Yttrium-90 Research Articles

Yttrium-90 Glass Microsphere Transarterial Radioembolization for Patients with Unresectable Liver-Dominant Breast Cancer Metastasis

Transarterial radioembolization (TARE) using Yttrium-90 (Y90) microspheres is a potential therapeutic option for treatment-refractory, unresectable, liver-dominant breast cancer metastases (LdBM). We hypothesized that Y90 TARE is an effective and safe treatment for delaying progression in patients with LdBM. In this IRB approved (MCC 18294) study, we retrospectively analyzed institutional database to identify patients with unresectable and chemotherapy-refractory LdBM who underwent Y90 TARE. We extracted patient demographics, systemic therapy details and imaging studies for response assessment. Liver function tests, CA15-3 level, Albumin-Bilirubin (ALBI) and Model for end-stage liver disease (MELD) score were assessed at baseline, 1- and 3-months post TARE to evaluate for hepatotoxicity. Hepatic progression-free (hPFS) and overall survival (OS) were estimated using Kaplan-Meier analysis, and compared using log-rank test. Cox regression was performed to evaluate the effect of predictors on defined outcomes. Maximum toxicity grade was reported using Common Terminology Criteria for Adverse Events version 5. Between 2010-2019, 32 patients with LdBM underwent 51 TARE sessions with Y90 glass microsphere. All patients progressed through systemic therapy. Median age was 61 years (range 27-81). Interval to develop liver metastasis from initial breast cancer diagnosis was 5-years (median). Median follow-up duration after TARE was 11 months (range, 1-44). 18 patients had sequential bilobar treatment, 1 sequential segmental, 9 unilobar right, 1 unilobar left, 2 segmental and 1 whole-liver single session TARE. Median hPFS and OS after TARE were 7-months (95% CI 5.0–9.1) and 13 months (95% CI 9.2–16.8), respectively. The 6-months and 1-year actuarial hPFS were 52% and 21%; and 1-year and 2-year OS were 58.5%, and 35.7%, respectively. Factors independently predicting worse hPFS were age <60 years (6-month hPFS 41.3% vs 62.5%, p = 0.04) and bilobar disease (33.3% vs. 68.8%, p = 0.005). On multivariate analysis, bilobar disease (p = 0.01) and high baseline CA 15-3 (p = 0.05) were predictors of longer OS. No significant change was noted in ALBI, MELD, total bilirubin, albumin and alkaline phosphatase levels at 1- and 3-months post-TARE. Grade 3 toxicity was noted in 3-patients (9.4%), all received sequential bilobar treatment, necessitating hospitalization for pain (2-patients), and worsening liver function (1-patient). The 30-day mortality was 3.1%; 1 patient died from radioembolization-induced liver disease. For patients with therapy-refractory unresectable LdBM, Y90 TARE is effective and relatively safe. TARE can potentially delay progression allowing patients with LdBM to continue systemic therapy longer.

Clinical Outcomes Of Patients With Primary Or Metastatic Liver Tumors Treated With Dose-Escalated Yttrium-90 (Y-90) Transarterial Radioembolization (TARE)

Clinical Outcomes Of Patients With Primary Or Metastatic Liver Tumors Treated With Dose-Escalated Yttrium-90 (Y-90) Transarterial Radioembolization (TARE)

Impact of Prior Y90 Dosimetry on Toxicity and Outcomes Following SBRT for Hepatocellular Carcinoma

