Rare primary liver cancers: An EASL position paper.

In recent years, owing to advances in our understanding of hepatocarcinogenesis, rare primary liver cancers (PLCs), including combined hepatocellular-cholangiocarcinoma, fibrolamellar carcinoma, and hepatic epithelioid hemangioendothelioma have garnered increased attention. In this position paper, an international panel of experts representing oncology, hepatology, pathology, radiology, surgery, and molecular biology has summarised the available information and evidence on the pathogenesis, diagnosis, and treatment of rare PLCs. While clinical trials of systemic treatments are underway for some rare PLCs, it is evident that more research, involving national and international collaboration, is required.

Ultrahigh-Spatial-Resolution Photon-counting Detector CT Angiography of Coronary Artery Disease for Stenosis Assessment.

Background Coronary CT angiography is a first-line test in coronary artery disease but is limited by severe calcifications. Photon-counting-detector (PCD) CT improves spatial resolution. Purpose To investigate the effect of improved spatial resolution on coronary stenosis assessment and reclassification. Materials and Methods Coronary stenoses were evaluated prospectively in a vessel phantom (in vitro) containing two stenoses (25%, 50%), and retrospectively in patients (in vivo) who underwent ultrahigh-spatial-resolution cardiac PCD CT (from July 2022 to April 2023). Images were reconstructed at standard resolution (section thickness, 0.6 mm; increment, 0.4 mm; Bv44 kernel), high spatial resolution (section thickness, 0.4 mm; increment, 0.2 mm; Bv44 kernel), and ultrahigh spatial resolution (section thickness, 0.2; increment, 0.1 mm; Bv64 kernel). Percentages of diameter stenosis (DS) were compared between reconstructions. In vitro values were compared with the manufacturer specifications of the phantom and patient results were assessed regarding effects on Coronary Artery Disease Reporting and Data System (CAD-RADS) reclassification. Results The in vivo sample included 114 patients (mean age, 68 years ± 9 [SD]; 71 male patients). In vitro percentage DS measurements were more accurate with increasing spatial resolution for both 25% and 50% stenoses (mean bias for standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 10.1%, 8.0%, and 2.3%; P < .001). In vivo results confirmed decreasing median percentage DS with increasing spatial resolution for calcified stenoses (n = 161) (standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 41.5% [IQR, 27.3%-58.2%], 34.8% [IQR, 23.7%-55.1%], and 26.7% [IQR, 18.6%-44.3%]; P < .001), whereas noncalcified (n = 13) and mixed plaques (n = 19) did not show evidence of a difference (P ≥ .88). Ultrahigh-spatial-resolution reconstructions led to reclassification of 62 of 114 (54.4%) patients to lower CAD-RADS category than that assigned using standard resolution. Conclusion In vivo and in vitro coronary stenosis assessment improved for calcified stenoses by using ultrahigh-spatial-resolution PCD CT reconstructions, leading to lower percentage DS compared with standard resolution and clinically relevant rates of reclassification. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by McCollough in this issue.

Effect of mild cortisol cosecretion on body composition and metabolic parameters in patients with primary hyperaldosteronism.

OBJECTIVE: To investigate the effects of simultaneous cortisol cosecretion (CCS) on body composition in computed tomography (CT)-imaging and metabolic parameters in patients with primary aldosteronism (PA) with the objective of facilitating early detection. DESIGN: Retrospective cohort study. PATIENTS: Forty-seven patients with PA and CCS confirmed by 1-mg dexamethasone suppression test (DST) with a cutoff of ≥1.8 µg/dL were compared with PA patients with excluded CCS (non-CCS, n = 47) matched by age and sex. METHODS: Segmentation of the fat compartments and muscle area at the third lumbar region was performed on non-contrast-enhanced CT images with dedicated segmentation software. Additionally, liver, spleen, pancreas and muscle attenuation were compared between the two groups. RESULTS: Mean cortisol after DST was 1.2 µg/dL (33.1 nmol/L) in the non-CCS group and 3.2 µg/dL (88.3 nmol/L) in the CCS group with mild autonomous cortisol excess (MACE). No difference in total, visceral and subcutaneous fat volumes was observed between the CCS and non-CCS group (p = .7, .6 and .8, respectively). However, a multivariable regression analysis revealed a significant correlation between total serum cholesterol and results of serum cortisol after 1-mg DST (p = .026). Classification of the patients based on visible lesion on CT and PA-lateralization via adrenal venous sampling also did not show any significant differences in body composition. CONCLUSION: MACE in PA patients does not translate into body composition changes on CT-imaging. Therefore, early detection of concurrent CCS in PA is currently only attainable through biochemical tests. Further investigation of the long-term clinical adverse effects of MACE in PA is necessary.

