Measurement of the Tumor-to-Normal Ratio for Radioembolization of Hepatocellular Carcinoma: A Prospective Study Comparing 2-Dimensional Perfusion Angiography, Technetium-99m Macroaggregated Albumin, and Yttrium-90 SPECT/CT.

PURPOSE: To calculate the preradioembolic tumor-to-normal (T:N) ratio in hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography and compare it with that calculated using technetium-99m macroaggregated albumin (99mTc MAA) single-photon emission computed tomography (SPECT)/computed tomography (CT). MATERIALS AND METHODS: This prospective single-arm study enrolled 15 participants with HCC who underwent 2D perfusion angiography immediately before the enrollment and with the microcatheter located at the same location as 99mTc MAA injection, after which SPECT/CT was performed. Quantitative digital subtraction angiography was used to calculate the area under the curve for the tumor and normal hepatic parenchyma and subsequently calculate the T:N ratio. The T:N ratio was calculated from the 99mTc MAA SPECT/CT and post-yttrium-90 bremsstrahlung SPECT/CT using dosimetry software. RESULTS: The mean participant age was 64.1 years ± 9.8, and the study included 14 (93%) men and 1 (7%) woman. The mean tumor size was 4.1 cm (SD ± 2.4), and all participants received segmental treatments with glass microspheres. The mean T:N ratio calculated by 99mTc MAA SPECT/CT was 2.28 (SD ± 0.89) vs 2.25 (SD ± 0.99) calculated by 2D perfusion angiography (P = .45). For the 13 participants who underwent selective internal radiation therapy (transarterial radioembolization), there was no significant difference between the T:N ratios calculated by 2D perfusion angiography and post-90Y SPECT/CT (2.25 [SD ± 1.05] vs 1.91 [SD ± 0.39]; P = .12). CONCLUSIONS: The T:N ratio calculated by 2D perfusion angiography correlated well with that calculated by 99mTc MAA SPECT/CT.

A Pilot Study of F-18 Fluciclovine-PET/CT as a Diagnostic Tool for Bone Metastases in Patients With Castrate Resistant Prostate Adenocarcinoma and Correlative Analysis of Blood and Bone Molecular Testing (The FACT Study).

BACKGROUND: Suspicious F-18 fluciclovine PET/CT findings for osseous metastases from prostate cancer (PC) were targeted for core needle biopsy. We correlated the maximum standardized uptake value (SUVmax) of biopsied lesions, with biopsy results, other diagnostic outcomes, and blood and tissue molecular analysis (TMA). MATERIAL AND METHODS: Patients with castrate resistant prostate cancer (CRPC) were recruited from a university oncology clinic. SUVmax, histology, blood, and TMA were correlated. RESULTS: Fifteen patients were enrolled and 12 underwent bone biopsies. Fifty percent of bone biopsies demonstrated malignancy. Higher SUVmax was associated with positive biopsies for adenocarcinoma (P = .003), and lesions with SUVmax ≥ 5.1 were all positive for malignancy. Significant correlation between blood and somatic TMA (P = .002) was also found. CONCLUSION: Higher uptake of F-18 fluciclovine was associated with higher predictive value for osseous metastasis on biopsy. There was a significant correlation between blood and TMA.

Friend or Foe? Locoregional Therapies and Immunotherapies in the Current Hepatocellular Treatment Landscape.

Over the last several decades, a number of new treatment options for patients with hepatocellular carcinoma (HCC) have been developed. While treatment decisions for some patients remain clear cut, a large numbers of patients have multiple treatment options, and it can be hard for multidisciplinary teams to come to unanimous decisions on which treatment strategy or sequence of treatments is best. This article reviews the available data with regard to two treatment strategies, immunotherapies and locoregional therapies, with a focus on the potential of locoregional therapies to be combined with checkpoint inhibitors to improve outcomes in patients with locally advanced HCC. In this review, the available data on the immunomodulatory effects of locoregional therapies is discussed along with available clinical data on outcomes when the two strategies are combined.

Percutaneous Radiofrequency Ablation to Occlude the Thoracic Duct: Preclinical Studies in Swine for a Potential Alternative to Embolization.

