90Y Radioembolization Research Articles

Yttrium-90 radioembolization of isolated hepatic adrenocortical carcinoma metastases with negative surgical pathology

BackgroundAdrenocortical carcinoma (ACC) is an uncommon malignancy with an estimated 15,400 new cases annually across the globe. The prognosis is generally poor as the disease is often already advanced at initial diagnosis due to non-specific symptoms. Even for local disease, recurrence after surgical resection is high. Treatment choices for advanced disease include mitotane, chemotherapy, ablation, chemoembolization, radioembolization, and external beam radiotherapy, with varying degrees of efficacy. To the best of our knowledge, there have only been two prior case studies of complete clinical and radiological response of stage 4 disease at 1 year and 2 years after yttrium-90 (90Y) microsphere selective internal radiation therapy (SIRT) of isolated hepatic metastases post-surgery and chemotherapy.Case presentationWe present a case of a 58-year-old man with metastatic ACC who was treated with 90Y resin microsphere (SIR-spheres) for local control of liver metastases leading to a surgically proven negative pathology after partial hepatectomy 7 months after SIRT. The patient was initially diagnosed with stage 1 ACC that progressed 6 years later to stage 4 disease with new liver metastases that were deemed unresectable at an outside institution. After review of the case at multidisciplinary tumor board, he was referred for liver directed therapy for local tumor control. Angiographic workup demonstrated partial extrahepatic supply to the tumors from the right inferior phrenic artery, which was successfully embolized on the day of SIRT for flow redistribution. As the patient was being treated with mitotane that suppresses steroid production, he developed post-SIRT adrenal crisis, which was successfully controlled with steroids, highlighting the need for pre SIRT stress dose steroids.ConclusionsThis case continues to add to the literature supporting 90Y radioembolization as an effective treatment for isolated hepatic ACC metastases. Our case is the first to demonstrate surgically proven negative pathology after radioembolization. Further prospective study is warranted to better establish efficacy as well as safety of SIRT for ACC liver metastases.

Safety and efficacy of repeat Y90 radioembolization to the same hepatic arterial territory.

To study the efficacy and safety of repeat transarterial radioembolization (TARE) to similar hepatic arterial territories. 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. 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. 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. 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.

90Y PET for Qualitative and Quantitative Assessment of Residual Activity in Delivery Apparatus After Radioembolization.

Assessment of residual activity is critical for quality assurance after 90Y radioembolization. The resin microsphere manufacturer's indirect method of estimating the residual activity is laborious and vulnerable to inaccuracies. Furthermore, the method cannot localize the exact site of residual activity. 90Y PET/CT for qualitative and quantitative assessment of residual activity has not, to our knowledge, been described. We show an example of 90Y PET/CT of residual activity in the delivery apparatus and catheters packed inside the delivery box. Focally intense residual activity was clearly localized to the stopcock junction. Residual activity was directly quantified by setting the PET volume-of-interest isocontour threshold to 1%.

Tumor response prediction in 90Y radioembolization with PET-based radiomics features and absorbed dose metrics

PurposeTo evaluate whether lesion radiomics features and absorbed dose metrics extracted from post-therapy 90Y PET can be integrated to better predict outcomes in microsphere radioembolization of liver malignanciesMethodsGiven the noisy nature of 90Y PET, first, a liver phantom study with repeated acquisitions and varying reconstruction parameters was used to identify a subset of robust radiomics features for the patient analysis. In 36 radioembolization procedures, 90Y PET/CT was performed within a couple of hours to extract 46 radiomics features and estimate absorbed dose in 105 primary and metastatic liver lesions. Robust radiomics modeling was based on bootstrapped multivariate logistic regression with shrinkage regularization (LASSO) and Cox regression with LASSO. Nested cross-validation and bootstrap resampling were used for optimal parameter/feature selection and for guarding against overfitting risks. Spearman rank correlation was used to analyze feature associations. Area under the receiver-operating characteristics curve (AUC) was used for lesion response (at first follow-up) analysis while Kaplan-Meier plots and c-index were used to assess progression model performance. Models with absorbed dose only, radiomics only, and combined models were developed to predict lesion outcome.ResultsThe phantom study identified 15/46 reproducible and robust radiomics features that were subsequently used in the patient models. A lesion response model with zone percentage (ZP) and mean absorbed dose achieved an AUC of 0.729 (95% CI 0.702–0.758), and a progression model with zone size nonuniformity (ZSN) and absorbed dose achieved a c-index of 0.803 (95% CI 0.790–0.815) on nested cross-validation (CV). Although the combined models outperformed the radiomics only and absorbed dose only models, statistical significance was not achieved with the current limited data set to establish expected superiority.ConclusionWe have developed new lesion-level response and progression models using textural radiomics features, derived from 90Y PET combined with mean absorbed dose for predicting outcome in radioembolization. These encouraging, but limited results, will need further validation in independent and larger datasets prior to any clinical adoption.

