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Tumors involving the caudate lobe present a unique therapeutic challenge due to their complex anatomy and the safety and efficacy of locoregional therapy can be variable. The purpose of this study is to analyze the outcomes of radiation segmentectomy for primary caudate lobe tumors.Eight patients [5 women and 3 men; median age = 69 y (range 50-79)] that underwent transarterial radioembolization (TARE) using yttrium-90 (Y90) glass microspheres for primary caudate lobe tumors (hepatocellular carcinoma = 6, intrahepatic cholangiocarcinoma = 2) from August 2017 to March 2021 were retrospectively analyzed. Descriptive statistics, treatment parameters, tumor response (using modified response evaluation criteria in solid tumors), adverse events [using common terminology criteria for adverse events (CTCAE)], and survival outcomes were evaluated.Eight primary caudate lobe tumors with a median size of 2.2 cm [interquartile range (IQR), 1.7-3.3] and Child-Pugh class A liver function underwent TARE of the caudate lobe. The median radiation dose was 596 Gy (IQR 356-1585), median total activity was 0.84 GBq (IQR 0.56-1.31), median specific activity was 473 Bq/sphere (IQR 226-671), and the median number of Y90 microspheres used was 1.4 million (IQR 1.2-3.4). All complications were CTCAE grade 1, and no clinically significant hilar plate complications were observed. In targeted tumors, complete response was seen in all patients. At a median follow-up period of 16.6 months (IQR 6.6-21.6) 75% (6/8) of patients were alive with no in-field progression.Radiation segmentectomy of primary caudate lobe tumors appears effective and is well tolerated in this limited case series within the described treatment parameters.Level 4, Case Series.

Since its first suggestion as possible option for liver radioembolization treatment, the therapeutic isotope holmium-166 (166Ho) caught the experts’ attention due to its imaging possibilities. Being not only a beta, but also a gamma emitter and a lanthanide, 166Ho can be imaged using single-photon emission computed tomography and magnetic resonance imaging, respectively. Another advantage of 166Ho is the possibility to perform the scout and treatment procedure with the same particle. This prospect paves the way to an individualized treatment procedure, gaining more control over dosimetry-based patient selection and treatment planning. In this review, an overview on 166Ho liver radioembolization will be presented. The current clinical workflow, together with the most relevant clinical findings and the future prospective will be provided.

The management of Renal cell carcinoma (RCC) patients with liver metastases is challenging. Liver-directed therapy, such as Transarterial radioembolization (TARE), is a reasonable option for these patients; however, its safety and efficacy are not well characterized. This study evaluated the safety and efficacy of TARE in patients with liver-dominant metastatic RCC. This is a retrospective, single-center study. Thirty-eight patients’ medical records were reviewed who underwent TARE between January 1, 2009, and December 31, 2019, in a tertiary cancer center. Two were excluded from further analysis. Thirty-six patients received 51 TARE treatments. Median follow-up time was 18.2 months. Imaging data were evaluated using mRECIST or RECIST 1.1 criteria. Toxicities, treatment responses, liver progression-free survival (LPFS), and median overall survival (OS) were calculated. Univariate and multivariate analyses were conducted to reveal predictors of OS. Median OS from TARE was 19.3 months (95% CI, 22.6–47.4) and from diagnosis of liver metastases was 36.5 months (95% CI: 26.4–49.8). Mild, grade 1 or 2, biochemical toxicity developed in 27 patients (75%). Grade 3–4 toxicity was noted in two patients (5.5%). The objective response rate was 89%; the disease control rate was 94% (21 complete response, 11 partial response, two stable disease, and two progressive disease). Univariate and multivariate analyses showed longer survival in patients who had objective response, lower lung shunt fraction, and better baseline liver function. TARE is safe and effective and led to promising overall survival in patients with liver-dominant metastatic RCC. Level of Evidence: Level 3, retrospective cohort study.

Purpose: Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative. Materials and methods: A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures. Results: A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2months while after TARE was 13.5months (95%C.I.: 11.4–16.1). The survival difference was small (d = 0.112) at 1year and negligible at 2years (d = 0.028) and at 3years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314). Conclusion: In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).

