Effect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma.

Background Image-guided tumor ablation is the first-line therapy for early-stage hepatocellular carcinoma (HCC), with ongoing investigations into its combination with immunotherapies. Matrix metalloproteinase (MMP) inhibition demonstrates immunomodulatory potential and reduces HCC tumor growth when combined with ablative treatment. Purpose To evaluate the effect of incomplete cryoablation with or without MMP inhibition on the local immune response in residual tumors in a murine HCC model. Materials and Methods Sixty 8- to 10-week-old female BALB/c mice underwent HCC induction with use of orthotopic implantation of syngeneic Tib-75 cells. After 7 days, mice with a single lesion were randomized into treatment groups: (a) no treatment, (b) MMP inhibitor, (c) incomplete cryoablation, and (d) incomplete cryoablation and MMP inhibitor. Macrophage and T-cell subsets were assessed in tissue samples with use of immunohistochemistry and immunofluorescence (cell averages calculated using five 1-µm2 fields of view [FOVs]). C-X-C motif chemokine receptor type 3 (CXCR3)- and interferon γ (IFNγ)-positive T cells were assessed using flow cytometry. Groups were compared using unpaired Student t tests, one-way analysis of variance with Tukey correction, and the Kruskal-Wallis test with Dunn correction. Results Mice treated with incomplete cryoablation (n = 6) showed greater infiltration of CD206+ tumor-associated macrophages (mean, 1.52 cells per FOV vs 0.64 cells per FOV; P = .03) and MMP9-expressing cells (mean, 0.89 cells per FOV vs 0.11 cells per FOV; P = .03) compared with untreated controls (n = 6). Incomplete cryoablation with MMP inhibition (n = 6) versus without (n = 6) led to greater CD8+ T-cell (mean, 15.8% vs 8.29%; P = .04), CXCR3+CD8+ T-cell (mean, 11.64% vs 8.47%; P = .004), and IFNγ+CD8+ T-cell infiltration (mean, 11.58% vs 5.18%; P = .02). Conclusion In a mouse model of HCC, incomplete cryoablation and systemic MMP inhibition showed increased cytotoxic CD8+ T-cell infiltration into the residual tumor compared with either treatment alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Gemmete in this issue.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Tumor response assessment in hepatocellular carcinoma treated with immunotherapy: imaging biomarkers for clinical decision-making.

OBJECTIVE: To compare the performance of 1D and 3D tumor response assessment for predicting median overall survival (mOS) in patients who underwent immunotherapy for hepatocellular carcinoma (HCC). METHODS: Patients with HCC who underwent immunotherapy between 2017 and 2023 and received multi-phasic contrast-enhanced MRIs pre- and post-treatment were included in this retrospective study. Tumor response was measured using 1D, RECIST 1.1, and mRECIST, and 3D, volumetric, and percentage quantitative EASL (vqEASL and %qEASL). Patients were grouped into disease control vs progression and responders vs non-responders. Kaplan-Meier curves analyzed with log-rank tests assessed the predictive value for mOS. Cox regression modeling evaluated the association of clinical baseline parameters with mOS. RESULTS: This study included 37 patients (mean age, 69.1 years [SD, 8.0]; 33 men). The mOS was 16.9 months. 3D vqEASL and %qEASL successfully stratified patients into disease control and progression (vqEASL: HR 0.21, CI: 0.55-0.08, p < 0.001; %qEASL: HR 0.18, CI: 0.83-0.04, p = 0.013), as well as responder and nonresponder (vqEASL: HR 0.25, CI: 0.08-0.74, p = 0.007; %qEASL: HR 0.17, CI: 0.04-0.72, p = 0.007) for predicting mOS. The 1D criteria, mRECIST stratified into disease control and progression only (HR 0.24, CI: 0.65-0.09, p = 0.002), and RECIST 1.1 showed no predictive value in either stratification. Multivariate Cox regression identified alpha-fetoprotein > 500 ng/mL as a predictor for poor mOS (p = 0.04). CONCLUSION: The 3D quantitative enhancement-based response assessment tool qEASL can predict overall survival in patients undergoing immunotherapy for HCC and could identify non-responders. CLINICAL RELEVANCE STATEMENT: Using 3D quantitative enhancement-based tumor response criteria (qEASL), radiologists' predictions of tumor response in patients undergoing immunotherapy for HCC can be further improved. KEY POINTS: MRI-based tumor response criteria predict immunotherapy survival benefits in HCC patients. 3D tumor response assessment methods surpass current evaluation criteria in predicting overall survival during HCC immunotherapy. Enhancement-based 3D tumor response criteria are robust prognosticators of survival for HCC patients on immunotherapy.