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPECT-CT: is there agreement between dosimetry methods?

BackgroundPrior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues.Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images.MethodsAbsorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest.ResultsDifferences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches.DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed.ConclusionsSignificant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver.An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

Impact of image reconstruction method on dose distributions derived from 90Y PET images: phantom and liver radioembolization patient studies

PET images acquired after liver 90Y radioembolization therapies are typically very noisy, which significantly challenges both visualization and quantification of activity distributions. To improve their noise characteristics, regularized iterative reconstruction algorithms such as block sequential regularized expectation maximization (Q.Clear for GE Healthcare, USA) have been proposed. In this study, we aimed to investigate the effects which different reconstruction algorithms may have on patient images, with reconstruction parameters initially narrowed down using phantom studies. Moreover, we evaluated the impact of these reconstruction methods on voxel-based dose distribution in phantom and patient studies (lesions and healthy livers). The International Electrotechnical Commission (IEC)/NEMA phantom, containing six spheres, was filled with 90Y and imaged using a GE Discovery 690 PET/CT scanner with time-of-flight enabled. The images were reconstructed using Q.Clear (with β parameter ranging from 0 to 8000) and ordered subsets expectation maximization. The image quality and quantification accuracy were evaluated by computing the hot () and cold () contrast recovery coefficients, background variability (BV) and activity bias. Next, dose distributions and dose volume histograms were generated using MIM® software’s SurePlan LiverY90 toolbox. Subsequently, parameters optimized in these phantom studies were applied to five patient datasets. Dose parameters, such as D max, D mean, D 70, and V 100Gy , were estimated, and their variability for different reconstruction methods was investigated. Based on phantom studies, the β parameter values optimized for image quality and quantification accuracy were 2500 and 300, respectively. When all investigated reconstructions were applied to patient studies, D mean, D50, D 70, and V 100Gy showed coefficients of variation below 8%; whereas the variability of D max was up to 30% for both phantom and patient images. Although β = 300−1000 would provide accurate activity quantification for a region of interest, when considering activity/dose voxelized distribution, higher β value (e.g. 4000–5000) would provide the greatest accuracy for dose distributions. In this 90Y radioembolization PET/CT study, the β parameter in regularized iterative (Q.Clear) reconstruction was investigated for image quality, accurate quantification and dose distributions based on phantom experiments and then applied to patient studies. Our results indicate that more accurate dose distribution can be achieved from smoother PET images, reconstructed with larger β values than those yielding the best activity quantifications but noisy images. Most importantly, these results suggest that quantitative measures, which are commonly used in clinics, such as SUVmax or SUVpeak( equivalent of D max), should not be employed for 90Y PET images, since their values would highly depend on the image reconstruction.

Prospective Study of Systemic Yttrium-90 Elution during Radioembolization of Hepatic Metastases

PurposeTo evaluate total blood radioactivity (BR) after SIR-Spheres yttrium-90 (90Y) radioembolization and differences in BR based on delivery method. Materials and MethodsTwenty participants with hepatic metastases undergoing first radioembolization were prospectively enrolled from December 2017 to June 2018. Blood samples were drawn at baseline and 0, 10, 20, 60, and 120 minutes after 90Y administration. BR was measured with a γ-counter and scaled by estimated blood volume. Percentage of instilled radioactivity in the bloodstream was calculated as area under the fitted curve, and differences between delivery methods were examined with nonparametric statistical tests. ResultsIn 10 participants, resin microspheres were instilled with 50% Isovue 300 diluted in saline solution in the D line, and 10 others were treated with dextrose 5% in water (D5W) in the D line. Median administered activities were 944 MBq (range, 746–1,993 MBq) and 1,213 MBq (range, 519–2,066 MBq), respectively. Fraction of 90Y in blood was significantly higher with dilute contrast agent than with D5W (median, 0.5% of injected activity vs 0.2%; P = .001). Among all participants, the maximum activity delivered was 2,066 MBq, and a maximum of 1% of administered radioactivity was measured as free 90Y in blood. Assuming these highest-case values and complete decay of all free 90Y in bone, a dose to red marrow of 132.3 mGy was calculated by Organ Level INternal Dose Assessment/EXponential Modeling. ConclusionsBlood sampling after radioembolization allowed for estimation of the time–activity curve and BR. Delivery with 50% contrast agent in saline solution resulted in a significant increase in BR vs D5W, even though the total BR for both groups was nominal.