Purpose To search for abscopal effects (AE) distant to the site of radiation after sequential Yittrium-90 (Y-90) radioembolization (RE) of liver malignancies. Methods and Materials In this retrospective analysis, all patients treated by RE between 2007 and 2018 (n = 907) were screened for the following setting/conditions: sequential RE of left and right liver lobe in two sessions, liver-specific MRI (MRI1) acquired max. 10 days before or after first RE (RE1), liver-specific MRI (MRI2) acquired with a minimum time interval of 20 days after MRI1, but before second RE (RE2). No systemic tumor therapies between MRI1 and MRI2. No patients with liver cirrhosis. Metastases > 5 mm in untreated liver lobes were compared in MRI1 and MRI2 and rated as follows: same size or larger in MRI2 = no abscopal effect (NAE); > 30% shrinkage without Y-90 contamination in SPECT/CT = abscopal effect (AE). Results Ninety six of 907 patients met aforementioned criteria. Median time-frame between RE1 and MRI2 was 34 (20–64) days. These 96 cases had 765 metastases which were evaluable (median 5(1–40) metastases per patient). Four patients could be identified with at least one shrinking metastasis of the untreated site: one patient with breast cancer (3 metastases: 0 NAE; 3 AE), one patient with prostate cancer (6 metastases: 3 NAE; 3 metastases > 30% shrinkage but possible Y-90 contamination) and two patients with shrinkage of one metastasis each but less than 30%. Conclusion Our retrospective study documents AE after RE of liver tumors in 1 out of 96 cases, 3 other cases remain unclear.

Hepatocellular carcinoma (HCC) has the tendency to invade the portal and/or hepatic venous system. The invasion of the right atrium is uncommonly observed and constitutes a treatment challenge. We report the case of a patient with HCC invading the right atrium treated with 90Yttrium-transarterial radioembolization (90Y-TARE). Following the treatment, organizing pneumonia secondary to nivolumab occurred, raising the question of an interaction between 90Y-TARE and nivolumab. Electronic supplementary material The online version of this article (10.1007/s00270-020-02605-3) contains supplementary material, which is available to authorized users.

Background: Y90 transarterial radioembolization (Y90-RE) may improve clinical outcomes of unresectable intrahepatic cholangiocarcinoma (ICC); however, the optimal timing for Y90-RE is still debated. The purpose of this multicenter study was to retrospectively evaluate clinical outcomes of RE in patients with unresectable ICC, comparing three different settings: chemotherapy naïve patients (group A), patients with disease control after first-line chemotherapy (group B) and patients with progression after first-line chemotherapy (group C). Materials and Methods: The study included 81 consecutive patients (49 male, mean age 62.4 ± 11.8years): 35 (43.2%) patients were in group A, 19 (23.5%) in group B, and 27 (33.3%) in group C. Preprocedural clinical variables, tumour response according to RECIST 1.1 and overall survival (OS) were analysed and compared. Results: Baseline demographic and clinical features did not differ significantly among groups, with the exception of prior surgical procedures that were significantly higher in group C patients, and macrovascular invasion that was more frequent in group B. Radiological response was available in 79 patients; objective response and disease control rates were 41.8% and 83.6%, respectively, without significant differences among groups. Median OS was 14.5months (95% CI: 11.1–16.9) and was not significantly different among treatment groups. At multivariate analysis, tumour burden > 50%, neutrophil-to-lymphocyte (N/L) ratio ≥ 3 and radiological progression as best response resulted to be significant (P < 0.05) independent factors, negatively associated with OS. Conclusion: Y90-RE is a valuable treatment option in unresectable ICC, irrespectively from the timing of treatment. Tumour extension, N/L ratio and radiological response affect post-treatment survival.

To investigate timing of Yttrium-90 radioembolization (Y90) during treatment course, genomics, and other clinical factors as predictors of overall survival (OS) in colorectal liver metastasis (CRLM) that have progressed on at least one line of chemotherapy. This was a retrospective study from 2013 to 2018 of patients with CRLM and genomic analysis prior to Y90 at a multihospital tertiary referral center. OS from liver metastasis diagnosis and predictors of OS were analyzed using Kaplan–Meier estimation with log-rank and Cox regression analyses. Overall, 58 patients with CRLM who progressed on at least one line of chemotherapy who had genomic analysis prior to Y90 were identified. Median OS after hepatic metastasis was 29.9 months. Of these, 16 (28%) patients received Y90 after failure of the first-line systemic chemotherapy. There was significantly prolonged OS in patients receiving Y90 immediately following failure of the first-line chemotherapy folinic acid, fluorouracil, oxaliplatin ((FOLFOX) ± bevacizumab) versus following multiple lines of chemotherapy (median OS of 46.3 vs. 26.6 months, P = 0.005). The presence of genetic mutation in tumor, MAPK pathway wild type, left-sided primary tumor, low MELD score, and non-diffuse unilobar disease were also found to be predictors prolonged survival on log-rank analysis (P’s