Short-Term Out-of-Pocket and Total Costs of Care After Ablation, Resection, or Transplant for Early-Stage Hepatocellular Carcinoma: A National SEER-Medicare Cost Comparison.

Background: Differences in survival and morbidity among treatment options (ablation, surgical resection, and transplant) for early-stage hepatocellular carcinoma (HCC) have been well-studied. Additional understanding of the costs of such care would help to identify drivers of high costs and potential barriers to care delivery. Objective: To quantify total and patient out-of-pocket costs for ablation, surgical resection, and transplant in the management of early-stage HCC and to identify factors predictive of these costs. Methods: This retrospective U.S. population-based study used the SEER-Medicare linked dataset to identify a sample of 1067 Medicare beneficiaries (mean age, 73 years; 674 men, 393 women) diagnosed with early-stage HCC (size ≤5 cm) treated with ablation (N=623), resection (N=201), or transplant (N=243) between January 2009 and December 2016. Total costs and patient out-of-pocket costs for the index procedure as well as for any care within 30 days and 90 days post-procedure were identified and stratified by treatment modality. Additional comparisons were performed among propensity-score matched subgroups of patients treated by ablation or resection (each N=172). Multivariable linear regression models were used to identify factors predictive of total costs and out-of-pocket costs for index procedures as well as for 30-day and 90-day post-procedure periods. Results: For ablation, resection, and transplant, median index-procedure total cost was $6689, $25,614, and $66,034; index-procedure out-of-pocket cost was $1235, $1650, and $1317; 30-day total cost was $9456, $29,754, and $69,856; 30-day out-of-pocket cost was $1646, $2208, and $3198; 90-day total cost was $14,572, $34,984, and $88,103; and 90-day out-of-pocket cost was $2138, $2462, and $3876, respectively (all p<.001). In propensity-matched subgroups, ablation and resection had median index-procedure, 30-day, and 90-day total costs of $6690 and $25,716, $9995 and $30,365, and $15,851 and $34,455, respectively. In multivariable analysis adjusting for socioeconomic factors, comorbidities, and liver-disease prognostic indicators, surgical treatment (resection or transplant) was predictive of significantly greater costs compared with ablation at all time points. Conclusion: Total and out-of-pocket costs for index procedures as well as for 30-day and 90-day post-procedure periods were lowest for ablation, followed by resection and then transplant. Clinical Impact: This comprehensive cost analysis could help inform future cost-effectiveness analyses.

Defining textbook outcome for selective internal radiation therapy of hepatocellular carcinoma: an international expert study.

BACKGROUND: A textbook outcome (TO) is a composite indicator covering the entire intervention process in order to reflect the "ideal" intervention and be a surrogate for patient important outcomes. Selective internal radiation therapy (SIRT) is a complex multidisciplinary and multistep intervention facing the challenge of standardization. This expert opinion-based study aimed to define a TO for SIRT of hepatocellular carcinoma. METHODS: This study involved two steps: (1) the steering committee (4 interventional radiologists) first developed an extensive list of possible relevant items reflecting an optimal SIRT intervention based on a literature review and (2) then conducted an international and multidisciplinary survey which resulted in the final TO. This survey was online, from February to July 2021, and consisted three consecutive rounds with predefined settings. Experts were identified by contacting senior authors of randomized trials, large observational studies, or studies on quality improvement in SIRT. This study was strictly academic. RESULTS: A total of 50 items were included in the first round of the survey. A total of 29/40 experts (73%) responded, including 23 interventional radiologists (79%), three nuclear medicine physicians (10%), two hepatologists, and one oncologist, from 11 countries spanning three continents. The final TO consisted 11 parameters across six domains ("pre-intervention workup," "tumor targeting and dosimetry," "intervention," "post-90Y imaging," "length of hospital stay," and "complications"). Of these, all but one were applied in the institutions of > 80% of experts. CONCLUSIONS: This multidimensional indicator is a comprehensive standardization tool, suitable for routine care, clinical round, and research.

Experimental VX2 Rabbit Liver Tumor Model in Carbon Tetrachloride-Induced Cirrhosis of the Liver.