S3275 Y90 Radioembolization: A Case Series in a Community-Based Setting

INTRODUCTION: Hepatocellular carcinoma (HCC) represents the second-most common cause of cancer mortality worldwide and the most common primary liver cancer in the United States. Loco-regional therapies (LRT) with curative intent include resection, energy ablation, chemo or radioembolization, and liver transplantation. Frequently sequencing of different therapeutic modalities is required for cure or prolongation of survival. Trans arterial LRT include chemoembolization (TACE) and Yttrium-90 radioembolization (Y-90 TARE) have been successfully utilized in the management of primary multicentric HCC, recurrent HCC after other LRT, as well as metastatic colorectal cancer and neuroendocrine carcinoma. Current scientific literature describes the methodology, safety and clinical outcomes from major academic centers. Our series describes the experience in the management of primary and secondary liver malignancies with Y-90 TARE a community hospital. METHODS: After IRB approval, we conducted a retrospective review. De-identified data was collected for patients treated with Y-90 TARE with primary, multicentric HCC, and patients with metastatic cancer who did not meet criteria for any other LRT. Baseline patient and tumor characteristics pre Y-90 TARE were assessed (Table 1). This series report the initial experience with forty-two patients. Of those, 20 patients that had complete data suitable for analysis Modified Resist criteria (mRESIST) was utilized to assess radiographic response within the first year of treatment. Complications that required post treatment emergency department (ED) visit or hospitalization within 30 and 90 days after Y-90 TARE were recorded. RESULTS: Of the twenty patients with pre and post therapy imaging, 40% had partial and stable responses, 15% had a complete response, and 5% had progressive disease. Of the 42 patients initially treated with Y-90 TARE, 52% did not undergo subsequent radioembolization treatment, 38% underwent one additional treatment and 10% required two or more. 5% of the patients required ED of hospitalization in the first 90 days after y 90 TARE. There were no deaths (Table 2). CONCLUSION: The management of hepatocellular carcinoma varies tremendously without one single modality being ideal. Surgical resection and transplantation remain as the gold standard for cure. Our series documents, Y-90 TARE to be a safe, reproducible technique in a community hospital with minimal morbidity and no mortality.Table 1.: Pre treatment baseline characteristicsTable 2.: Post treatment outcomes

Multiscale Computational Fluid Dynamics Modeling for Personalized Liver Cancer Radioembolization Dosimetry.

Yttrium-90 (90Y) radioembolization is a minimally invasive procedure increasingly used for advanced liver cancer treatment. In this method, radioactive microspheres are injected into the hepatic arterial bloodstream to target, irradiate, and kill cancer cells. Accurate and precise treatment planning can lead to more efficient and safer treatment by delivering a higher radiation dose to the tumor while minimizing the exposure of the surrounding liver parenchyma. Treatment planning primarily relies on the estimated radiation dose delivered to tissue. However, current methods used to estimate the dose are based on simplified assumptions that make the dosimetry results unreliable. In this work, we present a computational model to predict the radiation dose from the 90Y activity in different liver segments to provide a more realistic and personalized dosimetry. Computational fluid dynamics (CFD) simulations were performed in a 3D hepatic arterial tree model segmented from cone-beam CT angiographic data obtained from a patient with hepatocellular carcinoma (HCC). The microsphere trajectories were predicted from the velocity field. 90Y dose distribution was then calculated from the volumetric distribution of the microspheres. Two injection locations were considered for the microsphere administration, a lobar and a selective injection. Results showed that 22% and 82% of the microspheres were delivered to the tumor, after each injection, respectively, and the combination of both injections ultimately delivered 49% of the total administered 90Y microspheres to the tumor. Results also illustrated the nonhomogeneous distribution of microspheres between liver segments, indicating the importance of developing patient-specific dosimetry methods for effective radioembolization treatment.