Purpose To evaluate the efficacy of coil embolization to obtain intrahepatic redistribution in patients undergoing radioembolization. Materials and Method All patients treated with radioembolization at our institute were retrospectively analyzed, and all cases in which a tumor-feeding vessel was coil-embolized were selected. Two nuclear medicine physicians visually assessed the effect of redistribution. Furthermore, the redistribution of microspheres was measured by quantifying the activity distributed to the coil-embolized (dependent) segment relative to the other (non-dependent) segments and to the tumor(s) in that segment. Quantitative analysis was performed on post-treatment 90Y-PET and 166Ho-SPECT using Simplicit90Y software. Lesion response was measured according to RECIST 1.1 criteria at 3 months post-treatment. Results Out of 37 cases, 32 were suitable for quantitative analysis and 37 for qualitative analysis. In the qualitative analysis, redistribution was deemed successful in 69% of cases. The quantitative analysis showed that the median ratio of the activity to the dependent embolized segments and the non-dependent segments was 0.88 (range 0.26–2.05) and 0.80 (range 0.19–1.62) for tumors in dependent segments compared with tumors in non-dependent segments. Using a cutoff ratio of 0.7 (30% lower activity concentration in comparison with the rest of the liver), 57% of cases were successful. At 3 months post-treatment, 6% of dependent tumors had partial response, 20% progressive disease, and 74% stable disease. In non-dependent tumors, this was, respectively, 16%, 20%, and 64%. Conclusion Coil embolization of hepatic arteries to induce redistribution of microspheres has a limited success rate. Qualitative assessment tends to overrate redistribution.

To investigate the reduction of elevated shunts after treatment with sorafenib in hepatocellular carcinoma (HCC) patients planned for transarterial radioembolization (TARE).Sixteen HCC patients treated with sorafenib were investigated. Shunts were evaluated by SPECT/CT after Technetium-99 m Tc-macroaggregated albumin injection.All patients had high LSF (median 43.5%, range 28-86), and two (12.5%) of them had widespread intrahepatic shunts with concomitants elevated (36%) and acceptable (18%) lung shunt fraction (LSF). The mean duration of the sorafenib use was 134.4 ± 59.2 days. While one patient (6.25%) developed hand-foot syndrome, minor side effects were seen in all patients. After sorafenib use, LSF fell below 20% in eight patients, and TARE was applied to all of them. There was strong negative correlation between the failure of shunt reduction and presence of macrovascular invasion (ρ = - 0.775) and infiltrative tumour type (ρ = - 0.775).Sorafenib use may be beneficial in some selected HCC patients with elevated shunts. Expected results may not be obtained in patients with infiltrative tumour type or macrovascular invasion, but patients with nodular tumour type with the absence of macrovascular invasion may be appropriate candidates for shunt reduction with ensuring subsequent TARE. Further investigations with sufficient patient population and standardized protocols of follow-up periods are needed to clarify the values for sorafenib use in HCC patients with evaluated shunts.

To determine how particle density affects dose distribution and outcomes after lobar radioembolization.Matched pairs of patients, treated with glass versus resin microspheres, were selected by propensity score matching (114 patients), in this single-institution retrospective study. For each patient, tumor and liver particle density (particles/cmAs more particles were delivered, doses onThe number of particles delivered can be chosen to maximize the tumor dose and minimize the liver dose, based on tumor vascularity. Optimizing the particle density resulted in improved LPFS and overall survival.

Currently, the estimated absorbed radiation dose to the lung inA retrospective analysis was performed on 68 patients who had undergonePatient-specific lung masses were significantly different from the generic 1 kg when compared individually for each patient (p 0.0001). Median individualized lung mass was 0.71 (IQR: 0.59, 1.02) kg overall and was significantly different from the generic 1 kg lung mass for female patients [0.59 (0.50, 0.68) kg, (p 0.0001)] but not for male patients [0.99 (0.71, 1.14) kg, (p = 0.24)]. Median estimated lung absorbed dose was 4.48 (2.38, 11.71) Gy using a patient-specific lung mass and 3.45 (1.81, 6.68) Gy when assuming a 1 kg lung mass for all patients. The estimated lung absorbed dose was significantly different using a patient-specific versus generic 1 kg lung mass when comparing the doses individually for each patient (p 0.0001). The difference in the estimated lung absorbed dose between the patient-specific and generic 1 kg lung mass method was significant for female patients as a subgroup but not for male patients.The current method of assuming a 1 kg lung mass for all patients inaccurately estimates the lung absorbed dose inLevel 3, Retrospective Study.

