Hepatocellular Carcinoma Lesions Research Articles

A combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound in the Kupffer phase for the diagnosis of well-differentiated hepatocellular carcinoma and atypical focal liver lesions: a prospective, multicenter study.

The objective of this study was to develop a combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound (CEUS) during the Kupffer phase and to evaluate its value in differentiating well-differentiated hepatocellular carcinoma (w-HCC) from atypical benign focal liver lesions (FLLs). A total of 116 patients with preoperatively Sonazoid-CEUS confirmed w-HCC or benign FLL were selected from a prospective multiple study on the clinical application of Sonazoid in FLLs conducted from August 2020 to March 2021. According to the randomization principle, the patients were divided into a training cohort and a test cohort in a 7:3 ratio. Seventy-nine patients were used for establishing and training the radiomics model and combined model. In comparison, 37 patients were used for validating and comparing the performance of the models. The diagnostic efficacy of the models for w-HCC and atypical benign FLLs was evaluated using ROCs curves and decision curves. A combined model nomogram was created to assess its value in reducing unnecessary biopsies. Among the patients, there were 55 cases of w-HCC and 61 cases of atypical benign FLLs, including 28 cases of early liver abscess, 16 cases of atypical hepatic hemangioma, 8 cases of hepatocellular dysplastic nodules (DN), and 9 cases of focal nodular hyperplasia (FNH). The radiomics model and combined model we established had AUCs of 0.905 and 0.951, respectively, in the training cohort, and the AUCs of the two models in the test cohort were 0.826 and 0.912, respectively. The combined model outperformed the radiomics feature model significantly. Decision curve analysis demonstrated that the combined model achieved a higher net benefit within a specific threshold probability range (0.25 to 1.00). A nomogram of the combined model was developed. The combined model based on the radiomics features of Sonazoid-CEUS in the Kupffer phase showed satisfactory performance in diagnosing w-HCC and atypical benign FLLs. It can assist clinicians in timely detecting malignant FLLs and reducing unnecessary biopsies for benign diseases.

Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy

BackgroundTo investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC.MethodsHCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging.ResultsThe average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from − 29.03% to 34.78%.ConclusionsCTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

A simple “spraying” fluorescence‐guided surgery by AIE probes for liver tumor resection through configuration‐induced cross‐identification

AbstractSurgical resection is the preferred option for hepatocellular carcinoma (HCC), but surgical navigation technology using indocyanine green still has some drawbacks such as non‐specific imaging, thus it is very important to develop new fluorescence imaging technology. All‐cis hexaphenyl‐1,3‐butadiene derivative (ZZ‐HPB‐NC) with aggregation‐induced emission (AIE) feature has been reported to be quickly turned‐on fluorescent response in the intraoperative frozen‐section slides of HCC. However, the probe did not respond to normal liver tissue around HCC. In order to enhance the diagnostic rate and elucidate the response mechanism, all‐trans configuration EE‐HPB‐NC, was furtherly synthesized. Within two minutes, non‐cancer tissues could be fluorescently labeled by EE‐HPB‐NC by spraying, showing the same effect with ZZ‐HPB‐NC to HCC. The results indicated that the configuration‐induced cross‐identification fluorescence imaging strategy was achieved through the combination of ZZ‐ and EE‐HPB‐NC. Then the mechanism of HPB‐NC localization in HCC lesions was explored, and the binding of HPB‐NC with specific proteins in cells resulted in the AIE effect to label HCC cells. On this basis, the accuracy of specific fluorescence imaging for HCC was further verified on the mouse hepatic neoplasm models, indicating that it has clinical application potential for surgical fluorescence real‐time navigation.

Outcomes of Liver Resection and Transarterial Chemoembolization in Patients with Multinodular BCLC-A Hepatocellular Carcinoma.