Stereotactic body radiation therapy (SBRT) is the only non-invasive local therapy for the treatment of hepatocellular carcinoma (HCC) and is often utilized following transarterial embolization. There is a paucity of data reporting safety and outcomes of patients (pts) receiving SBRT after yttrium-90 (Y90). We evaluated the impact of Y90 and SBRT composite plan dosimetry on toxicity and outcomes of HCC pts. An IRB-approved registry of 260 liver SBRT pts was used. Pts included in analysis received Y90 prior to SBRT and had post-Y90 PET imaging (measuring Bremsstrahlung component of Y90). Volume of ablated liver was the sum of Y90 ablation region (using the sharp edge of PET gradient) and the SBRT volume receiving at least 30 Gy (V30). Characteristics between groups were compared using Chi-square and independent t-test. Clinical, imaging, and laboratory follow up are reported. Twenty eights pts with median follow up of 14 m (4.6-49.6) were included. Pts received 1 (N=15), 2 (N=10), or 3 (N=3) prior Y90 treatments, to a median volume of 286 cm3 (21-1512) a median 4.4 m (1.1-82.9) prior to SBRT. SBRT dose ranged from 24-50 Gy in 3-5 fractions with a median PTV of 117 cm3 (26-857). Y90 and V30 overlap ranged from 0-577 cm3 with a median of 80 cm3. Treatment intent was definitive in 23 pts, to downstage within transplant criteria in 3 pts, and as a bridge to transplant in 1 pt. Baseline Child-Pugh (CP) score was A, B, and C in 23, 3, 2 pts, respectively. At a median 9 m (1.5-46.4) after SBRT local control was 93%. Liver, nodal, and distant failure had an incidence of 11%, 3.6%, and 11%, respectively. Change in CP score was analyzed at 1-2 m and 3 m post SBRT. Twenty six patients had at least one calculable time point. Change in CP class from A to B was seen in 6 pts (26%), of which two recovered back to CP A by 3 m. The 3 CP B pts did not change class, and the 2 CP C pts received successful liver transplants 2-3 m after SBRT downstaging. Factors associated with an increase in CP score within 3 m of SBRT include SBRT mean liver dose (P=0.001), SBRT V30 (P=0.049), and <1200 cm3 of un-ablated liver (P=0.003). Volume of liver treated by Y90 and time between Y90 and SBRT was not associated with an increase in CP score within 3 m of SBRT. Non-hematologic toxicity include 2 acute biliary strictures (grade 2-3), 1 late biliary stricture (grade 2), 1 late chest wall pain (grade 1), and 1 late grade 2 radiographic myonecrosis. One CP A pt died 4 weeks after SBRT of cardiopulmonary comorbidities. Time between Y90 and SBRT, volume of liver exposed to prior Y90, and overlap between V30 and Y90 volumes do not appear to adversely impact CP score within 3 m of SBRT. As expected, dosimetric properties including mean liver dose, V30, and un-ablated liver volume <1200 cm3 are associated with an increase in CP score within 3 m of SBRT. Pts with HCC previously treated with Y90 appear to tolerate SBRT well with no clinically significant change in CP score, minimal toxicity, and excellent local control.

Liver-directed treatments of liver-dominant metastatic leiomyosarcoma

The purpose of this study was to determine the safety and efficacy of liver-directed therapies in patients with unresectable metastatic leiomyosarcoma to the liver. Liver-directed therapies included in this study were transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE), yttrium-90 (Y90) radioembolization, and percutaneous microwave ablation. This is a single institution retrospective study of unresectable metastatic leiomyosarcoma to the liver treated with DEB-TACE, radioembolization, or microwave ablation. DEB-TACE was performed using 70-150 or 100-300 µ doxorubicin-loaded drug-eluting LC beads. Radioembolization was performed using Y90 glass microspheres. Electronic medical records were retrospectively reviewed to evaluate clinical and biochemical toxicities, tumor response on imaging, overall survival (OS), and liver progression-free survival (PFS). A total of 24 patients with metastatic leiomyosarcoma to the liver who underwent liver-directed treatment were identified (8 males, 16 females; average age, 62.8±11.4 years). Of these patients, 13 underwent DEB-TACE, 6 underwent Y90, and 5 underwent ablation. Three patients received a combination of treatments: one received Y90 followed by DEB-TACE, one received ablation followed by DEB-TACE, and one received ablation followed by Y90. Of the 24 patients, 19 received prior chemotherapy. At 3-month follow-up, grade 1 or 2 lab toxicities were found in 20 patients; 3 patients had grade 3 toxicities. A grade 3 clinical toxicity was reported in one patient. MELD score was 7.5±1.89 at baseline and 8.8±4.2 at 3 months. Median OS was 59 months (95% CI, 39.8-78.2) from diagnosis, 27 months (95% CI, 22.9-31.0) from development of liver metastasis, and 9 months (95% CI, 0-21.4) from first liver-directed treatment. Median liver PFS was 9 months (95% CI, 1.4-16.6). Treatment with liver-directed therapies for patients with unresectable metastatic leiomyosarcoma to the liver is safe and can improve overall survival, with OS after liver-directed therapy being similar to patients who underwent surgical resection.