The liver represents the most frequent location of metastatic disease in colorectal cancer (CRC). In oligometastatic disease, while surgery remains the mainstay of treatment, loco-regional therapies allow to locally control tumor progression and prolong survival. There is consensus in the use of transhepatic arterial radioembolization (TARE) in metastatic CRC chemorefractory patients, with liver-only or liver-dominant disease. Beyond this indication, TARE may be considered in other clinical scenarios, such as in the second-line combined with chemotherapy, as a bridge in between different lines of systemic therapies, and as ablative technique under specific circumstances. This paper outlines the current evidence for TARE in mCRC and presents possible future indications and directions.

The liver is the most common site of metastasis for neuroendocrine tumors originating from the gastrointestinal tract. Neuroendocrine liver metastases (NELMs) portend a worsening clinical course, making local management important. Local treatment options include surgery, thermal ablation, and trans-catheter intra-arterial therapies, such as radioembolization. Radioembolization is generally preferred over other embolotherapies in patients with colonized biliary systems. Current best practice involves personalized treatment planning, optimizing tumor radiation absorbed dose and minimizing radiation to the normal hepatic parenchyma. As part of a multidisciplinary approach, radioembolization is a versatile embolotherapy offering neoadjuvant, palliative, and ablative treatment options for patients with NELMs.

Trans-arterial radioembolization is currently performed using

Radioembolisation is an established transarterial therapy for hepatocellular carcinoma and liver metastasis. Success of radioembolisation depends on meticulous angiography and accurate dosimetry. Intra-procedure catheter-directed CT-angiography is commonly performed to improve the efficacy and safety of radioembolisation. This review article will (1) introduce the differences between cone beam CT and hybrid angiography-CT, and (2) describe the benefits of catheter-directed CT-angiography in radioembolisation from both an interventional radiology and nuclear medicine perspective.

The aim of this short communication was to report the results of transarterial radioembolization (TARE) with Yttrium-90 (Y90) loaded resin microspheres in three toddlers with unresectable and systemic chemotherapy-resistant HB hepatoblastoma (HB). Six TARE procedures were performed on the patients. The dose required for treatment was calculated using partition model. Administered doses of Y90 were 1.369, 0.851, and 1.147 GBq. Complete radiological response in two patients and partial response enabling liver resection in one patient were achieved. Neither life-threatening nor minor complications developed after the treatment. These results demonstrates that HB is a radiosensitive neoplasm, and TARE-Y90 can be used as the primary, neoadjuvant and palliative treatment method in patients with unresectable and systemic chemotherapy-resistant HBs. However, studies with higher number of patients and long-term results are required.

To determine the rate of prophylactic embolization of extrahepatic vessels in patients undergoing yttrium-90 selective internal radiotherapy (90Y SIRT) for hepatocellular carcinoma (HCC) with the use of catheter-directed computed tomography hepatic angiography (CD-CTHA). This retrospective study included 186 HCC patients who received 90Y SIRT from May 2010 to June 2015 in a single institution. All procedures were performed in a hybrid angiography-CT suite equipped with digital subtraction angiography (DSA) and CD-CTHA capabilities. CD-CTHA was performed during pre-treatment hepatic angiography. 90Y SIRT was administered approximately 2 weeks later. Selective prophylactic embolization of extrahepatic vessels was performed if extrahepatic enhancement was seen on CD-CTHA or if an extrahepatic vessel opacified on DSA/CD-CTHA despite the final microcatheter position for 90Y microsphere delivery being beyond the origin of this vessel. Thirty-five patients (18.8%) required selective embolization of extrahepatic vessels. Technical success of 90Y SIRT was 99.5%. Two patients (1.1%) developed radiation-induced gastrointestinal ulceration, and one (0.54%) developed radiation-induced pneumonitis. Extrahepatic uptake of 90Y microspheres was seen in the gallbladder of one patient without significant complications. The use of CD-CTHA in 90Y SIRT of HCC was associated with a low rate of prophylactic embolization of extrahepatic vessels while maintaining a high technical success rate of treatment and low rate of complications. Level 4, case series.