This study aimed to compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) in patients with multinodular hepatocellular carcinoma (HCC) within the Milan criteria who were not eligible for liver transplantation. We retrospectively analyzed 483 patients with multinodular HCC within the Milan criteria, who underwent either LR or TACE as an initial therapy between 2013 and 2022. The overall survival (OS) in the entire population and recurrence-free survival (RFS) in patients who underwent LR and TACE and achieved a complete response were analyzed. Propensity score (PS) matching analysis was also used for a fair comparison of outcomes between the two groups. Among the 483 patients, 107 (22.2%) and 376 (77.8%) underwent LR and TACE, respectively. The median size of the largest tumor was 2.0 cm, and 72.3% of the patients had two HCC lesions. The median OS and RFS were significantly longer in the LR group than in the TACE group (p <0.01 for both). In the multivariate analysis, TACE (adjusted hazard ratio [aHR], 1.81 and aHR, 2.41) and large tumor size (aHR, 1.43 and aHR, 1.44) were significantly associated with worse OS and RFS, respectively. The PS-matched analysis also demonstrated that the LR group had significantly longer OS and RFS than the TACE group (PS <0.05). In this study, LR showed better OS and RFS than TACE in patients with multinodular Barcelona Clinic Liver Cancer stage A HCC. Therefore, LR can be considered an effective treatment option for these patients.

Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV) infection is a risk factor for development of cirrhosis and cholangiocarcinoma. Currently, surgical resection remains the only curative treatment option for cholangiocarcinoma. We aim to study the impact of HCV infection on outcomes of liver resection (LR) in intrahepatic cholangiocarcinoma (ICC). To study the outcomes of curative resection of ICC in patients with HCV (i.e., HCV+) compared to patients without HCV (i.e., HCV-). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the outcomes of LR in ICC in HCV+ patients compared to HCV- patients in tertiary care hospitals. PubMed, EMBASE, The Cochrane Library and Scopus were systematically searched from inception till August 2023. Included studies were RCTs and non-RCTs on patients ≥ 18 years old with a diagnosis of ICC who underwent LR, and compared outcomes between patients with HCV+ vs HCV-. The primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence. Seven articles, published between 2004 and 2021, fulfilled the selection criteria. All of the studies were retrospective studies. Age, incidence of male patients, albumin, bilirubin, platelets, tumor size, incidence of multiple tumors, vascular invasion, bile duct invasion, lymph node metastases, and stage 4 disease were comparable between HCV+ and HCV- group. Alanine transaminase [MD 22.20, 95%confidence interval (CI): 13.75, 30.65, P < 0.00001] and aspartate transaminase levels (MD 27.27, 95%CI: 20.20, 34.34, P < 0.00001) were significantly higher in HCV+ group compared to HCV- group. Incidence of cirrhosis was significantly higher in HCV+ group [odds ratio (OR) 5.78, 95%CI: 1.38, 24.14, P = 0.02] compared to HCV- group. Incidence of poorly differentiated disease was significantly higher in HCV+ group (OR 2.55, 95%CI: 1.34, 4.82, P = 0.004) compared to HCV- group. Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+ group (OR 8.31, 95%CI: 2.36, 29.26, P = 0.001) compared to HCV- group. OS was significantly worse in the HCV+ group (hazard ratio 2.05, 95%CI: 1.46, 2.88, P < 0.0001) compared to HCV- group. This meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC who underwent curative resection compared to HCV- patients.

Abstract 2583: [68Ga]Ga-RYZ-GPC3: A glypican-3 targeted diagnostic radiopharmaceutical for hepatocellular carcinoma molecular imaging