Predictive value of pre-infusion tumor growth rate for the occurrence and severity of CRS and ICANS in lymphoma under CAR T-cell therapy.

Chimeric antigen receptor T-cell therapy (CART) can be administered outpatient yet requires management of potential side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The pre-infusion tumor burden is associated with CRS, yet there is no data on the relevance of pre-infusion tumor growth rate (TGR). Our objective was to investigate TGR for the occurrence and severity of CRS and ICANS. Consecutive patients with available pre-baseline and baseline (BL) imaging before CART were included. TGR was determined as both absolute (abs) and percentage change (%) of Lugano criteria-based tumor burden in relation to days between exams. CRS and ICANS were graded according to ASTCT consensus criteria. Clinical metadata was collected including the international prognostic index (IPI), patient age, ECOG performance status, and LDH. Sixty-two patients were included (median age: 62 years, 40% female). The median pre-BL TGR [abs] and pre-BL TGR [%] was 7.5 mm2/d and 30.9%/d. Pre-BL TGR [abs] and pre-BL TGR [%] displayed a very weak positive correlation with the grade of CRS (r[abs] = 0.14 and r[%] = 0.13) and no correlation with ICANS (r[abs] = - 0.06 and r[%] = - 0.07). There was a weak positive correlation between grade of CRS and grade of ICANS (r = 0.35; p = 0.005) whereas there was no significant correlation of CRS or ICANS to any other of the examined parameters. The pre-infusion TGR before CART was weakly associated with the occurrence of CRS, but not the severity, whereas there were no significant differences in the prediction of ICANS. There was no added information when compared to pre-infusion tumor burden alone. Outpatient planning and toxicity management should not be influenced by the pre-infusion TGR.

High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series.

The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. Systematic studies are required to confirm this preliminary experience and to understand underlying mechanisms.

Prospective close monitoring of the effect of vascular-targeted photodynamic therapy and high intensity focused ultrasound of localized prostate cancer by multiparametric magnetic resonance imaging.

PURPOSE: The aim of this study is to describe the anatomical and functional changes observed in multiparametric magnetic resonance imaging (mpMRI) during follow-up after focal therapy (FT) for localized prostate cancer (PCa). MATERIALS AND METHODS: In this prospective study, we analyzed pre- and postoperatively acquired mpMRI of 10 patients after FT (7 days; 3, 6, 9, 12 months). 7/10 (70%) patients underwent vascular-targeted photodynamic therapy (VTP). 3/10 (30%) patients underwent high-intensity focused ultrasound (HIFU). MpMR image analysis was performed using a semi-automatic software for segmentation of the prostate gland (PG) and tumor zones. Signal intensities (SI) of T2-weighted (T2w), T1-weighted (T1w),diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) images as well as volumes of the prostate gland (PGV) and tumor volumes (TV) were evaluated at each time point. RESULTS: The results showed a significant increase of PGV 7 days after FT (p = 0.042) and a significant reduction of PGV between 7 days and 6, 9 and 12 months after FT (p < 0.001). The TV increased significantly 7 days after FT (p < 0.001) and decreased significantly between 7 days and 12 months after FT (p < 0.001). There was a significant increase in SI of the ADC in the ablation zone after 6, 9 and 12 months after FT (p < 0.001). 1/9 patients (11%) had recurrent tumor on rebiopsy characterized as a a small focal lesion on mpMRI with strong diffusion restriction (low SI on ADC map and high SI on b-value DWI). CONCLUSION: MpMRI is able to represent morphologic changes of the ablated zone after FT and might be helpful to detect recurrent tumor.