Liver cirrhosis is a major underlying factor in the development of hepatocellular carcinoma. Currently, there is an unmet need for midsize experimental vertebrate models that would offer reproducible implantable liver tumors in a cirrhotic liver background. This study establishes a protocol for a syngeneic rabbit model of VX2 liver cancer with underlying liver cirrhosis induced using carbon tetrachloride (CCl4). Male New Zealand white rabbits (n = 3) received CCl4 by intragastric administration once weekly. Concentrations started at 5% v/v CCl4 dissolved in olive oil. CCl4 dosing was progressively increased every week by 2.5% v/v increments for the duration of treatment (16 weeks total). VX2 tumors were then orthotopically implanted into the left hepatic lobe and allowed to grow for 3 weeks. Cross-sectional imaging confirmed the presence of hepatic tumors. Gross and histopathological evaluations showed reproducible tumor growth in the presence of liver cirrhosis in all animals.

Hepatic Hypertrophy in Normal and Cirrhotic Livers Following Portal Vein Embolization: Comparative Assessment of 2 Different Embolic Regimens in a Large Animal Model.

PURPOSE: To compare the mechanistic effects and hypertrophy outcomes using 2 different portal vein embolization (PVE) regimens in normal and cirrhotic livers in a large animal model. METHODS AND MATERIALS: The Institutional Animal Care and Use Committee approved all experiments conducted in this study. Fourteen female Yorkshire pigs were separated into a cirrhotic group (CG, n = 7) and non-cirrhotic group (NCG, n = 7) and further subgrouped into those using microspheres and coils (MC, n = 3) or n-butyl cyanoacrylate (nBCA, n = 3) and their corresponding controls (each n = 1). A 3:1 ethiodized oil and ethanol mixture was administered intra-arterially in the CG to induce cirrhosis 4 weeks before PVE. Animals underwent baseline computed tomography (CT), PVE including pre-PVE and post-PVE pressure measurements, and CT imaging at 2 and 4 weeks after PVE. Immunofluorescence stainings for CD3, CD16, Ki-67, and caspase 3 were performed to assess immune cell infiltration, hepatocyte proliferation, and apoptosis. Statistical significance was tested using the Student's t test. RESULTS: Four weeks after PVE, the percentage of future liver remnant (FLR%) increased by 18.8% (standard deviation [SD], 3.6%) vs 10.9% (SD, 0.95%; P < .01) in the NCG vs CG. The baseline percentage of standardized future liver remnant (sFLR%) for the controls were 41.6% for CG vs 43.6% for NCG. Based on the embolic agents used, the sFLR% two weeks after PVE was 58.4% (SD, 3.7%) and 52.2% (SD, 0.9%) (P < .01) for MC and 46.0% (SD, 2.2%) and 47.2% (SD, 0.4%) for nBCA in the NCG and CG, respectively. Meanwhile, the sFLR% 4 weeks after PVE was 60.5% (SD, 3.9%) and 54.9% (SD, 0.8%) (P < .01) and 60.4% (SD, 3.5%) and 54.2% (SD, 0.95%) (P < .01), respectively. Ki-67 signal intensity increased in the embolized lobe in both CG and NCG (P < .01). CONCLUSIONS: This preclinical study demonstrated that MC could be the preferred embolic of choice compared to nBCA when a substantial and rapid FLR increase is needed for resection, in both cirrhotic and non-cirrhotic livers.

Beyond Survival: Adverse Events and Care Delivery Outcomes after Early Liver Cancer Treatment in a Nationally Representative Cohort.