Abstract Introduction &amp; Purpose: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. To date, the imaging of HCC is difficult, insufficient for disease staging and barely improved over the past decades. Glypican-3 (GPC3) is a cell-surface receptor highly expressed by HCC and of diagnostic and prognostic value. GPC3 has been reported as potential target for diagnosis and treatment of HCC for nuclear theranostics. RYZ-GPC3 is a DOTA modified macrocyclic peptide with high affinity for GPC3, which may allow PET imaging or nuclear therapy. Here we report the first clinical results of [68Ga]Ga-RYZ-GPC3 PET-imaging in patients with known or suspected HCC. Methods: [68Ga]Ga-RYZ-GPC3 was obtained upon labeling the peptide precursor with 68Ga from a 68Ge/68Ga-generator and heating till 90⁰C for 10 min followed by sterile filtration. After administration of 2 MBq/kg [68Ga]Ga-RYZ-GPC3, a 60 min dynamic PET scan was acquired or multiple static PET/CT were acquired at 20 min, 1, 2 and 4 hours. Besides qualitative interpretation, standardized uptake values (SUVmax, SUVmean) were measured in various compartments; HCC lesions, healthy liver (HL), kidneys, blood pool activity in the left ventricle (BP) and gastric fundus. Additionally, tumor-to-healthy liver ratios (TLR) were calculated: SUVmean,HCC divided by SUVmean,HL. Results: Radiolabeling to obtain [68Ga]Ga-RYZ-GPC3 was near quantitative, making the production highly reliable. Eleven patients (4 patients dynamic; 7 patients static protocol) were scanned. One patient did not have an HCC. Another patient had a concurrent metastatic prostate adenocarcinoma, which did not show uptake, both qualitatively and quantitatively. All HCC lesions showed uptake in qualitative assessment, even in immunohistochemistry confirmed GPC3-negative HCC lesions (3 lesions). In 23 HCC lesions, including the aforementioned GPC3-negative lesions, mean SUVmax was 17.9 (range 2.7-95.3) and mean SUVmean was 10.2 (range 1.0-49.2) at 60 minutes. Uptake in HL and BP decrease over time and become negligible 45 minutes after administration (SUVmean &amp;lt;1.5). The opposite occurs for HCC and TLR, which continuously increase up to 4 hours after administration (TLR 4.4 to 19.2, at 18 minutes and 4 hours respectively). In individual lesion analysis, TLR was the highest at 60 or 120 minutes post-injection scans. Uptake in the gastric fundus, gradually increases in the first hour, and decreases gradually afterwards (SUVmean from 4.0 to 12.7, back to 10.1). Conclusions: [68Ga]Ga-RYZ-GPC3 is the first peptide based PET tracer that allows the high quality molecular imaging of HCC. Thereby [68Ga]Ga-RYZ-GPC3 is suitable for the selective diagnosis of HCC. In addition, based on the biodistribution and in vivo dynamics on these diagnostic images, RYZ-GPC3 is very likely to hold therapeutic potential upon labeling with a therapeutic isotope (e.g 177Lu or 225Ac). Citation Format: Arthur J.A.T. Braat, Alex J. Poot, Constantin Lapa, Marnix G.E.H. Lam, Wolfgang A. Weber, Anna Karmann, Ye Yuan, Jessica Rearden, Ken Song, Ralph A. Bundschuh. [68Ga]Ga-RYZ-GPC3: A glypican-3 targeted diagnostic radiopharmaceutical for hepatocellular carcinoma molecular imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2583.