ESR Essentials: staging and restaging with FDG-PET/CT in oncology-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Positron emission tomography (PET) stands as the paramount clinical molecular imaging modality, especially in oncology. Unlike conventional anatomical-morphological imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI), PET provides detailed visualizations of internal activity at the molecular and cellular levels. 18-fluorine-fluorodeoxyglucose ([18F]FDG)-PET combined with contrast-enhanced CT (ceCT) significantly improves the detection of various cancers. Appropriate patient selection is crucial, and physicians should carefully assess the appropriateness of [18F]FDG-PET/CT based on specific clinical criteria and evidence. Due to its high diagnostic accuracy, [18F]FDG-PET/CT is indispensable for evaluating the extent of disease, staging, and restaging known malignancies, and assessing the response to therapy. PET/CT imaging offers significant advantages in patient management, particularly by identifying occult metastases that might otherwise go undetected. This can help prevent unnecessary surgeries, allowing many patients to be redirected to systemic chemotherapy instead. However, it is important to note that the gold standard for surgical planning remains CT and/or MRI, depending on the body region. These imaging modalities, with or without associated angiography, provide superior contrast and spatial resolution, essential for detailed surgical preparation and planning. [18F]FDG-PET/CT has a central role in the precise and early diagnosis of cancer, contributing significantly to personalized treatment plans. However, it has limitations, including non-tumor-specific uptake and the potential to inaccurately capture the metabolic activity of certain tumor types due to low uptake in some well-differentiated tumor cell lines. Therefore, it should be utilized in clinical scenarios where it offers crucial diagnostic insights not readily available with other imaging modalities. KEY POINTS: Use [18F]FDG-PET/CT selectively based on clinical appropriateness criteria and existing evidence to optimize resource utilization and minimize patient exposure. Employ [18F]FDG-PET/CT in treatment planning and monitoring, particularly for assessing chemotherapy or radiotherapy response in FDG-avid lymphoma and solid tumors. When available, [18F]FDG-PET/CT can be integrated with other diagnostic tools, such as MRI, to enhance overall diagnostic accuracy.

ESR Essentials: role of PET/CT in neuroendocrine tumors-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Neuroendocrine neoplasms (NEN) originate from the secretory cells of the neuroendocrine system, with the majority arising in the gastrointestinal tract and pancreas. Given the heterogeneity in the biological behavior and morphological differentiation of these tumors, advanced imaging techniques are crucial for supporting the suspected diagnosis, accurate staging, and monitoring therapy. As most well-differentiated NEN demonstrate overexpression of somatostatin receptors (SSR) on the cell surface, SSR-directed PET/CT is considered the reference standard for imaging of this particular entity. SSR-PET/CT should be the imaging method of choice in every NEN G1 or G2 and considered for re-staging after both potentially curative and non-curative surgeries. The extent of SSR expression is also crucial for determining a patient's eligibility for peptide receptor radionuclide therapy (PRRT). PRRT utilizes [177Lu]Lu-DOTA-TATE to target the SSR receptor and can significantly prolong progression-free survival in patients with advanced, progressive neuroendocrine tumor of the gastroenteropancreatic system (GEP-NET). PET/CT is a central component of the multidisciplinary management of NEN. Variable follow-up intervals are recommended, considering that tumors with higher proliferation rates or advanced metastatic disease require more frequent assessments. The combination with other imaging modalities, like MRI, complements SSR-PET/CT, further enhancing overall diagnostic accuracy. KEY POINTS: Somatostatin receptor-PET/CT (SSR-PET/CT) is the guideline-recommended reference standard for imaging well-differentiated neuroendocrine tumors (NET). SSR-PET/CT should be the diagnostic imaging of choice for staging and post-therapy re-staging of grade 1 or 2 NET (G1 or G2). Variable follow-up intervals are recommended for NET G1 and G2. Tumors with higher proliferation rates or advanced metastatic disease necessitate more frequent assessments.

Clinical benefits of MRI-guided freehand biopsy of small focal liver lesions in comparison to CT guidance.