PURPOSE: To compare secondary outcomes after ablation (AB), surgical resection (SR), and liver transplant (LT) for small hepatocellular carcinomas (HCCs), including resource utilization and adverse event (AE) rates. MATERIALS AND METHODS: Using Surveillance, Epidemiology, and End Results Program (SEER)-Medicare, HCCs <5 cm that were treated with AB, SR, or LT in 2009-2016 (n = 1,067) were identified using Healthcare Common Procedure Coding System codes through Medicare claims. Index procedure length of stay, need for intensive care unit (ICU) level care, readmission rates, and AE rates at 30 and 90 days were compared using chi-square tests or Fisher exact tests. Examined AEs included hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease-related AEs, liver failure, and anesthesia-related AEs, identified by International Classification of Diseases, Ninth/10th Revision, codes. RESULTS: The median length of stay for initial treatment was 1 day, 6 days, and 7 days for AB, SR, and LT, respectively (P < .001). During initial hospital stay, 5.0%, 40.8%, and 63.4% of AB, SR, and LT cohorts, respectively, received ICU-level care (P < .001). By 30 and 90 days, there were significant differences among the AB, SR, and LT cohorts in the rate of postprocedural hemorrhage, abscess formation, biliary injury, pneumonia, sepsis, liver disease-related AEs, and anesthesia-related AEs (P < .05). By 90 days, the readmission rates after AB, SR, and LT were 18.6%, 28.2%, and 40.6% (P < .001), respectively. CONCLUSIONS: AB results in significantly less healthcare utilization during the initial 90 days after procedure compared with that after SR and LT due to shorter length of stay, lower intensity care, fewer readmissions, and fewer AEs.

MR Imaging-Based In Vivo Macrophage Imaging to Monitor Immune Response after Radiofrequency Ablation of the Liver.

PURPOSE: To establish molecular magnetic resonance (MR) imaging instruments for in vivo characterization of the immune response to hepatic radiofrequency (RF) ablation using cell-specific immunoprobes. MATERIALS AND METHODS: Seventy-two C57BL/6 wild-type mice underwent standardized hepatic RF ablation (70 °C for 5 minutes) to generate a coagulation area measuring 6-7 mm in diameter. CD68+ macrophage periablational infiltration was characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (n = 24). Twenty-one mice were subjected to a dose-escalation study with either 10, 15, 30, or 60 mg/kg of rhodamine-labeled superparamagnetic iron oxide nanoparticles (SPIONs) or 2.4, 1.2, or 0.6 mg/kg of gadolinium-160 (160Gd)-labeled CD68 antibody for assessment of the optimal in vivo dose of contrast agent. MR imaging experiments included 9 mice, each receiving 10-mg/kg SPIONs to visualize phagocytes using T2∗-weighted imaging in a horizontal-bore 9.4-T MR imaging scanner, 160Gd-CD68 for T1-weighted MR imaging of macrophages, or 0.1-mmol/kg intravenous gadoterate (control group). Radiological-pathological correlation included Prussian blue staining, rhodamine immunofluorescence, imaging mass cytometry, and immunohistochemistry. RESULTS: RF ablation-induced periablational infiltration (206.92 µm ± 12.2) of CD68+ macrophages peaked at 7 days after ablation (P < .01) compared with the untreated lobe. T2∗-weighted MR imaging with SPION contrast demonstrated curvilinear T2∗ signal in the transitional zone (TZ) (186 µm ± 16.9), corresponsing to Iron Prussian blue staining. T1-weighted MR imaging with 160Gd-CD68 antibody showed curvilinear signal in the TZ (164 µm ± 3.6) corresponding to imaging mass cytometry. CONCLUSIONS: Both SPION-enhanced T2∗-weighted and 160Gd-enhanced T1-weighted MR imaging allow for in vivo monitoring of macrophages after RF ablation, demonstrating the feasibility of this model to investigate local immune responses.

Machine Learning Models for Prediction of Posttreatment Recurrence in Early-Stage Hepatocellular Carcinoma Using Pretreatment Clinical and MRI Features: A Proof-of-Concept Study.