Transverse dose profile simulation of extruded lines for a 3D printed models for superficial skin cancer therapy

Abstract The short-range and sharp dose fall-off of beta particles in tissue make them an interesting option for use in the radiation therapy of superficial skin tumors. This can be used to protect bony or other sensitive structures located right beneath the tumor. In a previous study, we studied the feasibility of using 3D printing technology to create 2D radioactive models for the treatment of skin tumors. In the current study, the Monte Carlo method was used to simulate the transverse dose profile form 3D printed extruded line containing yttrium-90 (Y-90) particles. The time and activity required for treating a superficial skin tumor using these extruded lines were also calculated.

Albumin-bilirubin grade as a prognostic indicator for patients with non-hepatocellular primary and metastatic liver malignancy undergoing Yttrium-90 radioembolization using resin microspheres.

Studies have shown that the albumin-bilirubin (ALBI) grade can be a superior prognosticator for patients undergoing Yttrium-90 (Y90) glass microsphere radioembolization for hepatocellular carcinoma (HCC) compared to the Child-Pugh (CP) scoring system. Less is known about the applicability of this score in non-hepatocellular malignancies using Y90 resin microspheres. This study evaluates the ALBI grade's ability to predict overall survival and biochemical toxicity in patients undergoing resin Y90 radioembolization and body surface area dosimetry (BSA) for non-hepatocellular primary and metastatic liver malignancies compared to the CP class and Model for End-Stage Liver Disease (MELD) score. A retrospective review of patients with intrahepatic metastatic colorectal and neuroendocrine cancers and cholangiocarcinoma undergoing resin radioembolization from 2006-2015 at a single tertiary medical center was performed. ALBI, MELD, and CP scores were compared and correlated with biochemical toxicity and overall survival. There was a significant difference in overall survival between CP class A and class B liver function (P=0.04) for the entire patient cohort. ALBI grade (P=0.36) and MELD score (P=0.19) were not independently associated with survival. When stratified by CP class, the ALBI grade revealed a trend for survival difference in CP class B (P=0.05). Baseline ALBI grade was associated with post-procedural albumin reduction (P=0.01) and bilirubin elevation (P=0.007). ALBI grade predicted post-procedural biochemical toxicity, but did not predict survival after resin radioembolization of non-hepatocellular liver malignancies using BSA dosimetry. Given the heterogeneity of this study population, dedicated prospective analyses are required.

Efficacy and Tolerability of Selective Internal Radiotherapy With Yttrium-90 as Consolidation Treatment After Chemotherapy in Metastatic Colorectal Cancer

BackgroundSelective internal radiotherapy (SIRT) with yttrium-90 (Y-90)-labeled resin microspheres may have a role in consolidating the response to chemotherapy in patients with metastatic colorectal cancer unamenable to resection after assessment of the best response to first-line chemotherapy. Patients and MethodsThis was a retrospective analysis of outcomes in patients who had received SIRT as consolidation therapy after one or more lines of chemotherapy. Eligible patients were 18 years or older, had confirmed colorectal liver metastases, and had disease unsuitable for surgical resection or local ablation with curative intent. The primary endpoint was progression-free survival. ResultsSixty-eight patients with colorectal liver metastases were treated with at least one SIRT procedure after receiving one or more lines of chemotherapy. Median progression-free survival was significantly longer in patients who received SIRT after prior first-line chemotherapy compared to those who received SIRT after two or more lines of chemotherapy (9 vs. 3 months, respectively; hazard ratio = 0.07; 95% confidence interval, 0.02854‒0.2039; P < .001), and in patients with liver-only disease compared to those who had extrahepatic metastases (6.4 vs. 4.1 months, respectively; hazard ratio = 0.57; 95% confidence interval, 0.34-0.95; P = .0318). There were no grade 3 or higher adverse events. ConclusionSIRT represents a valid option for the treatment of colorectal liver metastases. Earlier use of SIRT may provide a greater survival benefit compared to that afforded by the procedure when used in salvage settings.

Long-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.

