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Purpose To use time-drive activity-based costing (TDABC) to characterize and compare costs of transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and ablation. Methods This three-part study involved (1) prospective observation to record resources used during TACE, TARE, and ablation and statistical evaluation of interobserver and interprocedure variability; (2) Bland-Altman analysis of prospective measurements and medical record time stamps to establish practicality of using retrospective data in place of direct observation; (3) retrospective time stamp assessment for 117 ablations, 61 TACE procedures, and 61 TARE procedures to reveal variability drivers. Results Ablation costs were lowest ($3,744), which were 74% of TACE costs ($5,089) and 18% of TARE costs ($20,818). Consumables were the greatest cost contributor, accounting for 65% of ablation, 58% of TACE, and 90% of TARE costs. A single consumable contributed to most of the overall costs: the ablation probe (42%), ethiodized oil for TACE (30%), and yttrium-90 microspheres for TARE (80%). Bland-Altman analysis showed agreement between retrospective time stamps and prospective measurements. Ablation costs increased from $3,288 to $4,245 to $4,461 for one, two, or three tumors treated. TACE cost increased from $5,051 to $5,296 for lobar versus selective approaches. Conclusion A bottom-up costing approach using TDABC is feasible to assess true costs of hepatocellular carcinoma treatments and demonstrates ablation costs are significantly less than those of TACE and TARE. Replication of these methods at other institutions can facilitate development of a bundled payment model to promote utilization of locoregional therapies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fastest-growing cancer worldwide, causing significant morbidity and mortality. Surgical resection, ablation, or transplantation is the best treatment option for patients with HCC. However, only about one-fifth of patients are suitable for such primary curative treatments due to underlying liver disease or rapid extension of the tumor. Image-guided locoregional therapies may prove an important alternative in this scenario, particularly transarterial radioembolization (TARE) with yttrium-90 (Y-90). Based on many studies, TARE can be considered a curative treatment option for patients with early-stage HCC, a bridge to transplantation, and a method for downstaging tumors to give patients with unresectable HCC a chance to potentially receive a curative treatment. TARE can be also combined with other treatment modalities to provide a better quality of life in patients when compared with systemic therapy in patients with unresectable HCC. Here, we discuss the use of TARE in the approach to HCC patients who are in early, intermediate, or advanced stages.

Purpose To evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver. Material and Methods From October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35–78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1–9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient. Results The overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4–14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3–9.5). No grade 3–5 adverse events were detected in either group. Conclusions HAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.

Transarterial radioembolization (TARE) using β-emitting yttrium-90 microspheres has been used for decades in patients with liver-dominant unresectable metastatic neuroendocrine tumors (mNETs). TARE is one of the embolotherapies supported by the National Comprehensive Cancer Network, among other guidelines, for progressive or symptomatic liver-dominant mNETs. Initial studies with relatively short-term follow-up have indicated that TARE is likely to be at least as effective in controlling symptoms and/or disease progression in the liver as bland or chemoembolization. However, more recent data have shed new light on the risk of long-term hepatotoxicity in patients with mNETs treated with TARE. In this article, we will discuss rationale for TARE, clinical indications, outcomes, and toxicity, as well as new strategies to enhance efficacy of TARE while reducing its toxicity in the treatment of liver-dominant mNETs.

Transarterial radioembolization with yttrium-90 microspheres is an established therapy for hepatocellular carcinoma. Post-procedural imaging is important for the assessment of both treatment response and procedural complications. A variety of challenging treatment-specific imaging phenomena complicate imaging assessment, such as changes in tumoral size, tumoral and peritumoral enhancement, and extrahepatic complications. A review of the procedural steps, emerging variations, and timelines for post-treatment tumoral and extra-tumoral imaging changes are presented, which may aid the reporting radiologist in the interpretation of post-procedural imaging. Furthermore, a description of post-procedural complications and their significance is provided.

Background Neoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated. Methods A single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed. Results Twenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17-88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3-33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3-10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9-46.8 months) from major hepatectomy and 37.6 months (range, 25.2-53.1 months) from TARE. Conclusions Major hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.

Purpose Preoperative hypertrophy induction of future liver remnant (FLR) reduces the risk of postoperative liver insufficiency after partial hepatectomy. One of the most commonly used methods to induce hypertrophy of FLR is portal vein embolization (PVE). Recent studies have shown that transarterial radioembolization (TARE) also induces hypertrophy of the contralateral liver lobe. The aim of our study was to evaluate contralateral hypertrophy after TARE versus after PVE taking into account the effect of cirrhosis. Methods Forty-nine patients undergoing PVE before hemihepatectomy and 24 patients with TARE as palliative treatment for liver malignancy were retrospectively included. Semi-automated volumetry of the FLR/contralateral liver lobe before and after intervention (20 to 65 days) was performed on CT or MRI, and the relative increase in volume was calculated. Cirrhosis was evaluated independently by two radiologists on CT/MRI, and interrater reliability was calculated. Results Hypertrophy after PVE was significantly more pronounced than after TARE (25.3% vs. 7.4%; p p = 0.002), whereas in patients with cirrhosis, the difference was not statistically significant (18.2% vs. 7.4%; p = 0.212). After PVE, hypertrophy in patients without cirrhosis was more pronounced than in patients with cirrhosis (25.9% vs. 18.2%; p = 0.203), while after TARE, hypertrophy was comparable in patients with and without cirrhosis (7.4% vs. 8.6%; p = 0.928). Conclusion TARE induces less pronounced hypertrophy of the FLR compared to PVE. Cirrhosis seems to be less of a limiting factor for hypertrophy after TARE, compared to PVE. Graphic abstract

Background Resection is the foundation for cure for colorectal cancer (CRC) liver metastases; however, only 20% of patients are suitable for surgery. Those suitable would be considered for resection or local therapies before being considered for regional therapies. Noncurative treatment is usually systemic chemotherapy. For patients with liver-only or liver-predominant metastases that are unresectable, regional therapies [conventional transarterial chemoembolization (cTACE), drug-eluting bead transarterial chemoembolization (DEB-TACE), and transarterial radioembolization (TARE)] may be considered. We review the current evidence for regional therapies for CRC liver metastases. Patients and Methods Literature searches (January 2000 to March 2019 or January 2010 to March 2019 depending on the specific systematic review question) were conducted, including Medline, Embase, Cochrane Library, and 2018 American Society of Clinical Oncology (ASCO) abstracts. Results A total of 4100 articles were identified; 15 studies were included in the review. There were no comparative data regarding the resectable population. There was either insufficient evidence (cTACE or DEB-TACE) or evidence against (TARE) the addition of regional therapies to systemic therapy in the first line in the unresectable population. There was either no evidence (cTACE) or weak evidence (DEB-TACE or TARE) for the addition of regional therapies with or without systemic therapy in the second line or later in the unresectable population. Conclusion Limited evidence supports the delivery of percutaneous regional therapies in patients with unresectable CRC liver metastases. There are strong data demonstrating positive effects of TARE within the liver, but they do not translate to a benefit in patient-important outcomes. DEB-TACE appears to offer a survival benefit in the second-line setting, although the evidence is limited by small sample size and larger trials are needed.