BACKGROUND. Posttreatment recurrence is an unpredictable complication after liver transplant for hepatocellular carcinoma (HCC) that is associated with poor survival. Biomarkers are needed to estimate recurrence risk before organ allocation. OBJECTIVE. This proof-of-concept study evaluated the use of machine learning (ML) to predict recurrence from pretreatment laboratory, clinical, and MRI data in patients with early-stage HCC initially eligible for liver transplant. METHODS. This retrospective study included 120 patients (88 men, 32 women; median age, 60.0 years) with early-stage HCC diagnosed who were initially eligible for liver transplant and underwent treatment by transplant, resection, or thermal ablation between June 2005 and March 2018. Patients underwent pretreatment MRI and posttreatment imaging surveillance. Imaging features were extracted from postcontrast phases of pretreatment MRI examinations using a pretrained convolutional neural network. Pretreatment clinical characteristics (including laboratory data) and extracted imaging features were integrated to develop three ML models (clinical model, imaging model, combined model) for predicting recurrence within six time frames ranging from 1 through 6 years after treatment. Kaplan-Meier analysis with time to recurrence as the endpoint was used to assess the clinical relevance of model predictions. RESULTS. Tumor recurred in 44 of 120 (36.7%) patients during follow-up. The three models predicted recurrence with AUCs across the six time frames of 0.60-0.78 (clinical model), 0.71-0.85 (imaging model), and 0.62-0.86 (combined model). The mean AUC was higher for the imaging model than the clinical model (0.76 vs 0.68, respectively; p = .03), but the mean AUC was not significantly different between the clinical and combined models or between the imaging and combined models (p > .05). Kaplan-Meier curves were significantly different between patients predicted to be at low risk and those predicted to be at high risk by all three models for the 2-, 3-, 4-, 5-, and 6-year time frames (p < .05). CONCLUSION. The findings suggest that ML-based models can predict recurrence before therapy allocation in patients with early-stage HCC initially eligible for liver transplant. Adding MRI data as model input improved predictive performance over clinical parameters alone. The combined model did not surpass the imaging model's performance. CLINICAL IMPACT. ML-based models applied to currently underutilized imaging features may help design more reliable criteria for organ allocation and liver transplant eligibility.

An Expert, Multidisciplinary Perspective on Best Practices in Biomarker Testing in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive malignancy that arises from the intrahepatic biliary tree and is associated with a poor prognosis. Until recently, the treatment landscape of advanced/metastatic iCCA has been limited primarily to chemotherapy. In recent years, the advent of biomarker testing has identified actionable genetic alterations in 40%-50% of patients with iCCA, heralding an era of precision medicine for these patients. Biomarker testing using next-generation sequencing (NGS) has since become increasingly relevant in iCCA; however, several challenges and gaps in standard image-guided liver biopsy and processing have been identified. These include variability in tissue acquisition relating to the imaging modality used for biopsy guidance, the biopsy method used, number of passes, needle choice, specimen preparation methods, the desmoplastic nature of the tumor, as well as the lack of communication among the multidisciplinary team. Recognizing these challenges and the lack of evidence-based guidelines for biomarker testing in iCCA, a multidisciplinary team of experts including interventional oncologists, a gastroenterologist, medical oncologists, and pathologists suggest best practices for optimizing tissue collection and biomarker testing in iCCA.

Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as "Preferred," "Other Recommended Regimens," or "Useful in Certain Circumstances." This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.

Comparison of metabolic and immunologic responses to transarterial chemoembolization with different chemoembolic regimens in a rabbit VX2 liver tumor model.

OBJECTIVES: The goal of this study was to investigate the effects of TACE using Lipiodol, Oncozene™ drug-eluting embolics (DEEs), or LUMI™-DEEs alone, or combined with bicarbonate on the metabolic and immunological tumor microenvironment in a rabbit VX2 tumor model. METHODS: VX2 liver tumor-bearing rabbits were assigned to five groups. MRI and extracellular pH (pHe) mapping using Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) were performed before and after intra-arterial therapy with conventional TACE (cTACE), DEE-TACE with Idarubicin-eluting Oncozene™-DEEs, or Doxorubicin-eluting LUMI™-DEEs, each with or without prior bicarbonate infusion, and in untreated rabbits or treated with intra-arterial bicarbonate only. Imaging results were validated with immunohistochemistry (IHC) staining of cell viability (PCNA, TUNEL) and immune response (HLA-DR, CD3). Statistical analysis was performed using Mann-Whitney U test. RESULTS: pHe mapping revealed that combining cTACE with prior bicarbonate infusion significantly increased tumor pHe compared to control (p = 0.0175) and cTACE alone (p = 0.0025). IHC staining revealed peritumoral accumulation of HLA-DR+ antigen-presenting cells and CD3 + T-lymphocytes in controls. cTACE-treated tumors showed reduced immune infiltration, which was restored through combination with bicarbonate. DEE-TACE with Oncozene™-DEEs induced moderate intratumoral and marked peritumoral infiltration, which was slightly reduced with bicarbonate. Addition of bicarbonate prior to LUMI™-beads enhanced peritumoral immune cell infiltration compared to LUMI™-beads alone and resulted in the strongest intratumoral immune cell infiltration across all treated groups. CONCLUSIONS: The choice of chemoembolic regimen for TACE strongly affects post-treatment TME pHe and the ability of immune cells to accumulate and infiltrate the tumor tissue. KEY POINTS: • Combining conventional transarterial chemotherapy with prior bicarbonate infusion increases the pHe towards a more physiological value (p = 0.0025). • Peritumoral infiltration and intratumoral accumulation patterns of antigen-presenting cells and T-lymphocytes after transarterial chemotherapy were dependent on the choice of the chemoembolic regimen. • Combination of intra-arterial treatment with Doxorubicin-eluting LUMI™-beads and bicarbonate infusion resulted in the strongest intratumoral presence of immune cells (positivity index of 0.47 for HLADR+-cells and 0.62 for CD3+-cells).