e16633 Background: Yttrium-90 (Y90) radioembolization is a catheter-based therapy utilized in the treatment of hepatic tumors such as hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; few have assessed long term hepatic function. These studies reported PFS ranging from 7.9 to 18 months (m), and median OS of 17.2 to 18 m for Child-Pugh (CP) Class A and 6.0 to 7.7 m for CP Class B. This study aimed to evaluate a clinical real-world experience of Y90 therapeutic effectiveness and long-term impact on hepatic function. Methods: A single-center retrospective chart review was performed for patients with a CP score of A or B who received Y90 for primary HCC between 2008 and 2016. Model for end stage liver disease (MELD) and CP scores were calculated for the day of treatment and at 1, 3, 6, 12, and 24 m post procedure. OS and PFS were characterized using a Kaplan-Meier survival analysis and a multivariate model. Results: 134 patients were included. Mean age was 60 years old, ranging from 44-90. Underlying liver disease included HCV – 66%, ETOH cirrhosis – 23%, NAFLD – 19%, HBV – 5%. CP Class A patients (79%) had a median OS of 16.59 m (95% CI: 8.90 to 23.10m) from date of Y90 treatment compared to a median of 7.90 m (95% CI: 4.60 to 15.64 m) for CP Class B. CP Class A patients had a median PFS of 3.45 m (95% CI: 2.99 to 5.55 m) from date of Y90 treatment compared to a median of 3.71 m (95% CI: 2.07 to 8.28 m) for CP Class B patients. These differences were not statistically significant. Median OS from date of diagnosis for the entire study population was 29.37 m (95% CI: 23.00 to 38.77 m). MELD scores were statistically significantly higher at 1, 3, 6 and 12 m post-treatment than on Day 0, with significant recovery at 24 vs 3 m. Older age, higher T stage, higher MELD and CP scores, and patients with a history of portal vein thrombosis (PVT) had significantly lower OS. PFS was significantly shorter in those with advanced stage at diagnosis and higher CP score. Conclusions: While our study supports the literature for OS in Y90 patients, we found a shorter PFS in this population. This may reflect the utilization of RECIST in clinical trials vs clinical radiology practice in determining progression. Over time, the most significant factors associated with OS were age, MELD and CP scores and PVT. For PFS, CP score and stage at diagnosis were significant. The increasing MELD and CP scores over time reflect a possible mix of radio embolization‐induced liver disease and progression of HCC. The downtrend at 24 m is likely due to durable survivors with significant benefit from therapy and no long-term complications from Y90.

Initial report of treatment of uveal melanoma with hepatic metastases with yttrium90 internal radiation followed by ipilimumab and nivolumab.

10025 Background: Hepatic metastases from uveal melanoma have no established therapy, with a median survival of only 6-12 months. To date therapy with checkpoint inhibitors has yielded minimal results. To take advantage of possible synergy between radiation and immunotherapy we treated patients with yttrium90 internal radiation followed by immunotherapy. Methods: Patients received yttrium90 (Sir-Spheres) via hepatic artery infusion in two treatments, one to each lobe 3-4 weeks apart, followed in 3-6 weeks by ipilimumab and nivolumab for 4 doses, then nivolumab maintenance. Results: We are presenting interim results because of the excessive toxicity seen when these FDA-approved modalities were used in sequence with the FDA-approved dosages. Initially dosing of yttrium90 (Y90) followed the package insert “BSA method” but after 8 patients we had 5 cases of grade 3-4 hepatic toxicity; in 4 cases the toxicity was observed after just the Y90. One case of cirrhosis occurred in a patient whose liver received 40-45Gy; her cirrhosis was felt most likely due to the Y90. Y90 dosing was then reduced to limit dosage to normal liver to 35Gy, and none of the next 5 patients have had more than grade 2 hepatic toxicity. Dosage to the normal liver is approximated by the MIRD formula: Actual delivered liver dose [Gy] = 50 * Administered activity [GBq] * (1 – Lung shunt fraction) / kg of treated liver. If calculated dose was &gt; 35GY, dosage in GBq is reduced proportionally. Toxicity in the first 5 patients to receive immunotherapy included one grade 4, two grade 3 and two grade 2 hepatic toxicities, and only 3 of the 5 patients received more than one dose of ipilimumab. We then reduced dosing of ipilimumab from 3mg/kg x 4 to 1mg/kg x 4 because of this excessive autoimmune toxicity. Of 13 patients, 10 received both Y90 and immunotherapy, and 3 had responses (1 CR, 2 PR) with 3 patients stable &gt; 5months. Median progression-free survival for all patients is 27 weeks and median overall survival is greater than 48 weeks. Treatment with Y90 produced an over 50% fall in peripheral blood lymphocytes which was reversed in most patients by the immunotherapy. Conclusions: With dose modifications this therapy appears feasible and objective tumor responses were seen. Sequential therapy with Y90 and immunotherapy appears tolerable if radiation to normal liver is limited to 35Gy and ipilimumab dose is 1mg/kg. Clinical trial information: NCT02913417.

