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.

Applicability of Bosniak 2019 for renal mass classification on portal venous phase at the era of spectral CT imaging using rapid kV-switching dual-energy CT.

OBJECTIVES: To evaluate the applicability of Bosniak 2019 criteria on a monophasic portal venous phase using rapid kilovoltage-switching DECT (rsDECT). MATERIALS AND METHODS: One hundred twenty-seven renal masses assessed on rsDECT were included, classified according to Bosniak 2019 classification using MRI as the reference standard. Using the portal venous phase, virtual monochromatic images at 40, 50, and 77 keV; virtual unenhanced (VUE) images; and iodine map images were reconstructed. Changes in attenuation values between VUE and 40 keV, 50 keV, and 77 keV measurements were computed and respectively defined as ∆HU40keV, ∆HU50keV, and ∆HU77keV. The values of ∆HU40keV, ∆HU50keV, and ∆HU77keV thresholds providing the optimal diagnostic performance for the detection of internal enhancement were determined using Youden index. RESULTS: Population study included 25 solid renal masses (25/127, 20%) and 102 cystic renal masses (102/127, 80%). To differentiate solid to cystic masses, the specificity of the predefined 20 HU threshold reached 88% (95%CI: 82, 93) using ∆HU77keV and 21% (95%CI: 15, 28) using ∆HU40keV. The estimated optimal threshold of attenuation change was 19 HU on ∆HU77keV, 69 HU on ∆HU50eV, and 111 HU on ∆HU40eV. The rsDECT classification was highly similar to that of MRI for solid renal masses (23/25, 92%) and for Bosniak 1 masses (62/66, 94%). However, 2 hyperattenuating Bosniak 2 renal masses (2/26, 8%) were classified as solid renal masses on rsDECT. CONCLUSION: DECT is a promising tool for Bosniak classification particularly to differentiate solid from Bosniak I-II cyst. However, known enhancement thresholds must be adapted especially to the energy level of virtual monochromatic reconstructions. CLINICAL STATEMENT: DECT is a promising tool for Bosniak classification; however, known enhancement thresholds must be adapted according to the types of reconstructions used and especially to the energy level of virtual monochromatic reconstructions. KEY POINTS: • To differentiate solid to cystic renal masses, predefined 20 HU threshold had a poor specificity using 40 keV virtual monochromatic images. • Most of Bosniak 1 masses according to MRI were also classified as Bosniak 1 on rapid kV-switching dual-energy CT (rsDECT). • Bosniak 2 hyperattenuating renal cysts mimicked solid lesion on rsDECT.

Chest Computed Tomography Characteristics of Critically Ill COVID-19 Patients with Auto-antibodies Against Type I Interferons.

PURPOSE: Patients with auto-antibodies neutralizing type I interferons (anti-IFN auto-Abs) are at risk of severe forms of coronavirus disease 19 (COVID-19). The chest computed tomography (CT) scan characteristics of critically ill COVID-19 patients harboring these auto-Abs have never been reported. METHODS: Bicentric ancillary study of the ANTICOV study (observational prospective cohort of severe COVID-19 patients admitted to the intensive care unit (ICU) for hypoxemic acute respiratory failure between March 2020 and May 2021) on chest CT scan characteristics (severity score, parenchymal, pleural, vascular patterns). Anti-IFN auto-Abs were detected using a luciferase neutralization reporting assay. Imaging data were collected through independent blinded reading of two thoracic radiologists of chest CT studies performed at ICU admission (± 72 h). The primary outcome measure was the evaluation of severity by the total severity score (TSS) and the CT severity score (CTSS) according to the presence or absence of anti-IFN auto-Abs. RESULTS: Two hundred thirty-one critically ill COVID-19 patients were included in the study (mean age 59.5 ± 12.7 years; males 74.6%). Day 90 mortality was 29.5% (n = 72/244). There was a trend towards more severe radiological lesions in patients with anti-IFN auto-Abs than in others, not reaching statistical significance (median CTSS 27.5 (21.0-34.8) versus 24.0 (19.0-30.0), p = 0.052; median TSS 14.5 (10.2-17.0) versus 12.0 (9.0-15.0), p = 0.070). The extra-parenchymal evaluation found no difference in the proportion of patients with pleural effusion, mediastinal lymphadenopathy, or thymal abnormalities in the two populations. The prevalence of pulmonary embolism was not significantly different between groups (8.7% versus 5.3%, p = 0.623, n = 175). CONCLUSION: There was no significant difference in disease severity as evaluated by chest CT in severe COVID-19 patients admitted to the ICU for hypoxemic acute respiratory failure with or without anti-IFN auto-Abs.

Glomerular Filtration Rate Measured Based on Iomeprol Clearance Assessed at CT Urography in Living Kidney Donor Candidates.