Abstract 2585: First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma

Abstract Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The American Association for the Study of Liver Disease recommends surveillance for high-risk individuals with abdominal ultrasound, triple phase contrast CT or MRI. However, these imaging techniques have limited sensitivity in classifying lesions smaller than 2 centimeters. The use of [18F]FDG Positron Emission Tomography (PET) is constrained due to insufficient uptake by HCC lesions over background liver uptake. Hence, there is an urgent need for more precise radiotracers for HCC. This study introduces the development of a novel radiotracer that binds to glypican-3 (GPC3), a cell membrane-anchored oncofetal protein overexpressed in HCC with minimal normal tissue expression. Methods: [68Ga]Ga-RYZ-GPC3 is composed of a small macrocyclic peptide binder with high affinity to GPC3 linked with a tetraxetan moiety capable of chelating a variety of radioisotopes including positron-emitting 68Ga and other radiometals. The unlabeled binder to GPC3 was synthesized by the sponsor and provided to three imaging centers in India as part of investigator-initiated trials reviewed and approved by each site’s institutional review board and ethics committee. Labeling with 68Ga and quality checks of the product was performed locally at each center. Patients with high clinical suspicion or with confirmed HCC who gave informed consent received injections of 1.5-5.5 mCi of [68Ga]Ga-RYZ-GPC3 and underwent PET-CT scanning at predetermined intervals. Some patients underwent companion [18F]FDG PET-CT scans in accordance with local guidelines. Results: A total of 64 patients underwent [68Ga]Ga-RYZ-GPC3 PET-CT scans. The median age within the cohort was 61 (41-83), 22% were female. Liver cirrhosis was present in 72% of patients, attributed to hepatitis B, hepatitis C or NASH in 17%, 13% and 20% of cases. Notably, 92% of patients exhibited at least one positive lesion on [68Ga]Ga-RYZ-GPC3 scans. The median SUVmax of GPC3-avid liver lesions was 15.5 (range 1.1 to 137.0) while the median liver SUVmean was 1.6 (0.3-7.9). Physiologic uptake was predominantly observed in the kidneys, the primary route of clearance, with a median SUVmean of 10.9 (2.2-20.7). Additionally, 20 patients underwent [18F]FDG PET-CT scan for comparison. The median SUVmax of lesions on 68Ga-RYZ-GPC3 vs [18F]FDG PET was 11.0 (1.1-137.0) vs 3.8 (1.2-12.2). Conclusion: Early human imaging results in patients with HCC indicate that [68Ga]Ga-RYZ-GPC3 has high tumor lesion specificity compared to normal liverand demonstrates the potential of [68Ga]Ga-RYZ-GPC3 to improve detection of HCC over conventional [18F]FDG PET-CT. In addition, the binder could be complexed with a therapeutic radioisotope as a novel targeted therapeutic option for HCC. Further investigation of this first-in-class binder to HCC is warranted. Citation Format: Chandresakhar Bal, Sanjana Ballal, Kumar Kallur, Anna Karmann, Ye Yuan, Jessica Rearden, Kathryn Shah, Charlotte Lorenz, Susan Moran, Ken Song, Ishita Sen. First in human study with a novel peptide binder to glypican-3, demonstrates high specificity as a PET imaging agent in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2585.

Multiparametric magnetic resonance imaging for hepatocellular carcinoma, part1 : Morphology and dynamic perfusion imaging in primary diagnostics and treatment monitoring

Radiology plays akey role in the diagnosis and monitoring of hepatocellular carcinoma (HCC). Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are used to identify HCC lesions. Multiparametric MRI provides detailed insights into the tumor biology through the analysis of morphology, perfusion and diffusion. In this way preoperative decisions can be optimized. The guidelines recommend using contrast-enhanced MRI or ultrasound for the diagnosis of HCC. The preferred method is MRI due to its superiority in the detection of small lesions The treatment response is evaluated using modified response evaluation criteria for solid tumors (RECIST) and the European Association for the Study of the Liver (EASL) criteria. The use of multiparametric MRI in conjunction with the liver imaging reporting and data system (LI-RADS) plays overall acentral role in the precise diagnosis and monitoring of the treatment of HCC.

Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.

Automatic segmentation of hepatocellular carcinoma on dynamic contrast-enhanced MRI based on deep learning

Objective. Precise hepatocellular carcinoma (HCC) detection is crucial for clinical management. While studies focus on computed tomography-based automatic algorithms, there is a rareness of research on automatic detection based on dynamic contrast enhanced (DCE) magnetic resonance imaging. This study is to develop an automatic detection and segmentation deep learning model for HCC using DCE. Approach: DCE images acquired from 2016 to 2021 were retrospectively collected. Then, 382 patients (301 male; 81 female) with 466 lesions pathologically confirmed were included and divided into an 80% training-validation set and a 20% independent test set. For external validation, 51 patients (42 male; 9 female) in another hospital from 2018 to 2021 were included. The U-net architecture was modified to accommodate multi-phasic DCE input. The model was trained with the training-validation set using five-fold cross-validation, and furtherly evaluated with the independent test set using comprehensive metrics for segmentation and detection performance. The proposed automatic segmentation model consisted of five main steps: phase registration, automatic liver region extraction using a pre-trained model, automatic HCC lesion segmentation using the multi-phasic deep learning model, ensemble of five-fold predictions, and post-processing using connected component analysis to enhance the performance to refine predictions and eliminate false positives. Main results. The proposed model achieved a mean dice similarity coefficient (DSC) of 0.81 ± 0.11, a sensitivity of 94.41 ± 15.50%, a precision of 94.19 ± 17.32%, and 0.14 ± 0.48 false positive lesions per patient in the independent test set. The model detected 88% (80/91) HCC lesions in the condition of DSC > 0.5, and the DSC per tumor was 0.80 ± 0.13. In the external set, the model detected 92% (58/62) lesions with 0.12 ± 0.33 false positives per patient, and the DSC per tumor was 0.75 ± 0.10. Significance. This study developed an automatic detection and segmentation deep learning model for HCC using DCE, which yielded promising post-processed results in accurately identifying and delineating HCC lesions.

