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Therapeutic efficacy of lenvatinib for hepatocellular carcinoma with iso-high intensity in the hepatobiliary phase of Gd-EOB-DTPA-MRI.

ABSTRACT: Previous studies have reported that hepatocellular carcinoma (HCC) harboring WNT/β-catenin mutations exhibits iso-high intensity by gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI, i.e. EOB-MRI) during the hepatobiliary phase (HBP), thus indicating that EOB-MRI may help clinicians identify an immune exclusion class, which might not respond to treatment with immune checkpoint inhibitors. The present study analyzed the efficacy of lenvatinib for HCC with iso-high intensity during the HBP of EOB-MRI. Overall, 52 patients who underwent EOB-MRI for 140 HCC nodules were classified into iso-high-intensity and low-intensity groups during the HBP of EOB-MRI. The clinical and histological characteristics, and different responses to treatment of both groups were analyzed. The expression levels of β-catenin and glutamine synthetase, indicative of WNT/β-catenin mutations, were enhanced in the HCC with iso-high-intensity group. Nine patients had iso-high intensity, whereas 43 patients had low intensity. Tumor size was larger, and the levels of antagonist-II or vitamin K absence were higher in the iso-high-intensity group. Furthermore, 3/9 patients in the iso-high-intensity group had objective responses compared with 13/43 patients in the low-intensity group. Disease control was observed in 5/9 patients in the iso-high-intensity group and 26/43 patients in the low-intensity group. Median overall survival was 29.8 months for the iso-high-intensity group compared with 20.8 months for the low-intensity group. In the iso-high-intensity group, the median progression-free survival rate was 6.7 months compared with 5.6 months in the low-intensity group. No differences in best percentage change from baseline tumor size were observed in either group. Although few patients were included in this study, the present findings suggested that the efficacy of lenvatinib was unaffected by signal intensity during the HBP of EOB-MRI.

SUBMITTER: Kuwano A

PROVIDER: S-EPMC8764652 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundNuclear protein Ki-67 indicates the status of cell proliferation and has been regarded as an attractive biomarker for the prognosis of HCC. The aim of this study is to investigate which radiomics model derived from different sequences and phases of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI was superior to predict Ki-67 expression in hepatocellular carcinoma (HCC), then further to validate the optimal model for preoperative prediction of Ki-67 expression in HCC.MethodsThis retrospective study included 151 (training cohort: n = 103; validation cohort: n = 48) pathologically confirmed HCC patients. Radiomics features were extracted from the artery phase (AP), portal venous phase (PVP), hepatobiliary phase (HBP), and T2-weighted (T2W) images. A logistic regression with the least absolute shrinkage and selection operator (LASSO) regularization was used to select features to build a radiomics score (Rad-score). A final combined model including the optimal Rad-score and clinical risk factors was established. Receiver operating characteristic (ROC) curve analysis, Delong test and calibration curve were used to assess the predictive performance of the combined model. Decision cure analysis (DCA) was used to evaluate the clinical utility.ResultsThe AP radiomics model with higher decision curve indicating added more net benefit, gave a better predictive performance than the HBP and T2W radiomic models. The combined model (AUC = 0.922 vs. 0.863) including AP Rad-score and serum AFP levels improved the predictive performance more than the AP radiomics model (AUC = 0.873 vs. 0.813) in the training and validation cohort. Calibration curve of the combined model showed a good agreement between the predicted and the actual probability. DCA of the validation cohort revealed that at a range threshold probability of 30-60%, the combined model added more net benefit compared with the AP radiomics model.ConclusionsA combined model including AP Rad-score and serum AFP levels based on enhanced MRI can preoperatively predict Ki-67 expression in HCC.

