Improving artificial intelligence pipeline for liver malignancy diagnosis using ultrasound images and video frames.

Recent developments of deep learning methods have demonstrated their feasibility in liver malignancy diagnosis using ultrasound (US) images. However, most of these methods require manual selection and annotation of US images by radiologists, which limit their practical application. On the other hand, US videos provide more comprehensive morphological information about liver masses and their relationships with surrounding structures than US images, potentially leading to a more accurate diagnosis. Here, we developed a fully automated artificial intelligence (AI) pipeline to imitate the workflow of radiologists for detecting liver masses and diagnosing liver malignancy. In this pipeline, we designed an automated mass-guided strategy that used segmentation information to direct diagnostic models to focus on liver masses, thus increasing diagnostic accuracy. The diagnostic models based on US videos utilized bi-directional convolutional long short-term memory modules with an attention-boosted module to learn and fuse spatiotemporal information from consecutive video frames. Using a large-scale dataset of 50 063 US images and video frames from 11 468 patients, we developed and tested the AI pipeline and investigated its applications. A dataset of annotated US images is available at https://doi.org/10.5281/zenodo.7272660.

Impact of radiological response and pattern of progression in patients with HCC treated by atezolizumab-bevacizumab.

BACKGROUND AND AIMS: We aim to assess the role of radiological response to atezolizumab-bevacizumab in patients with HCC to predict overall survival. APPROACH AND RESULTS: We retrospectively included patients with HCC treated by atezolizumab-bevacizumab in 2 tertiary centers. A retrospective blinded analysis was performed by 2 radiologists to assess Response Evaluation Criteria in Solid Tumor (RECIST 1.1) and modified RECIST (mRECIST) criteria at 12 weeks. Imaging response and treatment decisions in the multidisciplinary tumor board at 12 weeks were registered. Among 125 patients, 9.6% and 20.8% had a response, 39.2% and 35.2% had stable disease, and 51.2% and 44% had progression, according to RECIST 1.1 and mRECIST, respectively, with a substantial interobserver agreement (k coefficient=0.79). Metastasis was independently associated with a higher risk of progression. Patients classified as responders did not reach median survival, which was 16.2 and 15.9 months for patients classified as stable and 9.1 and 9.0 months for patients classified as progressors, in RECIST 1.1 and mRECIST criteria, respectively. We observed a wide variability in the identification of progression in the multidisciplinary tumor board in clinical practice compared with the blind evaluation by radiologists mainly due to discrepancy in the evaluation of the increase in size of intrahepatic lesions. The appearance of new extrahepatic lesions or vascular invasion lesions was associated with a worse overall survival ( p =0.032). CONCLUSIONS: RECIST 1.1 and mRECIST criteria predict overall survival with more responders identified by mRECIST and the appearance of new extrahepatic lesion or vascular invasion was associated with a poor prognosis. A noticeable discrepancy was observed between patients classified as progressors at reviewing and the decision reached during the multidisciplinary tumor board.

MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial-level analysis.

BACKGROUND: In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. METHODS: After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. RESULTS: Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. CONCLUSIONS: PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.

Stratifying ICIs-responsive tumor microenvironment in HCC: from parsing out immune-hypoxic crosstalk to clinically applicable MRI-radiomics models.

BACKGROUND: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC). METHODS: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability. RESULTS: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75). CONCLUSION: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification.

Development of a Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration of Imaging Features.

BACKGROUND: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. METHODS: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. RESULTS: We identified 383 patients with HCC with imaging and survival outcomes, n = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. CONCLUSIONS: Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC.

Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria.

Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe Mito-Rh-S which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. Mito-Rh-S has an ultrafast response rate (2 s) and large emission shift (115 nm). Mito-Rh-S was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of Mito-Rh-S demonstrated that Fe2+- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe2+ and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, Mito-Rh-S can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.

Tumor Microenvironment Activatable Nanoprodrug System for In Situ Fluorescence Imaging and Therapy of Liver Cancer.