Non-contrast short MRI surveillance for HCC screening: the study protocol of the SMS-HCC prospective multicenter study

Hepatocellular carcinoma (HCC) comprises 75 to 85% of all primary liver cancers. Current guidelines recommend a biannual HCC surveillance using ultrasound (US) for high-risk patients. However, due to its low sensitivity for detection of early-stage HCC lesions, there is an urgency for more sensitive surveillance tools. Here, we describe the potential of a short MRI surveillance (SMS) protocol for HCC, including axial T1-weighted in-out phase, fat-saturated T2-weighted, and diffusion-weighted sequences. In this prospective, multicenter, patient cohort study, patients will be recruited from existing HCC surveillance cohorts of six medical centers in The Netherlands. Surveillance patients who undergo biannual US, will be invited for SMS on the same day for 3 years. In case of a suspicious finding on either US or SMS, patients will be invited for a full MRI liver protocol including gadolinium-based contrast agent intravenous injection within 2 weeks. To our knowledge, this will be the first study to perform a head-to-head comparison with a paired US-MRI design. We hypothesize that the sensitivity of SMS for detection of early-stage HCC will be higher than that of US leading to improved survival of surveillance patients through timely HCC diagnosis. Furthermore, we hypothesize that the SMS-HCC protocol will prove cost-effective.Relevance statement The US sensitivity for detecting early-stage HCC has been reported to be less than 50%. We expect that the proposed SMS will detect at least twice as many early-stage HCC lesions and therefore prove to be cost-effective.Key points• The low sensitivity of US necessitates better imaging tools for HCC screening.• This is the first study with a paired US-MRI design.• This design will allow a head-to-head comparison in both diagnostics and patient-acceptance.• We expect that SMS can contribute to a higher survival rate.Graphical

Dynamic Contrast Enhanced-MRI and Apparent Diffusion Coefficient Quantitation for Differentiate Hepatocellular Carcinoma from Hepatocellular Adenoma.

Due to their overlapping radiological characteristics, hepatic lesions, such as hepatocellular carcinoma (HCC) and hepatocellular adenoma (HCA), present a substantial diagnostic challenge. Accurate differentiation between HCC and HCA is essential for the best clinical treatment and therapeutic decision-making. This study aims to assess the potential role of DCE-MRI and Apparent Diffusion Coefficient (ADC) quantitation in the diagnosis of hepatocellular carcinoma (HCC) from hepatocellular adenoma (HCA). 103 patients (56 HCC, 47 HCA) with histopathologically proven hepatocellular lesions were the subjects of a cross-sectional investigation. A standardized imaging technique was used for DCE-MRI on all patients. Diffusion-weighted imaging (DWI) provided the ADC values. The diagnostic efficacy of DCE-MRI and ADC in differentiation was evaluated using statistical analyses, such as t-tests and receiver operating characteristic (ROC) curve analysis. SPSS VER 16 was used for the analysis of the collected data. A total of 103 patients (female: male= 52:51, 57.14±3.09 years) were included in the study. The study revealed significant differences in DCE-MRI parameters and ADC values between HCC and HCA lesions. ADC value was significantly lower in HCC than in HCA (p < 0.001). The area under the curve (AUC) was 0.78 (95% CI: 0.69-0.87) for ADC, 0.84 (95% CI: 0.76-0.91) for Ktrans, and 0.72 (95% CI: 0.62-0.82) for Ve. Sensitivity and specificity for ADC were 76.59% and 71.42%, respectively. Also, PPV and NPV of ADC were 69.23% and 78.43%, respectively. Sensitivity and specificity for Ktrans were 82.14% and 76.59%, respectively. Also, PPV and NPV of Ktrans were 80.7% and 78.26%, respectively. In conclusion, DCE-MRI-derived parameters, along with ADC values, exhibit promise as non-invasive tools for differentiating HCC from HCA.