PURPOSE: To investigate the feasibility of percutaneous radiofrequency (RF) ablation to occlude the thoracic duct (TD) in a swine model with imaging and histologic correlation. MATERIALS AND METHODS: Six swine underwent TD RF ablation. Two terminal (4 hours, 1 open and 1 percutaneous) and 4 survival (30 days, all percutaneous) studies were performed. Two 20-gauge needles were placed adjacent to the TD under direct visualization after right thoracotomy or under fluoroscopic guidance using a percutaneous transabdominal approach after intranodal lymphangiography. RF electrodes were advanced through the needles, and ablation was performed at 90°C for 90 seconds. Lymphangiography was performed, and the TD and adjacent structures were resected and examined microscopically at the end of each study period. RESULTS: Four of 6 subjects survived the planned study period and underwent follow-up lymphangiography. Two subjects in the survival group were euthanized early-1 after developing an acute chylothorax and 1 because of gastric volvulus 14 days after ablation. Occlusion of the targeted TD segment was noted on lymphangiography in 3 of the 4 remaining subjects (2 acute and 1 survival). Histology 4 hours after RF ablation demonstrated necrosis of the TD wall and hemorrhage within the lumen. Histology at 14 and 30 days revealed fibrosis with hemosiderin-laden macrophages replacing the ablated TD. Collagen degeneration within the aortic wall involving a maximum of 60% thickness was noted in 5 of the 6 subjects. CONCLUSIONS: Percutaneous RF ablation can achieve short-segment TD occlusion. Further study is needed to improve safety and demonstrate clinical efficacy in treating TD leaks.

Clinical and Dosimetric Implications of Calculating Lung Shunt Fraction for Hepatic 90Y Radioembolization Using SPECT/CT Versus Planar Scintigraphy.

BACKGROUND. Accurate assessment of hepatopulmonary shunting, typically performed by planar scintigraphy, is critical in planning 90Y radioembolization. High lung shunt fractions (LSFs) may alter treatment. OBJECTIVE. The purpose of this study is to compare LSFs calculated from planar scintigraphy versus SPECT/CT in patients with high planar LSFs (> 15%) and to describe the potential clinical and dosimetric implications of SPECT/CT LSF calculations. METHODS. This retrospective study included 36 patients (29 men and seven women; mean age, 62.4 ± 9.8 [SD] years) who underwent 99mTc-macroaggregated albumin (MAA) planar scintigraphy for planning hepatic radioembolization, had a planar LSF greater than 15%, and underwent concurrent SPECT/CT. Clinically reported planar LSFs were recorded. SPECT/CT LSFs were retrospectively calculated using automatically generated volumetric ROIs around the lungs and liver with subsequent manual adjustments. Total lung and perfused liver doses were calculated using a medical internal radiation dose model. Values derived from planar and SPECT/CT data were compared using Mann-Whitney U tests. Multivariable regression analysis was performed of factors associated with the discrepancy in LSF between the techniques. RESULTS. Mean planar LSF was 25.1% ± 11.6%, and mean SPECT/CT LSF was 16.0% ± 9.3% (p < .001). Mean lung dose was 18.8 ± 8.0 Gy for planar LSF versus 12.3 ± 7.2 Gy for SPECT/CT LSF (p < .001). Mean perfused liver dose was 92.9 ± 36.1 Gy using planar LSF versus 102.7 ± 39.1 Gy using SPECT/CT LSF (p < .001). In multivariable analysis, a larger discrepancy in LSF between planar scintigraphy and SPECT/CT was associated with a body mass index (weight in kilograms divided by the square of height in meters) of 26 or higher (p = .02), maximum tumor size of less than 9 cm (p = .05), and left hepatic intraarterial injection (p = .02). Fourteen of 36 patients did not undergo upfront radioembolization due to a planar LSF greater than 20% and instead underwent shunt-reducing embolization with subsequent radioembolization (n = 7), transarterial chemoembolization (n = 5), or no treatment (n = 2). Five of these 14 patients had a SPECT/CT LSF of less than 20% and would have been eligible for upfront radioembolization based on SPECT/CT LSF. Seven of 29 patients treated with radioembolization underwent prescribed dose reductions based on planar LSF; six of these patients would have qualified for standard radioembolization without dose reduction using SPECT/CT LSF. CONCLUSION. Planar scintigraphy yields greater LSFs compared with SPECT/CT, possibly leading to unnecessary shunt-reducing procedures and prescribed dose reductions. CLINICAL IMPACT. SPECT/CT should be considered for clinical LSF calculations before radioembolization in patients with high LSFs.

Quantitative Assessment of the Hemodynamic Effects of Intra-Arterial Nitroglycerin on Hepatocellular Carcinoma using Two-Dimensional Perfusion Angiography.