Background Estimating glomerular filtration rate (GFR) from serum creatinine can be inaccurate, and current procedures for measuring GFR are time-consuming and cumbersome. Purpose To develop a method for measuring GFR based on iomeprol clearance assessed at CT urography in kidney donor candidates and compare this with iohexol clearance (reference standard for measuring GFR). Materials and Methods This cross-sectional retrospective study included data from kidney donor candidates who underwent both iohexol clearance and CT urography between July 2016 and October 2022. CT-measured GFR was calculated as the iomeprol excretion rate in the urinary system between arterial and excretory phases (Hounsfield units times milliliters per minute) divided by a surrogate for serum iomeprol concentration in the aorta at the midpoint (in Hounsfield units). Performance of CT-measured GFR was assessed with use of mean bias (mean difference between CT-measured GFR and iohexol clearance), precision (the distance between quartile 1 and quartile 3 of the bias [quartile 3 minus quartile 1], with a small value indicating high precision), and accuracy (percentage of CT-measured GFR values falling within 10%, 20%, and 30% of iohexol clearance values). Intraobserver agreement was assessed for 30 randomly selected individuals with the Lin concordance correlation coefficient. Results A total of 75 kidney donor candidates were included (mean age, 51 years ± 13 [SD]; 45 female). The CT-measured GFR was unbiased (1.1 mL/min/1.73 m2 [95% CI: -1.9, 4.1]) and highly precise (16.2 mL/min/1.73 m2 [quartiles 1 to 3, -6.6 to 9.6]). The accuracy of CT-measured GFR within 10%, 20%, and 30% was 61.3% (95% CI: 50.3, 72.4), 88.0% (95% CI: 80.7, 95.4), and 100%, respectively. Concordance between CT-based GFR measurements taken 2 months apart was almost perfect (correlation coefficient, 0.99 [95% CI: 0.98, 0.99]). Conclusion In living kidney donors, GFR measured based on iomeprol clearance assessed at CT urography showed good agreement with GFR measured based on iohexol clearance. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Davenport in this issue.

MRI features associated with HCC histologic subtypes: a western American and European bicenter study.

OBJECTIVES: To evaluate if preoperative MRI can predict the most frequent HCC subtypes in North American and European patients treated with surgical resection. METHODS: A total of 119 HCCs in 97 patients were included in the North American group and 191 HCCs in 176 patients were included in the European group. Lesion subtyping was based on morphologic features and immuno-histopathological analysis. Two radiologists reviewed preoperative MRI and evaluated the presence of imaging features including LI-RADS major and ancillary features to identify clinical, biologic, and imaging features associated with the main HCC subtypes. RESULTS: Sixty-four percent of HCCs were conventional. The most frequent subtypes were macrotrabecular-massive (MTM-15%) and steatohepatitic (13%). Necrosis (OR = 3.32; 95% CI: 1.39, 7.89; p = .0064) and observation size (OR = 1.011; 95% CI: 1.0022, 1.019; p = .014) were independent predictors of MTM-HCC. Fat in mass (OR = 15.07; 95% CI: 6.57, 34.57; p < .0001), tumor size (OR = 0.97; 95% CI: 0.96, 0.99; p = .0037), and absence of chronic HCV infection (OR = 0.24; 95% CI: 0.084, 0.67; p = .0068) were independent predictors of steatohepatitic HCC. Independent predictors of conventional HCCs were viral C hepatitis (OR = 3.20; 95% CI: 1.62, 6.34; p = .0008), absence of fat (OR = 0.25; 95% CI: 0.12, 0.52; p = .0002), absence of tumor in vein (OR = 0.34; 95% CI: 0.13, 0.84; p = .020), and higher tumor-to-liver ADC ratio (OR = 1.96; 95% CI: 1.14, 3.35; p = .014) CONCLUSION: MRI is useful in predicting the most frequent HCC subtypes even in cohorts with different distributions of liver disease etiologies and tumor subtypes which might have future treatment and management implications. KEY POINTS: • Representation of both liver disease etiologies and HCC subtypes differed between the North American and European cohorts of patients. • Retrospective two-center study showed that liver MRI is useful in predicting the most frequent HCC subtypes.

Chest PET/MRI in Solid Cancers: Comparing the Diagnostic Performance of a Free-Breathing 3D-T1-GRE Stack-of-Stars Volume Interpolated Breath-Hold Examination (StarVIBE) Acquisition With That of a 3D-T1-GRE Volume Interpolated Breath-Hold Examination (VIBE) for Chest Staging During Whole-Body PET/MRI.