Dose calculation for transarterial radioembolization (TARE) with glass yttrium-90 (Y90) labeled microspheres is based on liver lobe and tumor volumes, currently measured from preprocedural MRI or CT. The variable time between MRI and radioembolization may not account for relevant tumor progression. Advances in cone beam computed tomography (CBCT) allow for intra-procedural assessment of these volumes that avoids this factor. Liver lobe and hepatocellular carcinoma tumor volume measurements and dose calculations using intra-procedural CBCT were compared to those using preprocedural MRI in order to determine feasibility. Retrospective analysis was performed in 20 patients with proven hepatocellular carcinoma (HCC) who underwent planning angiography with open trajectory CBCT acquisitions prior to radioembolization, and an MRI performed within 6 weeks prior to treatment planning. Liver lobe and tumor burden volumes were measured based on CBCT using embolization planning and guidance software and measured on preprocedural MRI using standard volume analysis software. Y90 doses were subsequently calculated using each measured volume. Comparisons of volume measurements and calculated Y90 doses between the two modalities were evaluated for significance using paired t tests. All target liver lobes and all tumors were completely depicted on CBCT. Mean liver lobe and tumor burden volumes measured on intra-procedural CBCT and preprocedural MRI showed no significant difference (p = 0.71). Mean calculated Y90 dose based on each modality showed no significant difference (p = 0.18). Lobar and tumor volume measurement with CBCT is a reliable alternative to measurement with preprocedural MRI. Utilization of CBCT 3D segmentation software during planning angiography may be useful to provide up-to-date volume measurements and dose calculations prior to radioembolization.

To evaluate the influence of sarcopenia on survival in patients with hepatocellular carcinoma (HCC) treated withThis single-center retrospective cohort study analyzed 82 consecutive patients (65 men and 17 women, mean age 65 years, range 31-83 years) with HCC treated withSarcopenia was identified in 30% (25/82) of patients. Death was reported for 49% (32/65) of males and 71% (8/17) of females (mean follow-up 19.6 months, range 21 days-58 months). Patients with sarcopenia were found to have increased mortality at 180 days (31.8% vs. 8.9%) and 1 year (68.2% vs. 21.2%). Sarcopenia was an independent predictor of mortality adjusted for BCLC stage and sub-analysis demonstrated that sarcopenia independently predicted increased mortality for patients with BCLC stage B disease.Sarcopenia was associated with increased 180-day and 1-year mortality in HCC patients undergoing

Metformin is associated with improved outcomes after external radiation and chemotherapy but has not been studied for Y-90 radiation segmentectomy (RS). This study evaluates the effect of metformin on tumor response after Y-90 RS in patients with hepatocellular carcinoma (HCC). A retrospective analysis of patients with HCC who underwent Y-90 RS between 2014–2018 was performed. Comparisons were made between all patients taking and not taking metformin, and diabetic patients taking and not taking metformin. Tumor response was analyzed with logistic regression to compare absolute and percent change in total tumor diameter (TTD) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was evaluated using Kaplan–Meier estimation and log-rank analysis. A total of 106 patients underwent 112 Y-90 RS, of which 40 were diabetic (38.8%) and 19 (18.4%) were on metformin. At baseline, the two groups of patients on metformin and not on metformin had no significant difference in age, Child–Pugh score, MELD score, ALBI grade, total tumor diameter, and size of dominant tumor. The only significant baseline difference was ECOG status. Uni- and multivariate analysis demonstrated a larger reduction in TTD and objective response by mRECIST criteria for patients undergoing Y-90 RS on metformin compared to those not on metformin. OS was similar between patients taking and not taking metformin (p = 0.912). Metformin may be associated with increased tumor response after Y-90 RS in patients with HCC. III, Retrospective Study.

To compare radioembolization treatment zone volumes from mapping cone beam CT (CBCT) versus planning CT/MRI and to model their impact on dosimetry.Y90 cases were retrospectively identified in which intra-procedural CBCT angiograms were performed. Segmental and lobar treatment zone volumes were calculated with semi-automated contouring using Couinaud venous anatomy (planning CT/MRI) or tumor angiosome enhancement (CBCT). Differences were compared with a Wilcoxon signed-rank test. Treatment zone-specific differences in segmental volumes by volumetric method were also calculated and used to model differences in delivered dose using medical internal radiation dosimetry (MIRD) at 200 and 120 Gy targets. Anatomic, pathologic, and technical factors likely affecting segmental volumes by volumetric method were evaluated.Forty segmental and 48 lobar CBCT angiograms and corresponding planning CT/MRI scans were included. Median Couinaud- and CBCT-derived segmental volumes were 281 and 243 mL, respectively (p = 0.005). Differences between Couinaud and CBCT lobar volumes (right, left) were not significant (p = 0.24, p = 0.07). Couinaud overestimated segmental volumes in 28 cases by a median of 98 mL (83%) and underestimated in 12 cases by median 69 mL (20%). At a 200 Gy dose target, Couinaud estimates produced median delivered doses of 367 and 160 Gy in these 28 and 12 cases. At a 120 Gy target, Couinaud produced doses of 220 and 96 Gy. Proximal vs. distal microcatheter positioning, variant arterial anatomy, and tumor location on or near segmental watersheds were leading factors linked to volumetric differences.Use of CBCT-based volumetry may allow more accurate, personalized dosimetry for segmental Y90 radioembolization.