Yttrium-90 radioembolization for breast cancer with liver metastases: A focus on mortality, adverse reactions, and radiological response.

e13065 Background: Breast cancer associated with liver metastases (BCLM) occurs later in the progression of metastatic breast cancer and carries a poorer prognosis than bone or soft tissue metastases (Pagani). As systemic therapy begins to prolong progression, there is an inherent necessity for localized therapy directed at distant metastases. Further, there is some evidence to suggest that interventional techniques can prolong survival and palliate symptoms although data is lacking in this area (Hoe). Here we present findings describing the mortality benefit, adverse effects, and radiological response to Yttrium-90 (Y-90) radioembolization in BCLM patients. Methods: All patients with BCLM who received Y-90 radioembolization at St. Vincent Hospital from 2013-2018 were included in data collection. Digital chart review was utilized for data collection. To be eligible for the study, patients must have image or biopsy proven metastatic breast cancer to the liver, active unresectable disease not appropriate for ablation, ECOG performance status of 0-2, Bilirubin &lt; 2.0 mg/dL, and no other evidence of liver disease. Patients with a life expectancy less than 2 months were excluded. Results: Twenty-five patients with BCLM underwent Y-90 radioembolization of hepatic metastases. Median survival after therapy was 495 days, or 16 months compared to the median survival rate of 4 months for BCLM patients reported by previous studies (Hoe). At 3 month follow up CT, 48% of patients experienced significant reduction in hepatic tumor burden, only 20% had worsening disease. 16% of patients reported abdominal pain. Median increase in bilirubin was 0.1. Median post procedural AST was 47, and ALT 40. Six patients experienced ascites requiring paracentesis, which occurred on average 14.3 months after Y-90 therapy. There were zero cases of pancreatitis and Radioembolization Induced Liver Disease (REILD). Conclusions: In patients with BCLM who undergo Y-90 radioembolization there seems to be a mortality benefit compared to traditional therapies. Further, there is a radiological reduction in tumor burden, and only minimal adverse effects.

A cost analysis of SIR-Spheres yttrium-90 resin microspheres versus tyrosine kinase inhibitors in the treatment of unresectable hepatocellular carcinoma in France, Italy, Spain and the UK

Background and aims: A wide range of treatment options are available for hepatocellular carcinoma (HCC), including systemic treatment with tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib, immunotherapies, locoregional therapies such as selective internal radiation therapy (SIRT) and treatments with curative intent such as resection, radiofrequency ablation and liver transplantation. Given the substantial economic burden associated with HCC treatment, the aim of the present analysis was to establish the cost of using SIRT with SIR-Spheres yttrium-90 (Y-90) resin microspheres versus TKIs from healthcare payer perspectives in France, Italy, Spain and the United Kingdom (UK).Methods: A cost model was developed to capture the costs of initial systemic treatment with sorafenib (95%) or lenvatinib (5%) versus SIRT in patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stages B and C. A nested Markov model was utilized to model transitions between progression-free survival (PFS), progression and death, in addition to transitions between subsequent treatment lines. Cost and resource use data were identified from published sources in each of the four countries.Results: Relative to TKIs, SIRT with SIR-Spheres Y-90 resin microspheres were found to be cost saving in all four country settings, with the additional costs of the microspheres and the SIRT procedure being more than offset by reductions in drug and drug administration costs, and treatment of adverse events. Across the four country settings, total cost savings with SIR-Spheres Y-90 resin microspheres fell within the range 5.4–24.9% and SIRT resulted in more patients ultimately receiving treatments with curative intent (4.6 vs. 1.4% of eligible patients).Conclusion: SIR-Spheres Y-90 resin microspheres resulted in cost savings relative to TKIs in the treatment of unresectable HCC in all four country settings, while increasing the proportion of patients who become eligible for treatments with curative intent.

4:12 PM Abstract No. 145 Yttrium-90 radiation segmentectomy for hepatic metastases: a multi-institutional study of safety and efficacy