Repeated radioembolization in advanced liver cancer.

BackgroundTo evaluate safety and clinical outcome of repeated transarterial 90Y (yttrium) radioembolization (TARE) in primary and metastatic liver cancer.MethodsBetween 2009 and 2018, n=288 patients underwent TARE for treatment of malignant liver disease in a tertiary care hospital. This retrospective single center study analyzed the safety and outcome of patients (n=11/288) undergoing repeated resin microsphere TARE. Included patients suffered from hepatocellular carcinoma (n=3), colorectal cancer (n=2), breast cancer (n=2), intrahepatic cholangiocarcinoma (n=3), and neuroendocrine carcinoma (n=1). All patients had shown either partial response (n=9) or stable disease (n=2) after first TARE. Lab parameters, response assessed by the Response Evaluation Criteria in Solid Tumors (mRECIST/RECIST) at 3 months and overall survival was analyzed. Additionally, patients with repeated TARE were compared to a matched control group (n=56) with single TARE therapy. Kaplan Meier analysis was performed to analyze survival.ResultsPatients after repeated TARE showed similar increase in lab parameters as compared to their first TARE. No case of radioembolization induced liver disease was observed. While n=5/11 patients showed a partial response and n=4/11 patients a stable disease after repeated TARE, only n=2/11 patients suffered from progressive disease. Median overall survival was 20.9±11.9 months for the repeated TARE group while it was 5.9±16.2 months for the control group.ConclusionsRepeated 90Y TARE is safe and can be of benefit for patients yielding a comparable degree of local disease control compared to patients with singular TARE.

Yttrium-90 radioembolization as a possible new treatment for brain cancer: proof of concept and safety analysis in a canine model

PurposeTo evaluate the safety, feasibility, and preliminary efficacy of yttrium-90 (90Y) radioembolization (RE) as a minimally invasive treatment in a canine model with presumed spontaneous brain cancers.MaterialsThree healthy research dogs (R1–R3) and five patient dogs with spontaneous intra-axial brain masses (P1–P5) underwent cerebral artery RE with 90Y glass microspheres (TheraSphere). 90Y-RE was performed on research dogs from the unilateral internal carotid artery (ICA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) while animals with brain masses were treated from the ICA. Post-treatment 90Y PET/CT was performed along with serial neurological exams by a veterinary neurologist. One month after treatment, research dogs were euthanized and the brains were extracted and sent for microdosimetric and histopathologic analyses. Patient dogs received post-treatment MRI at 1-, 3-, and 6-month intervals with long-term veterinary follow-up.ResultsThe average absorbed dose to treated tissue in R1–R3 was 14.0, 30.9, and 73.2 Gy, respectively, with maximum doses exceeding 1000 Gy. One month after treatment, research dog pathologic analysis revealed no evidence of cortical atrophy and rare foci consistent with chronic infarcts, e.g., < 2-mm diameter. Absorbed doses to masses in P1–P5 were 45.5, 57.6, 58.1, 45.4, and 64.1 Gy while the dose to uninvolved brain tissue was 15.4, 27.6, 19.2, 16.7, and 33.3 G, respectively. Among both research and patient animals, 6 developed acute neurologic deficits following treatment. However, in all surviving dogs, the deficits were transient resolving between 7 and 33 days post-therapy. At 1 month post-therapy, patient animals showed a 24–94% reduction in mass volume with partial response in P1, P3, and P4 at 6 months post-treatment. While P2 initially showed a response, by 5 months, the mass had advanced beyond pre-treatment size, and the dog was euthanized.ConclusionThis proof of concept demonstrates the technical feasibility and safety of 90Y-RE in dogs, while preliminary, initial data on the efficacy of 90Y-RE as a potential treatment for brain cancer is encouraging.

Correlation of Y90-absorbed radiation dose to pathological necrosis in hepatocellular carcinoma: confirmatory multicenter analysis in 45 explants.