To compare the efficacies of glass and resin-based Yttrium-90 microspheres by comparing absorbed tumor dose (TD) with both tumor response (TR) and overall survival (OS) in patients with chemorefractory intrahepatic cholangiocarcinoma (ICC). Post-Y90 treatment bremsstrahlung SPECT/CT of 38 consecutive patients receiving 45 treatments (21 resin microspheres, 24 glass microspheres) were analyzed retrospectively. MIM software v6.9.4 (MIM Software Inc, Cleveland, OH) was used to calculate targeted tumors’ dose volume histogram. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response 3 months post-treatment. Kaplan Meier estimation was used for survival analysis. T-test was used to compare the devices on various dosimetric parameters. Thresholds for TD to predict TR with ≥ 80% specificity were as follows: mean TD (Resin: 78.9 Gy; Glass: 254.7 Gy), maximum TD (Resin: 162.9 Gy; Glass: 591 Gy), minimum TD (Resin: 53.7 Gy; Glass: 149.1 Gy). Microsphere type had no effect on survival from first Y90 (Resin: 11.2 mo; Glass 10.9 mo [p = 0.548]). In patients receiving resin microspheres, mean TD ≥ 75 Gy or maximum TD ≥ 150 Gy was associated with median OS of 20.2 mo compared to 6.5 mo for those receiving less (p = 0.001, 0.002, respectively). For patients treated with glass microspheres, those receiving a mean TD ≥ 150 Gy had a median OS of 14.6 mo vs. 2.6 mo for those receiving less (p = 0.031). TD thresholds predictive of TR and OS differ significantly between glass and resin microspheres. However, microsphere type has no impact on survival in patients with chemorefractory ICC. Level 3, Retrospective Study.

To evaluate the efficacy and safety of Y90 radiation segmentectomy (RS) vs. percutaneous microwave ablation (MWA) in patients with solitary HCC ≤ 4 cm.From 2014 to 2017, 68 consecutive treatment naïve patients were included (34 per treatment arm). Chi-square and t-test were used to evaluate differences in baseline demographics between groups. Objective response was evaluated using mRECIST and toxicity using CTCAE. Overall survival (OS) and progression free survival (PFS) in the targeted tumor and the remainder of liver from initial treatment was calculated using Kaplan-Meier estimation. Propensity score matching was then performed with n = 24 patients matched in each group. Similar outcome analysis was then pre-formed.In the overall study population, both groups had similar baseline characteristics with the exception of larger lesions in the RS group. There was no difference in toxicity, objective tumor response, OS and non-target liver PFS between the MWA and RS group (p's 0.05). In the matched cohort, the objective tumor response was 82.6% in MWA vs. 90.9%% in RS (p = 0.548). The mean OS in the MWA group (44.3 months) vs RS (59.0 months; p = 0.203). The targeted tumor mean PFS for the MWA groups was 38.6 months vs. 57.8 months in RS group (p = 0.005). There was no difference overall PFS and toxicity between the 2 matched groups.Our data suggest Y90 RS achieves similar tumor response and OS with a similar safety compared to MWA in the management of HCC lesions ≤ 4 cm. Additionally, targeted tumor PFS appears to be prolonged in the RS group with similar non-target liver PFS between RS and MWA group.

Portal vein embolization (PVE) is an established neoadjuvant method to induce future liver remnant hypertrophy prior to surgical resection of hepatic tumors. The purpose of our study was to examine the feasibility of PVE with glassTwenty-two rats were assigned to four groups for Y90 PVE to the right median lobe: very high- (273.8 MBq; n = 2), high- (99.9 MBq; n = 10), medium- (48.1 MBq; n = 5), and low-dose (14.8 MBq; n = 5). An untreated control group included seven rats.Ex vivo measurements confirmed 91-97% activity was localized to the target lobe (n = 4). The percent growth of the target lobe relative to baseline was - 5.0% (95% CI - 17.0-6.9%) for high-, medium dose rats compared to + 18.6% (95% CI + 7.6-29.7%) in the low-dose group at 12-weeks (p = 0.0043). Radiation fibrosis increased in a dose-dependent fashion. Fibrotic area/microsphere was 22,893.5, 14,946.2 ± 2253.3, 15,304.5 ± 4716.6, and 5268.8 ± 2297.2 μmY90 PVE was feasible in the rat model, resulted in target lobe atrophy, and dose-dependent increases in hepatic fibrosis at 12 weeks. The onset of imaging-based volumetric changes was 8-12 weeks.