Yttrium-90 (Y-90) radiation segmentectomy has shown great promise for treatment of localized primary liver cancer. This study assessed outcomes of segmental Y-90 radioembolization for hepatic metastases, not amenable to surgical resection or ablation. A retrospective review was performed on patients with hepatic metastases treated with radiation segmentectomy at two institutions over 6 years (2012-2018). 32 patients with 53 tumors (14 patients with >1 tumor) underwent segmental radioembolization, with ablative-level doses exceeding 200 Gy to perfused tissue. Patients were not candidates for surgical resection or thermal ablation due to medical comorbidities, presence of extrahepatic disease, tumor size, or tumor location. Hepatic metastases were from colorectal cancer (34%), neuroendocrine tumors (28%), sarcoma (19%), and others (19%). 62% of patients had liver-only disease, and 38% had liver-dominant disease. 75% of patients had an ECOG performance status of 0. All patients had normal liver function tests at baseline. With the exception of biologic agents, ongoing systemic chemotherapy was not discontinued. Toxicity, tumor response, tumor progression, and survival were assessed. Median tumor size was 3.6 cm (range, 1.2-6.1 cm). Toxicity rates were low, with no hepatic-related CTCAE grade 3 or 4 toxicity and a 6% rate of CTCAE grade 3 leukopenia. Target tumor objective RECIST response rate was 74% (19% complete response, 55% partial response) and disease control was 89%. For patients with hypervascular tumors (n = 22), target tumor objective mRECIST response rate was 100%, with a complete response in 86%. During a median follow-up of 12 months, overall survival was 94% and target tumor progression occurred in 25% of treated tumors. Y-90 radiation segmentectomy for hepatic metastases demonstrates high rates of tumor response with low rates of target tumor progression. Toxicities are minimal, despite many patients receiving concurrent chemotherapy. Radiation segmentectomy should be considered for patients with liver-dominant metastatic disease who are not ideal candidates for surgical resection or ablation.

Abstract No. 409 Survival and hepatic biochemical toxicities in patients treated with hepatic Yttrium-90 radioembolization for renal cell carcinoma metastases to the liver

To evaluate differences in biochemical toxicities and survival of patients who received whole liver versus partial liver Yttrium-90 (Y-90) glass microsphere radioembolization for renal cell carcinoma metastases (RCC) to the liver. A retrospective review of medical records was performed for 31 patients who received glass Y-90 microsphere hepatic radioembolization for metastatic RCC between July 2010 and July 2017 at a single institution. Patients were separated by whether they received whole liver (n = 12) or partial liver (n = 19) treatment, with the latter group encompassing single segmental, unilobar, and multisegmental treatment. Biochemical toxicities regarding AST, ALT, alkaline phosphatase, albumin, and total bilirubin were evaluated according to CTCAE 5.0 grading at most recent follow-up. Median follow-up from the last radioembolization for whole liver treatment was 12.66 months (range, 1 – 49.74 months) and for partial liver was 9.2 months (range, 1 – 72.6 months). Average dose per treatment for those receiving whole liver treatment was 140.58 Gy ± 32.62 and for partial liver treatment was 142.93 Gy ± 39.95. Patients receiving whole liver treatment displayed highest biochemical toxicity grades at most recent follow-up of 1, 2, 3, and 4 at rates of 25%, 33%, 33%, and 8.3% respectively. Patients receiving partial liver treatment displayed highest grades of 1, 2, and 3 at rates of 37%, 15.7%, and 5.2% respectively. There was a statistically significant difference in median survival from the date of liver metastases diagnosis, with 23.24 months for the whole liver group and 34.55 months for the partial liver group (P = 0.042). There was no statistically significant difference in survival from the date of radioembolization between the partial and whole liver groups, 21.56 vs. 16.41 months, respectively (P = 0.115). Patients receiving whole liver treatment experienced higher biochemical toxicities and shorter overall median survival from the date of diagnosis of liver metastases compared to partial liver treatment, which could be related to larger tumors burden, and/or higher radiation exposure.

3:00 PM Abstract No. 237 Additive benefit of yttrium-90 radioembolization to systemic therapy in patients with hepatic metastases from colorectal cancer in the salvage setting: results of a propensity-score matched study