To study the correlation between absorbed perfused liver dose using Y90 radioembolization and degree of hepatocellular carcinoma (HCC) necrosis in liver explants in a multicenter cohort analysis METHODS: A retrospective analysis of 45 HCC patients treated between 2014 and 2017 is presented. Inclusion criteria were treatment-naïve solitary HCC ≤ 8cm and Child-Pugh A liver status using the radiation segmentectomy approach. All patients underwent liver resection or transplantation (LT). Liver explants were examined per institutional routine protocols to assess histopathological viability of HCC. Tumor pathological necrosis was classified into complete (100% necrosis), extensive (> 50% and ≤ 99%) necrosis, and partial (< 50%) necrosis. Absorbed perfused liver doses were estimated using MIRD calculations. Associations between dose and degree of necrosis were studied. Thirty-four (76%) patients underwent LT, and 11 (24%) patients underwent hepatic resection. Median radiation dose was 240 (IQR: 136-387) Gy. Thirty (67%) patients had complete pathologic necrosis (CPN) at explant, while 10 (22%) and 5 (11%) had extensive and partial necrosis, respectively. There were significant differences among perfused liver doses that exhibited partial, extensive, and complete necrosis (p = 0.001). Twenty-four out of twenty-eight (86%) patients who had dose > 190Gy achieved CPN, while 11/17 (65%) who had < 190Gy did not (Fisher's exact test; p = 0.001). Using binary logistic regression, only absorbed radiation dose was significantly associated with CPN (p = 0.01), while tumor size was not (p = 0.35). All patients receiving > 400Gy exhibited CPN. Radiation segmentectomy for early HCC with ablative dosing > 400Gy results in CPN. This represents the new standard target dose for radiation segmentectomy.

Estimation of Yttrium-90 Distribution in Liver Radioembolization using Computational Fluid Dynamics and Deep Neural Networks.

Yttrium-90 (90Y) radioembolization is a liver cancer therapy based on 90Y microspheres injected into the hepatic artery. Current dosimetry methods used to estimate the absorbed dose in order to prescribe the 90Y activity to inject are not accurate, which can affect the treatment effectiveness. A new dosimetry based on the hemodynamics simulation of the hepatic arterial tree, CFDose, aimed at overcoming some of the limitations of the current methods. However, due to the expensive computational cost of computational fluid dynamics (CFD) simulations, this method needs to be accelerated before it can be used in real-time during treatment planning. In this paper, we introduce a convolutional neural network model trained with the CFD results of a patient with hepatocellular carcinoma to predict the 90Y distribution under different downstream vasculature resistance conditions. The model performance was evaluated using two metrics, the mean squared error and prediction accuracy. The prediction accuracy showed that the average difference between the actual and predicted data was less than 1%. The proposed model could estimate the 90Y distribution significantly faster than a CFD simulation.

Assessment of Hepatocellular Carcinoma Response to 90Y Radioembolization Using Dynamic Contrast Material-enhanced MRI and Intravoxel Incoherent Motion Diffusion-weighted Imaging.

To quantify diffusion and perfusion changes in hepatocellular carcinoma (HCC) induced by yttrium 90 (90Y) radioembolization and to assess the value of dynamic contrast material-enhanced (DCE) MRI and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) for predicting HCC response. Institutional review board approval was obtained for this prospective study (clinical trial registry NCT01871545). Twenty-four participants with HCC (mean age, 69 years ± 9 [standard deviation], 18 men) underwent multiparametric MRI, including IVIM DWI and gadoxetic acid DCE MRI before (n = 24) and 6 weeks (n = 21) after radioembolization. IVIM DWI and DCE MRI histogram parameters were quantified in HCCs and liver parenchyma. HCC response was assessed by using modified Response Evaluation Criteria in Solid Tumors at 6 weeks and 6-12 months after radioembolization. Logistic regression analysis was used to evaluate the diagnostic performance of baseline MRI and clinical parameters for prediction of response. Twenty-five HCCs were analyzed (mean size, 3.6 cm ± 1.9). Radioembolization resulted in significantly decreased perfusion (DCE MRI arterial flow, P = .002; IVIM pseudodiffusion coefficient [D*], P = .014). Multivariate logistic regression selected combined serum α-fetoprotein and portal flow (F p ) skewness (area under the curve [AUC] = 0.924) and combined D* standard deviation and F p kurtosis (AUC = 0.916) for prediction of objective and complete response at 6 weeks, respectively. Standard deviation of DCE MRI parameter arterial fraction was selected as the optimal predictor for complete response at 6-12 months (AUC = 0.857). Diffusion and perfusion MRI can be used to evaluate the response of HCC to radioembolization. Pretreatment DCE MRI histogram parameters may be useful for radioembolization treatment stratification. Supplemental material is available for this article. © RSNA, 2020.

