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Simple Summary: Recently, favorable outcomes have been reported for hepatocellular carcinoma treated with transarterial chemoembolization (TACE) combined with lenvatinib (LEN-TACE). However, the optimal treatment protocol remains unclear. In this study, we performed a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE). The objective was to assess changes in tumor hemodynamics following the 4-day lenvatinib administration and to evaluate the outcomes of this combined therapy. A significant decrease in intra-tumor flow after lenvatinib was observed, with a 100% technical success rate and no severe adverse events. Complete response rates (CR) at 1 month were 75%, and the 12-month progression-free survival (PFS) rate was 75.0%. The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction radio by lenvatinib prior to TACE (r = −0.55). The short-term LEN-TACE is feasible and safe, demonstrating promising results, including a high CR rate and prolonged PFS. Aim: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. Methods: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4–12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. Results: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = −0.55). The 12-month progression-free survival (PFS) rate was 75.0%. Conclusions: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory. [ABSTRACT FROM AUTHOR]

Background: Efficacy of treatments for colorectal liver metastases after failure of first-line chemotherapy is limited. The aim of this study was to prospectively evaluate the feasibility, tolerability, and pharmacokinetics of selective transarterial chemoembolization (TACE) with irinotecan-loaded 40 μm microspheres combined with systemic FOLFIRI for colorectal liver metastases refractory to oxaliplatin regimen.Methods: The dose escalation study was conducted in three patient groups with different amounts of irinotecan loaded (50, 75 and 100 mg per mL-microspheres). Selective catheterization was performed to embolize subsegments or segments of located tumors using TACE navigation system. FOLFIRI was administrated 7 days after TACE. Plasma concentration was measured before and time points after administration.Results: Nine patients successfully underwent a total of 22 TACE procedures. Dose-limiting toxicity did not appear at any level. The overall response rate was 55.6%. The median progression free and overall survival were 8.1 and 18.2 months, respectively. The AUC and Cmax of plasma SN-38 per 1 mg injected irinotecan dose were significantly higher in irinotecan-loaded microspheres compared with FOLFIRI (P = 0.009 and P <  0.001, respectively).Conclusion: Selective TACE using 40 μm irinotecan-loaded microspheres combined with systemic FOLFIRI was feasible and safe even when a high dose of irinotecan was loaded. Irinotecan-loaded microspheres resulted in a higher plasma concentration and AUC of SN-38 than treatment with FOLFIRI. Further large scale trials to evaluate the efficacy are mandatory.Trial Registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, Registration number; UMIN000015367 ; Registered date; 08,10,2014. [ABSTRACT FROM AUTHOR]