Purpose: The careful evaluation of MDCT is an essential step for the treatment planning in pre-treatment imaging work-up for Trans-Arterial Radio Embolization (TARE). It may provide unique volumetric data (CTVs), which are information useful for an effective and safe TARE. The purpose of this study is to demonstrate that the radiographer is able to calculate CTVs of TARE simulation with the same precision as the interventional radiologist. Methods: This study retrospectively considers 17 consecutive patients (8 males, 9 females; mean age 66.3 ± 13.2 years) who underwent pre-treatment work-up for TARE, between May 2019 and February 2020 (trial ID:2234 - protocol). For each patient, four specific parameters are evaluated from MDCT achieved during treatment simulation: healthy liver volume (HLV), the whole hepatic parenchyma (THV = healthy liver and TTV = tumour) involved by TARE, and whole liver volume (WLV). Four independent observers—R1 (expert interventional radiologist), T1, T2, and T3 (radiographers, with different experiences in the field of interventional radiology)—are involved in the imaging analysed. Results: All the 4 observers detected the same number of hepatic lesion(s) per patient. Regarding the three radiographers, the intra-observer reliability for CTVs is very high 0.997 to 1.000 (95%CI). Also inter-observer reproducibility between radiographers is excellent regarding CTVs, 0.965 to 0.999 (95%CI). The accuracy of radiographer evaluation is very high 0.964 to 0.999 (95%CI). Conclusions and implications for practice: The high intra- and inter-observer reproducibility shows that a properly trained radiographers might have the same accuracy as interventional radiologists, in assessing liver CTV data for planning TARE.

Background: Trans-arterial radioembolization (TARE) has shown promising results in treating hepatocellular carcinoma (HCC). We identified independent predictors of radiological complete response (CR) in patients with intrahepatic HCC who were treated with TARE. Methods: Patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited. CR was defined according to the modified Response Evaluation Criteria in Solid Tumors. Cox regression analysis was used to determine independent predictors of CR. Results: The median age of study participants (83 men and 19 women) was 64.3 years. The mean survival after TARE was 55.5 months, and 21 (20.6%) patients died during the study period. Patients who achieved CR (14 patients, 13.7%) had significantly higher serum albumin level (median 4.1 vs. 3.9 g/dL), lower total bilirubin level (median 0.6 vs. 0.7 mg/dL), lower aspartate aminotransferase level (median 30.0 vs. 43.0 IU/L), lower alkaline phosphatase level (median 79.0 vs. 103.0 IU/L), lower alpha-fetoprotein level (median 12.7 vs. 39.9 ng/mL), lower des-gamma-carboxyprothrombin level (median 575.5 vs. 2772.0 mAU/mL), lower model for end-stage liver disease (MELD) score (median 6.0 vs. 7.0), and smaller maximal tumor diameter (median 6.3 vs. 9.0 cm) compared to those who did not achieve CR (all p &lt, 0.005). Multivariate Cox regression analysis showed that lower MELD score (hazard ratio (HR) = 0.436, p = 0.015) and maximal tumor size &lt, 9 cm (HR = 11.180, p = 0.020) were independent predictors of an increased probability of radiological CR after TARE. Conclusions: Low MELD score and small maximal tumor size were independently associated with an increased probability of CR after TARE in patients with intrahepatic HCC.

Purpose Liver metastasis in genitourinary (GU) malignancies signifies a poor prognosis and has a negative effect on patient survival. Selected patients with metastatic GU malignancies have liver-dominant disease. Liver-directed therapies (LDT) with conventional transarterial chemoembolization (cTACE) and transarterial radioembolization (TARE) have been well studied in primary liver cancer and metastatic hepatic disease and proven to be safe and efficacious in selected populations. Materials and Methods From 2005 to 2016, 32 patients with metastatic renal, bladder, or prostate cancer and liver-dominant metastases treated with cTACE or TARE were identified. Retrospective review of patient records was performed to assess baseline characteristics, imaging treatment response, survival, and treatment toxicity. Results The median survival from diagnosis of liver metastasis was 37 months in renal cell carcinoma (RCC), 8 months in transitional cell carcinoma (TCC), and 6 months in prostate carcinoma. 90% of patients with RCC maintained their ECOG performance status one-month post-treatment, as did 64% of the bladder and prostate groups. LDT was well tolerated for the most part. Conclusion LDT in patients with metastatic GU cancer is well tolerated and can lead to improved survival for some patients. Further studies are necessary to determine which patients may benefit the most.

BACKGROUND: US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. PURPOSE: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. RESULTS: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). CONCLUSION: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020

Background/aim To evaluate the predictive value of metabolic activity assessed by 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with hepatocellular carcinoma (HCC) undergoing Yttrium-90 (Y-90) transarterial radioembolization (TARE). Methods Between 2009 and 2013, a total of 40 patients with HCC were treated with Y-90 TARE. Before each treatment, 18 F-FDG PET/CT was performed. Maximum standardized uptake value (SUVmax) and tumor-to-non-tumorous liver uptake ratio (TLR; tumor SUVmax/non-tumorous liver mean SUV) were measured for each patient. Tumor response was evaluated in accordance with modified RECIST criteria at 3-month intervals after Y-90 TARE. Statistical analysis was performed using the chi-squared test, Kaplan-Meier analysis, and the Cox proportional hazards model. Results The median patient age was 56.5 years. Twenty-nine patients (72.5%) were men; 36 patients (90.0%) were classified as Child-Pugh class A. Thirty-three patients (82.5%) showed disease control in treated lesions at 3 months after Y-90 TARE. Eleven patients (27.5%) showed progression-free survival. However, low and high TLR (relative to the median value of 2.1) did not affect rates of disease control, progression-free survival, or overall survival. No predictive factors could be identified for disease progression or death in patients with HCC undergoing Y-90 TARE. Conclusions TLR-based stratification is a simple method, but it may not be useful in treatment planning for HCC patient undergoing Y-90 TARE. Further studies with large number of patients are needed.

Transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres is a liver-directed treatment for primary and secondary hepatic malignancies. Personalized dosimetry aims for maximum treatment effect and reduced toxicity. We aimed to compare pre-treatment voxel-based dosimetry from 99mTc macroaggregated albumin (MAA) SPECT/CT with post-treatment 90Y PET/CT for absorbed dose values, and to evaluate image quality of 90Y SiPM-based PET/CT. Forty-two patients (28 men, 14 women, mean age: 67 ± 11 years) with advanced hepatic malignancies were prospectively enrolled. Twenty patients were treated with glass and 22 with resin microspheres. Radiation absorbed doses from planning 99mTc-MAA SPECT/CT and post-therapy 90Y PET/CT were assessed. 90Y PET/CT images were acquired for 20 min and reconstructed to produce 5-, 10-, 15-, and 20-min datasets, then evaluated using the 5-point Likert scale. The mean administered activity was 3.44 ± 1.5 GBq for glass and 1.62 ± 0.7 GBq for resin microspheres. The mean tumor absorbed doses calculated from 99mTc-MAA SPECT/CT and 90Y PET/CT were 175.69 ± 113.76 Gy and 193.58 ± 111.09 Gy (P = 0.61), respectively for glass microspheres; they were 60.18 ± 42.20 Gy and 70.98 ± 49.65 Gy (P = 0.37), respectively for resin microspheres. The mean normal liver absorbed doses from 99mTc-MAA SPECT/CT and 90Y PET/CT were 32.70 ± 22.25 Gy and 30.62 ± 20.09 Gy (P = 0.77), respectively for glass microspheres; they were 18.33 ± 11.08 Gy and 24.32 ± 15.58 Gy (P = 0.17), respectively for resin microspheres. Image quality of 90Y PET/CT at 5-, 10-, 15-, and 20-min scan time showed a Likert score of 3.6 ± 0.54, 4.57 ± 0.58, 4.84 ± 0.37, and 4.9 ± 0.3, respectively. 99mTc-MAA SPECT/CT demonstrated great accuracy for treatment planning dosimetry. SiPM-based PET/CT scanner showed good image quality at 10-min scan time, acquired in one bed position. A PET/CT scan time of 5 min showed acceptable image quality and suffices for dosimetry and treatment verification. This allows for inclusion of 90Y PET/CT in busy routine clinical workflows. Studies with larger patient cohorts are needed to confirm these findings.