BACKGROUND: Whole-body positron emission tomography/magnetic resonance imaging (WB-PET/MRI) is increasingly used in oncology. However, chest staging remains challenging. PURPOSE: To compare the diagnostic performance of a free-breathing 3D-T1-GRE stack-of-stars volume interpolated breath-hold examination (StarVIBE) with that of a 3D-T1-GRE volume interpolated breath-hold examination (VIBE) during WB-PET/MRI for chest staging. STUDY TYPE: Retrospective, cohort study. POPULATION: One hundred and twenty-three patients were referred for initial staging of solid cancer, 46 of whom had pulmonary nodules and 14 had pulmonary metastasis. FIELD STRENGTH/SEQUENCE: Free-breathing 3D-T1-GRE stack-of-stars (StarVIBE) and Cartesian 3D-T1-GRE VIBE at 3.0 T. ASSESSMENT: Image quality was assessed using a 4-point scale and using the signal-to-noise ratio (SNR) of lung parenchyma and contrast-to-noise ratio (CNR) of pulmonary nodules. Diagnostic performances of both sequences were determined by three independent radiologists for detection of pulmonary nodules, lymph node involvement, and bone metastases using chest CT, pathology, and follow-up as reference standards. STATISTICAL TESTS: Paired Student's t-test; chi-squared; Fisher's exact test. A P value <0.05 was considered statistically significant. RESULTS: StarVIBE quality was judged as better in 34% of cases and at least equivalent to VIBE in 89% of cases, with significantly higher quality scores (4 [4-4] vs. 3 [3-4], respectively). SNR and CNR values were significantly higher with StarVIBE (8 ± 1.3 and 9.7 ± 4.6, respectively) than with VIBE (1.8 ± 0.2 and 5.5 ± 3.3, respectively). Compared to VIBE, StarVIBE showed significantly higher sensitivity (73% [95% CI 62-82] vs. 44% [95% CI 33-55], respectively) and specificity (95% [95% CI 88-99] vs. 67% [95% CI 56-77]) for pulmonary nodules detection and significantly higher sensitivity (100% [95% CI 89-100] vs. 67% [95% CI 48-82], respectively) for detection of lymph node involvement. Sensitivities for bone metastases detection were not significantly different (100% [95% CI 88-100] vs. 82% [95% CI 63-94], P = 0.054). DATA CONCLUSION: Owing to improved SNR and CNR and spatial resolution, a free-breathing 3D stack-of-stars T1-GRE sequence improves chest staging in comparison with standard 3D-T1-GRE VIBE and may be integrated in WB-PET/MRI acquisitions for initial staging of solid cancer. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Optimization of whole-body 2-[18F]FDG-PET/MRI imaging protocol for the initial staging of patients with myeloma.

OBJECTIVE: To determine the optimal 2-[18F]FDG-PET/MRI imaging protocol for the initial staging of patients with suspected or confirmed multiple myeloma. METHODS: Radiologists and nuclear medicine specialists reviewed all PET/MRI exams of 104 patients with a monoclonal gammopathy (MG). The presence of focal and diffuse bone marrow involvement (BMI) was assessed using 4 different image datasets: WB-MRI, PET, WB-PET/MRI, and WB-DCE-PET/MRI. A reference standard was established by a panel review of all baseline and follow-up imaging, and biological and pathological information. The diagnostic performance for each image dataset to detect BMI was evaluated and compared (Fisher's exact test). RESULTS: Sensitivity, specificity, and accuracy for focal BMI of WB-MRI was 87%, 97%, and 92%; of PET was 78%, 97%, and 95%; of WB-PET/MRI was 93%, 97%, and 95%; and of WB-DCE-PET/MRI was 93%, 97%, and 95%, respectively. WB-PET/MRI and WB-DCE-PET/MRI were statistically superior to PET (p = 0.036) without decreasing specificity. The sensitivity, specificity, and accuracy of WB-MRI for diffuse BMI detection was 91%, 80%, and 85%; of 3DT1-PET was 53%, 89%, and 74%; of WB-PET/MRI was 98%, 66%, and 79%; and of WB-DCE-PET/MRI was 98%, 59%, and 75%, respectively. PET lacked sensitivity compared to all other dataset studies (p < 0.0001). WB-MRI had the best accuracy without reaching statistical significance when compared to the other datasets. CONCLUSION: The WB-PET/MRI dataset including T1 and T2 Dixon, WB-DWI, and PET images provides optimal diagnostic performance to detect both focal lesions and diffuse BMI, with limited added value of WB-DCE for baseline staging of patients with MG. Key Points • The combination of morphological and functional MRI sequences and metabolic (2-[18F]FDG-PET) images increases the diagnostic performance of PET/MRI to detect focal bone lesions. • The adjunction of dynamic contrast-enhanced sequences did not improve diagnostic performance.

Autofluorescence imaging within the liver: a promising tool for the detection and characterization of primary liver tumors.

OBJECTIVES: To assess the performance of 405 nm-induced autofluorescence for the characterization of primary liver nodules on ex vivo resected specimens. MATERIALS AND METHODS: Forty resected liver specimens bearing 53 primary liver nodules were included in this IRB-approved prospective study. Intratissular spectroscopic measurements were performed using a 25-G fibered-needle on all ex vivo specimens: 5 autofluorescence measurements were performed in both nodules and adjacent parenchyma. The spectra derivatives of the 635 and 670 nm autofluorescence peaks observed in nodules and in adjacent liver parenchyma were compared (Kruskal-Wallis and Mann-Whitney when appropriate). RESULTS: A total of 42 potentially evolutive primary liver nodules-34 hepatocellular carcinomas, 4 intrahepatic cholangiocarcinomas, 4 hepatocellular adenomas-and 11 benign nodules-5 focal nodular hyperplasias, 6 regenerative nodules-were included. Both 635 and 670 nm Δderivatives were significantly higher in benign as compared to potentially evolutive (PEV) nodules (respectively 32.9 ± 4.5 vs 15.3 ± 1.4; p < 0.0001 and 5.7 ± 0.6 vs 2.5 ± 0.1; p < 0.0001) with respective sensitivity and specificity of 78% and 91% for distinguishing PEV from benign nodules. CONCLUSION: 405 nm-induced autofluorescence enables the discrimination of benign from PEV primary liver nodules, suggesting that autofluorescence imaging could be used to optimize US targeted liver biopsies. KEY POINTS: • 405 nm-induced autofluorescence can distinguish liver tumors from the adjacent liver parenchyma. • The analysis of autofluorescence imaging observed within primary liver tumors can discriminate benign tumors from those requiring follow-up or targeted liver biopsy. • In current practice, autofluorescence imaging could be embedded within biopsy needle, to enable, in addition to ultrasound guidance, optimal targeting of liver nodules which could optimize tissue sampling.