To compare lung shunt fraction (LSF) prior to Y-90 radioembolization calculated using planar imaging versus SPECT/CT in patients with hepatocellular carcinoma (HCC). A single institution retrospective analysis of technetium-99m macroaggregated albumin (Tc-99m MAA) LSF studies for 293 consecutive patients with HCC between 2013 and 2018 was performed. LSF using planar imaging (PLSF) was compared to retrospectively calculated LSF using SPECT/CT (SLSF) via semiautomated segmentation using MIM v.6.9. Sub-analyses of patients were performed based on PLSF range, tumor size, BCLC stage, and Child–Pugh (C–P) score. Mean LSF absolute discrepancy between sub-groups was analyzed. Comparisons were performed using paired t tests and linear regression analysis. Mean PLSF, 8.27%, was greater than mean SLSF, 3.27% (p

PurposeTo evaluate the combination of 90Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model.Materials and methodsAn initial dose finding study was performed in 6 White New Zealand rabbits to identify a therapeutic but subcurative dose of Y90. In total, 29 rabbits were used in four groups: Y90 treatment (n = 8), DEBIRI treatment (n = 6), Y90 + DEBIRI treatment (n = 7), and an untreated control group (n = 8). Hepatic toxicity was evaluated at baseline, 24h, 72h, 1week, and 2weeks. MRI tumor volume (TV) and enhancing tumor volume were assessed baseline and 2weeks. Tumor area and necrosis were evaluated on H&E for pathology.ResultsInfused activities of 84.0-94.4MBq (corresponding to 55.1-72.7Gy) were selected based on the initial dose finding study. Infusion of DEBIRI after Y90 was technically feasible in all cases (7/7). Overall, 21/29 animals survived to 2weeks, and the remaining animals had extrahepatic disease on necropsy. Liver transaminases were elevated with Y90, DEBIRI, and Y90 + DEBIRI compared to control at 24h, 72h, and 1week post-treatment and returned to baseline by 2weeks. By TV, Y90 + DEBIRI was the only treatment to show statistically significant reduction at 2weeks compared to the control group (p = 0.012). The change in tumor volume (week 2-baseline) for both Y90 + DEBIRI versus control (p = 0.002) and Y90 versus control (p = 0.014) was significantly decreased. There were no statistically significant differences among groups on pathology.ConclusionIntra-arterial Y90 + DEBIRI was safe and demonstrated enhanced antitumor activity in rabbit VX2 tumors. This combined approach warrants further investigation.

Objective After yttrium-90 (90Y) radioembolization, residual activity and its consequences for dosimetric calculations are often not reported. The manufacturer for glass microspheres prescribes standard residual activity measurements by a survey meter, but the validity lacks evidence. This study aims to verify the accuracy of the survey meter approach for measuring residual activity of glass microspheres after treatment with glass microspheres. Methods To validate the accuracy of the survey meter approach, the measured residual activity of glass microspheres by survey meter was compared with measurements by PET. A sample of these waste containers was also measured by dose calibrator to confirm the accuracy of the PET. Results Twenty-four waste containers from glass microsphere treatments were prospectively scanned with 90Y-PET/CT. Bland–Altman plots showed substantial disagreement in residual activity measured by survey meter versus the residual activity measured by PET and dose calibrator, whereas the correlation between PET and dose calibrator was excellent (ρ = 0.99). Conclusion This study found a significant disagreement between the residual activities measured by the survey meter, compared to measurements by PET and dose calibrator. If relatively high amounts of residual activity are encountered using the exposure rate measurement with a survey meter, additional quantification should be considered using either PET/CT or a dose calibrator measurement.

PURPOSE: To identify baseline characteristics and long-term prognostic factors in non-transplant patients with unresectable hepatocellular carcinoma (HCC) who had prolonged survival after treatment with yttrium-90 radioembolization (Y90). MATERIALS AND METHODS: 67 "Super Survivors" (defined as ≥3 years survival after Y90) were identified within our 1,000-patient Y90 database (2003–2017). Baseline imaging and follow-up occurred at 1 months and every 3 months thereafter. Overall survival (OS) was calculated with Kaplan-Meier estimates with log-rank test in sub-groups: Child-Pugh (CP) score, distribution of disease, portal vein thrombus (PVT), and technique (segmental vs lobar Y90). RESULTS: Median age 69.5 years (range: 45–94 years); 69% male; 60% solitary HCC; 79% unilobar disease; 12% PVT; 10% ascites; Barcelona Clinic Liver Cancer Stage A-54%/B-28%/C-16%/D-2%; CP A-70%/B-28%/C-2%. Longest baseline tumor diameter was 5.4 ± 4.0cm (mean ± SD). All patients had an imaging response (either partial or complete response). Median OS was 67.5 months (95% confidence interval; 55.2–82.5). CP score and main PVT stratified median OS (p=0.0007 and p=0.0187, respectively). Beyond 3 years, segmental vs lobar Y90 was associated with improved OS with a median OS of 80.2 vs 46.7 months, respectively (p=0.0024). Dosing >200Gy was not a significant predictor of improved OS. CONCLUSIONS: Super survivors spanning the BCLC Staging System maintained durable OS after radioembolization that was stratified by the extent of underlying liver disease. The common variable among all patients was an imaging response. Segmental vs lobar Y90 may have a long-term associated OS benefit.