Transarterial radioembolization (TARE) is one of the therapeutic options for hepatocellular carcinoma (HCC). This study aimed to investigate the predictors and prognostic values of achieving curative treatments after TARE. Overall, 143 patients with intrahepatic HCC treated with TARE between 2011 and 2017 were recruited from two Korean tertiary institutes. Twenty-seven patients received curative treatments after TARE. Younger age than 65 years and AFP of ≤200 ng/mL independently predicted the increased probability of achieving curative treatment after TARE, and the curative treatment after TARE provided a survival benefit in patients with intrahepatic HCC.

Studies have shown intra-arterial therapies to be effective in controlling neuroendocrine liver metastases (NELMs), but the evidence supporting the selection of specific methods is limited. This meta-analysis is the first to compare survival outcomes between transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) in the treatment of NELM. A systematic search according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in PubMed and Embase databases was conducted in February 2020 for published studies comparing survival outcomes between TACE and TARE in the treatment of NELM. Six eligible cohort studies with a total of 643 patients were identified. The TACE and TARE groups were similar in terms of age, sex, hepatic tumor burden, tumor grade, and Eastern Cooperative Oncology Group (ECOG) score. The patients treated with TACE had significantly better overall survival (odds ratio [OR], 1.92; 95% confidence interval [CI] 1.14–3.22, p = 0.014) than those treated with TARE. Overall survival ranged from 16.8 to 81.9 months with TACE and from 14.5 to 66.8 months with TARE. No significant differences in hepatic progression-free survival (OR, 1.01; 95% CI 0.75–1.35; p = 0.96) or tumor response were observed within the first 3 months (OR, 2.87; 95% CI 0.81–10.21; p = 0.10) or thereafter (OR, 0.98; 95% CI 0.12–7.86; p = 0.99). The complication rates were similar between the two groups, with 6.9% of the TACE patients versus 8.5% of TARE patients reporting major complications (OR, 1.16; 95% CI 0.54–2.48; p = 0.71) and respectively 44.6% and 58.8% of the TACE and TARE patients reporting minor adverse events (OR, 1.08; 95% CI 0.39–2.99; p = 0.88). Despite similar tumor responses, an overall survival benefit was associated with TACE treatment of NELM compared with TARE treatment. Randomized controlled trials are warranted to confirm this finding and clarify whether certain subpopulations benefit from different transarterial methods.

Infiltrative-appearance hepatocellular carcinoma presents a challenge to clinicians as diagnostic criteria continue to evolve and evidence-based treatment guidelines have yet to be established. While transarterial radioembolization has shown efficacy in hepatocellular carcinoma, many studies exclude infiltrative-appearance HCC in their analysis. The purpose of this study was to describe imaging features of infiltrative-appearance hepatocellular carcinoma and evaluate effects of radioembolization on survival. In a retrospective review, infiltrative HCC patients treated from 2008 to 2017 were identified. Patients were divided into two groups: TARE versus systemic therapy/palliative care. Demographics, dates of diagnosis/expiry, albumin, international normalized ratio (INR), sodium, alpha-fetoprotein (AFP), creatinine, Child-Pugh class, model for end-stage liver disease (MELD) score, bilirubin, radiation dose and volume were collected. Patients with bilirubin > 3 were excluded. Mann–Whitney U test and Fisher’s exact test assessed differences between groups. Kaplan–Meier survival and Cox proportional hazard analyses were performed. Fifty-three patients were identified, 15 underwent TARE while 38 served as control. Mean age was 60, 43 patients were male. The mean overall survival was 16.2 months for the TARE group and 5.3 months for the control group (Log-rank p

To analyze hepatobiliary specific contrast agent (HBA) dynamic MRI signal intensity (SI) differences between treated liver (TL) and untreated liver (UL) parenchyma in patients following transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) using yttrium-90 containing glass microspheres. This was a single institution retrospective study of patients with HCC treated with lobar or segmental TARE who received pre- and post-treatment HBA multiphase MRI within a 3-year period. Patients with prior locoregional therapies or multiple TAREs were excluded. SI was obtained by drawing a 2D ROI on T1-weighted non-contrast, arterial (25 s.), portal venous (60 s.), transitional (180 s.), and hepatobiliary (HB) (1200 s.) phase sequences in the (TL) angiosome and UL. HB phase signal enhancement characteristics were correlated with TARE dose thresholds ( 190 Gy) using the medical internal radiation dose (MIRD) methodology. 282 patients received TARE using glass microspheres during the study period and 58 patients who met inclusion criteria were analyzed. Median dose was 141.5 Gy MIRD [IQR 122.0, 161.5; range 100–540 Gy]). Statistically significant differences were present between treated and non-treated liver on non-contrast (− 28.0, p = 0.003), arterial (38.5, p = 0.013), and HB phases (− 95.8, p ≤ 0.001). Median follow-up time to furthest post-treatment MRI was 6 months (range 3-11 months). There was no significant SI difference on portal venous or transitional phases. HB phase SI changes in the TL compared to UL were significant at all TARE dose thresholds (p < 0.05). SI differences between treated and untreated liver after TARE are most significant on the HB phase and present at all evaluated dose levels at a median of 6 months after treatment. These findings support the parenchymal ablative potential for TARE and the necessity to consider liver function loss within targeted liver volumes.

The evolution of locoregional therapies in the last decade has been refined with improved patient selection and a development of a more personalized approach. In doing so, there has been associated improved outcomes and less toxicity. With the rapidly changing landscape of systemic therapy, the role of locoregional therapies alone or in combination for downstaging and curative intent will continue to evolve.

Purpose To compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET). Materials and Methods This study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above. Results Chronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4–5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005). Conclusions Delayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.

Purpose To assess the overall survival (OS) and progression-free survival (PFS) of unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass-microsphere transarterial radioembolization (TARE) with and without concurrent sorafenib. Methods OS and PFS were analyzed in 55 patients with an intrahepatic tumor (IHT) ≤50% without advanced or aggressive disease features (ADFs), which was referred to presence of infiltrative/ill-defined HCC, macrovascular invasion, or extrahepatic disease treated with only TARE (TARE_alone) and in 74 patients with IHT ≤50% with ADFs or IHT >50% treated with TARE and sorafenib (TARE_sorafenib). Prognostic factors for OS and PFS were identified using univariate and multivariate analyses. Results Median OS and PFS of TARE_alone patients were 21.6 (95% CI 6.1-37.1) and 9.1(95% CI 5.2-13.0) months, respectively, and for TARE_sorafenib patients 12.4 (95% CI 9.1-15.6) and 5.1 (95% CI 2.6-7.5) months, respectively. Better OS was associated with serum AFP