Utility of Early Posttreatment PET/CT Evaluation Using FDG or 18F-FCH to Predict Response to 90Y Radioembolization in Patients With Hepatocellular Carcinoma.

BACKGROUND. Assessment of hepatocellular carcinoma (HCC) treatment response after transarterial radioembolization (TARE) is challenging, because response by conventional imaging criteria may not become apparent until 6 months after treatment. Though HCC exhibits variable avidity for FDG, some cases of HCC without avidity for FDG show avidity for 18F-fluorocholine (18F-FCH). OBJECTIVE. The purpose of this study was to evaluate the utility of early posttreatment evaluation by PET/CT using FDG or 18F-FCH to predict 6-month treatment response and survival after TARE in patients with HCC. METHODS. This retrospective study included 37 patients (mean age, 67 years; 34 men, three women) with documented HCC treated by TARE who underwent both pre-treatment FDG PET/CT and 18F-FCH PET/CT and early FDG PET/CT and/or 18F-FCH PET/CT 4-8 weeks after treatment; FDG PET/CT and 18F-FCH PET/CT examinations were performed on separate dates. Only one of 73 initially identified potentially eligible patients was excluded because of lack of HCC avidity for both FDG and 18F-FCH. Response assessment by modified RECIST (mRECIST) on multiphase CT or MRI was performed at 1 month and 6 months in 23 patients. Early responses seen on PET/CT and 1-month mRECIST response were assessed as predictors of 6-month mRECIST response. Univariable and multivariable predictors of overall survival (OS) were identified. RESULTS. On pretreatment PET/CT, 28 (76%) patients were FDG-positive (showed visual uptake on FDG PET/CT and tumor-to-normal liver ratio > 1.15), 15 (41%) were FCH-positive (showed visual uptake on 18F-FCH PET/CT), and six (16%) were both FDG-positive and FCH-positive. Twelve of 28 FDG-positive HCCs exhibited early response by FDG PET/CT; seven of 15 FCH-positive HCCs exhibited early response by 18F-FCH PET/CT. Twelve (52%) patients exhibited 6-month mRECIST response. Response seen on early posttreatment PET/CT exhibited 100% (12/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response, whereas 1-month mRECIST response exhibited 67% (8/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response. Response seen on early posttreatment PET/CT was a significant independent predictor of OS on univariable (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; p = .03) and multivariable (HR, 0.2; 95% CI, 0.1-0.8; p = .01) analyses. CONCLUSION. Early evaluation after TARE by PET/CT using FDG or 18F-FCH may pre dict 6-month response and OS in patients with HCC. CLINICAL IMPACT. Early posttreatment evaluation with PET/CT could help more reliably identify true nonresponders after TARE, which in turn could prompt early response-adapted therapeutic management.

Liver resection for single large hepatocellular carcinoma: a prognostic factors study.

INTRODUCTION AND OBJECTIVES: Liver resection is the only curative therapeutic option for large hepatocellular carcinoma (> 5 cm), but survival is worse than in smaller tumours, mostly due to the high recurrence rate. There is currently no proper tool for stratifying relapse risk. Herein, we investigated prognostic factors before hepatectomy in patients with a single large hepatocellular carcinoma (HCC). MATERIAL AND METHODS: We retrospectively identified 119 patients who underwent liver resection for a single large HCC in 2 tertiary academic French centres and collected pre- and post-operative clinical, biological and radiological features. The primary outcome was overall survival at five years. Secondary outcomes were recurrence-free survival at five years and prognostic factors for recurrence. RESULTS: A total of 84% of the patients were male, and the median age was 66 years old (IQR 58-74). Thirty-nine (33%) had Child-Pugh A cirrhosis, and the mean Model for End-Stage Liver Disease (MELD) score was 6 (6-6). The aetiology of liver disease was predominantly alcohol-related (48%), followed by nonalcoholic steatohepatitis (22%), hepatitis B (18%) and hepatitis C (10%). The mean tumour size was 70 mm (55-110). The median overall survival was 72.5 months (IC 95%: 56.2-88.7), and the five-year overall survival was 55.1 ± 5.5%. The median recurrence-free survival was 26.6 months (95% CI: 16.0-37.1), and the five-year recurrence-free survival rate was 37.8 ± 5%. In multivariate analysis, preoperative prognostic factors for recurrence were baseline alpha-fetoprotein (AFP) > 7 ng/mL (p<0.001), portal veinous invasion (p=0.003) and cirrhosis (p=0.020). Using these factors, we created a simple recurrence-risk scoring system that classified three groups with distinct disease-free survival medians (p<0.001): no risk factors (65 months), 1 risk factor (36 months), and ≥2 risk factors (8.9 months). CONCLUSION: Liver resection is the only curative option for large HCC, and we confirmed that survival could be acceptable in experienced centres. Recurrence is the primary issue of surgery, and we proposed a simple preoperative score to help identify patients with the most worrisome prognosis and possible candidates for combined therapy.