PURPOSE: To determine the hemodynamic effects of intra-arterial nitroglycerin on hepatocellular carcinoma (HCC) using 2-dimensional (2D) perfusion angiography. MATERIALS AND METHODS: Two-dimensional perfusion angiograms obtained prior to radioembolization from September 2019 to February 2020 were retrospectively reviewed. The inclusion criteria were the presence of Liver Imaging Reporting and Data System-5 tumors and angiographically distinguishable tumor and background liver. The exclusion criteria were previously treated tumors and motion-degraded studies. Thirteen patients with 2D perfusion angiograms obtained before and 2 minutes ± 1 after the administration of intra-arterial nitroglycerin were analyzed. The mean patient age was 72 years ± 9 and 11 of 13 (85%) had cirrhosis. The mean maximum tumor dimension was 4.6 cm ± 2.1. Eight tumors were in the right lobe and 5 were in the left lobe. The tumor and background liver 2D perfusion data were processed and the areas under the time-density curves were calculated. The relative perfusion of HCC to background liver was compared before and after nitroglycerin administration using a 2-tailed paired t-test. RESULTS: The mean rate of contrast administration was 1.4 mL/s ± 0.7 and the mean volume administered was 7.1 mL ± 3.3. The mean nitroglycerin dose was 281 µg ± 69. Ten of 13 patients (77%) demonstrated a relative increase in tumor perfusion. The mean HCC to background liver area under the curve ratio was 1.94 ± 0.76 before and 2.40 ± 0.89 after nitroglycerin administration (P < .05). CONCLUSIONS: Intra-arterial nitroglycerin increases previously untreated HCC perfusion relative to background liver as measured by 2D perfusion angiography, but this effect is variable among patients and should be validated with 3-dimensional imaging techniques.

Same-Day Repeat Hepatopulmonary Shunt Measurement during Planning Angiography for Hepatic Radioembolization.

This report describes a technique for measuring lung shunt fraction (LSF) twice in a single session during planning arteriography for radioembolization using low and standard dose technetium-99m macroaggregated albumin (99mTc-MAA). A patient with a 16.0 cm hepatocellular carcinoma and LSF of 70% was treated with lenvatinib for 4 weeks. Planning arteriography with administration of 0.5 millicuries of 99mTc-MAA was then performed. Arterial access was maintained while the LSF was calculated, which was persistently elevated at 54%. Embolization of arteriovenous shunts was performed during the same session and 5.0 millicuries of 99mTc-MAA were administered. The repeat LSF was 29%. Successful radioembolization was subsequently performed.

Gallbladder Cryoablation for Chronic Cholecystitis in High-Risk Surgical Patients: 1-Year Clinical Experience with Imaging Follow-up.

PURPOSE: To assess the short-term safety and efficacy of gallbladder cryoablation in high-risk patients. MATERIALS AND METHODS: A single-center, retrospective review of clinical and imaging follow-up from patients who were referred for gallbladder cryoablation between August 2018 and July 2019 was performed. All patients had serious pre-procedural comorbidities and were unacceptable surgical candidates (mean age, 52.5 years; mean American Society of Anesthesiologists score, 3.67). Primary efficacy measures included technical success, absence of symptoms after cholecystostomy tube removal, and imaging evidence of cystic duct obstruction and gallbladder involution. The primary safety measure was the absence of Society of Interventional Radiology moderate or greater adverse events. RESULTS: Technical success was 86%, with 1 of 7 patients unable to undergo cryoablation because of adhesions preventing hydrodissection of the colon away from the gallbladder. Mean duration of clinical follow-up after discharge was 278 days (range, 59-498 days). Abdominal pain was absent in all patients after ablation. Cholecystostomy tubes were removed immediately after ablation (n = 5) or on post-procedure day 11 (n = 1). Computed tomography or magnetic resonance imaging was obtained at 1-3 months (n = 6), 4-6 months (n = 4), and 6-12 months (n = 5) after the procedure and demonstrated gallbladder involution in 5 of 6 patients. One patient had asymptomatic distention of the gallbladder on follow-up imaging. Hepatobiliary iminodiacetic acid scans were completed in 5 of 6 patients 1 month after ablation and demonstrated cystic duct occlusion in all 5 patients. One moderate adverse event (infection) and 1 life-threatening adverse event (hemorrhage) occurred. CONCLUSIONS: Gallbladder cryoablation might be a viable treatment option for high-risk patients with gallbladder disease and warrants further investigation.

First in-Human Gallbladder Cryoablation in a Patient with Acute Calculous Cholecystitis Initially Treated with a Cholecystostomy Tube.