Background Little is known about factors that influence the efficacy of transarterial radioembolization (TARE). Purpose To determine the relationship between tumor radiation-absorbed dose and survival and tumor response in locally advanced inoperable hepatocellular carcinoma treated with TARE. Materials and Methods This was a secondary analysis of prospectively acquired data (between December 2011 and March 2015) from participants who received TARE in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma (SARAH) trial (ClinicalTrials.gov identifier: NCT01482442). Tumor-absorbed dose was computed using technetium 99m (99mTc) macroaggregated human albumin (MAA) SPECT/CT. Visual agreement among CT, 99mTc-MAA SPECT/CT, and yttrium 90 (90Y) SPECT/CT or PET/CT was scored as optimal, suboptimal, or not optimal. Overall survival (OS) and tumor response at 6-month follow-up CT (Response Evaluation Criteria in Solid Tumors, version 1.1) were assessed. OS was evaluated using Kaplan-Meier tests. A propensity score comparing participants receiving a tumor dose greater than or equal to 100 Gy (best cut-off according to the receiver operating characteristic curve and median tumor radiation-absorbed dose values in the study groups) with those receiving sorafenib was calculated. Results One hundred twenty-one participants (median age, 67 years; interquartile range [IQR]: 61-73 years; 110 men) were evaluated in the dose-survival group, and 109 (median age, 66 years; IQR: 61-71 years; 100 men) were evaluated in the dose-tumor response group. In the dose-survival group, median OS was 9.3 months (95% confidence interval [CI]: 6.7 months, 10.7 months), and median tumor radiation-absorbed dose was 112 Gy (IQR: 68-220 Gy). Participants who received at least 100 Gy (n = 67) had longer survival than those who received less than 100 Gy (median, 14.1 months [95% CI: 9.6 months, 18.6 months] vs 6.1 months [95% CI: 4.9 months, 6.8 months], respectively; P < .001), and those with optimal agreement (n = 24) had the longest median OS (24.9 months; 95% CI: 9.6 months, 33.9 months). In the dose-tumor response group, tumor radiation-absorbed dose was higher in participants with disease control versus those with progressive disease (median, 121 Gy [IQR: 86-190 Gy] vs 85 Gy [IQR: 58-164 Gy]; P = .02). The highest disease control rate was observed in 31 of 40 participants (78%) with a tumor radiation-absorbed dose greater than or equal to 100 Gy and optimal agreement. Conclusion Higher tumor radiation-absorbed dose computed at technetium 99m macroaggregated human albumin SPECT/CT was associated with better overall survival and disease control in hepatocellular carcinoma treated with transarterial radioembolization with yttrium 90 in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma trial. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Sofocleous and Kamarinos in this issue.

In this review we summarize the current evidence on the role of PET/CT with different probes for radioembolization therapy monitoring in HCC patients. Typical clinical examples are also provided to underline the utility of choline PET in this context. PubMed database was searched from 2000 until March 2020. Overall, 11C-acetate and radiolabeled choline PET have a higher sensitivity in the diagnosis of primary or recurrent HCC as compared to 18F-FDG. On the other hand, 18F-FDG PET/CT can provide useful prognostic information, especially for palliative treatments. Radiolabeled choline better predicts response to loco-regional treatment and provides a better differentiation of disease recurrence from treatment-related changes, as compared to other morphological imaging. HCC staging is better performed with PET/CT, thus allowing for a more adequate selection of patients candidate to transarterial radioembolization.

Background Transarterial radioembolization (TARE) is a locoregional minimally invasive therapeutic strategy to treat primary and secondary hepatic neoplasia. Aim The objective was to assess TARE-induced immuno-oncological effects and its perspective for potential therapy improvement by using a combinatory strategy with immune checkpoint inhibitors (ICI). Results Yttrium-90 (90Y) TARE is used in patients with persisting liver function as the first- and second-line treatment for cholangiocarcinoma and hepatocellular carcinoma and chemotherapy refractory liver metastasis of different primaries. Combination therapy with 90Y TARE and ICI may synergistically improve antitumoral immunity and patient outcome. Currently, there are no clinical studies with published data regarding this combination therapy and the subsequently induced immunological effects. Clinical data on other isotopes, e.g., holmium-166 (166Ho), are also lacking. Conclusion The clinical evidence of combined treatment with TARE and ICI must be considerably improved. This innovative therapy concept must be studied in new trials assessing the immunological data, including cellular phenotypes, activation, functions, and biomarkers. This may provide valid, sensitive, and specific models in order to evaluate the optimal therapy concept and/or the therapy combination for the best patient outcome.

OBJECTIVE. Treatment options for hepatocellular carcinoma (HCC) continue to expand. However, given the complexity of the patients including factors such as codominant cirrhosis or portal hypertension and transplant status, it can be difficult to know which treatment is most advantageous. The choice of HCC treatment is perhaps most complex in the setting of HCCs that are 3-5 cm. This article reviews the evidence for locoregional therapies in treating 3- to 5-cm HCCs. CONCLUSION. Combination therapy with transarterial chemoembolization (TACE) and ablation has the most robust and highest level of evidence to support its efficacy and therefore should be considered first-line therapy for nonresectable HCCs that measure 3-5 cm. The studies support that TACE followed by ablation is superior to either TACE alone or ablation alone. Data for transarterial radioembolization (TARE) to treat HCCs in this specific size range are very limited. Additional data are needed about the comparative effectiveness of TACE-ablation combination and TARE and how the TACE-ablation combination compares with surgical resection.

Objectives Yttrium-90 transarterial radioembolization (TARE) is a safe, effective modality of locoregional therapy for intermediate and advanced-stage hepatocellular carcinoma (HCC). We aim to identify novel predictors of important outcomes of TARE therapy. Methods A single-center retrospective study of 166 patients treated with TARE for HCC at Mayo Clinic Rochester between 2005-2015 and followed until December 2017. Multivariate logistic and stepwise regression analysis models were used to identify variables associated with overall survival (OS) and progression-free survival (PFS). Results The median OS and the median PFS were12.9 (95% CI: 11.0-17.3), and 8 months (95% CI: 6-11), respectively. Macrovascular invasion (HR: 1.9 [1.3-2.8]), Child-Pugh score (CPS) B or C vs. A (HR: 1.8 [1.2-2.7]), Eastern Cooperative Oncology Group Performance status (ECOG-PS) 2 or 1 vs. 0 (HR: 1.6 [1.1-2.4]) and activity (A) of administered radiation dose (HR: 1.005[1.00-1.010), independently correlated with poorer OS. Infiltrative HCC (HR: 2.4 [1.3-4.5), macrovascular invasion (HR: 1.6 [1.1-2.7]), and high activity of administered radiation dose (HR: 1.005 [1.00-1.010) were associated with worse PFS. Conclusion In HCC patients treated with TARE; macrovascular invasion, the activity of radiation dose, CPS, ECOG-PS, and infiltrative HCC predict OS and PFS.

Transarterial radioembolization (TARE) is, by all standards, a radiation therapy. As such, according to Euratom Directive 2013/59, it should be optimized by a thorough treatment plan based on the distinct evaluation of absorbed dose to the lesions and to the non-tumoural liver (two-compartment dosimetry). Since the dosimetric prediction with 99mTc albumin macro-aggregates (MAA) of non-tumoural liver is much more accurate than the same prediction on lesions, treatment planning should focus on non-tumoural liver rather than on lesion dosimetry. The aim of this study was to determine a safety limit through the analysis of pre-treatment dosimetry with 99mTc-MAA single photon emission computed tomography (SPECT/CT), in order to deliver the maximum tolerable absorbed dose to non-tumoural liver. Data from intermediate/advanced hepato-cellular carcinoma (HCC) patients treated with 90Y glass microspheres were collected in this single-arm retrospective study. Injection was always lobar, even in case of bilobar disease, to avoid treating the whole liver in a single session. A three-level definition of liver decompensation (LD) was introduced, considering toxicity only in cases of liver decompensation requiring medical action (LD type C, LDC). We report LDC rates, receiver operating characteristic (ROC) analysis between LDC and NO LDC absorbed dose distributions, normal tissue complication probability (NTCP) curves and uni- and multivariate analysis of risk factors associated with toxicity. A 6-month timeline was defined as necessary to capture all treatment-related toxicity events. Previous transarterial chemoembolization (TACE), presence or extension of portal vein tumoural thrombosis (PVTT) and tumour pattern (nodular versus infiltrative) were not associated with tolerance to TARE. On the contrary, at the multivariate analysis, the absorbed dose averaged over the whole non-tumoural liver (including the non-injected lobe) was a prognostic indicator correlated with liver decompensation (odds ratio = 4.24). Basal bilirubin > 1.1 mg/dL was a second even more significant risk factor (odds ratio = 6.35). NTCP analysis stratified with this bilirubin cut-off determined a 15% liver decompensation risk at 50 Gy/90 Gy for bilirubin >/

OBJECTIVE. The aim of this study was to evaluate the amount of free radioactivity in renal and intestinal excretions during the first 48 hours after transarterial radioembolization (TARE) procedure...