We describe the clinical effects of short-term lenvatinib administration prior to conventional transarterial chemoembolization (cTACE) on tumor vasculature. Two patients with unresectable hepatocellular carcinoma underwent high-resolution digital subtraction angiography (DSA) and perfusion four-dimensional computed tomography during hepatic arteriography (4D-CTHA) before and after administration of lenvatinib treatment. The doses and periods of lenvatinib administration were, respectively, 12 mg/day for 7 days and 8 mg/day for 4 days. In both cases, high-resolution DSA revealed a decrease in dilatation and tortuosity of the tumor vessels. Furthermore, the tumor staining became more refined, and newly formed tiny tumor vessels were observed. Perfusion 4D-CTHA revealed a decrease in arterial blood flow to the tumor by 28.6% (from 487.9 to 139.5 mL/min/100 mg) and 42.5% (from 288.2 to 122.6 mL/min/100 mg) in the two cases, respectively. The cTACE procedure resulted in good lipiodol accumulation and complete response. Patients have remained recurrence-free for 12 and 11 months after the cTACE procedure, respectively. The administration of short-term lenvatinib in these two cases resulted in the normalization of tumor vessels, which likely led to improved lipiodol accumulation and a favorable antitumor effect. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, the indication for transarterial chemoembolization (TACE) of intermediate stage hepatocellular carcinoma (HCC) with a high tumor burden remains controversial. TACE has the advantage of a high possibility of achieving complete response (CR). This study aimed to clarify prognosis and identify predictors of CR by TACE in intermediate stage HCC beyond up-to-7 criteria. Overall, 56.9% of patients obtained CR, which contributed to prolonging survival. On multivariate analysis, the predictor of CR was HCC within up-to-11 criteria. In this study, the treatment strategy for intermediate stage HCC based on the 7–11 criteria is suggested. Aim: To clarify the prognosis and identify predictors for obtaining a complete response (CR) by transarterial chemoembolization (TACE) in intermediate stage HCC beyond up-to-7 criteria. Methods: Of the 120 patients with intermediate stage HCC who were treated by TACE as the initial treatment from February 2007 to January 2016, 72 finally matched the following inclusion criteria: beyond up-to-7 criteria; Child–Pugh score under 7; and no combined therapy within 4 weeks after the initial TACE. The CR rate and overall survival (OS) were evaluated. Logistic regression analysis was performed to identify predictors of CR. The deterioration of liver function after TACE was also evaluated. Results: The CR rate was 56.9%, and the overall median survival time (MST) was 37.7 months. The MST was 38.7 months in the CR group and 28.0 months in the non-CR group (p = 0.018). HCC within up-to-11 criteria was the only predictor of CR. The CR rate and MST were 70.7% and 37.7 months, respectively, in patients with HCC within up-to-11 criteria and 38.7% and 32.7 months, respectively, in the patients beyond up-to-11 criteria. Deterioration of the Child–Pugh score after the initial TACE and the 2nd TACE occurred in 24.2% and 12.0%, respectively, and deterioration of the modified albumin-bilirubin (mALBI) grade occurred in 17.6% and 7.4%, respectively. Conclusion: TACE can achieve high CR rates with prolonged overall survival for intermediate stage HCC beyond up-to-7 criteria. The predictor of CR was within up-to-11 criteria. Deterioration of liver function was not severe, but requires caution. Multidisciplinary approach as additional treatment after TACE is important. [ABSTRACT FROM AUTHOR]

Simple Summary: Transarterial chemoembolization (TACE) is the recommended treatment for intermediate-stage hepatocellular carcinoma (HCC), and its role as a curative treatment is now greater than previously due to the introduction of targeted molecular and immunotherapies. An important current concern is patient selection in TACE for intermediate-stage HCC, which includes an extremely heterogeneous population. The hepatobiliary phase (HEB) in gadoxetic acid disodium-enhanced MRI (EOB-MRI) is related to β-catenin, so EOB-MRI could be a molecular imaging biomarker reflecting tumor biology. Although HCC with signal heterogeneity in the HBP of EOB-MRI showed malignant behavior, no previous study has evaluated prognosis after TACE based on signal heterogeneity quantified in the HBP of EOB-MRI. In this study, we showed a quantitative analysis of tumor signal heterogeneity in HBP on EOB-MRI was valuable in predicting the prognosis after TACE and suggested a treatment strategy for patients with intermediate-stage HCC based on this quantitative evaluation. Background: In the era of local and systemic therapies for intermediate-stage hepatocellular carcinoma (HCC), personalized therapy has become available. The aim of our study was to evaluate the usefulness of quantitative analysis of pretreatment gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) to predict prognosis following transarterial chemoembolization (TACE). Methods: This retrospective study included patients with treatment-naïve intermediate-stage HCC who underwent EOB-MRI before the initial TACE and were treated by initial TACE between February 2007 and January 2016. Signal heterogeneity in the hepatobiliary phase (HBP) of EOB-MRI was quantitatively evaluated by the coefficient of variation (CV). The cutoff CV value was determined using the Classification and Regression Tree algorithm. Results: A total of 64 patients were enrolled. In multivariate analysis, High CV (≥0.16) was significantly associated with poor prognosis (p = 0.038). In a subgroup analysis of patients within up-to-7 criteria, MST was significantly shorter in the High CV group than in the Low CV group (37.7 vs. 82.9 months, p = 0.024). In patients beyond up-to-7 criteria, MST was 18.0 and 38.3 months in the High CV and Low CV groups, respectively (p = 0.182). In both groups scanned at 1.5 T or 3.0 T, High CV was significantly associated with poor prognosis (p = 0.001 and 0.003, respectively). Conclusion: CV of the tumor in the HBP of EOB-MRI is a valuable prognostic factor of TACE. [ABSTRACT FROM AUTHOR]