The development of new imaging and treatment nanoprodrug systems is highly demanded for diagnosis and therapy of liver cancer, a severe disease characterized by a high recurrence rate. Currently, available small molecule drugs are not possible for cancer diagnosis because of the fast diffusion of imaging agents and low efficacy in treatment due to poor water solubility and significant toxic side effects. In this study, we report the development of a tumor microenvironment activatable nanoprodrug system for the diagnosis and treatment of liver cancer. This nanoprodrug system can accumulate in the tumor site and be selectively activated by an excess of hydrogen peroxide (H2O2) in the tumor microenvironment, releasing near-infrared solid-state organic fluorescent probe (HPQCY-1) and phenylboronic acid-modified camptothecin (CPT) prodrug. Both HPQCY-1 and CPT prodrugs can be further activated in tumor sites for achieving more precise in situ near-infrared (NIR) fluorescence imaging and treatment while reducing the toxic effects of drugs on normal tissues. Additionally, the incorporation of hydrophilic multivalent chitosan as a carrier effectively improved the water solubility of the system. This research thus provides a practical new approach for the diagnosis and treatment of liver cancer.

Cascading Detection of Hydrogen Sulfide and N-Acetyltransferase 2 in Hepatocellular Carcinoma Cells Using a Two-Photon Fluorescent Probe.

Hydrogen sulfide (H2S), a critical gas signaling molecule, and N-acetyltransferase 2 (NAT2), a key enzyme in drug metabolism, are both known active biomarkers for liver function. However, the interactions and effects of H2S and NAT2 in living cells or lesion sites remain unknown due to the lack of imaging tools to achieve simultaneous detection of these two substances, making it challenging to implement real-time imaging and precise tracking. Herein, we report an activity-based two-photon fluorescent probe, TPSP-1, for the cascade detection of H2S and NAT2 in living liver cells. Continuous conversion from TPSP-1 to TPSP-3 was achieved in liver cells and tissues. Significantly, leveraging the outstanding optical properties of this two-photon fluorescent probe, TPSP-1, has been effectively used to identify pathological tissue samples directly from clinical liver cancer patients. This work provides us with this novel sensing and two-photon imaging probe, which can be used as a powerful tool to study the physiological functions of H2S and NAT2 and will help facilitate rapid and accurate diagnosis and therapeutic evaluation of hepatocellular carcinoma.

The radiomics nomogram predicts the prognosis of pancreatic cancer patients with hepatic metastasis after chemoimmunotherapy.

OBJECTIVE: To construct a prognostic model based on MR features and clinical data to evaluate the progression free survival (PFS), overall survival (OS) and objective response rate (ORR) of pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy. METHODS: 105 pancreatic cancer patients with hepatic metastases who received chemoimmunotherapy were assigned to the training set (n = 52), validation set (n = 22), and testing set (n = 31). Multi-lesion volume of interest were delineated, multi-sequence radiomics features were extracted, and the radiomics models for predicting PFS, OS and ORR were constructed, respectively. Clinical variables were extracted, and the clinical models for predicting PFS, OS and ORR were constructed, respectively. The nomogram was jointly constructed by radiomics model and clinical model. RESULT: The ORR exhibits no significant correlation with either PFS or OS. The area under the curve (AUC) of nomogram for predicting 6-month PFS reached 0.847 (0.737-0.957), 0.786 (0.566-1.000) and 0.864 (0.735-0.994) in the training set, validation set and testing set, respectively. The AUC of nomogram for predicting 1-year OS reached 0.770 (0.635-0.906), 0.743 (0.479-1.000) and 0.818 (0.630-1.000), respectively. The AUC of nomogram for predicting ORR reached 0.914 (0.828-1.00), 0.938 (0.840-1.00) and 0.846 (0.689-1.00), respectively. CONCLUSION: The prognostic models based on MR imaging features and clinical data are effective in predicting the PFS, OS and ORR of chemoimmunotherapy in pancreatic cancer patients with hepatic metastasis, and can be used to evaluate the prognosis of patients.

ACG Clinical Guideline: Focal Liver Lesions.

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.

Cost-Effectiveness Analysis of Hepatocellular Carcinoma Surveillance in Nonalcoholic Fatty Liver Disease Cirrhosis Using US Visualization Score C-Triggered Abbreviated MRI.

INTRODUCTION: Ultrasound (US) is associated with severe visualization limitations (US Liver Imaging Reporting and Data System visualization score C) in one-third of patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis undergoing hepatocellular carcinoma (HCC) screening. Data suggest abbreviated MRI (aMRI) may improve HCC screening efficacy. This study analyzed the cost-effectiveness of HCC screening strategies, including an US visualization score-based approach with aMRI, in patients with NAFLD cirrhosis. METHODS: We constructed a Markov model simulating adults with compensated NAFLD cirrhosis in the United States undergoing HCC screening, comparing strategies of US plus visualization score, US alone, or no surveillance. We modeled aMRI in patients with visualization score C and negative US, while patients with scores A/B did US alone. We performed a sensitivity analysis comparing US plus visualization score with US plus alpha fetoprotein or no surveillance. The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. Sensitivity analyses were performed for all variables. RESULTS: US plus visualization score was the most cost-effective strategy, with an ICER of $59,005 relative to no surveillance. The ICER for US alone to US plus visualization score was $822,500. On sensitivity analysis, screening using US plus visualization score remained preferred across several parameters. Even with alpha fetoprotein added to US, the US plus visualization score strategy remained cost-effective, with an ICER of $62,799 compared with no surveillance. DISCUSSION: HCC surveillance using US visualization score-based approach, using aMRI for visualization score C, seems to be the most cost-effective strategy in patients with NAFLD cirrhosis.