Transarterial radioembolization (TARE) with Yttrium-90 ((90)Y) microspheres is a liver-directed therapy for primary and metastatic disease. This manuscript provides a review of the clinical literature on TARE indications and efficacy with overviews of patient-selection and toxicity. Current dosimetry models used in practice are safe, relatively simple, and easy for clinicians to use. Planning currently relies on the imperfect surrogate, (99m)Tc macroaggregated albumin. Post-therapy quantitative imaging ((90)Y SPECT/CT or (90)Y PET/CT) of microspheres can be used to calculate the macroscopic in vivo absorbed dose distribution. Similar to the evolution of other brachytherapy dose calculations, TARE is moving toward more patient-specific dosimetry that includes calculating and reporting nonuniform dose distributions throughout tumors and normal uninvolved liver.

With increasing use of radiation for hepatocellular carcinoma (HCC) through transarterial radioembolization (TARE) and stereotactic body radiation therapy (SBRT), there is concern for increased radiation-related complications when using SBRT after TARE. This study compares safety of SBRT after segmental TARE versus transarterial chemoembolization (TACE).A retrospective review identified patients receiving SBRT after TACE or TARE for HCC from 2011 to 2017. TARE was delivered subselectively to individual segments using yttrium-90 with Theraspheres. Patients were assessed over time for Child-Turcott-Pugh (CTP)/albumin-bilirubin (ALBI) scores, and Common Terminology Criteria for Adverse Events version 4.0 grade ≥3 events. Linear mixed models were used to examine the trend of CTP and ALBI over time and compare groups. Secondary endpoints were objective response rate via modified Response Evaluation Criteria in Solid Tumors (RECIST), local control, and overall survival.Ninety-nine patients met criteria with median follow-up of 9.8 months (range, 0.9-47): 31 had SBRT after segmental TARE and 68 patients post-TACE. The groups were well balanced with regard to etiology of HCC, baseline CTP and ALBI scores, and SBRT dose, but there were significant differences in baseline Eastern Cooperative Oncology Group performance status, Barcelona Clinic Liver Cancer staging, and median follow-up. There was a significant increase in post-SBRT CTP and ALBI scores (P.0001) for both groups. However, there was no significant difference in rise in CTP (P = .11) or ALBI score (P = .82) over time between SBRT post-TACE versus post-segmental TARE. There was no significant increase in ≥grade 3 toxicity postsegmental TARE. There was also no significant difference in local controls (P = 1.0) and overall survival (P = .26) between cohorts, but objective response rate was worse post-TARE.SBRT after segmental TARE with Theraspheres appears to have acceptable tolerability and is effective compared with SBRT after TACE. Longer follow-up with larger numbers is needed to verify these data.

Purpose To identify and characterize the delayed effects of transarterial radioembolization (TARE) on the liver. Materials and Methods A single-institution retrospective analysis was undertaken of all patients who received TARE between 2005 and 2014 and survived at least 1 year from the initial TARE (n = 106). Patients were evaluated for the presence or absence of radioembolization-induced chronic hepatotoxicity (RECHT) occurring at least 6 months after TARE. The mean age of patients was 63 years of age, and the malignancy most commonly treated was neuroendocrine tumor (54%). Adjudication of hepatic decompensation to RECHT versus alternative causes was performed by a multidisciplinary panel of specialists from hepatology, radiation oncology, and interventional radiology. Results Eight patients were excluded from analysis because of liver transplantation (2) or incomplete data (6). RECHT occurred in 13 of 98 patients (13%), and 5 deaths (5%) occurred from hepatic decompensation. There were a total of 69 toxicity events in patients developing RECHT. The most common events were elevation of alkaline phosphatase (10), decrease in serum albumin (10), and development of ascites (9). RECHT patients had a higher intrahepatic tumor volume (P = .021) and a higher number of hepatic comorbidities leading to cirrhosis (P = .015). Conclusions Delayed radiation-induced hepatic toxicity occurred in 13% of patients following radioembolization, with 5 fatalities adjudicated to be a result of the treatment. Tumor involvement of greater than 50% of the liver and cirrhosis were predisposing factors for RECHT.

Background In patients with hepatic neuroendocrine tumors (NETs) locoregional therapies such as transarterial radioembolization (TARE) are increasingly applied. Response evaluation remains challenging and previous studies assessing response with diffusion-weighted imaging (DWI) have been inconclusive. Purpose To perform a feasibility study to evaluate if response assessment with quantitative apparent diffusion coefficient (ADC) in patients with liver metastases of NETs after TARE will be possible. Material and Methods Retrospectively, 43 patients with 120 target lesions who obtained abdominal magnetic resonance imaging (MRI) with DWI 39±28 days before and 74±46 days after TARE were included. Intralesional ADC (ADCmin, ADCmax, and ADCmean) were measured for a maximum number of three lesions per patient on baseline and post-interventional DWI. Tumor response was categorized according to RECIST 1.1 and mRECIST. Results TARE resulted in partial remission (PR) in 23% (63%), in stable disease (SD) in 73% (23%), in progressive disease (PD) in 5% (7%) and in complete response (CR) in 0% (1%) according to RECIST 1.1 (mRECIST, respectively). ADC values increased significantly ( Pmean values were slightly higher for responders compared to non-responders ( PConclusion ADC values seem to represent an additional marker for treatment response evaluation after TARE in patients with secondary hepatic NET. A conclusive study seems feasible though patient-based evaluation and overall survival and progression free survival as alternate primary endpoints should be considered.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are often amenable to locoregional therapy, including percutaneous ablation, transarterial chemoembolization (TACE), or transarterial radioembolization (TARE). TARE is a technique that delivers a high dose of radiation to the tumor, while limiting the dose to the normal liver parenchyma and the adjacent organs. It has been shown to effectively provide disease control with relatively few toxicities, and in certain cases results in a complete response. It is the preferred therapy as a bridge to liver transplant and can provide necessary compensatory future liver remnant hypertrophy before planned surgical resection.

Technetium-99m macroaggregated albumin is used to estimate lung shunt fraction (LSF) prior to yttrium-90 (Y90). Studies have debated the safety and efficacy of Y90 in patients with LSF > 15%. We aimed to assess the role of Y90 in hepatocellular carcinoma (HCC) with LSF > 15%. With IRB approval, we searched our prospectively acquired database of HCC patients with Y90 treated with LSF > 15%. Median LSF and liver and lung doses were calculated. The response was assessed using RECIST. Overall survival (OS) was calculated from date of first Y90. A total of 103 HCC patients underwent Y90. The median baseline LSF was 24.4% (IQR 18.1–28.8). Patients exhibited multifocal disease (59/103, 60%) and median tumor size of 7.85 cm (IQR 5.2, 10.57). BCLC class was A, B, C, and D in 7 (7%), 5 (5%), 85 (83%), and 6 (6%) patients, respectively. The median liver dose was 84.6 Gy (IQR 57.4, 107.55). The median lung dose per session and cumulatively was 22.9 Gy (IQR 15–28) and 29.5 Gy (IQR 20.5–44.3). Thirty-three patients (32%) demonstrated partial response, 57 stable disease, and 13 (13%) had progressive disease. The median OS was 7.3 months (95% CI 5.3, 11.47). Twenty patients (19%) had non-specific pulmonary symptoms (cough, shortness of breath, wheezing) in the 1-year post-Y90. The median time to the appearance of non-specific pulmonary symptoms was 63 days (range 7–224). Thoracic imaging demonstrated no pulmonary fibrosis/injury following treatment in any patient. Y90 can be performed in patients with LSF > 15%. The RECIST response was identified in 32% of the patients. In isolation, LSF > 15% should not deter from treatment with Y90.

Purpose To evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC). Methods A prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS). Results Sixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6–18.1). Overall survival was 8.7 months (95% CI, 5.3–12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6–3.1), and LPFS was 3.1 months (95% CI, 1.3–4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1–2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3. Conclusions Patients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.