Feasibility of Combination Intra-arterial Yttrium-90 and Irinotecan Microspheres in the VX2 Rabbit Model.

To evaluate the combination of 90Y radioembolization (Y90) and drug-eluting bead irinotecan (DEBIRI) microspheres in the VX2 rabbit model. An 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. Infused 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. Intra-arterial Y90 + DEBIRI was safe and demonstrated enhanced antitumor activity in rabbit VX2 tumors. This combined approach warrants further investigation.

Observing Durable Responses and a Prolonged Survival Tail in Advanced Hepatocellular Carcinoma with Portal Vein Invasion Treated with Y90 Radioembolization.

Observing Durable Responses and a Prolonged Survival Tail in Advanced Hepatocellular Carcinoma with Portal Vein Invasion Treated with Y90 Radioembolization.

Yttrium-90 Radioembolization and Tumor Hypoxia: Gas-challenge BOLD Imaging in the VX2 Rabbit Model of Hepatocellular Carcinoma

To use a rapid gas-challenge blood oxygen-level dependent magnetic resonance imaging exam to evaluate changes in tumor hypoxia after 90Y radioembolization (Y90) in the VX2 rabbit model. White New Zealand rabbits (n = 11) provided a Y90 group (n = 6 rabbits) and untreated control group (n = 5 rabbits). R2* maps were generated with gas-challenges (O2/room air) at baseline, 1 week, and 2 weeks post-Y90. Laboratory toxicity was evaluated at baseline, 24 hours, 72 hours, 1 hours, and 2 weeks. Histology was used to evaluate tumor necrosis on hematoxylin and eosin and immunofluorescence imaging was used to assess microvessel density (CD31) and proliferative index (Ki67). At baseline, median tumor volumes and time to imaging were similar between groups (p = 1.000 and p = 0.4512, respectively). The median administered dose was 50.4 Gy (95% confidence interval:44.8-55.9). At week 2, mean tumor volumes were 5769.8 versus 643.7 mm3 for control versus Y90 rabbits, respectively (p = 0.0246). At two weeks, ΔR2* increased for control tumors to 12.37 ± 12.36sec-1 and decreased to 4.48 ± 9.00sec-1 after Y90. The Pearson correlation coefficient for ΔR2* at baseline and percent increase in tumor size by two weeks was 0.798 for the Y90 group (p = 0.002). There was no difference in mean microvessel density for control versus Y90 treated tumors (p = 0.6682). The mean proliferative index was reduced in Y90 treated tumors at 30.5% versus 47.5% for controls (p = 0.0071). The baseline ΔR2* of tumors prior to Y90 may be a predictive imaging biomarker of tumor response and treatment of these tumors with Y90 may influence tumor oxygenation over time.

Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Analysis

PurposeTo report outcomes of yttrium-90 (90Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). Materials and MethodsRetrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ2 tests. Survival after diagnosis and after treatment was assessed by Kaplan–Meier method. ResultsGrade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21–37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8–13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after 90Y radioembolization (4%). ConclusionsThis study provides observational data of treatment outcomes after 90Y radioembolization in patients with unresectable ICC.

Genomic biomarkers to determine survival in Multicenter Study of RAS mutations (MURAS) in patients with colorectal liver metastases receiving Y90 radioembolization treatment.