Predicting Survival After Hepatocellular Carcinoma Resection Using Deep Learning on Histological Slides.

BACKGROUND AND AIMS: Standardized and robust risk-stratification systems for patients with hepatocellular carcinoma (HCC) are required to improve therapeutic strategies and investigate the benefits of adjuvant systemic therapies after curative resection/ablation. APPROACH AND RESULTS: In this study, we used two deep-learning algorithms based on whole-slide digitized histological slides (whole-slide imaging; WSI) to build models for predicting survival of patients with HCC treated by surgical resection. Two independent series were investigated: a discovery set (Henri Mondor Hospital, n = 194) used to develop our algorithms and an independent validation set (The Cancer Genome Atlas [TCGA], n = 328). WSIs were first divided into small squares ("tiles"), and features were extracted with a pretrained convolutional neural network (preprocessing step). The first deep-learning-based algorithm ("SCHMOWDER") uses an attention mechanism on tumoral areas annotated by a pathologist whereas the second ("CHOWDER") does not require human expertise. In the discovery set, c-indices for survival prediction of SCHMOWDER and CHOWDER reached 0.78 and 0.75, respectively. Both models outperformed a composite score incorporating all baseline variables associated with survival. Prognostic value of the models was further validated in the TCGA data set, and, as observed in the discovery series, both models had a higher discriminatory power than a score combining all baseline variables associated with survival. Pathological review showed that the tumoral areas most predictive of poor survival were characterized by vascular spaces, the macrotrabecular architectural pattern, and a lack of immune infiltration. CONCLUSIONS: This study shows that artificial intelligence can help refine the prediction of HCC prognosis. It highlights the importance of pathologist/machine interactions for the construction of deep-learning algorithms that benefit from expert knowledge and allow a biological understanding of their output.

Multiphase Liver MRI for Identifying the Macrotrabecular-Massive Subtype of Hepatocellular Carcinoma.

Background The recently described "macrotrabecular-massive" (MTM) histologic subtype of hepatocellular carcinoma (HCC) (MTM-HCC) represents an aggressive form of HCC and is associated with poor survival. Purpose To investigate whether preoperative MRI can help identify MTM-HCCs in patients with HCC. Materials and Methods This retrospective study included patients with HCC treated with surgical resection between January 2008 and February 2018 and who underwent preoperative multiphase contrast material-enhanced MRI. Least absolute shrinkage and selection operator (LASSO)-penalized and multivariable logistic regression analyses were performed to identify clinical, biologic, and imaging features associated with the MTM-HCC subtype. Early recurrence (within 2 years) and overall recurrence were evaluated by using Kaplan-Meier analysis. Multivariable Cox regression analysis was performed to determine predictors of early and overall recurrence. Results One hundred fifty-two patients (median age, 64 years; interquartile range, 56-72 years; 126 men) with 152 HCCs were evaluated. Twenty-six of the 152 HCCs (17%) were MTM-HCCs. LASSO-penalized logistic regression analysis identified substantial necrosis, high serum α-fetoprotein (AFP) level (>100 ng/mL), and Barcelona Clinic Liver Cancer (BCLC) stage B or C as independent features associated with MTM-HCCs. At multivariable analysis, substantial necrosis (odds ratio = 32; 95% confidence interval [CI] = 8.9, 114; P < .001), high serum AFP level (odds ratio = 4.4; 95% CI = 1.3, 16; P = .02), and BCLC stage B or C (odds ratio = 4.2; 95% CI = 1.2, 15; P = .03) were independent predictors of MTM-HCC subtype. Substantial necrosis helped identify 65% (17 of 26; 95% CI: 44%, 83%) of MTM-HCCs (sensitivity) with a specificity of 93% (117 of 126; 95% CI: 87%, 97%). In adjusted models, only the presence of satellite nodules was independently associated with both early (hazard ratio = 3.7; 95% CI: 1.5, 9.4; P = .006) and overall (hazard ratio = 3.0; 95% CI: 1.3, 7.2; P = .01) tumor recurrence. Conclusion At multiphase contrast-enhanced MRI, substantial necrosis helped identify macrotrabecular-massive hepatocellular carcinoma subtype with high specificity. © RSNA, 2020.

Intrahepatic immune changes after hepatitis c virus eradication by direct-acting antiviral therapy.