Background To compare outcomes for patients with colorectal cancer liver metastases (CRCLM) treated by drug-eluting bead chemoembolization (DEB-TACE) or radioembolization (TARE). Patients and methods A single-center retrospective review was carried out on 202 patients with CRCLM, treated by DEB-TACE (n=47) or TARE (n=155) patients. Propensity-matching yielded 44 pairs. Paired statistical analysis was performed on matched pair demographics, treatment response, and survival. Results Patients treated with DEB-TACE had worse extra-hepatic metastasis (68.1 vs. 47.7%, p=0.014) and ≥10 liver lesions (42.2 vs. 68.8%, p=0.001). Matched patients treated with DEB-TACE had a trend towards worse toxicity (27% vs. 9.1% (p=0.057). Index DEB-TACE treatment was not a prognostic factor for overall survival (hazard ratio=0.94, 95% confidence intervaI=0.54-1.65; p=0.83). Conclusion In the matched CRCLM cohort, there was a trend towards worse toxicity post-DEB-TACE treatment, but it was not an independent prognostic factor for survival.

Objectives Patients with hepatocellular carcinoma (HCC) and gross vascular invasion (GVI) have poor outcomes with systemic therapy such as sorafenib. Both external beam radiation therapy (EBRT) and transarterial radioembolization (TARE) have been utilized for this patient population. We sought to compare outcomes using dual modality radiation (EBRT+TARE) versus EBRT alone in patients with HCC and GVI. Materials and methods Between 2011 and 2017, 45 patients with HCC and GVI were treated with EBRT±TARE at our institution. Progression-free survival (PFS) and overall survival (OS) were assessed and compared using Kaplan-Meier method and log-rank test. Univariable and multivariable Cox proportional hazards regression was used to assess the impact of the variables stage, etiology of cirrhosis, Child-Pugh (CP) score, and Karnofsky Performance Score (KPS) on PFS and OS. Results Patient characteristics were well-balanced except for KPS (80 vs. 90) and CP score. Median OS for patients receiving EBRT+TARE was 263 days (95% confidence interval [CI]: 167, -) versus 193 days (95% CI: 51, 262) for EBRT alone (P=0.049). However, this did not hold up on MVA. When EBRT and TARE were delivered within 2 months as planned (n=12), median PFS was 218 days (95% CI: 44, -) for dual modality radiation versus 63 days (95% CI: 38, 137) for EBRT alone (P=0.048). When EBRT and TARE were delivered within 6 months, the difference in PFS was no longer seen (P=NS), because some patients received TARE as a salvage therapy. Conclusions Dual modality radiation with EBRT and TARE may be associated with improved OS in patients with HCC and GVI. Dual modality radiation may be associated with improved PFS in patients with HCC and GVI compared with EBRT alone when EBRT and TARE are delivered within 2 months of each other as part of a planned dual modality treatment strategy. However, since this is a retrospective study with inherent selection bias, these findings need further validation in a prospective clinical trial for patients with HCC and GVI.

Purpose To determine patient preference for transradial access (TRA) or transfemoral access (TFA) after experiencing both. Materials and Methods A randomized controlled crossover trial was conducted at a single institution. Thirty patients with hepatocellular carcinoma undergoing mapping and transarterial radioembolization (TARE) were enrolled to experience 1 TRA and 1 TFA procedure each, with randomization of which access approach was experienced first. Surveys assessing pain and quality of life (QOL) were administered after each procedure. Access site preference was collected after completion of both procedures. Results Twenty-two subjects (73.3%) preferred TRA, 4 (13.3%) preferred TFA, and 4 (13.3%) had no preference; 14 (46.7%) reported bruising after TRA, and 17 (53.3%) reported bruising after TFA. TRA was associated with significantly lower pain scores overall during the procedure, at the access site during the procedure, and in the recovery room compared with TFA (2.0 vs 2.9, P = .0046; 2.0 vs 3.0, P = .0004; 2.1 vs 2.9, P = .0357). Pain score after discharge was not significantly different (1.4 vs 1.5, P = .4235). QOL scores were not significantly different between TRA and TFA. No significant differences were found for fluoroscopy time, air kerma, dose-area product, or procedure time between TRA and TFA for either mapping (P = .1442, P = .5871, P = .6667, P = .6131) or radioembolization (P = .8574, P = .2344, P = .1119, P =.8474). For radioembolizations, TRA had significantly shorter recovery times compared with TFA (108 min vs 153 min, P = .0193). Conclusions Patients exhibited a strong preference for TRA. With TRA, patients experienced less periprocedural pain and shorter recovery times without significant differences in radiation exposure or procedure length.

Transarterial radioembolization (TARE), also called radioembolization or selective internal radiation therapy, is an interventional radiology technique used to treat primary liver tumors and liver metastases. The aim of this therapy is to deliver tumoricidal doses of radiation to liver tumors while selecting a safe radiation dose limit for nontumoral liver and lung tissue. Hence, correct treatment planning is essential to obtaining good results. However, this treatment invariably results in some degree of irradiation of normal liver parenchyma, inducing different radiologic findings that may affect follow-up image interpretation. When evaluating treatment response, the treated area size, tumor necrosis, devascularization, and changes seen at functional MRI must be taken into account. Unlike with other interventional procedures, with TARE, it can take several months for the tumor response to become evident. Ideally, responding lesions will show reduced size and decreased enhancement 3-6 months after treatment. In addition, during follow-up, there are many imaging findings related to the procedure itself (eg, peritumoral edema, inflammation, ring enhancement, hepatic fibrosis, and capsular retraction) that can make image interpretation and response evaluation difficult. Possible complications, either hepatic or extrahepatic, also can occur and include biliary injuries, hepatic abscess, radioembolization-induced liver disease, and radiation pneumonitis or dermatitis. A complete understanding of these possible posttreatment changes is essential for correct radiologic interpretations during the follow-up of patients who have undergone TARE. ©RSNA, 2019.

OBJECTIVE To identify an imaging predictor for the assessment of early treatment response to yttrium-90 transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC), using a quantitative assessment of dynamic computed tomography (CT) images. MATERIALS AND METHODS Dynamic contrast-enhanced CT was obtained pre- and 4 weeks post-TARE in 44 patients (34 men, 10 women; mean age, 60 years) with HCC. Computer software was developed for measuring the percentage increase in the combined delayed-enhancing area and necrotic area (pD + N) and the percentage increase in the necrotic area (pNI) in the tumor-containing segments pre- and post-TARE. Local progression-free survival (PFS) was compared between patient groups using Cox regression and Kaplan-Meier analyses. RESULTS Post-TARE HCC with pD + N ≥ 35.5% showed significantly longer PFS than those with pD + N < 35.5% (p = 0.001). The local tumor progression hazard ratio was 17.3 (p = 0.009) for pD + N < 35.5% versus pD + N ≥ 35.5% groups. HCCs with a high pNI tended to have longer PFS, although this difference did not reach statistical significance. CONCLUSION HCCs with a larger pD + N are less likely to develop local progression after TARE.