OBJECTIVES: To compare clinical success, procedure time, and complication rates between MRI-guided and CT-guided real-time biopsies of small focal liver lesions (FLL) < 20 mm. METHODS: A comparison of a prospectively collected MRI-guided cohort (n = 30) to a retrospectively collected CT-guided cohort (n = 147) was performed, in which patients underwent real-time biopsies of small FLL < 20 mm in a freehand technique. In both groups, clinical and periprocedural data, including clinical success, procedure time, and complication rates (classified according to CIRSE guidelines), were analyzed. Wilcoxon rank sum test, Pearson's chi-squared test, and Fisher's exact test were used for statistical analysis. Additionally, propensity score matching (PSM) was performed using the following criteria for direct matching: age, gender, presence of liver cirrhosis, liver lobe, lesion diameter, and skin-to-target distance. RESULTS: The median FLL diameter in the MRI-guided cohort was significantly smaller compared to CT guidance (p < 0.001; 11.0 mm vs. 16.3 mm), while the skin-to-target distance was significantly longer (p < 0.001; 90.0 mm vs. 74.0 mm). MRI-guided procedures revealed significantly higher clinical success compared to CT guidance (p = 0.021; 97% vs. 79%) as well as lower complication rates (p = 0.047; 0% vs. 13%). Total procedure time was significantly longer in the MRI-guided cohort (p < 0.001; 38 min vs. 28 min). After PSM (n = 24/n = 38), MRI-guided procedures still revealed significantly higher clinical success compared to CT guidance (p = 0.039; 96% vs. 74%). CONCLUSION: Despite the longer procedure time, freehand biopsy of small FLL < 20 mm under MR guidance can be considered superior to CT guidance because of its high clinical success and low complication rates. CLINICAL RELEVANCE STATEMENT: Biopsy of small liver lesions is challenging due to the size and conspicuity of the lesions on native images. MRI offers higher soft tissue contrast, which translates into a higher success of obtaining enough tissue material with MRI compared to CT-guided biopsies. KEY POINTS: • Image-guided biopsy of small focal liver lesions (FLL) is challenging due to inadequate visualization, leading to sampling errors and false-negative biopsies. • MRI-guided real-time biopsy of FLL < 20 mm revealed significantly higher clinical success (p = 0.021; 97% vs. 79%) and lower complication rates (p = 0.047; 0% vs. 13%) compared to CT guidance. • Although the procedure time is longer, MRI-guided biopsy can be considered superior for small FLL < 20 mm.

Reliability and practicability of PSMA-RADS 1.0 for structured reporting of PSMA-PET/CT scans in prostate cancer patients.

OBJECTIVES: As structured reporting is increasingly used in the evaluation of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) for prostate cancer, there is a need to assess the reliability of these frameworks. This study aimed to evaluate the intra- and interreader agreement among readers with varying levels of experience using PSMA-RADS 1.0 for interpreting PSMA-PET/CT scans, even when blinded to clinical data, and therefore to determine the feasibility of implementing this reporting system in clinical practice. METHODS: PSMA-PET/CT scans of 103 patients were independently evaluated by 4 readers with different levels of experience according to the reporting and data system (RADS) for PSMA-PET/CT imaging PSMA-RADS 1.0 at 2 time points within 6 weeks. For each scan, a maximum of five target lesions were freely chosen and stratified according to PSMA-RADS 1.0. Overall scan score and compartment-based scores were assessed. Intra- and interreader agreement was determined using the intraclass correlation coefficient (ICC). RESULTS: PSMA-RADS 1.0 demonstrated excellent interreader agreement for both overall scan scores (ICC ≥ 0.91) and compartment-based scores (ICC ≥ 0.93) across all four readers. The framework showed excellent intrareader agreement for overall scan scores (ICC ≥ 0.86) and compartment-based scores (ICC ≥ 0.95), even among readers with varying levels of experience. CONCLUSIONS: PSMA-RADS 1.0 is a reliable method for assessing PSMA-PET/CT with strong consistency and agreement among readers. It shows great potential for establishing a standard approach to diagnosing and planning treatment for prostate cancer patients, and can be used confidently even by readers with less experience. CLINICAL RELEVANCE STATEMENT: This study underlines that PSMA-RADS 1.0 is a valuable and highly reliable scoring system for PSMA-PET/CT scans of prostate cancer patients and can be used confidently by radiologists with different levels of experience in routine clinical practice. KEY POINTS: PSMA-RADS version 1.0 is a scoring system for PSMA-PET/CT scans. Its reproducibility needs to be analyzed in order to make it applicable to clinical practice. Excellent interreader and intrareader agreement for overall scan scores and compartment-based scores using PSMA-RADS 1.0 were seen in readers with varying levels of experience. PSMA-RADS 1.0 is a reliable tool for accurately diagnosing and planning treatment for prostate cancer patients, and can be used confidently in clinical routine.

