Yttrium-90 Research Articles

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.

Yttrium-90 Synovectomy in Hemophilic Arthropathy: An Institutional Experience for 15 Years.

Objective:The objective of this study is to assess the efficacy of Yttrium-90 (Y-90) radiation synovectomy in decreasing the recurrent bleeding episodes in hemophilic joints.Subjects and Methods:A retrospective analysis of patients who had Y-90 synovectomy from January 2001 to January 2016 was done. Among them, patients with minimum follow-up of 6 months were selected. The response in terms of decrease in the number of bleeding episodes was evaluated.Results:A total of 167 patients (243 joints) with hemophilia had radiation synovectomy over 15 years. Those with a minimum follow-up of 6 months were 155 joints (115 patients). The age ranged from 5 to 43 years and included 113 male and two female patients. Data for 11 joints were unavailable as these patients were lost to follow-up. The assessment of response for the remaining 144 joints was done based on the data available for different follow-up periods. They were divided into the following – 7 months to 2 years (89 joints), 3–5 years (6 joints), 6–10 years (39 joints), and above 11 years (10 joints). Overall, 37.4% of the joints had complete response, 56% had partial response, and 6% of the joints had no response.Conclusion:Radiation synovectomy is a noninvasive and effective modality which decreases the bleeding episodes in hemophiliac joints and improves the quality of life remarkably.

A multiwell applicator for conformal brachytherapy of superficial skin tumors: A simulation study.

Brachytherapy of thin skin tumors using beta particles can protect underlying sensitive structures such as the bone because of the rapid dose falloff of this type of radiation in tissue. The current work describes a skin brachytherapy applicator, based on beta radiation, that can provide the needed cell-killing radiation dose matched to the shape of individual skin tumors. The applicator and its template were fabricated using 3D printing technology. Any clinically approved beta-emitting isotope in the form of a radioactive gel could theoretically be used in this applicator. Monte Carlo simulations were employed to study the capability of the applicator in conforming dose distribution based on the shape of the tumor. Dose profile in the shallow depth, transverse dose profiles at different depths, and the percent depth dose from this applicator were calculated. The radioisotope of choice for our calculations was Yttrium-90 (Y-90). Using the proposed applicator, it is possible to create a desired dose profile matching the tumor surface shape. The short-range of the beta radiation, together with the dose conforming capability of the applicator, may lead to minimal interactions with the healthy tissue around the skin lesion.

A Pilot Feasibility Study of Yttrium-90 Liver Radioembolization Followed by Durvalumab and Tremelimumab in Patients with Microsatellite Stable Colorectal Cancer Liver Metastases.

Radioembolization with yttrium-90 resin microspheres can be combined safely with full doses of durvalumab and tremelimumab in patients with metastatic colorectal cancer. Regional radioembolization with yttrium-90 resin microspheres did not result in any hepatic or extrahepatic responses to a combination of durvalumab and tremelimumab. The lack of immunomodulatory responses to yttrium-90 on biopsies before and after treatment rules out a potential role for this strategy in converting a "cold tumor" into an "inflamed," immune responsive tumor. PD-1 inhibitors have been ineffective in microsatellite stable (MSS) metastatic colorectal cancer (CRC). Preclinical models suggest that radiation therapy may sensitize MSS CRC to PD-1 blockade. Patients with MSS metastatic CRC with liver-predominant disease who progressed following at least one prior line of treatment were treated with yttrium-90 (Y90) radioembolization to the liver (SIR-Spheres; Sirtex, Woburn, MA) followed 2-3 weeks later by the combination of durvalumab and tremelimumab. A Simon two-stage design was implemented, with a planned expansion to 18 patients if at least one response was noted in the first nine patients. Nine patients enrolled in the first stage of the study, all with progressive disease (PD) during or after their first two cycles of treatment. Per preplanned design, the study was closed because of futility. No treatment-related grade 3 or greater toxicities were recorded. Correlative studies with tumor biopsies showed low levels of tumor-infiltrating lymphocyte (TIL) infiltration in tumor cancer islands before and after Y90 radioembolization. Y90 radioembolization can be added safely to durvalumab and tremelimumab but did not promote tumor-directed immune responses against liver-metastasized MSS CRC.

PET/CT Imaging Characteristics After Radioembolization of Hepatic Metastasis from Breast Cancer.

To define positron emission tomography/computed tomography (PET/CT) imaging characteristics during follow-up of patients with metastatic breast cancer (MBC) treated with yttrium-90 (Y90) radioembolization (RE). From January 2011 to October 2017, 30 MBC patients underwent 38 Y90 glass or resin RE treatments. Pre-RE PET/CT was performed on average 51days before RE. There were 68 PET/CTs performed after treatment. Response was assessed using modified PERCIST criteria focusing on the hepatic territory treated with RE, normalizing SUVpeak to the mean SUV of liver uninvolved by tumor. An objective response (OR) was defined as a decrease in SUVpeak by at least 30%. Of the 68 post-RE scans, 6 were performed at 0-30days, 15 at 31-60days, 9 at 61-90days, 13 at 91-120days, 14 scans at 121-180days, and 11 scans at > 180days after RE. Of the 30 patients, 25 (83%) achieved OR on at least one follow-up. Median survival was 15months after the first RE administration. Highest response rates occurred at 30-90days, with over 75% of cases demonstrating OR at that time. After 180days, OR was seen in only 25%. There was a median TTP of 169days among responders. In MBC, follow-up PET/CT after RE demonstrates optimal response rates at 30-90days, with progression noted after 180days. These results help to guide the timing of imaging and also to inform patients of expected outcomes after RE.

