non-responders after each transarterial chemoembolization (TACE) session using the 3D quantitative criteria of the European Association for the Study of the Liver (qEASL) in hepatocellular carcinoma (HCC) patients. METHODS: A total of 94 consecutive patients who underwent MR imaging before and after TACE were retrospectively included. Volumetric tumor enhancement (qEASL) was expressed in cubic centimeters (cm3). The Kaplan-Meier method with the log-rank test was used to calculate the overall survival (OS) for the non-/responders. RESULTS: In total, 28 (29.8%) patients showed a response after the first TACE. These responders demonstrated a clear trend toward longer OS compared with the non-responders (36.7 vs. 21.5 months, p = 0.071). Of the 43 initial non-responders who underwent a second TACE within 3 months and had complete follow-up imaging, 15/43 (34.9%) achieved a response, and their median OS was significantly longer than that of the 28 non-responders to the second TACE (47.8 vs. 13.6 months, p = 0.01). Furthermore, there was no significant difference in OS between the 28 patients who achieved a response after the first TACE and the 15 initial non-responders who achieved a response after the second TACE (36.7 vs. 47.8 months, p = 0.701). The difference in OS between the responders and non-responders after the third TACE was not significant (11.4 months vs. 13.5 months, p = 0.986). CONCLUSION: Our study quantitatively demonstrated that a second TACE can be beneficial in terms of tumor response and survival for HCC patients who do not initially respond to TACE.

Predicting Infiltrative Hepatocellular Carcinoma Patient Outcome Post-TACE: MR Bias Field Correction Effect on 3D-quantitative Image Analysis.

Background and Aims: To investigate the impact of MR bias field correction on response determination and survival prediction using volumetric tumor enhancement analysis in patients with infiltrative hepatocellular carcinoma, after transcatheter arterial chemoembolization (TACE). Methods: This study included 101 patients treated with conventional or drug-eluting beads TACE between the years of 2001 and 2013. Semi-automated 3D quantification software was used to segment and calculate the enhancing tumor volume (ETV) of the liver with and without bias-field correction on multi-phasic contrast-enhanced MRI before and 1-month after initial TACE. ETV (expressed as cm3) at baseline imaging and the relative change in ETV (as % change, ETV%) before and after TACE were used to predict response and survival, respectively. Statistical survival analyses included Kaplan-Meier curve generation and Cox proportional hazards modeling. Q statistics were calculated and used to identify the best cut-off value for ETV to separate responders and non-responders (ETV cm3). The difference in survival was evaluated between responders and non-responders using Kaplan-Meier and Cox models. Results: MR bias field correction correlated with improved response calculation from baseline MR as well as survival after TACE; using a 415 cm3 cut-off for ETV at baseline (hazard ratio: 2.00, 95% confidence interval: 1.23-3.26, p=0.01) resulted in significantly improved response prediction (median survival in patients with baseline ETV <415 cm3: 19.66 months vs. ≥415 cm3: 9.21 months, p<0.001, log-rank test). A ≥41% relative decrease in ETV (hazard ratio: 0.58, 95%confidence interval: 0.37-0.93, p=0.02) was significant in predicting survival (ETV ≥41%: 19.20 months vs. ETV <41%: 8.71 months, p=0.008, log-rank test). Without MR bias field correction, response from baseline ETV could be predicted but survival after TACE could not. Conclusions: MR bias field correction improves both response assessment and accuracy of survival prediction using whole liver tumor enhancement analysis from baseline MR after initial TACE in patients with infiltrative hepatocellular carcinoma.

Intra-arterial therapy of neuroendocrine tumour liver metastases: comparing conventional TACE, drug-eluting beads TACE and yttrium-90 radioembolisation as treatment options using a propensity score analysis model.

OBJECTIVES: To compare efficacy, survival outcome and prognostic factors of conventional transarterial chemoembolisation (cTACE), drug-eluting beads TACE (DEB-TACE) and yttrium-90 radioembolisation (Y90) for the treatment of liver metastases from gastroenteropancreatic (GEP) neuroendocrine tumours (NELM). METHODS: This retrospective analysis included 192 patients (58.6 years mean age, 56% men) with NELM treated with cTACE (N = 122), DEB-TACE (N = 26) or Y90 (N = 44) between 2000 and 2014. Radiologic response to therapy was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) and World Health Organization (WHO) criteria using periprocedural MR imaging. Survival analysis included propensity score analysis (PSA), median overall survival (MOS), hepatic progression-free survival, Kaplan-Meier using log-rank test and the uni- and multivariate Cox proportional hazards model (MVA). RESULTS: MOS of the entire study population was 28.8 months. As for cTACE, DEB-TACE and Y90, MOS was 33.8 months, 21.7 months and 23.6 months, respectively. According to the MVA, cTACE demonstrated a significantly longer MOS as compared to DEB-TACE (p <.01) or Y90 (p = .02). The 5-year survival rate after initial cTACE, DEB-TACE and Y90 was 28.2%, 10.3% and 18.5%, respectively. CONCLUSIONS: Upon PSA, our study suggests significant survival benefits for patients treated with cTACE as compared to DEB-TACE and Y90. This data supports the therapeutic decision for cTACE as the primary intra-arterial therapy option in patients with unresectable NELM until proven otherwise. KEY POINTS: • cTACE achieved a significantly longer overall survival in patients with unresectable NELM. • Patients treated with cTACE showed a prolonged hepatic progression-free survival. • cTACE, DEB-TACE and Y90 radioembolisation demonstrated comparable safety and toxicity profiles. • Age >70 years, extrahepatic metastases and tumour burden >50% were identified as negative predictors. • Propensity score analysis suggests the superiority of cTACE over DEB-TACE and Y90.