Our purpose was to identify baseline imaging features in patients with liver cancer that correlate with 90Y distribution on postprocedural SPECT and predict tumor response to transarterial radioembolization (TARE). Methods: This retrospective study was approved by the institutional review board and included 38 patients with hepatocellular carcinoma (HCC) (n = 23; 18/23 men; mean age, 62.39 ± 8.62 y; 34 dominant tumors) and non-HCC hepatic malignancies (n = 15; 9/15 men; mean age, 61.13 ± 11.51 y; 24 dominant tumors) who underwent 40 resin-based TARE treatments (August 2012 to January 2018). Multiphasic contrast-enhanced MRI or CT was obtained before and Bremsstrahlung SPECT within 2 h after TARE. Total tumor volume (cm3) and enhancing tumor volume (ETV [cm3] and % of total tumor volume), and total and enhancing tumor burden (%), were volumetrically assessed on baseline imaging. Up to 2 dominant tumors per treated lobe were analyzed. After multimodal image registration of baseline imaging and SPECT/CT, 90Y distribution was quantified on SPECT as tumor-to-normal-liver ratio (TNR). Response was assessed according to RECIST1.1 and quantitative European Association for the Study of the Liver criteria. Clinical parameters were also assessed. Statistical tests included Mann-Whitney U, Pearson correlation, and linear regression. Results: In HCC patients, high baseline ETV% significantly correlated with high TNR on SPECT, demonstrating greater 90Y uptake in the tumor relative to the liver parenchyma (P < 0.001). In non-HCC patients, a correlation between ETV% and TNR was observed as well (P = 0.039). Follow-up imaging for response assessments within 1-4 mo after TARE was available for 23 patients with 25 treatments. The change of ETV% significantly correlated with TNR in HCC (P = 0.039) but not in non-HCC patients (P = 0.886). Additionally, Child-Pugh class B patients demonstrated significantly more 90Y deposition in nontumorous liver than Child-Pugh A patients (P = 0.021). Conclusion: This study identified ETV% as a quantifiable imaging biomarker on preprocedural MRI and CT to predict 90Y distribution on postprocedural SPECT in HCC and non-HCC. However, the relationship between the preferential uptake of 90Y to the tumor and tumor response after radioembolization could be validated only for HCC.

A common form of treatment for patients with hepatocellular carcinoma (HCC) is transarterial radioembolization (TARE) with non-degradable glass or resin microspheres (MS) labeled with 90Y (90Y-MS). To further simplify the dosimetry calculations in the clinical setting, to have more control over the particle size and to change the permanent embolization to a temporary one, we developed uniformly-sized, biodegradable 188Re-labeled MS (188Re-MS) as a new and easily imageable TARE agent. Methods: MS made of poly(L-lactic acid) were produced in a flow focusing microchip. The MS were labeled with 188Re using a customized kit. An orthotopic HCC animal model was developed in male Sprague Dawley rats by injecting N1-S1 cells directly into the liver using ultrasound guidance. A suspension of 188Re-MS was administered via hepatic intra-arterial catheterization 2 weeks post-inoculation of the N1-S1 cells. The rats were imaged by SPECT 1, 24, 48, and 72 h post-radioembolization. Results: The spherical 188Re-MS had a diameter of 41.8 ± 6.0 µm (CV = 14.5%). The site and the depth of the injection of N1-S1 cells were controlled by visualization of the liver in sonograms. Single 0.5 g tumors were grown in all rats. 188Re-MS accumulated in the liver with no deposition in the lungs. 188Re decays to stable 188Os by emission of β¯ particles with similar energy to those emitted by 90Y while simultaneously emitting γ photons, which were imaged directly by single photon computed tomography (SPECT). Using Monte Carlo methods, the dose to the tumors was calculated to be 3-6 times larger than to the healthy liver tissue. Conclusions: 188Re-MS have the potential to become the next generation of β¯-emitting MS for TARE. Future work revolves around the investigation of the therapeutic potential of 188Re-MS in a large-scale, long-term preclinical study as well as the evaluation of the clinical outcomes of using 188Re-MS with different sizes, from 20 to 50 µm.

The preferred treatment for hepatocellular carcinoma (HCC) is surgery, which is the only way to achieve long-term survival and even a cure. However, the vast majority of patients with liver cancer in China are already in the middle to advanced stage of the disease and no longer have the opportunity to undergo surgery. The goal of conversion therapy is to transform unresectable advanced liver cancer or potentially resectable liver cancer into resectable cancer, so it has become a topic of interest in the treatment of advanced liver cancer. Common modalities of conversion therapy are: local treatment (TACE, TARE, or HAIC), systemic treatment (targeted therapy alone or combined with immunotherapy), and a therapeutic alliance (TACE combined with radiation therapy, TACE combined with targeted therapy, HAIC combined with targeted therapy, or HAIC combined with targeted therapy and immunotherapy). The plan for maintenance treatment after conversion therapy is determined based on the outcome of conversion therapy to obtain the best survival benefit for patients.

(1) Background: To demonstrate correlation between skeletal muscle depletion measured before and after one month of TARE treatment and its induced local response rate. (2) Material and methods: For this retrospective, single center study, we evaluated 86 patients with HCC treated with TARE. Sarcopenia status was measured using the psoas muscle index (PMI). The PMI was calculated according to the formula: PMI [mm/m2]: [(minor diameter of left psoas + major diameter of left psoas + minor diameter of right psoas + major diameter of right psoas)/4]/height in m2. Population was divided in two groups according to the delta value of PMI measured at the time of TARE and one month after TARE, a group in which the delta PMI was stable or increased (No-Sarcopenia group, n = 42) vs. a group in which the delta-PMI decreased (Sarcopenia group, n = 44). Patient response was evaluated at 1, 3 and 6 months after TARE treatment with CT/MRI. (3) Results: When the radiological response of the tumor was evaluated according to the mRECIST criteria, the two groups were similar in terms of rates of complete response (p = 0.42), partial response (p = 0.26) and stable disease (p = 0.59). Progressive disease (PD) was more commonly observed in the Sarcopenia group (38.6% vs. 11.9%, p = 0.006). (4) Conclusions: Worsening of sarcopenia status measured one month after TARE is able to predict patients who will undergo disease progression.

Background Adjuvant sorafenib may further enhance the efficacy of transarterial radioembolization for the treatment of hepatocellular carcinoma. Aims To evaluate the efficacy and safety of radioembolization plus sorafenib in hepatocellular carcinoma patients. Methods With a literature search through October 2020, we identified 9 studies (632 patients). Primary outcome was overall survival. Results were expressed as pooled median, odds ratio, or hazard ratio and 95% confidence intervals. Results Pooled overall survival after radioembolization plus sorafenib was 10.79 months (95% confidence interval 9.19–12.39) and it was longer in Barcelona Clinic Liver Cancer (BCLC) B (14.47 months, 9.07–19.86) as compared to BCLC C patients (10.22 months, 7.53–12.9). No difference between combined therapy versus radioembolization alone was observed in terms of overall survival (hazard ratio 1.07, 0.89–1.30). Pooled median progression-free survival was 6.32 months (5.68–6.98), with 1-year progression-free survival pooled rate of 38.5% (12.7%-44.2%). No difference in progression-free survival (hazard ratio 0.94, 0.79–1.12) between the two treatments was observed. Pooled rate of severe adverse events was 48.9% (26.7%-71.2%), again with no difference between the two treatment regimens (odds ratio 1.52, 0.15–15.02). Conclusions The association of sorafenib does not seem to prolong survival nor delay disease progression in patients treated with radioembolization.