Preserved prenatal lung growth assessed by fetal MRI in the omicron-dominated phase of the SARS-CoV-2 pandemic.

OBJECTIVES: With SARS-CoV-2 evolving, disease severity and presentation have changed due to changes in mechanisms of entry and effector site as well as due to effects of vaccination- and/or infection-acquired immunity. We re-assessed fetal lung pathology in pregnancies with uncomplicated SARS-CoV-2 infections during the late, omicron-dominated pandemic phase to inform disease understanding and pregnancy consultation. METHODS: In this case-control study, fetal lung volumes were assessed by fetal MRI in 24 pregnancies affected by mild maternal SARS-CoV-2 infection during the omicron-dominated pandemic phase with prevailing immunity through vaccination and/or prior SARS-CoV-2 infection. RESULTS: Fetal lung volumes (normalized to estimated fetal weight) in 24 pregnancies (GA 33.3 ± 3.8, 12 female fetuses) following mild, uncomplicated SARS-CoV-2 infection did not differ significantly from both, published reference values (96.3% ± 22.5% of 50th percentile reference values, p = 0.43), or fetal lung volumes of a site-specific, non-COVID control group (n = 15, 94.2% ± 18.5%, p = 0.76). Placental assessment revealed no group differences in thrombotic changes or placental heterogeneity (p > 0.05, respectively), and fetal lung volume did not correlate with placental heterogeneity when adjusting for gestational age at scan (p > 0.05). CONCLUSION: Assessment of fetal lung volume by MRI revealed unaffected lung growth in pregnancies affected by uncomplicated SARS-CoV-2 infection in the omicron-dominated pandemic phase in the presence of prevailing hybrid immunity. This finding contrasts sharply with the observed reduction in fetal lung volume following maternal alpha-variant infection in the pre-vaccination era and might reflect tropism- as well as immunity-related effects. KEY POINTS: Question: Is fetal lung development affected by mild maternal SARS-CoV-2 infection during the omicron-dominated phase of the pandemic? FINDINGS: Fetal lung volume in 24 affected pregnancies did not differ significantly from published reference values or fetal lung volumes in 15 site-specific, non-COVID-affected control pregnancies. CLINICAL RELEVANCE: Preserved fetal lung volume following mild maternal SARS-CoV-2 infection during the omicron-dominated phase contrasts with previous findings of reduced volume in unvaccinated pregnancies during the alpha-dominated pandemic phase. These observations might reflect tropism- as well as immunity-related effects.

Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

OBJECTIVES: To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. METHODS: In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. RESULTS: Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). CONCLUSIONS: BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. CLINICAL RELEVANCE STATEMENT: Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

Immune Modulation in Untreated, Contralateral Hepatic Metastases after Yttrium-90 Radioembolization of Microsatellite Stable Colorectal Cancer.

PURPOSE: To assess immunogenic effects in unembolized contralateral tumor after single lobar yttrium-90 transarterial radioembolization (90Y-TARE) of colorectal liver metastases (CRLMs). MATERIAL AND METHODS: The analysis comprised 10 patients with microsatellite stable (MSS) CRLM scheduled for staged treatment in the prospective AROMA trial. Eligibility criteria included bilobar metastatic disease with >5 lesions without any treatment within 3 weeks. Baseline biopsy was followed by initial 90Y-TARE treatment of 1 liver lobe, followed by a second biopsy of yet untreated tumors in the other liver lobe at a median of 13 days (range, 4-49 days) immediately before second treatment. Tumor biopsies and peripheral blood mononuclear cells (PBMCs) were collected before treatments for immune cell analysis. Patients were stratified into responders and nonresponders based on tumor control or progression during follow-up. RESULTS: At baseline, responders (n = 4) displayed lower concentrations of FoxP3+ cells and colocation of CD4+FoxP3+ cells than nonresponders (both P = .02) in tumor tissues. At second biopsy, nonresponders showed a higher CD68+ macrophage density (P = .0014) than responders. Responders displayed fewer CD4+FoxP3+ T cells than CD8+ T cells at all time points (P = .02 and P = .0428). Nonresponders demonstrated a trending increase in CD68+ macrophages (P = .062), as well as a higher CD8+PD1+/CD8+ ratio (P = .062). PBMCs of nonresponders displayed lower CD8+PD1+ T cells and CD8+PD1+/CD8+ ratio at both time points. CONCLUSIONS: 90Y-TARE induces local immunogenic effects in nonexposed MSS CRLM, as well as systemic exhaustion of immune cells in nonresponders. Clinical implications such as a prognostic role or synergism of 90Y-TARE and checkpoint inhibition in MSS CRLM warrant further investigation.