e16119 Background: Assessment of the clinical outcomes and prognostic value of genomic mutations in colorectal liver metastases treated with Y90 radioembolization. Methods: Multi-institution retrospective study of patients who underwent Y-90 radioembolization treatment after tumor genotyping was completed for CRLM. Patients treated between 2008 and 2019 were included from 7 institutions within the United States and Europe. Patient demographics, tumor characteristics, pre- and post- treatment regimens, serum laboratory evaluation and overall survival were analyzed between patients with differing histopathologic and genomic status. Tumor genotyping was obtained for KRAS, BRAF, PIK3CA, AKT, MEK, NRAS and MMR genes. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 434 patients treated with Y90 radioembolization fulfilled the inclusion criteria. Of the total cohort, 399 patients were available who had sufficient documented tumor profiling data. Average age at diagnosis was found to be 58.8 years for all patients (60.1% male, 39.9% female). Decreased survival post Y-90 treatment was shown in those patients with increased number of documented tumor mutations (n = 0,1 or ≥2 mutations: median OS 9.63 mos vs. 6.2 mos vs. 5.3 mos; p &lt; 0.0001). Additionally, the median survival in patients with mutated BRAF was 5.0 months, as compared to 9.4 months in those patients with wild-type BRAF (p = 0.0009). Primary colon cancer sidedness was also shown to demonstrate significant difference in survival post-Y90 treatment with left sided primaries showing improved median overall survival (left = 7.5 mos vs. right = 6.3 mos; p = 0.04.) Patient demographics including gender, age and race were not shown to be significant in overall survival post-Y90 treatment (p-values &gt; 0.05). Number of tumor mutations (p &lt; 0.0001, HR = 1.69 CI: 1.39-2.05), BRAF status (p = 0.02, HR = 2.6 CI:1.20-4.9), primary sidedness (p = 0.01, HR = 0.65 CI:0.47-0.90), pre-treatment neutrophil-lymphocyte ratio (p = 0.04, HR = 1.42 CI: 1.02-1.98) and KRAS mutation status (p &lt; 0.0001, HR = 1.81 CI: 1.45-2.26) all persisted as significant predictors of survival on multivariate analysis. Conclusions: Number of tumor mutations, BRAF mutation status, primary tumor sidedness, neutrophil-lymphocyte ratio and KRAS mutation status are all shown to be significant prognostic factors in patients with colorectal liver metastases receiving Y90 radioembolization.

Long-term results of selective internal radioembolization (SIRT) to control progressive liver metastases of gastro-intestinal stromal tumors (GIST) beyond treatment with tyrosine kinase inhibitors (TKI).

11538 Background: Liver and peritoneum are the main area of metastatic spread in GIST. Liver resection does not play a role for hepatic metastases in comparison to f.e. colorectal cancer. If hepatic metastases are the only or major area of tumor progression and are resistant to available TKIs due to a missing mutation in KIT/PDGFRA/SDH ( ‘wildtype’) or after treatment with 1st/2nd/3rd/4th line therapy, interventional radioembolization with yttrium-90 (90Y) microspheres are promising treatment options, as radiation doses as high as 200Gy can be applied locally. We analyzed the long-term results of SIRT with respect to hepatic-progression-free survival (HEP-PFS) in a consecutive cohort of patients.. Methods: From 1/2008 to 1/2018, 25 pts (12f, 13m) with biopsy proven liver metastases of GIST which were the only (n = 13) or the dominant site of progression (n = 12) were treated by SIRT. Median age at GIST diagnosis had been 51.8 yrs and when receiving SIRT was 57.6yrs (range, 18–75yrs). The mutational status was ‘wildtype’ (n = 7, 2 NF-1), exon 11 (n = 7), exon 11+2nd mutation (n = 6), exon 9 (n = 3), exon 9+2ndmut (n = 1), and, exon 13 (n = 1). All patients except of two had prior TKI therapy: 1 line n = 3, 2 lines n = 11, 3-4 lines n = 9. Follow-up after SIRT was done via dynamic MRI and contrast-enhanced (CE)-CT, the median follow-up is 30.6 mos (range, 12-100mos) and all patients were followed until death. Results: The median hepatic-progression free survival (HEP-PFS) after SIRT was 17 months (range, 5-53+, 95%CI 11.8-22.1 mos). Of the patients with concomitant extrahepatic disease, the extraHEP-PFS was median 10 months. Twelve patients received next-line TKI therapy for progressive extrahepatic disease, whereas six patients required this for progressive liver metastases. When comparing the results according to the mutational status, patients with a ‘wildtype’ tumor showed a better median HEP-PFS of 19 mos (range, 12-53+, 95%CI 16.7-21.2 mos.) in comparison to KIT exon 9/11/13 mutated patients with only 14 months (range, 4-34 mos., 95%CI 6.5-21.4 mos), p &lt; 0.11 (Wilcoxon). Conclusions: 90Y radioembolization (SIRT) offers a safe and effective treatment for patients with liver metastases of GISTs being the dominant site of tumor progression and with no drug treatment options available. In patients known to have no mutation in KIT/PDGFRA (wt, also NF-1 associated) it looks whether the results might be even more promising and SIRT could be used in early treatment lines.