The benefit of yttrium-90 (Y90) radioembolization in the setting of hepatic metastases from colorectal cancer is controversial in the salvage setting. This study assessed the efficacy of adding Y90 radioembolization to systemic therapy in patients with metastatic colorectal cancer to the liver. In this retrospective propensity-score, matched-pair study, 21 patients who underwent radioembolization plus systemic therapy were matched with a cohort of 173 patients who received systemic chemotherapy alone in the salvage setting. Patients were matched one-to-one on the basis of their Eastern Cooperative Oncology Group Performance Status (ECOG), presence of extrahepatic disease, and presence of KRAS mutation on tumor genetic testing. Survival data was calculated using Kaplan-Meier analysis with regards to both date of primary diagnosis and date of hepatic metastases. Survival curves were statistically compared using the Gehan-Breslow-Wilcoxon test. All 21 patients in each study arm matched all three matching criteria. Radioembolization was done with either glass (n = 3), resin (n = 17), or combination (n = 1) Y90 microspheres, in a unilobar (n = 4), sequential bilobar (n = 13), or whole liver (n = 4) approach using standard dosimetry parameters. Patients who underwent radioembolization plus systemic therapy versus those who had systemic therapy alone had similar demographics with regards to median age (62 v 59 years) and gender (14 v 14 male). Median survival from date of primary diagnosis was 38 v 25 months in radioembolization versus control (hazard ratio, 0.67, 95% CI 0.34 to 1.32). Median survival from date of hepatic metastases was 31 v 20 months in radioembolization versus control (hazard ratio, 0.62, 95% CI, 0.32 to 1.20). Comparison of survival curves demonstrated significantly improved survival from date of hepatic metastases (P = 0.03) with clinically-meaningful improved survival from date of primary diagnosis (P = 0.17) in patients who underwent radioembolization. The addition of radioembolization with yttrium-90 to systemic therapy in patients with metastatic colorectal cancer to the liver may benefit patients with limited treatment options in the salvage setting.

Abstract No. 549 Assessing the need for repeat dosimetry estimates for recurrent Yttrium-90 (Y90) radioembolization: is there a need for repeat macroaggregated albumin mapping prior to additional Y90 treatments of the same arterial distribution?

Abstract No. 549 Assessing the need for repeat dosimetry estimates for recurrent Yttrium-90 (Y90) radioembolization: is there a need for repeat macroaggregated albumin mapping prior to additional Y90 treatments of the same arterial distribution?

Abstract No. 550 Comparison of efficacy of primary Yttrium-90 radiation segmentectomy versus percutaneous microwave ablation in patients with ≤4-cm hepatocellular carcinoma

Current guidelines including Barcelona Clinic Liver Cancer (BCLC) criteria recommend thermal ablation for patients with 3 or fewer, <3-cm hepatocellular carcinoma (HCC) who are not surgical candidates. The objective of this study was to compare the tumor response and overall survival (OS) in patients with solitary, small (<4 cm) HCC treated with primary percutaneous microwave ablation (MWA) vs. Yttrium-90 (Y90) radioembolization radiation segmentectomy (RS). From March 2014 to March 2017, 118 consecutive treatment naïve patients with solitary HCC ≤4 cm were included. Baseline characteristics including patient age, gender, MELD score, BCLC stage and Child-Pugh (CP) scores were compared between the two groups using t-test and chi-square. Tumor response at 3 months post therapy was evaluated using modified Response Evaluation Criteria in Solid Tumors (m-RECIST). Survival from initial treatment was calculated using Kaplan-Meier estimation. Statistical analysis was performed using SPSS v25 (IBM, Armonk, NY) with significance set at 0.05. Overall, 118 consecutive patients were included of whom 75 patients were treated with MWA and 43 patients were treated with Y90 RS. Five of 75 patients (6.7%) in the MWA group and 2 of 43 patients in the RS were lost to follow-up. Median follow-up for the entire cohort was 30.2 months. The MWA group had smaller lesions diameter compared (1.7 cm) vs. those with RS (2.7 cm, P = 0.001). The MWA group had more patients who were ≤65 years (53.9% of patients) vs. RS group (37.2%, P = 0.079). While the MWA group had larger proportion of higher CP score (30.7% of CP B for MWA vs. 11.6% of CP B RS, P = 0.05), the RS group had higher BCLC B stage (76.7%) vs. 60.0% for MWA (P = 0.01). The incidence of favorable tumor response (partial or complete response) was similar for the two groups; 85.8% for MWA vs. 87.8% for RS (P = 0.49). There was no difference in OS from first procedure in the MWA group (46.4 months) vs. RS (43.7 months; P = 0.907). Our data suggests Y90 RS is noninferior to percutaneous MWA in the management of HCC lesions ≤4 cm with similar medium-term OS outcomes.Tabled 1MWAY90RSImaging Response (mRESIST) Complete Response57(76.0%)32(74.4%) Partial Response3(2.67%)4(9.30%) Stable Disease4(5.33%)2(4.65%)P=0.487 Progression of Disease6(8.0%)3(6.98%)Overall Survival (months)95% Confidence Interval46.3843.68P=0.907(41.47-51.286)(36.72-50.64) Open table in a new tab

Personalized Dosimetry for Liver Cancer Y-90 Radioembolization Using Computational Fluid Dynamics and Monte Carlo Simulation.