Background Lymph node metastasis (LNM) is a risk factor for poor long-term outcomes and a prognostic factor for disease-free survival in colon cancer. Preoperative lymph node status evaluation remains a challenge. The purpose of this study is to determine whether tumor size measured by multidetector computed tomography (MDCT) could be used to predict LNM and N stage in colon cancer. Material and methods One hundred six patients with colon cancer who underwent radical surgery within 1 week of MDCT scan were enrolled. Tumor size including tumor length (Tlen), tumor maximum diameter (Tdia), tumor maximum cross-sectional area (Tare), and tumor volume (Tvol) were measured to be correlated with pathologic LNM and N stage using univariate logistic regression analysis, multivariate logistic analysis, and receiver operating characteristic (ROC) curve analysis. Results The inter- and intraobserver reproducibility of Tlen (intraclass correlation coefficient [ICC] = 0.94, 0.95, respectively), Tdia (ICC = 0.81, 0.93, respectively), Tare (ICC = 0.97, 0.91, respectively), and Tvol (ICC = 0.99, 0.99, respectively) parameters measurement are excellent. Univariate logistic regression analysis showed that there were significant differences in Tlen, Tdia, Tare, and Tvol between positive and negative LNM (p < 0.001, 0.001, < 0.001, < 0.001, respectively). Multivariate logistic regression analysis revealed that Tvol was independent risk factor for predicting LNM (odds ratio, 1.082; 95% confidence interval for odds ratio, 1.039, 1.127, pp < 0.001, 0.041, < 0.001, < 0.001, respectively), N0 from N2 (all p < 0.001), N0 from N1-2 (p < 0.001, 0.001, < 0.001, < 0.001, respectively), and N0-1 from N2 (p < 0.001, 0.001, < 0.001, < 0.001, respectively). The area under the ROC curve (AUC) was higher for Tvol than that of Tlen, Tdia, and Tare in identifying LNM (AUC = 0.83, 0.82, 0.69, 0.79), and distinguishing N0 from N1 stage (AUC = 0.79, 0.78, 0.63, 0.74), N0 from N2 stage (AUC = 0.92, 0.89, 0.80, 0.89, respectively), and N0-1 from N2 stage (AUC = 0.84, 0.79, 0.76, 0.83, respectively). Conclusion Tumor size was correlated with regional LNM in resectable colon cancer. In particularly, Tvol showed the most potential for noninvasive preoperative prediction of regional LNM and N stage.

Objective Transarterial radioembolisation (TARE) is a promising technique for unresectable primary tumours of the liver. We present our clinical experience and the response to treatment and survival data of patients with hepatocellular carcinoma (HCC) who were treated with Y-90 radioembolisation in our hospital's angiography department. Material and methods The data of all the patients with HCC referred to our department for Y-90 treatment were analysed retrospectively. The patients were selected according to the treatment protocol criteria, and lung shunt fraction was evaluated using macroaggregated albumin scintigraphy before radioembolisation. Patients with compatible blood tests and lung shunt fraction rates were chosen for treatment with Y-90 TARE. Results Twenty-four patients were suitable for Y-90 treatment. The patients were treated with 137 ± 44.6 (80-245) Gy Y-90 glass microspheres. The treatment results were evaluated using modified RECIST criteria, and the partial response, complete response, stable disease and progression rates were found to be 54.2, 16.7, 20.8 and 8.3%, respectively. The median survival rate following treatment was 10 months. Higher alpha-fetoprotein (AFP) levels were related to decreased survival, and posttreatment AFP levels had a significant effect on mortality rates. Higher survival rates were detected in the patients who were treated more selectively than the group treated via a lobar approach. Conclusion Y-90 microsphere radioembolisation is a safe method and may be helpful in treating patients with unresectable hepatocellular tumours. More favourable results were obtained in the patients treated using the more selective approach. AFP levels before and after treatment could predict survival rates.

Introduction We aim to assess the outcomes of percutaneous ablation of locally advanced HCC in a tertiary center, which is usually not indicated. We compared to sorafenib or trans-arterial radioembolization (TARE). Methods We included 272 patients with HCC and tumor portal invasion treated by percutaneous ablation (n = 44) assessed retrospectively from one center compared to a control group from the SARAH trial including patients treated with sorafenib (n = 123) or TARE (n = 105). A propensity-score matching was performed in a subgroup of patients with similar baselines characteristics. Results 84% of patients treated by ablation were male with a unique nodule (median size 50 mm) in 72.7% of the case. Complete tumor ablation was achieved in 75% of the patients with 20% Dindo–Clavien III–V adverse events including 6.8% of 90-days mortality. Sum of tumor size ≥70 mm was associated with incomplete ablation (p = 0.0239) and a higher risk of death (p = 0.0375). Patients in control group had a higher tumor burden, and more Vp3/4 compared to ablation group. Median overall survival was similar in the ablation and in the control group (16.4 and 14.0 months respectively, p = 0.48). The median progression-free survival was 6.6 months in ablation group compared to 4.2 months in the control group (p = 0.12). Conclusion Percutaneous ablation for locally advanced HCC was feasible and associated with similar long-term outcomes to sorafenib or TARE.

BACKGROUND Transarterial radioembolization (TARE) is widely used for the treatment of hepatocellular carcinoma (HCC), but early treatment response can be very difficult to assess. The aim was to evaluate 18F-fluorocholine PET/computed tomography (CT) to assess the treatment response in patients with intermediate or locally advanced HCC. METHODS Between March 2019 and July 2020, nine HCC patients treated with TARE, who underwent PET/CT at baseline and 1 month after treatment, were enrolled. The maximum, mean (SUVmean), and peak (SUVpeak) standardized uptake value (SUV), SUV normalized by lean body mass (SUL), and total lesion glycolysis (TLG) were measured. Statistical analysis used the Mann-Whitney test to evaluate the differences in parameters between responders (partial and complete response) and nonresponders (stable or progressive disease) at the 6-month follow-up, according to the modified Response Evaluation Criteria in Solid Tumors. RESULTS Three patients were nonresponders (progressive disease and stable disease) and six were responders. Delta SUVmean, delta SUL, and delta TLG could predict an early response (P = 0.02, P = 0.04, and P = 0.02, respectively). None of the pre-therapeutic parameters were correlated with the response. Post-therapeutic SUL, SUVmean, TLG, and SUVpeak were also predictive of the response. CONCLUSIONS Our preliminary results showed that changes in certain metabolic parameters (from baseline PET to 1-month PET) are predictive of the response to TARE in HCC (Delta SUVmean, delta TLG, and delta SUL). The absence of post-treatment inflammation could lead to a better prediction than MRI evaluation. This study suggests that 1-month 18F-choline PET/CT could modify the clinical management predicting responders.Video Abstract: http://links.lww.com/NMC/A193.

Objective: To study the efficacy and safety of repeat transarterial radioembolization (TARE) to similar hepatic arterial territories. Methods: Between 3/2011 and 4/2019, 26 patients (25 males and 1 Female, Mean Age: 65 yo, SD: 11.7 yo, Range: 18–83.0 yo) received TARE with Y90 glass microspheres to treat recurrent or residual primary disease in similar hepatic arterial lobe or segments. Tumor response was evaluated by imaging using the modified-RECIST criteria. Incidence of RILD and adverse events were categorized by a standardized scale using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Results: Mean cumulative activity after the first treatment was 2.50 GBq (SD:1.04 GBq, Range:0.61–4.93 GBq) and second treatment was 2.27 GBq (SD:1.01 GBq, Range:0.92–5.46 GBq). Mean interval time between initial and repeat treatments was 9.6 months (Range: 1–53 months). Tumor responses were complete, partial, or progression in 73% (n = 19/26), 23% (n = 6/26), and 4% (n = 1/26) in repeat treatment patients, respectively. The incidence of RILD was 0%. Toxicity after first and second treatment was seen in 19% (n = 5/26) & 23% (n = 6/26) patients, respectively, and were all of CTCAE Grade 2. No significant predictors of treatment toxicity for repeat treatment were identified except increased MELD score (p = 0.04). Kaplan-Meier survival analysis in patients with repeat treatment showed a median survival of 15.0 months (95% CI 8.8–21.1 months) and 19.0 months (95% CI 8.1–29.9 months) in patients who only received one treatment with a p value of 0.485. Conclusion: Repeat TARE with glass microspheres was an effective and safe treatment strategy for disease management in patients with residual or recurrent disease to the similar hepatic arterial territories without any major treatment related toxicity. Advances in knowledge: Although safety and efficacy of repeat radioembolism has been studied, no study has focused on repeat treatment to similar hepatic arterial territories. The current study shows that repeat treatment to the same hepatic arterial territory is as safe as single treatment to the same territory.