Interpretation, Reporting, and Clinical Applications of Liver MR Elastography.

Chronic liver disease is highly prevalent and often leads to fibrosis or cirrhosis and complications such as liver failure and hepatocellular carcinoma. The diagnosis and staging of liver fibrosis is crucial to determine management and mitigate complications. Liver biopsy for histologic assessment has limitations such as sampling bias and high interreader variability that reduce precision, which is particularly challenging in longitudinal monitoring. MR elastography (MRE) is considered the most accurate noninvasive technique for diagnosing and staging liver fibrosis. In MRE, low-frequency vibrations are applied to the abdomen, and the propagation of shear waves through the liver is analyzed to measure liver stiffness, a biomarker for the detection and staging of liver fibrosis. As MRE has become more widely used in clinical care and research, different contexts of use have emerged. This review focuses on the latest developments in the use of MRE for the assessment of liver fibrosis; provides guidance for image acquisition and interpretation; summarizes diagnostic performance, along with thresholds for diagnosis and staging of liver fibrosis; discusses current and emerging clinical applications; and describes the latest technical developments.

The Future Role of Abdominal US in Hepatocellular Carcinoma Surveillance.

Abdominal US is currently the best-validated surveillance strategy for hepatocellular carcinoma (HCC) in at-risk patients. It is the only modality shown to have completed all five phases of validation and can achieve high sensitivity and specificity for HCC detection, especially when conducted by expert sonographers in high-volume centers. However, US also has limitations, including operator dependency and varying sensitivity in clinical practice. Further, the sensitivity of US for early-stage HCC detection is lower in patients with obesity or nonviral liver disease, increasingly common populations undergoing surveillance. Imaging-based and blood-based surveillance strategies, including abbreviated MRI and biomarker panels, may overcome some limitations of US-based surveillance. Both strategies have promising test performance in phase II and phase III biomarker studies and are undergoing prospective validation. Considering the variation in HCC risk and test performance between patients, there will likely be a shift away from a one-size-fits-all approach and toward precision screening, in which the "best" test is selected based on individual patient characteristics. In this upcoming era of precision HCC screening among patients with cirrhosis, US will likely continue to have an important, albeit reduced, surveillance role.

LI-RADS CT and MRI Ancillary Feature Association with Hepatocellular Carcinoma and Malignancy: An Individual Participant Data Meta-Analysis.

Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Crivellaro in this issue.

CT-guided High-Dose-Rate Brachytherapy versus Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma.

Background CT-guided high-dose-rate (HDR) brachytherapy (hereafter, HDR brachytherapy) has been shown to be safe and effective for patients with unresectable hepatocellular carcinoma (HCC), but studies comparing this therapy with other local-regional therapies are scarce. Purpose To compare patient outcomes of HDR brachytherapy and transarterial chemoembolization (TACE) in patients with unresectable HCC. Materials and Methods This multi-institutional retrospective study included consecutive treatment-naive adult patients with unresectable HCC who underwent either HDR brachytherapy or TACE between January 2010 and December 2022. Overall survival (OS) and progression-free survival (PFS) were compared between patients matched for clinical and tumor characteristics by propensity score matching. Not all patients who underwent TACE had PFS available; thus, a different set of patients was used for PFS and OS analysis for this treatment. Hazard ratios (HRs) were calculated from Kaplan-Meier survival curves. Results After propensity matching, 150 patients who underwent HDR brachytherapy (median age, 71 years [IQR, 63-77 years]; 117 males) and 150 patients who underwent TACE (OS analysis median age, 70 years [IQR, 63-77 years]; 119 male; PFS analysis median age, 68 years [IQR: 63-76 years]; 119 male) were analyzed. Hazard of death was higher in the TACE versus HDR brachytherapy group (HR, 4.04; P < .001). Median estimated PFS was 32.8 months (95% CI: 12.5, 58.7) in the HDR brachytherapy group and 11.6 months (95% CI: 4.9, 22.7) in the TACE group. Hazard of disease progression was higher in the TACE versus HDR brachytherapy group (HR, 2.23; P < .001). Conclusion In selected treatment-naive patients with unresectable HCC, treatment with CT-guided HDR brachytherapy led to improved OS and PFS compared with TACE. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Chapiro in this issue.