A 71-year-old poor surgical candidate with acute calculous cholecystitis was initially managed with cholecystostomy tube drainage for 28 days. He subsequently underwent gallbladder cryoablation under moderate sedation with 3 cryoprobes and 2 separate 10-8-10 freeze-thaw cycles targeting the gallbladder neck/body and fundus followed by cholecystostomy tube removal. He was discharged 1 day after ablation. Magnetic resonance and hepatobiliary iminodiacetic acid scan 1 month postablation demonstrated a thick-walled, distended gallbladder and no filling of the cystic duct. Magnetic resonance 3 months postablation demonstrated retraction of the gallbladder wall with luminal collapse. The patient denied any pain after discharge and is asymptomatic 3 months after ablation.

Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma.

Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.

Cryoablation in the liver: how accurately does the iceball predict the ablation zone?

PURPOSE: To evaluate the accuracy with which the iceball predicts the realized ablation zone in patients undergoing cryoablation of the liver. MATERIALS AND METHODS: Continuous patients who underwent cryoablation of primary or secondary malignancies of the liver were retrospectively reviewed. Iceball and ablation zone dimensions on 1 month follow up imaging were collected in three orientations, the long axis (LA), perpendicular transverse (PTR), and perpendicular craniocaudal (PCC). Factors which may predict differences in the measurements were evaluated with regression analysis. Oncologic outcomes were also collected. RESULTS: The mean size of the iceball was 5.5 ± 1.1 cm, 3.9 ± 1.1 cm, and 4.4 ± 1.4 cm in the LA, PTR, and PCC orientations, respectively. The mean size of the one-month ablation cavity was 4.3 ± 1.3 cm, 3 ± 1.1 cm, and 3 ± 1.3 cm in the LA, PTR, and PCC orientations, respectively. The iceball was significantly larger than the ablation zone in all orientations (p < 0.001). When comparing HCC and non-HCC patients the Kaplan-Meier analysis of TTLP, the Kaplan Meier curves deviated significantly (p = 0.015, HR 2.26 (95%CI 1.17-4.37)). When a similar analysis was performed looking at TTP again the curves diverged significantly (p = 0.002, HR 2.4 (95%CI 1.37-4.19)). CONCLUSION: The iceball seems to overestimate the realized ablation zone by about 1 cm in all orientations during hepatic cryoablation.

Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

PURPOSE: Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. MATERIALS AND METHODS: Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. RESULTS: 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. CONCLUSION: TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

Role of the Interventional Radiologist in the Treatment of Desmoid Tumors.

Desmoid tumors are locally aggressive soft tissue tumors with variable clinical presentation. As is the case with most relatively rare tumors, a multidisciplinary team approach is required to best manage these patients. Surgical resection, systemic therapy, and radiation therapy have classically been mainstays of treatment for desmoid tumors; however, a more conservative "wait-and-see" approach has been adopted given their high recurrence rates and significant morbidity associated with the aforementioned therapies. Given the challenges of classical treatment methods, interventional radiologists have begun to play a significant role in minimally invasive interventions for desmoid tumors. Herein, the authors review imaging characteristics of desmoid tumors, current management recommendations, and minimally invasive therapeutic intervention options.

Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions.

In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.

Prior ablation and progression of disease correlate with higher tumor-to-normal liver 99mTc-MAA uptake ratio in hepatocellular carcinoma.

PURPOSE: Factors affecting tumor-to-normal tissue ratio (T:N) have implications for patient selection, dosimetry, and outcomes when considering radioembolization for HCC. This study sought to evaluate patient, disease specific, and technical parameters that predict T:N as measured on planning pre-90Y radioembolization 99mTc-MAA scintigraphy for hepatocellular carcinoma (HCC). METHODS: 99mTc-MAA hepatic angiography procedures with SPECT/CT over a 4-year period were reviewed. Data recorded included patient demographics, details of underlying liver disease, tumor size, history of prior treatments for HCC and technical parameters from angiography. Anatomic-based segmentation was performed in 93 cases for measurement of tumor and perfused liver volumes and SPECT counts. T:N were calculated and correlated with collected variables. RESULTS: Mean calculated T:N was 2.52. History of prior ablation was significantly correlated with higher T:N (mean 3.39 vs 2.24, p = 0.003). Cases in which mapping was being performed for treatment of disease progression was significantly correlated with higher T:N (mean 3.35 vs 2.14, p = 0.001). Larger tumor size trended toward lower T:N (p = 0.052). CONCLUSION: Patients with history of ablation and those undergoing treatment for disease progression have higher T:N and, therefore, could be considered for radioembolization preferentially over alternative treatments.