BACKGROUND & AIMS: The recent approval of direct acting anti-virals (DAA) has dramatically changed the landscape of hepatitis C virus (HCV) therapy. Whether viral clearance could promote liver carcinogenesis is debated. It has been hypothesized that changes in intrahepatic immune surveillance following viral cure could favour tumour growth. This study aimed at characterizing the intrahepatic immune changes induced by HCV cure following DAA therapy. METHODS: Patients with compensated cirrhosis who underwent surgical resection for hepatocellular carcinoma (HCC) after sustained virological response (SVR) to DAA therapy were included. A control group of untreated HCV-infected patients with compensated cirrhosis was selected. RNA was extracted from tumoral and non-tumoral tissues and analysed using the Nanostring Immuno-Oncology-360 panel. Immune cells were quantified by immunohistochemistry. RESULTS: Twenty patients were included: 10 patients with a DAA-induced SVR and 10 untreated controls. All of them had a de novo BCLC 0/A HCC. Non-tumoral tissue profiling showed down-regulation of interferon-related genes (including MX1, ISG15 and IFIT1) after DAA therapy. No other differences in immune profiles/immune cell densities were identified between the two groups. The intra-tumoral immune profiles of HCCs that occurred after DAA therapy were not qualitatively or quantitatively different from those of tumours occurring in untreated patients. CONCLUSION: In conclusion, removal of HCV infection after DAA-based therapy results only in a down-regulation of interferon-stimulated genes in non-tumoral tissues from patients with cirrhosis who develop HCC. These minor changes in the liver immune microenvironment are unlikely to favour HCC occurrence or recurrence after DAA-induced SVR.

Prognostic value of anthropometric measures extracted from whole-body CT using deep learning in patients with non-small-cell lung cancer.

INTRODUCTION: The aim of the study was to extract anthropometric measures from CT by deep learning and to evaluate their prognostic value in patients with non-small-cell lung cancer (NSCLC). METHODS: A convolutional neural network was trained to perform automatic segmentation of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscular body mass (MBM) from low-dose CT images in 189 patients with NSCLC who underwent pretherapy PET/CT. After a fivefold cross-validation in a subset of 35 patients, anthropometric measures extracted by deep learning were normalized to the body surface area (BSA) to control the various patient morphologies. VAT/SAT ratio and clinical parameters were included in a Cox proportional-hazards model for progression-free survival (PFS) and overall survival (OS). RESULTS: Inference time for a whole volume was about 3 s. Mean Dice similarity coefficients in the validation set were 0.95, 0.93, and 0.91 for SAT, VAT, and MBM, respectively. For PFS prediction, T-stage, N-stage, chemotherapy, radiation therapy, and VAT/SAT ratio were associated with disease progression on univariate analysis. On multivariate analysis, only N-stage (HR = 1.7 [1.2-2.4]; p = 0.006), radiation therapy (HR = 2.4 [1.0-5.4]; p = 0.04), and VAT/SAT ratio (HR = 10.0 [2.7-37.9]; p < 0.001) remained significant prognosticators. For OS, male gender, smoking status, N-stage, a lower SAT/BSA ratio, and a higher VAT/SAT ratio were associated with mortality on univariate analysis. On multivariate analysis, male gender (HR = 2.8 [1.2-6.7]; p = 0.02), N-stage (HR = 2.1 [1.5-2.9]; p < 0.001), and the VAT/SAT ratio (HR = 7.9 [1.7-37.1]; p < 0.001) remained significant prognosticators. CONCLUSION: The BSA-normalized VAT/SAT ratio is an independent predictor of both PFS and OS in NSCLC patients. KEY POINTS: • Deep learning will make CT-derived anthropometric measures clinically usable as they are currently too time-consuming to calculate in routine practice. • Whole-body CT-derived anthropometrics in non-small-cell lung cancer are associated with progression-free survival and overall survival. • A priori medical knowledge can be implemented in the neural network loss function calculation.

Hepatobiliary MR contrast agent uptake as a predictive biomarker of aggressive features on pathology and reduced recurrence-free survival in resectable hepatocellular carcinoma: comparison with dual-tracer 18F-FDG and 18F-FCH PET/CT.

OBJECTIVES: To compare the performance of the quantitative analysis of the hepatobiliary phase (HBP) tumor enhancement in gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI and of dual-tracer 18F-FDG and 18F-fluorocholine (FCH) PET/CT for the prediction of tumor aggressiveness and recurrence-free survival (RFS) in resectable hepatocellular carcinoma (HCC). METHODS: This retrospective, IRB approved study included 32 patients with 35 surgically proven HCCs. All patients underwent Gd-BOPTA-enhanced MRI including delayed HBP images, 18F-FDG PET/CT, and (for 29/32 patients) 18F-FCH PET/CT during the 2 months prior to surgery. For each lesion, the lesion-to-liver contrast enhancement ratio (LLCER) on MRI HBP images and the SUVmax tumor-to-liver ratio (SUVT/L) for both tracers were calculated. Their predictive value for aggressive pathological features-including the histological grade and microvascular invasion (MVI)-and RFS were analyzed and compared using area under receiver operating characteristic (AUROC) curves and Cox regression models, respectively. RESULTS: The AUROCs for the identification of aggressive HCCs on pathology with LLCER, 18F-FDG SUVT/L, and 18F-FCH SUVT/L were 0.92 (95% CI 0.78, 0.98), 0.89 (95% CI 0.74, 0.97; p = 0.70), and 0.64 (95% CI 0.45, 0.80; p = 0.035). At multivariate Cox regression analysis, LLCER was identified as an independent predictor of RFS (HR (95% CI) = 0.91 (0.84, 0.99), p = 0.022). LLCER - 4.72% or less also accurately predicted moderate-poor differentiation grade (Se = 100%, Sp = 92.9%) and MVI (Se = 93.3%, Sp = 60%) and identified patients with poor RFS after surgical resection (p = 0.030). CONCLUSIONS: HBP tumor enhancement after Gd-BOPTA injection may help identify aggressive HCC pathological features, and patients with reduced recurrence-free survival after surgical resection. KEY POINTS: • In patients with resectable HCC, the quantitative analysis of the HBP tumor enhancement in Gd-BOPTA-enhanced MRI (LLCER) accurately identifies moderately-poorly differentiated and/or MVI-positive HCCs. • After surgical resection for HCC, patients with LLCER - 4.72% or less had significantly poorer recurrence-free survival than patients with LLCER superior to - 4.72%. • Gd-BOPTA-enhanced MRI with delayed HBP images may be suggested as part of pre-surgery workup in patients with resectable HCC.