Radiological age assessment based on clavicle ossification in CT: enhanced accuracy through deep learning.

BACKGROUND: Radiological age assessment using reference studies is inherently limited in accuracy due to a finite number of assignable skeletal maturation stages. To overcome this limitation, we present a deep learning approach for continuous age assessment based on clavicle ossification in computed tomography (CT). METHODS: Thoracic CT scans were retrospectively collected from the picture archiving and communication system. Individuals aged 15.0 to 30.0 years examined in routine clinical practice were included. All scans were automatically cropped around the medial clavicular epiphyseal cartilages. A deep learning model was trained to predict a person's chronological age based on these scans. Performance was evaluated using mean absolute error (MAE). Model performance was compared to an optimistic human reader performance estimate for an established reference study method. RESULTS: The deep learning model was trained on 4,400 scans of 1,935 patients (training set: mean age = 24.2 years ± 4.0, 1132 female) and evaluated on 300 scans of 300 patients with a balanced age and sex distribution (test set: mean age = 22.5 years ± 4.4, 150 female). Model MAE was 1.65 years, and the highest absolute error was 6.40 years for females and 7.32 years for males. However, performance could be attributed to norm-variants or pathologic disorders. Human reader estimate MAE was 1.84 years and the highest absolute error was 3.40 years for females and 3.78 years for males. CONCLUSIONS: We present a deep learning approach for continuous age predictions using CT volumes highlighting the medial clavicular epiphyseal cartilage with performance comparable to the human reader estimate.

miRNome Profiling Analysis Reveals Novel Hepatocellular Carcinoma Diagnostic, Prognostic and Treatment-Related Candidate Biomarkers: Post hoc Analysis of SORAMIC Trial.

INTRODUCTION: Early diagnosis of hepatocellular carcinoma (HCC) as well as evaluation of prognosis and prediction of treatment efficacy remains challenging due to the missing specific non-invasive biomarkers. The aim of this study was to identify disease-specific microRNA (miRNA) patterns for diagnosis, prediction of prognosis, and treatment response in patients with HCC. METHODS: The study population included 42 HCC patients from SORAMIC clinical trial: 22 patients received sorafenib monotherapy, 20 patients underwent 90Y radioembolization in combination with sorafenib. 20 individuals were included in the control group. HCC patients underwent collection of plasma samples before and 7-9 weeks after the beginning of the treatment. Isolation of circulating miRNAs, preparation of small RNA sequencing libraries and next-generation sequencing were performed. Association analysis for novel diagnostic, prognostic, and treatment-related candidate biomarkers was performed. RESULTS: A total of 42 differentially expressed (16 up-regulated and 26 down-regulated) miRNAs were identified comparing baseline and control group plasma samples. hsa-miR-215-5p and hsa-miR-192-5p were down-regulated, while hsa-miR-483-5p and hsa-miR-23b-3p were up-regulated comparing baseline and 7-9 weeks post-sorafenib monotherapy samples. hsa-miR-215-5p was the sole down-regulated miRNA in the same combination therapy comparison. hsa-miR-183-5p, hsa-miR-28-3p, and hsa-miR-1246 were found to be significantly up-regulated comparing non-responders versus responders to sorafenib. High hsa-miR-215-5p expression was significantly associated with worse HCC patients' prognosis. CONCLUSIONS: Systematic miRNA profiling of highly characterized samples from SORAMIC study revealed a subset of potential miRNA biomarkers for HCC diagnosis and prognosis of sorafenib-treated patients' survival.

Efficacy and Safety of Local Liver Radioablation in Hepatocellular Carcinoma Lesions within and beyond Limits of Thermal Ablation.