Quantitative Automated Segmentation of Lipiodol Deposits on Cone-Beam CT Imaging Acquired during Transarterial Chemoembolization for Liver Tumors: A Deep Learning Approach.

PURPOSE: To show that a deep learning (DL)-based, automated model for Lipiodol (Guerbet Pharmaceuticals, Paris, France) segmentation on cone-beam computed tomography (CT) after conventional transarterial chemoembolization performs closer to the "ground truth segmentation" than a conventional thresholding-based model. MATERIALS AND METHODS: This post hoc analysis included 36 patients with a diagnosis of hepatocellular carcinoma or other solid liver tumors who underwent conventional transarterial chemoembolization with an intraprocedural cone-beam CT. Semiautomatic segmentation of Lipiodol was obtained. Subsequently, a convolutional U-net model was used to output a binary mask that predicted Lipiodol deposition. A threshold value of signal intensity on cone-beam CT was used to obtain a Lipiodol mask for comparison. The dice similarity coefficient (DSC), mean squared error (MSE), center of mass (CM), and fractional volume ratios for both masks were obtained by comparing them to the ground truth (radiologist-segmented Lipiodol deposits) to obtain accuracy metrics for the 2 masks. These results were used to compare the model versus the threshold technique. RESULTS: For all metrics, the U-net outperformed the threshold technique: DSC (0.65 ± 0.17 vs 0.45 ± 0.22, P < .001) and MSE (125.53 ± 107.36 vs 185.98 ± 93.82, P = .005). The difference between the CM predicted and the actual CM was 15.31 mm ± 14.63 versus 31.34 mm ± 30.24 (P < .001), with lesser distance indicating higher accuracy. The fraction of volume present ([predicted Lipiodol volume]/[ground truth Lipiodol volume]) was 1.22 ± 0.84 versus 2.58 ± 3.52 (P = .048) for the current model's prediction and threshold technique, respectively. CONCLUSIONS: This study showed that a DL framework could detect Lipiodol in cone-beam CT imaging and was capable of outperforming the conventionally used thresholding technique over several metrics. Further optimization will allow for more accurate, quantitative predictions of Lipiodol depositions intraprocedurally.

Impact of Chemoembolic Regimen on Immune Cell Recruitment and Immune Checkpoint Marker Expression following Transcatheter Arterial Chemoembolization in a VX2 Rabbit Liver Tumor Model.

PURPOSE: To characterize the effects of commonly used transcatheter arterial chemoembolization (TACE) regimens on the immune response and immune checkpoint marker expression using a VX2 rabbit liver tumor model. MATERIALS AND METHODS: Twenty-four VX2 liver tumor-bearing New Zealand white rabbits were assigned to 7 groups (n = 3 per group) undergoing locoregional therapy as follows: (a) bicarbonate infusion without embolization, (b) conventional TACE (cTACE) using a water-in-oil emulsion containing doxorubicin mixed 1:2 with Lipiodol, drug-eluting embolic-TACE with either (c) idarubicin-eluting Oncozene microspheres (40 µm) or (d) doxorubicin-eluting Lumi beads (40-90 µm). For each therapy arm (b-d), a tandem set of 3 animals with additional bicarbonate infusion before TACE was added, to evaluate the effect of pH modification on the immune response. Three untreated rabbits served as controls. Tissue was harvested 24 hours after treatment, followed by digital immunohistochemistry quantification (counts/µm2 ± SEM) of tumor-infiltrating cluster of differentiation 3+ T-lymphocytes, human leukocyte antigen DR type antigen-presenting cells (APCs), cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway axis expression. RESULTS: Lumi-bead TACE induced significantly more intratumoral T-cell and APC infiltration than cTACE and Oncozene-microsphere TACE. Additionally, tumors treated with Lumi-bead TACE expressed significantly higher intratumoral immune checkpoint markers compared with cTACE and Oncozene-microsphere TACE. Neoadjuvant bicarbonate demonstrated the most pronounced effect on cTACE and resulted in a significant increase in intratumoral cluster of differentiation 3+ T-cell infiltration compared with cTACE alone. CONCLUSIONS: This preclinical study revealed significant differences in evoked tumor immunogenicity depending on the choice of chemoembolic regimen for TACE.