Metastatic melanoma: pretreatment contrast-enhanced CT texture parameters as predictive biomarkers of survival in patients treated with pembrolizumab.

PURPOSE: To determine whether texture analysis features on pretreatment contrast-enhanced computed tomography (CT) images can predict overall survival (OS) and progression-free survival (PFS) in patients with metastatic malignant melanoma (MM) treated with an anti-PD-1 monoclonal antibody, pembrolizumab. MATERIALS AND METHODS: This institutional-approved retrospective study included 31 patients with metastatic MM treated with pembrolizumab. Texture analysis of 74 metastatic lesions was performed on CT scanners obtained within 1 month before treatment. Mean gray-level, entropy, kurtosis, skewness, and standard deviation values were derived from the pixel distribution histogram before and after spatial filtration at different anatomic scales, ranging from fine to coarse. Lasso penalized Cox regression analyses were performed to identify independent predictors of OS and PFS. RESULTS: Median OS and PFS were 357 days (range 42-1355) and 99 days (range 35-1185), respectively. Skewness at coarse texture scale (SSF = 6; HR (CI 95%) = 6.017 (1.39, 26.056), p = 0.016), Response evaluation criteria in solid tumors (RECIST) conclusion (HR (CI 95%) = 3.41 (1.17, 9.89), p = 0.024), and body weight (HR (CI 95%) = 0.96 (0.92, 0.995), p = 0.026) were independent predictors of OS. Skewness at coarse texture scale (SSF = 6; HR (CI 95%) = 4.55 (1.46, 14.13), p = 0.0089) and RECIST conclusion (HR (CI 95%) = 10.63 (3.11, 36.29), p = 0.00016) were independent predictors of PFS. Skewness values above - 0.55 at coarse texture scale were significantly associated with both lower OS and lower PFS after administration of pembrolizumab. CONCLUSION: Pretreatment CT texture analysis-derived tumor skewness may act as predictive biomarker of OS and PFS in patients with metastatic MM treated with pembrolizumab. KEY POINTS: • Pretreatment skewness at coarse texture scale in metastases from malignant melanoma was an independent predictor of overall survival and progression-free survival. • Skewness values above -0.55 at coarse texture scale were significantly associated with both lower OS and lower PFS after administration of pembrolizumab. • In patients with metastatic MM, texture analysis performed on pretreatment CT may act as a useful tool to select the best candidates for pembrolizumab therapy.

Hepatocellular carcinoma: CT texture analysis as a predictor of survival after surgical resection.

OBJECTIVES: To determine whether image texture parameters analysed on pre-operative contrast-enhanced computed tomography (CT) can predict overall survival and recurrence-free survival in patients with hepatocellular carcinoma (HCC) treated by surgical resection. METHODS: We retrospectively included all patients operated for HCC who had liver contrast-enhanced CT within 3 months prior to treatment in our centre between 2010 and 2015. The following texture parameters were evaluated on late-arterial and portal-venous phases: mean grey-level, standard deviation, kurtosis, skewness and entropy. Measurements were made before and after spatial filtration at different anatomical scales (SSF) ranging from 2 (fine texture) to 6 (coarse texture). Lasso penalised Cox regression analyses were performed to identify independent predictors of overall survival and recurrence-free survival. RESULTS: Forty-seven patients were included. Median follow-up time was 345 days (interquartile range [IQR], 176-569). Nineteen patients had a recurrence at a median time of 190 days (IQR, 141-274) and 13 died at a median time of 274 days (IQR, 96-411). At arterial CT phase, kurtosis at SSF = 4 (hazard ratio [95% confidence interval] = 3.23 [1.35-7.71] p = 0.0084) was independent predictor of overall survival. At portal-venous phase, skewness without filtration (HR [CI 95%] = 353.44 [1.31-95102.23], p = 0.039), at SSF2 scale (HR [CI 95%] = 438.73 [2.44-78968.25], p = 0.022) and SSF3 (HR [CI 95%] = 14.43 [1.38-150.51], p = 0.026) were independently associated with overall survival. No textural feature was identified as predictor of recurrence-free survival. CONCLUSIONS: In patients with resectable HCC, portal venous phase-derived CT skewness is significantly associated with overall survival and may potentially become a useful tool to select the best candidates for resection. KEY POINTS: • HCC heterogeneity as evaluated by texture analysis of contrast-enhanced CT images may predict overall survival in patients treated by surgical resection. • Among texture parameters, skewness assessed at different anatomical scales at portal-venous phase CT is an independent predictor of overall survival after resection. • In patients with HCC, CT texture analysis may have the potential to become a useful tool to select the best candidates for resection.