INTRODUCTION: CT-guided interstitial brachytherapy (iBT) radiotherapy has been established in the treatment of liver tumors. With iBT, hepatocellular carcinoma (HCC) lesions can be treated beyond the limits of thermal ablation (i.e., size and location). However, a comprehensive analysis of the efficacy of iBT in patients within and beyond thermal ablation limits is lacking. MATERIALS AND METHODS: A total of 146 patients with 216 HCC lesions have been analyzed retrospectively. Clinical and imaging follow-up data has been collected. Lesions were evaluated in terms of suitability for thermal ablation or not. The correlation between local tumor control (LTC), time to progression (TTP), overall survival (OS), and clinical and imaging parameters have been evaluated using univariable and multivariable Cox regression analyses. RESULTS: LTC rates at 12 months, 24 months, and 36 months were 87%, 75%, and 73%, respectively. 65% of lesions (n = 141) were not suitable for radiofrequency ablation (RFA). The median TTP was 13 months, and the median OS was not reached (3-year OS rate: 70%). No significant difference in LTC, TTP, or OS regarding RFA suitability existed. However, in the overall multivariable analysis, lesion diameter >5 cm was significantly associated with lower LTC (HR: 3.65, CI [1.60-8.31], p = 0.002) and shorter TTP (HR: 2.08, CI [1.17-3.70], p = 0.013). Advanced BCLC stage, Child-Pugh Stage, and Hepatitis B were associated with shorter OS. CONCLUSION: iBT offers excellent LTC rates and OS in local HCC treatment regardless of the limits of thermal ablation, suggesting further evidence of its alternative role to thermal ablation in patients with early-stage HCC.

Association between Long-Term Exposure to Traffic-Related Air Pollution and Cardio-Metabolic Phenotypes: An MRI Data-Based Analysis.

Long-term exposure to traffic-related air pollution (TRAP) is associated with cardiometabolic disease; however, its role in subclinical stages of disease development is unclear. Thus, we aimed to explore this association in a cross-sectional analysis, with cardiometabolic phenotypes derived from magnetic resonance imaging (MRI). Phenotypes of the left (LV) and right cardiac ventricle, whole-body adipose tissue (AT), and organ-specific AT were obtained by MRI in 400 participants of the KORA cohort. Land-use regression models were used to estimate residential long-term exposures to TRAP, e.g., nitrogen dioxides (NO2) or particle number concentration (PNC). Associations between TRAP and MRI phenotypes were modeled using linear regression. Participants' mean age was 56 ± 9 years, and 42% were female. Long-term exposure to TRAP was associated with decreased LV wall thickness; a 6.0 µg/m3 increase in NO2 was associated with a -1.9% [95% confidence interval: -3.7%; -0.1%] decrease in mean global LV wall thickness. Furthermore, we found associations between TRAP and increased cardiac AT. A 2,242 n/cm3 increase in PNC was associated with a 4.3% [-1.7%; 10.4%] increase in mean total cardiac AT. Associations were more pronounced in women and in participants with diabetes. Our exploratory study indicates that long-term exposure to TRAP is associated with subclinical cardiometabolic disease states, particularly in metabolically vulnerable subgroups.

Metabolomic Analysis of Human Cirrhosis and Hepatocellular Carcinoma: A Pilot Study.

BACKGROUND: Molecular changes in HCC development are largely unknown. As the liver plays a fundamental role in the body's metabolism, metabolic changes are to be expected. AIMS: We aimed to identify metabolomic changes in HCC in comparison to liver cirrhosis (LC) patients, which could potentially serve as novel biomarkers for HCC diagnosis and prognosis. METHODS: Metabolite expression from 38 HCC from the SORAMIC trial and 32 LC patients were analyzed by mass spectrometry. Metabolites with significant differences between LC and HCC at baseline were analyzed regarding expression over follow-up. In addition, association with overall survival was tested using univariate Cox proportional-hazard analysis. RESULTS: 41 metabolites showed differential expression between LC and HCC patients. 14 metabolites demonstrated significant changes in HCC patients during follow-up. Campesterol, lysophosphatidylcholine, octadecenoic and octadecadienoic acid, and furoylglycine showed a differential expression in the local ablation vs. palliative care group. High expression of eight metabolites (octadecenoic acid, 2-hydroxybutyrate, myo-inositol, isocitrate, erythronic acid, creatinine, pseudouridine, and erythrol) were associated with poor overall survival. The association between poor OS and octadecenoic acid and creatinine remained statistically significant even after adjusting for tumor burden and LC severity. CONCLUSION: Our findings give promising insides into the metabolic changes during HCC carcinogenesis and provide candidate biomarkers for future studies. Campesterol and furoylglycine in particular were identified as possible biomarkers for HCC progression. Moreover, eight metabolites were detected as predictors for poor overall survival.