Nivolumab has recently received approval by the Food and Drug Administration for treatment of advanced hepatocellular carcinoma (HCC) in patients previously treated with sorafenib. Nivolumabs' overall response rate of 20% (El-Khoueiry et al. in Lancet 389:2492-2502, 2017) is a step forward for these patients, but there is significant room for improvement. We describe a case of combining Y-90 radioembolization with nivolumab for treatment of angioinvasive HCC, which successfully bridged patient to partial hepatectomy. Surgical pathology showed negative margins with complete pathological response. With the introduction of immunotherapy for HCC, combining Y-90 radioembolization with immunotherapy may enhance the anti-tumoral immune response of checkpoint inhibitors.

To retrospectively compare early response to yttrium-90 radioembolization (Y90) according to volumetric iodine uptake (VIU) changes, Response Evaluation Criteria In Solid Tumor 1.1 (RECIST 1.1) and modified RECIST (mRECIST) in patients with intermediate-advanced hepatocellular carcinoma (HCC) and to explore their association with survival. Twenty-four patients treated with Y90 and evaluated with dual-energy computed tomography before and 6 weeks after treatment were included. VIU was measured on late arterial phase spectral images; 6-week VIU response was defined as: complete response (CR, absence of enhancing tumor), partial response (PR, ≥ 15% VIU reduction), progressive disease (PD, ≥ 10% VIU increase) and stable disease (criteria of CR/PR/PD not met). RECIST 1.1 and mRECIST were evaluated at 6 weeks and 6 months. Responders included CR and PR. Overall survival (OS) was evaluated by Kaplan–Meier analysis and compared by Cox regression analysis. High intraobserver and interobserver agreements were observed in VIU measurements (k > 0.98). VIU identified a higher number of responders (18 patients, 75%), compared to RECIST 1.1 (12.5% at 6 weeks and 23.8% at 6 months) and mRECIST (29.2% at 6 weeks and 61.9% at 6 months). There was no significant correlation between OS and RECIST 1.1 (P = 0.45 at 6 weeks; P = 0.21 at 6 months) or mRECIST (P = 0.38 at 6 weeks; P = 0.79 at 6 months); median OS was significantly higher in VIU responders (17.2 months) compared to non-responders (7.4 months) (P = 0.0022; HR 8.85; 95% CI 1.29–88.1). VIU is highly reproducible; as opposite to mRECIST and RECIST 1.1, early VIU response correlates with OS after Y90 in intermediate-advanced HCC patients.

To investigate prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) therapy-naive patients after yttrium-90 (Y-90) radioembolization (RE) therapy. Between 2005 and 2016, 21 patients with ICC were treated with Y-90 RE only and their survival data were analyzed. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The overall median survival was 15 months. Survival was significantly (p = 0.009) prolonged in patients with tumor burden of ≤ 25% (n = 8, OS 37.5 months) versus those with a tumor burden of 25–50% (n = 13, OS 15 months). The other variables: tumor morphology (infiltrative vs. peripheral), tumor distribution (solitary vs. multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs. non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases (metastasis vs. no metastasis) and RECIST criteria, had no significant impact on survival. Tumor burden represents a key prognostic factor of survival in therapy-naive patients with unresectable ICC treated with Y-90 RE therapy only.

In this study, we aim to compare the effects of prognostic indicators on survival analysis for Barcelona Clinic Liver Cancer (BCLC) C patients undergoing yttrium-90 radioembolization (Y-90). A prospectively acquired database (2003–2017) for BCLC C hepatocellular carcinoma (HCC) patients that underwent radioembolization with Y-90 was searched. The criteria for BCLC C status (Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or 2, metastases, and/or portal vein thrombosis (PVT)) were recorded. Kaplan–Meier survival analyses were performed from the date of the first radioembolization with Y-90, censored to curative treatment, to determine median overall survival (OS). Cox regression hazards model was used for multivariate analyses. Significance was set at P