Deep Learning Combined with Radiologist's Intervention Achieves Accurate Segmentation of Hepatocellular Carcinoma in Dual-Phase Magnetic Resonance Images.

Segmentation of hepatocellular carcinoma (HCC) is crucial; however, manual segmentation is subjective and time-consuming. Accurate and automatic lesion contouring for HCC is desirable in clinical practice. In response to this need, our study introduced a segmentation approach for HCC combining deep convolutional neural networks (DCNNs) and radiologist intervention in magnetic resonance imaging (MRI). We sought to design a segmentation method with a deep learning method that automatically segments using manual location information for moderately experienced radiologists. In addition, we verified the viability of this method to assist radiologists in accurate and fast lesion segmentation. In our study, we developed a semiautomatic approach for segmenting HCC using DCNN in conjunction with radiologist intervention in dual-phase gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid- (Gd-EOB-DTPA-) enhanced MRI. We developed a DCNN and deep fusion network (DFN) trained on full-size images, namely, DCNN-F and DFN-F. Furthermore, DFN was applied to the image blocks containing tumor lesions that were roughly contoured by a radiologist with 10 years of experience in abdominal MRI, and this method was named DFN-R. Another radiologist with five years of experience (moderate experience) performed tumor lesion contouring for comparison with our proposed methods. The ground truth image was contoured by an experienced radiologist and reviewed by an independent experienced radiologist. The mean DSC of DCNN-F, DFN-F, and DFN-R was 0.69 ± 0.20 (median, 0.72), 0.74 ± 0.21 (median, 0.77), and 0.83 ± 0.13 (median, 0.88), respectively. The mean DSC of the segmentation by the radiologist with moderate experience was 0.79 ± 0.11 (median, 0.83), which was lower than the performance of DFN-R. Deep learning using dual-phase MRI shows great potential for HCC lesion segmentation. The radiologist-aided semiautomated method (DFN-R) achieved improved performance compared to manual contouring by the radiologist with moderate experience, although the difference was not statistically significant.

Outcome of transarterial radioembolization in patients with hepatocellular carcinoma as a first-line interventional therapy and after a previous transarterial chemoembolization.

Due to a lack of data, there is an ongoing debate regarding the optimal frontline interventional therapy for unresectable hepatocellular carcinoma (HCC). The aim of the study is to compare the results of transarterial radioembolization (TARE) as the first-line therapy and as a subsequent therapy following prior transarterial chemoembolization (TACE) in these patients. A total of 83 patients were evaluated, with 38 patients having undergone at least one TACE session prior to TARE [27 male; mean age 67.2 years; 68.4% stage Barcelona clinic liver cancer (BCLC) B, 31.6% BCLC C]; 45 patients underwent primary TARE (33 male; mean age 69.9 years; 40% BCLC B, 58% BCLC C). Clinical [age, gender, BCLC stage, activity in gigabecquerel (GBq), Child-Pugh status, portal vein thrombosis, tumor volume] and procedural [overall survival (OS), local tumor control (LTC), and progression-free survival (PFS)] data were compared. A regression analysis was performed to evaluate OS, LTC, and PFS. No differences were found in OS (95% CI: 1.12, P = 0.289), LTC (95% CI: 0.003, P = 0.95), and PFS (95% CI: 0.4, P = 0.525). The regression analysis revealed a relationship between Child-Pugh score (P = 0.005), size of HCC lesions (>10 cm) (P = 0.022), and OS; neither prior TACE (Child-Pugh B patients; 95% CI: 0.120, P = 0.729) nor number of lesions (>10; 95% CI: 2.930, P = 0.087) correlated with OS. Prior TACE does not affect the outcome of TARE in unresectable HCC.

Treatment of hepatocellular carcinoma with a portal vein tumor thrombus and pulmonary metastases of rectal cancer with microsatellite stability using atezolizumab plus bevacizumab.