Diffusion-weighted MRI (DWI) for assessment of response to high-dose-rate CT-guided brachytherapy (HDR-BT) of hepatocellular carcinoma.

BACKGROUND: High-dose-rate computed tomography (CT)-guided brachytherapy (HDR-BT) has shown promising results in patients with hepatocellular carcinoma (HCC). While growing evidence shows clear limitations of mRECIST, diffusion-weighted imaging (DWI) has relevant potential in improving the response assessment. PURPOSE: To assess whether DWI allows evaluation of short- and long-term tumor response in patients with HCC after HDR-BT. MATERIAL AND METHODS: A total of 22 patients with 11 non-responding HCCs (NR-HCC; local tumor recurrence within two years) and 24 responding HCCs (R-HCC; follow-up at least two years) were included in this retrospective bi-center study. HCCs were treated with HDR-BT and patients underwent pre- and post-interventional magnetic resonance imaging (MRI). Analyses of DWI were evaluated and compared between pre-interventional MRI, 1.follow-up after 3 months and 2.follow-up at the time of the local tumor recurrence (in NR-HCC) or after 12 months (in R-HCC). RESULTS: ADCmean of R-HCC increased significantly after HDR-BT on the first and second follow-up (ADCmean: 0.87 ± 0.18 × 10-3 mm2/s [pre-interventional]: 1.14 ± 0.23 × 10-3 mm2/s [1. post-interventional]; 1.42 ± 0.32 × 10-3 mm2/s [2. post-interventional]; P < 0.001). ADCmean of NR-HCC did not show a significant increase from pre-intervention to 1. post-interventional MRI (ADCmean: 0.85 ± 0.24 × 10-3 mm2/s and 1.00 ± 0.30 × 10-3 mm2/s, respectively; P = 0.131). ADCmean increase was significant between pre-intervention and 2. follow-up (ADCmean: 1.03 ± 0.19 × 10-3 mm2/s; P = 0.018). There was no significant increase of ADCmean between the first and second follow-up. There was, however, a significant increase of ADCmin after 12 months (ADCmin: 0.87 ± 0.29 × 10-3 mm2/s) compared to pre-interventional MRI and first follow-up (P < 0.005) only in R-HCC. CONCLUSION: The tumor response after CT-guided HDR-BT was associated with a significantly higher increase in ADCmean and ADCmin in short- and long-term follow-up.

Diagnostic performance and interreader agreement of individual and combined non-enhanced and contrast-enhanced MR imaging parameters in adhesive capsulitis of the shoulder.

OBJECTIVE: The aims of our study were to analyze agreement among readers with different levels of expertise and diagnostic performance of individual and combined imaging signs for the diagnosis of adhesive capsulitis of the shoulder. METHODS: In a retrospective study, contrast-enhanced shoulder MRIs of 60 patients with and 120 without clinically diagnosed adhesive capsulitis were evaluated by three readers independently. As non-enhanced imaging signs, readers evaluated signal intensity and thickness of the axillary recess capsule, thickness of the rotator interval capsule and the coracohumeral ligament as well as obliteration of subcoracoid fat. Furthermore, contrast enhancement of axillary recess and rotator interval capsule were evaluated. Data analysis included interreader reliability, ROC analysis, and logistic regression (p < 0.05). RESULTS: Contrast-enhanced parameters showed substantially higher agreement among readers (ICC 0.79-0.80) than non-enhanced parameters (0.37-0.45). AUCs of contrast-enhanced signs (95.1-96.6%) were significantly higher (p < 0.01) than of non-enhanced imaging signs (61.5-85.9%) when considered individually. Combined evaluation of axillary recess signal intensity and thicknesses of axillary recess or rotator interval-when at least one of two signs was rated positive-increased accuracy compared to individual imaging signs, however not statistically significant. CONCLUSION: Contrast-enhanced imaging signs show both distinctly higher agreement among readers and distinctly higher diagnostic performance compared to non-enhanced imaging signs based on the imaging protocol used in this study. Combined evaluation of parameters showed a tendency to increase discrimination; however, the effect on diagnosis of ACS was not statistically significant.