Locoregional Therapy in the Management of Intrahepatic Cholangiocarcinoma: Is There Sufficient Evidence to Guide Current Clinical Practice?

PURPOSE OF REVIEW: Intrahepatic cholangiocarcinoma (iCCA) carries a dismal prognosis and, despite increasing incidence, still lacks effective treatments. In this scenario, locoregional therapies (LRT) are gaining interest as they may be effective at local tumor control and complementary to surgical and non-surgical approaches. In this article, we will review the evolving role of LRT performed by interventional radiologists in the management of iCCA. RECENT FINDINGS: Accumulating retrospective evidence indicates that ablative therapies and transarterial embolizations are of benefit for iCCA with unresectable disease, demonstrating promising safety profiles and prolonged or comparable survival outcomes compared to systemic therapy and surgery. Additionally, for surgical candidates, portal ± hepatic venous embolization can improve the safety of hepatectomy by inducing preoperative hypertrophy of the non-involved liver lobe. LRTs are playing an increasingly important role in the multimodal treatment of iCCA from various perspectives with reduced toxicity relative to traditional treatments. To expand the scope of applications for LRTs in this setting, future prospective randomized studies are needed to confirm their efficacy and advantage.

Management of Refractory Ascites Due to Portal Hypertension: Current Status.

Refractory ascites is a costly and debilitating condition that occurs most frequently in the setting of substantial cirrhotic portal hypertension, where it portends a poor prognosis. Many treatment options are available, among them medical management, serial large volume paracenteses, transjugular intrahepatic portosystemic shunts, and implanted drainage devices. Although the availability of multiple therapies ensures that most patients will achieve satisfactory results, it can be challenging for the provider to select the appropriate treatment for each specific patient. This article reviews the available therapeutic options for refractory ascites and incorporates available data and clinical experience to suggest a linear stepwise management approach to enhance patient outcomes.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

Systematic Reviews and Meta-Analyses of Portal Vein Embolization, Associated Liver Partition and Portal Vein Ligation, and Radiation Lobectomy Outcomes in Hepatocellular Carcinoma Patients.

PURPOSE OF REVIEW: To understand portal vein embolization (PVE), associated liver partition and portal vein ligation (ALPPS) and radiation lobectomy (RL) outcomes in hepatocellular carcinoma (HCC) patients. Systematic reviews of future liver remnant (FLR) percent hypertrophy, proportion undergoing hepatectomy and proportion with major complications following PVE, ALPPS, and RL were performed by searching Ovid MEDLINE, Ovid EMBASE, The Cochrane Library, and Web of Science. Separate meta-analyses using random-effects models with assessment of study heterogeneity and publication bias were performed whenever allowable by available data. RECENT FINDINGS: Of the 10,616 articles screened, 21 articles with 636 subjects, 4 articles with 65 subjects, and 4 articles with 195 subjects met the inclusion criteria for systematic reviews and meta-analyses for PVE, ALPPS, and RL, respectively. The pooled estimate of mean percent FLR hypertrophy was 30.9% (95%CI: 22-39%, Q = 4034.8, p < 0.0001) over 40.3 +/- 26.3 days for PVE, 54.9% (95%CI: 36-74%, Q = 73.8, p < 0.0001) over 11.1 +/- 3.1 days for ALPPS, and 29.0% (95%CI: 23-35%, Q = 56.2, p < 0.0001) over 138.5 +/- 56.5 days for RL. The pooled proportion undergoing hepatectomy was 91% (95%CI: 83-95%, Q = 43.9, p = 0.002) following PVE and 98% (95%CI: 50-100%, Q = 0.0, p = 1.0) following ALPPS. The pooled proportion with major complications was 5% (95%CI: 2-10%, Q = 7.3, p = 0.887) following PVE and 38% (95%CI: 18-63%, Q = 10.0, p = 0.019) following ALPPS. Though liver hypertrophy occurs following all three treatments in HCC patients, PVE balances effective hypertrophy with a short time frame and low major complication rate.