Yttrium-90 (Y-90) transarterial radioembolization uses radioactive microspheres injected into the hepatic artery to irradiate liver tumors internally. One of the major challenges is the lack of reliable dosimetry methods for dose prediction and dose verification. We present a patient-specific dosimetry approach for personalized treatment planning based on computational fluid dynamics (CFD) simulations of the microsphere transport combined with Y-90 physics modeling called CFDose. The ultimate goal is the development of a software to optimize the amount of activity and injection point for optimal tumor targeting. We present the proof-of-concept of a CFD dosimetry tool based on a patient's angiogram performed in standard-of-care planning. The hepatic arterial tree of the patient was segmented from the cone-beam CT (CBCT) to predict the microsphere transport using multiscale CFD modeling. To calculate the dose distribution, the predicted microsphere distribution was convolved with a Y-90 dose point kernel. Vessels as small as 0.45mm were segmented, themicrosphere distribution between the liver segments using flow analysis was predicted,the volumetric microsphere and resulting dose distribution in the liver volume were computed. The patient was imaged with positron emission tomography (PET) 2h after radioembolization to evaluate the Y-90 distribution. The dose distribution was found to be consistent with the Y-90 PET images. These results demonstrate the feasibility of developing a complete framework for personalized Y-90 microsphere simulation and dosimetry using patient-specific input parameters.

Yttrium-90 microsphere radioembolisation for unresectable hepatocellular carcinoma.

Due to a comment received and due to some other identified methodological problems, the present review is withdrawn.

Correlating serum alpha-fetoprotein in hepatocellular carcinoma with response to Yttrium-90 transarterial radioembolization with glass microspheres (TheraSphere™)

BackgroundFew studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC. MethodsPatients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed. ResultsSeventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2–112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8–11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75–1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p < 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01–1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03–1.25, p = 0.018). ConclusionPre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

Safe hepatectomy after arterial-based liver directed therapy

Presenter: Aneil Sood | Indiana University Background: Liver directed therapy (LDT) for primary and secondary liver cancer has been increasingly utilized in patients with technically unresectable liver tumors, or in patients with surgically prohibitive underlying liver disease or medical comorbidities. Recent studies have shown that transarterial radioembolization (TARE) may reduce tumor burden and permit hepatectomy for complete tumor clearance. The short- and long-term outcomes of patients undergoing hepatectomy following TARE are reported in this study. Methods: An observational study of patients undergoing partial hepatectomy after TARE with yttrium-90 (Y90) between 2013-2018 was performed. Demographics, comorbidities, TARE specific variables, perioperative outcomes, and long-term outcomes were recorded. Variables specific to TARE included the number of procedures, arterial selectivity of embolization, and total millicurie (mCi) dose. Operative variables included the extent of hepatectomy, estimated blood loss (EBL), duration of operation, major postoperative morbidity (Clavien-Dindo Grade III-V complications), hospital readmission, and 30-day mortality. Long-term outcomes were recorded as pattern of recurrence, disease-free survival, and overall survival. Results: Eight patients (6 females, 2 males; mean age 60.4 +/- 1.8 years) underwent TARE for initially unresectable liver cancer, including hepatocellular carcinoma (n = 5), metastatic cancer (pancreatic neuroendocrine n = 1, pulmonary neuroendocrine n = 1), and cholangiocarcinoma (n = 1). The mean total dose of Y90 was 86.1 +/- 14.4 mCi during a single procedure (n = 4) or over two procedures (n = 4). Selective TARE was performed in five patients (63%) and nonselective in three patients (38%). The mean time from TARE to hepatectomy was 12.4 +/- 4 months. Six of the 8 patients (75%) required major hepatectomy (all open technique). Mean EBL was 1056 +/- 294 mL, and mean operative time was 271 +/- 43 minutes. Postoperatively, major morbidity was seen in three patients (38%) and included organ-space surgical site infection (n = 1), pneumonia requiring reintubation (n = 1), and bile leak (n = 2). Readmission occurred in four patients (50%). There were no 30-day mortalities. After a median follow-up of 37 months, recurrence was observed in four patients (50%); three patients developed hepatic recurrence, and one patient developed peritoneal recurrence. The mean disease-free survival and overall survival were 18.1 +-/ 5.0 months and 33.8 +/- 8.4 months, respectively. Conclusion: Hepatectomy following liver-directed therapy with Y90 radioembolization appears to be a safe treatment paradigm for patients with advanced stage liver cancer and can result in good long-term outcomes.