Project description:ObjectivesThe accurate prediction of post-hepatectomy early recurrence in patients with hepatocellular carcinoma (HCC) is crucial for decision-making regarding postoperative adjuvant treatment and monitoring. We aimed to explore the feasibility of deep learning (DL) features derived from gadoxetate disodium (Gd-EOB-DTPA) MRI, qualitative features, and clinical variables for predicting early recurrence.MethodsIn this bicentric study, 285 patients with HCC who underwent Gd-EOB-DTPA MRI before resection were divided into training (n = 195) and validation (n = 90) sets. DL features were extracted from contrast-enhanced MRI images using VGGNet-19. Three feature selection methods and five classification methods were combined for DL signature construction. Subsequently, an mp-MR DL signature fused with multiphase DL signatures of contrast-enhanced images was constructed. Univariate and multivariate logistic regression analyses were used to identify early recurrence risk factors including mp-MR DL signature, microvascular invasion (MVI), and tumor number. A DL nomogram was built by incorporating deep features and significant clinical variables to achieve early recurrence prediction.ResultsMVI (p = 0.039), tumor number (p = 0.001), and mp-MR DL signature (p < 0.001) were independent risk factors for early recurrence. The DL nomogram outperformed the clinical nomogram in the training set (AUC: 0.949 vs. 0.751; p < 0.001) and validation set (AUC: 0.909 vs. 0.715; p = 0.002). Excellent DL nomogram calibration was achieved in both training and validation sets. Decision curve analysis confirmed the clinical usefulness of DL nomogram.ConclusionThe proposed DL nomogram was superior to the clinical nomogram in predicting early recurrence for HCC patients after hepatectomy.Key points• Deep learning signature based on Gd-EOB-DTPA MRI was the predominant independent predictor of early recurrence for hepatocellular carcinoma (HCC) after hepatectomy. • Deep learning nomogram based on clinical factors and Gd-EOB-DTPA MRI features is promising for predicting early recurrence of HCC. • Deep learning nomogram outperformed the conventional clinical nomogram in predicting early recurrence.

Project description:BackgroundGadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can detect more lesions through the image contrast of hepatobiliary phase. Body mass index (BMI) reflects the composition ratio of human tissue, which is an influencing factor of magnetic resonance image contrast. Meanwhile, Gd-EOB-DTPA is recommended to use the minimum dose when the diagnosis demands could be met. The aim of this paper was to investigate the effect of BMI on hepatobiliary phase image contrast and explore the feasibility of using low-dose Gd-EOB-DTPA to obtain good hepatobiliary phase image contrast in patients with normal and lean BMI.MethodsEighty-two patients who had previously undergone Gd-EOB-DTPA-enhanced MRI (0.025 mmol/kg) were collected and divided into group A (BMI <24 kg/m2) and group B (BMI ≥24 kg/m2) according to Chinese BMI standards. Liver-to-portal vein contrast ratio (LPC20) and liver-to-spleen contrast ratio (LSC20) in hepatobiliary phase (20 min after injection) were calculated. Thirty patients with a BMI <24 kg/m2 who were about to receive Gd-EOB-DTPA-enhanced MRI were randomly divided into group C (0.0125 mmol/kg) and group D (0.025 mmol/kg). Image acquisition was performed at 10, 15, and 20 min after injection. LPC10, LPC15, LPC20 and LSC10, LSC15, LSC20 in corresponding phases were calculated.ResultsIn retrospective grouping study, compared with group B, group A's LPC20 was significantly higher [2.63 (2.42-3.00) vs. 2.22 (1.97-2.67); P<0.01]. In prospective grouping study, there were no differences in LPC15, LSC15, LPC20 and LSC20 between group C and group D. Intragroup comparison in each group showed that LPC15 (group C: 2.67±0.33; group D: 2.61±0.21) and LPC20 (group C: 2.74±0.37; group D: 2.72±0.27) were higher than LPC10 (group C: 2.19±0.18; group D: 1.94±0.17) (all P<0.01), while there were no changes between LPC15 and LPC20.ConclusionsUnder conventional dose, hepatobiliary phase image contrast in patients with a BMI <24 was higher, which was mainly manifested in the high LPC. For patients with a BMI <24 kg/m2, using a half conventional dose (0.0125 mmol/kg), good hepatobiliary phase image contrast can still be obtained at 15-20 min after administration.

Project description:IntroductionImmune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation.MethodsA total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images.ResultsThe median PFS was 2.7 (95% confidence interval [CI]: 1.4-4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0-18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86-2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules.ConclusionThe TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.

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Therapeutic efficacy of lenvatinib for hepatocellular carcinoma with iso-high intensity in the hepatobiliary phase of Gd-EOB-DTPA-MRI.

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