Herein, we report the successful treatment using atezolizumab plus bevacizumab of a patient with hepatocellular carcinoma (HCC) with a portal vein tumor thrombus and multiple pulmonary metastases from rectal cancer with microsatellite stability. This patient developed rectal cancer with synchronous pulmonary metastases and HCC. After resecting the primary lesion of the rectal cancer, transcatheter arterial chemoembolization was performed for the HCC. Drug therapy was planned for multiple pulmonary metastases of rectal cancer; however, the early development of recurrent HCC with portal vein tumor thrombus had to be highly prioritized, and atezolizumab plus bevacizumab was introduced. Following the disappearance of the recurrent HCC lesion, the metastatic pulmonary nodules shrunk into scar-like spots. The treatment for both HCC and pulmonary metastases of rectal cancer were considered to result in clinical complete response.

Sonographic appearance of focal liver lesions and likelihood of hepatocellular carcinoma in adult Thais with chronic hepatitis B virus infection.

The objective of our study was to study and compare the sonographic findings of hepatocellular carcinoma (HCC) and benign liver lesions, and apply these to an HCC surveillance program in patient with chronic hepatitis B virus (HBV). Sonographic findings of HCC and benign liver lesions were retrospectively reviewed following diagnosis based on either computer tomography or magnetic resonance imaging from July 2010 to December 2020. Multiple sonographic features were analyzed, including internal echogenicity, rim characteristics, and posterior acoustic enhancement. Associations between sonographic characteristics and HCC were assessed using uni- and multi-variate logistic regression analyses. Of the focal liver lesions in 337 chronic HBV patients, there were 25 HCC and 410 benign lesions, with median sizes of 1.6 and 1.0 cm, respectively. Three ultrasound patterns, homogeneous hypoechogenicity, heterogeneous echogenicity, and hypoechoic rims were more frequently found in HCC than in benign lesions. Moreover, the hypoechoic rim feature was the only sonographic pattern independently associated with HCC (Odds ratio, 68.05; 95% confidence interval, 7.37-628.10; p-values < 0.001). In a subgroup analysis of the lesions sized 2 cm or smaller, no sonographic findings were associated with HCC. A hypoechoic rim was a sonographic feature independently associated with HCC. These findings may aid in improving HCC detection and guiding management during HCC screening and surveillance with ultrasound.

TPA: Two-stage progressive attention segmentation framework for hepatocellular carcinoma on multi-modality MRI.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) plays a crucial role in the diagnosis and measurement of hepatocellular carcinoma (HCC). The multi-modality information contained in the multi-phase images of DCE-MRI is important for improving segmentation. However, this remains a challenging task due to the heterogeneity of HCC, which may cause one HCC lesion to have varied imaging appearance in each phase of DCE-MRI. In particular, some phases exhibit inconsistent sizes and boundaries will result in a lack of correlation between modalities, and it may pose inaccurate segmentation results. We aim to design a multi-modality segmentation model that can learn meaningful inter-phase correlation for achieving HCC segmentation. In this study, we propose a two-stage progressive attention segmentation framework (TPA) for HCC based on the transformer and the decision-making process of radiologists. Specifically, the first stage aims to fuse features from multi-phase images to identify HCC and provide localization region. In the second stage, a multi-modality attention transformer module (MAT) is designed to focus on the features that can represent the actual size. We conduct training, validation, and test in a single-center dataset (386 cases), followed by external test on a batch of multi-center datasets (83 cases). Furthermore, we analyze a subgroup of data with weak inter-phase correlation in the test set. The proposed model achieves Dice coefficient of 0.822 and 0.772 in the internal and external test sets, respectively, and 0.829, 0.791 in the subgroup. The experimental results demonstrate that our model outperforms state-of-the-art models, particularly within subgroup. The proposed TPA provides best segmentation results, and utilizing clinical prior knowledge for network design is practical and feasible.

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma.