Iso- or hyperintensity of hepatocellular adenomas on hepatobiliary phase does not always correspond to hepatospecific contrast-agent uptake: importance for tumor subtyping.

PURPOSE: This study was conducted in order to evaluate if iso- or hyperintensity of HCAs on HBP is systematically related to a high uptake of hepatospecific contrast agent, using a quantitative approach. METHODS: This bicentric retrospective study included all patients with histologically confirmed and subtyped HCA from 2009 to 2017 who underwent MRI with HBP after Gd-BOPTA injection and who showed iso- or hyperintensity on HBP. The signal intensity of tumors on pre- and postcontrast images and the presence of hepatic steatosis were noted. Contrast uptake on HBP was quantified using the liver-to-lesion contrast enhancement ratio (LLCER) and compared between HCA subtypes (Wilcoxon signed-rank test). Categorical variables were compared using chi-square tests. RESULTS: Twenty-four HCAs showed iso- or hyperintensity on HBP, specifically 17 inflammatory (IHCAs) and 7 ß-catenin HCAs (BHCAs). Eighteen HCAs (75%) (17 IHCAs and 1 BHCAs) had a LLCER < 0% (median - 13.6%, group 1), of which 94% were hyperintense on precontrast T1-W images, with background hepatic steatosis. Six HCAs (25%) had LLCER ≥ 0% (median 2.9%, group 2), and all were BHCAs. A LLCER ≥ 1.6% was associated with the diagnosis of BHCA with a sensitivity of 86% and a specificity of 100%. CONCLUSION: In conclusion, iso- or hyperintensity of hepatocellular adenomas on HBP does not necessarily correspond to an increased hepatospecific contrast-agent uptake. In IHCA, tumor hyperintensity on precontrast images and the underlying steatosis likely explain such iso- or hyperintensity, which do show reduced HBP contrast-agent uptake. On the other hand, marked contrast uptake can be observed, especially in BHCA. KEY POINTS: • Iso- or hyperintensity on HBP does not necessarily reflect a high uptake of hepatospecific contrast agent. • Discrepancies between qualitative signal intensity and quantitative hepatospecific contrast uptake can be explained in IHCA by a combination of tumor hyperintensity on precontrast images and underlying hepatic steatosis. • In BHCA, iso- or hyperintensity on HBP does actually correspond to a greater contrast uptake than that of the liver, demonstrated by an increased lesion-to-liver contrast enhancement ratio (LLCER).

Advanced Hepatocellular Carcinoma: Pretreatment Contrast-enhanced CT Texture Parameters as Predictive Biomarkers of Survival in Patients Treated with Sorafenib.

Purpose To determine whether texture features on pretreatment contrast material-enhanced computed tomographic (CT) images can help predict overall survival (OS) and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. Materials and Methods This retrospective study included 92 patients with advanced HCC treated with sorafenib between January 2009 and April 2015 at two independent university hospitals. Sixty-four of the 92 patients (70%) (six women, 58 men; median age, 66 years) were included from institution 1 and constituted a training cohort; 28 patients (30%) (five women, 23 men; median age, 64 years) were included from institution 2 and constituted a validation cohort. Pretreatment CT texture analysis was performed on late arterial and portal venous phase HCC images. Mean gray-level intensity, entropy, kurtosis, skewness, and standard deviation values were derived from the pixel distribution histogram before and after spatial filtration at different anatomic scales ranging from fine to coarse texture. Lesion heterogeneity was also visually graded on a 4-point scale. Correlations between visual analysis and texture parameters were assessed with the Spearman rank correlation. Univariate Kaplan-Meier and multivariate Cox proportional hazards regression analyses were performed in the training cohort to identify independent predictors of OS and TTP. Their predictive capacity was tested on the validation cohort by using Kaplan-Meier analysis. Results Visual analysis of tumor heterogeneity correlated with entropy at both arterial (P = .012) and portal venous (P = .038) phases. Portal phase-derived entropy at fine (hazard ratio [HR], 5.08; P = .0033), medium (HR, 2.23; P = .019), and coarse (HR, 2.26; P = .0032) texture scales was identified as an independent predictor of OS and confirmed in the validation cohort (P < .05). The difference in median survival between patients in the validation cohort with entropy values below and above the identified threshold was 272 days (with fine texture) and 741 days (with medium and coarse textures). Arterial phase-derived texture parameters (P > .085) and visual analysis (P > .11) were not associated with changes in survival. Conclusion Pretreatment portal venous phase-derived tumor entropy may be a predictor of survival in patients with advanced HCC treated with sorafenib.