The impact of antiangiogenic therapy combined with Transarterial Chemoembolization on enhancement based quantitative tumor response assessment in patients with hepatocellular carcinoma.

PURPOSE: To investigate whether bevacizumab compromises early response assessment after Transarterial Chemoembolization (TACE) in patients with hepatocellular carcinoma by 3D quantitative European Association for the Study of the Liver (qEASL) criteria in comparison to other imaging-based criteria. MATERIALS AND METHODS: Each of 14 patients receiving TACE and bevacizumab was matched with two patients receiving TACE alone. Baseline and Follow-up MRI was retrospectively analyzed regarding qEASL and other imaging-based criteria. RESULTS: Percentage-based qEASL achieved significant separation in both therapy arms (p=0.046 and p=0.015). Response and Overall Survival showed similar association among treatment groups (p=0.749). CONCLUSIONS: Anti-angiogenic therapy with bevacizumab does not impede early response assessment by qEASL.

Liver tissue classification in patients with hepatocellular carcinoma by fusing structured and rotationally invariant context representation.

This work addresses multi-class liver tissue classification from multi-parameter MRI in patients with hepatocellular carcinoma (HCC), and is among the first to do so. We propose a structured prediction framework to simultaneously classify parenchyma, blood vessels, viable tumor tissue, and necrosis, which overcomes limitations related to classifying these tissue classes individually and consecutively. A novel classification framework is introduced, based on the integration of multi-scale shape and appearance features to initiate the classification, which is iteratively refined by augmenting the feature space with both structured and rotationally invariant label context features. We study further the topic of rotationally invariant label context feature representations, and introduce a method for this purpose based on computing the energies of the spherical harmonic decompositions computed at different frequencies and radii. We test our method on full 3D multi-parameter MRI volumes from 47 patients with HCC and achieve promising results.

Transarterial Chemoembolization for the Treatment of Advanced-Stage Hepatocellular Carcinoma.

It remains controversial whether transarterial chemoembolization (TACE) should be performed in patients with advanced-stage hepatocellular carcinoma (HCC). The present large retrospective cohort study aimed to define the survival outcome following TACE of advanced HCC and to identify the prognostic factors. Five hundred eight patients with Barcelona Clinic Liver Cancer (BCLC) C-stage HCC, Child-Pugh A/B who were treated with TACE between November 1998 and December 2013 were identified. There was no significant difference in overall survival (OS) between patients with Eastern Cooperative Oncology Group (ECOG) 0 and those with ECOG ≥1 (10.5 months vs. 11.9 months, P = 0.87). The median OS of patients without portal vein tumor thrombosis (PVTT) was longer than that of patients with PVTT (16.9 vs. 6.1 months, P < 0.001). Child-Pugh B class, PVTT, extrahepatic metastasis, tumor size ≥5 cm, number of tumors ≥3, and alpha-fetoprotein ≥400 ng/dL were significantly associated with decreased survival and were used for determining the risk scores. All patients were divided into two groups (low-risk and high-risk groups) according to the cutoff value of 6.5 for risk scores. The patients with a value <6.5 (low-risk group) had significantly longer survival than those with >6.5 (high-risk group) (24.1 vs. 7.5 months, respectively; P < 0.001). TACE is an effective therapy for select patients with advanced stage HCC and may provide equal or improved survival as compared with reported outcomes with sorafenib. The results highlight the need for a differentiated approach to therapeutic recommendations for patients with BCLC C.

Improved Visibility of Metastatic Disease in the Liver During Intra-Arterial Therapy Using Delayed Arterial Phase Cone-Beam CT.

PURPOSE: To compare the visibility of liver metastases on dual-phase cone-beam CT (DP-CBCT) and digital subtraction angiography (DSA), with reference to preinterventional contrast-enhanced magnetic resonance imaging (CE-MRI) of the liver. METHODS: This IRB-approved, retrospective study included 28 patients with neuroendocrine (NELM), colorectal (CRCLM), or sarcoma (SLM) liver metastases who underwent DP-CBCT during intra-arterial therapy (IAT) between 01/2010 and 10/2014. DP-CBCT was acquired after a single contrast agent injection in the tumor-feeding arteries at early and delayed arterial phases (EAP and DAP). The visibility of each lesion was graded by two radiologists in consensus on a three-rank scale (complete, partial, none) on DP-CBCT and DSA images using CE-MRI as reference. RESULTS: 47 NELM, 43 CRCLM, and 16 SLM were included. On DSA 85.1, 44.1, and 37.5 % of NELM, CRCLM, and SLM, were at least partially depicted, respectively. EAP-CBCT yielded significantly higher sensitivities of 88.3 and 87.5 % for CRCLM and SLM, respectively (p < 0.01), but not for NELM (89.4 %; p = 1.0). On DAP-CBCT all NELM, CRCLM, and SLM were visible (p < 0.001). Complete depiction was achieved on DSA for 59.6, 16.3, and 18.8 % of NELM, CRCLM, and SLM, respectively. The complete depiction rate on EAP-CBCT was significantly higher for CRCLM (46.5 %; p < 0.001), lower for NELM (40.4 %; p = 0.592), and similar for SLM (25 %, p = 0.399). On DAP-CBCT however, the highest rates of complete depiction were found-NELM (97.8 %; p = 0.008), CRCLM (95.3 %; p = 0.008), and SLM (100 %; p < 0.001). CONCLUSION: DAP-CBCT substantially improved the visibility of liver metastases during IAT. Future studies need to evaluate the clinical impact.