467 Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable HCC, but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. Methods: This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intra-abdomen based on a radiological evaluation adopted from RECIST v 1.1. Up to 2 lesions were chosen as target lesions in each organ for the organ-specific response evaluation. Results: The median age was 60 years. The majority of study patients were male in both groups (83.4% and 85.8% in the atezolizumab-bevacizumab and lenvatinib groups, respectively). The etiology of HCC was similar between the two groups: hepatitis B virus infection was the most common etiology in both groups (73.3% and 65.7% in the atezolizumab-bevacizumab and lenvatinib groups, respectively), while 21.2% and 29.0% of patients had non-viral HCC, respectively. Extrahepatic spread was identified in 76.0% and 74.6% of patients in the atezolizumab-bevacizumab and lenvatinib groups, respectively: lung, LN, and intra-abdominal metastases were present in 39.6% vs. 39.1%, 30.0% vs. 33.1% and 16.6% vs. 15.4% of patients, respectively. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was higher overall in the atezolizumab-bevacizumab group than in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9%, and 33.3% vs. 15.0% for intrahepatic, lung, LN and intra-abdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6% and 36.0% vs. 12.5%, respectively. Among patients with a non-viral etiology, atezolizumab-bevacizumab was not clearly associated with a better organ-specific response for the LN and intra-abdominal lesions: 20.0% vs. 54.5% and 20.0% vs. 25.0%, respectively, for a ≥ 30% reduction in the tumor burden. Conclusions: Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.

Value of computed tomography-based lipiodol retention pattern in the assessment of hepatocellular carcinoma complete response following conventional transarterial chemoembolization

BackgroundConventional transarterial chemoembolization (cTACE) has emerged as a major treatment modality for unresectable hepatocellular carcinoma (HCC). Efforts have recently been made to identify biomarkers of HCCs that can potentially predict the response of lesions to transarterial chemoembolization (TACE) therapy. The goal of these efforts is to simplify the decision-making process on whether a patient should choose cTACE or pursue other treatment options. Among these, computed tomography (CT) based lipiodol retention analysis has shown promise in providing valuable insights into post-TACE outcomes. This study aimed to investigate the value of CT-based lipiodol retention pattern in predicting recurrence after a state of complete response (CR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) guideline post-cTACE.MethodsFrom January 2022 to June 2023, a cohort of 30 patients with 40 HCCs who received a primary cTACE session were identified. The study included patients who underwent 1st cTACE session with no more than three HCCs. Ten HCC lesions were eliminated owing to different reasons (illustrated in the flow chart). Tumor response was evaluated based on mRECIST on 1st follow-up CT with a particular focus on tumors demonstrating a complete response. Patterns of lipiodol retention within these tumors were categorized as complete lipiodol retention pattern (C-Lip), covering the whole tumor, or incomplete lipiodol retention pattern (I-Lip). Recurrence was defined when reappearance of enhancement on arterial-phase images of the treated lesion with subsequent washout on portal/delayed phase images occurred corresponding to findings of restricted diffusion on follow-ups DCE-MRI.ResultsA total of 30 HCCs with a CR were classified into 21 (70%) with C-Lip and 9 (30%) with I-Lip. After a median follow-up of 6.00 ± 2.27 months (3–9 months), 8/9 (88.9%) I-Lip and 5/21 (23.8%) C-Lip showed recurrence on follow-up (DCE-MRI), (p < 0.01), with no significant difference in the time of progression (mean 5.57 ± 2.69 for C-Lip vs. 6.00 ± 2.27 months for I-Lip, with (p < 0.5).ConclusionsHCCs exhibit complete lipiodol retention alongside mRECIST CR possess a reduced susceptibility of recurrence, thereby potentially benefiting from MRI during subsequent evaluations. Conversely, the presence of incomplete lipiodol retention in conjunction with mRECIST CR is an indication of a high risk of recurrence and may require further treatment.

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma.

Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable hepatocellular carcinoma (HCC), but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. We aimed to investigate the organ-specific response patterns among unresectable HCC patients treated with first-line atezolizumab-bevacizumab or lenvatinib. This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intraabdomen based on a radiological evaluation adopted from RECIST v 1.1. The median age was 60years. Hepatitis B infection was the most common etiology (n = 270, 69.9%), and 291 (75.4%) patients had a viral etiology. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was overall higher in the atezolizumab-bevacizumab group than that in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9% and 33.3% vs. 15.0% for intrahepatic, lung, LN, and intraabdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6%, and 36.0% vs. 12.5%, respectively. Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.