Association of LI-RADS and Histopathologic Features with Survival in Patients with Solitary Resected Hepatocellular Carcinoma.

Background Both Liver Imaging Reporting and Data System (LI-RADS) and histopathologic features provide prognostic information in patients with hepatocellular carcinoma (HCC), but whether LI-RADS is independently associated with survival is uncertain. Purpose To assess the association of LI-RADS categories and features with survival outcomes in patients with solitary resected HCC. Materials and Methods This retrospective study included patients with solitary resected HCC from three institutions examined with preoperative contrast-enhanced CT and/or MRI between January 2008 and December 2019. Three independent readers evaluated the LI-RADS version 2018 categories and features. Histopathologic features including World Health Organization tumor grade, microvascular and macrovascular invasion, satellite nodules, and tumor capsule were recorded. Overall survival and disease-free survival were assessed with Cox regression models. Marginal effects of nontargetoid features on survival were estimated using propensity score matching. Results A total of 360 patients (median age, 64 years [IQR, 56-70 years]; 280 male patients) were included. At CT and MRI, the LI-RADS LR-M category was associated with increased risk of recurrence (CT: hazard ratio [HR] = 1.83 [95% CI: 1.26, 2.66], P = .001; MRI: HR = 2.22 [95% CI: 1.56, 3.16], P < .001) and death (CT: HR = 2.47 [95% CI: 1.72, 3.55], P < .001; MRI: HR = 1.80 [95% CI: 1.32, 2.46], P < .001) independently of histopathologic features. The presence of at least one nontargetoid feature was associated with an increased risk of recurrence (CT: HR = 1.80 [95% CI: 1.36, 2.38], P < .001; MRI: HR = 1.93 [95% CI: 1.81, 2.06], P < .001) and death (CT: HR = 1.51 [95% CI: 1.10, 2.07], P < .010) independently of histopathologic features. In matched samples, recurrence was associated with the presence of at least one nontargetoid feature at CT (HR = 2.06 [95% CI: 1.15, 3.66]; P = .02) or MRI (HR = 1.79 [95% CI: 1.01, 3.20]; P = .048). Conclusion In patients with solitary resected HCC, LR-M category and nontargetoid features were negatively associated with survival independently of histopathologic characteristics. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kartalis and Grigoriadis in this issue.

Comparison of Four Diagnostic Guidelines for Hepatocellular Carcinoma Using Gadoxetic Acid-enhanced Liver MRI.

Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) (P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

Efficacy and Safety of Radiation Segmentectomy with 90Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (90Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months (n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

Liver Imaging Reporting and Data System Contrast-Enhanced US Nonradiation Treatment Response Assessment Version 2024.

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) standardizes the imaging technique, reporting lexicon, disease categorization, and management for patients with or at risk for hepatocellular carcinoma (HCC). LI-RADS encompasses HCC surveillance with US; HCC diagnosis with CT, MRI, or contrast-enhanced US (CEUS); and treatment response assessment (TRA) with CT or MRI. LI-RADS was recently expanded to include CEUS TRA after nonradiation locoregional therapy or surgical resection. This report provides an overview of LI-RADS CEUS Nonradiation TRA v2024, including a lexicon of imaging findings, techniques, and imaging criteria for posttreatment tumor viability assessment. LI-RADS CEUS Nonradiation TRA v2024 takes into consideration differences in the CEUS appearance of viable tumor and posttreatment changes within and in close proximity to a treated lesion. Due to the high sensitivity of CEUS to vascular flow, posttreatment reactive changes commonly manifest as areas of abnormal perilesional enhancement without washout, especially in the first 3 months after treatment. To improve the accuracy of CEUS for nonradiation TRA, different diagnostic criteria are used to evaluate tumor viability within and outside of the treated lesion margin. Broader criteria for intralesional enhancement increase sensitivity for tumor viability detection. Stricter criteria for perilesional enhancement limit miscategorization of posttreatment reactive changes as viable tumor. Finally, the TRA algorithm reconciles intralesional and perilesional tumor viability assessment and assigns a single LI-RADS treatment response (LR-TR) category: LR-TR nonviable, LR-TR equivocal, or LR-TR viable.