Predictors of Overall and Progression-Free Survival in Patients with Ocular Melanoma Metastatic to the Liver Undergoing Y90 Radioembolization.

To investigate predictors of overall survival (OS) and progression-free survival (PFS) in patients with ocular melanoma metastatic to the liver undergoing yttrium-90 (Y90) radioembolization, including the effect of concurrent immunotherapy. An IRB-approved retrospective review of 24 patients with ocular melanoma metastatic to the liver who underwent Y-90 treatment between June 2003 and January 2018 was performed. Data regarding patients' performance status at the time of Y90, intra-/extrahepatic tumor burden, and treatment response were evaluated. RECIST was used to determine objective tumor response. Kaplan-Meier analysis was used to calculate OS and PFS from the first Y90 therapy. Log-rank analysis was used to determine predictors of prolonged OS and PFS. Median OS from primary diagnosis and diagnosis of liver metastases was 66months (mo) and 26.3mo, respectively. Median OS for those who received immunotherapy within 3months of undergoing Y90 was prolonged at 26.0mo versus 9.5mo for others (p = 0.014). Median OS for patients with an ECOG performance status of 0 was prolonged at 26mo versus 5.5mo for others (p = 0.003). Median hepatic PFS was prolonged in patients treated with Y-90 on concurrent immunotherapy at 10.3mo versus 2.7mo for TARE only (p = 0.002). Patients with an ECOG performance status of 0 had prolonged PFS (p = 0.002). Concurrent immunotherapy and an ECOG performance status of 0 at the time of Y90 therapy appear to be predictors of prolonged OS and PFS in patients with ocular melanoma metastatic to the liver.

Algorithms and Analyses for Joint Spectral Image Reconstruction in Y-90 Bremsstrahlung SPECT

Quantitative yttrium-90 (Y-90) SPECT imaging is challenging due to the nature of Y-90, an almost pure beta emitter that is associated with a continuous spectrum of bremsstrahlung photons that have a relatively low yield. This paper proposes joint spectral reconstruction (JSR), a novel bremsstrahlung SPECT reconstruction method that uses multiple narrow acquisition windows with accurate multi-band forward modeling to cover a wide range of the energy spectrum. Theoretical analyses using Fisher information and Monte-Carlo (MC) simulation with a digital phantom show that the proposed JSR model with multiple acquisition windows has better performance in terms of covariance (precision) than previous methods using multi-band forward modeling with a single acquisition window, or using a single-band forward modeling with a single acquisition window. We also propose an energy-window subset (ES) algorithm for JSR to achieve fast empirical convergence and maximum-likelihood based initialization for all reconstruction methods to improve quantification accuracy in early iterations. For both MC simulation with a digital phantom and experimental study with a physical multi-sphere phantom, our proposed JSR-ES, a fast algorithm for JSR with ES, yielded higher recovery coefficients (RCs) on hot spheres over all iterations and sphere sizes than all the other evaluated methods, due to fast empirical convergence. In experimental study, for the smallest hot sphere (diameter 1.6cm), at the 20th iteration the increase in RCs with JSR-ES was 66 and 31% compared with single wide and narrow band forward models, respectively. JSR-ES also yielded lower residual count error (RCE) on a cold sphere over all iterations than other methods for MC simulation with known scatter, but led to greater RCE compared with single narrow band forward model at higher iterations for experimental study when using estimated scatter.

Feasibility of Yttrium-90 Radioembolization Dose Calculation Utilizing Intra-procedural Open Trajectory Cone Beam CT.

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.

2706 Ischemic Duodenal Ulcer: A Rare Complication of Embolization of the Gastroduodenal Artery in Yttrium-90 Radioembolization Therapy

INTRODUCTION: Selective internal radiation therapy (radioembolization) with yttrium-90 (Y-90) resin microspheres is an effective and increasingly popular treatment option for unresectable primary and metastatic liver malignancies. Gastric complications are detected in 4% to 27% of liver radioembolization cases. Most of these cases arise from non-targeted flow of microspheres with aberrant deposition into various non-selected organs. The gastroduodenal artery is routinely embolized prior to deposition Y-90 microspheres to decrease the risk of non-targeted dissemination of the microspheres. We present a rare case of duodenal ulcer which developed as a result of ischemia induced by embolization of the gastroduodenal artery. CASE DESCRIPTION/METHODS: A 68 year-old woman with a history of stage IV colon adenocarcinoma with metastasis to the liver presented to the hospital with a several week history of severe abdominal pain two months after receiving radioembolization therapy with Y-90 microspheres. She was found to have a duodenal ulcer and was treated with acid suppression therapy. She was re-evaluated six months later for severe abdominal pain. Repeat endoscopy showed a larger duodenal ulcer with multiple coils eroding through the center of the ulcer bed suggesting ischemic injury caused directly from the embolization coils. She was treated with acid suppressive therapy with resolution of her symptoms. DISCUSSION: Radioembolization with Y-90 microspheres is now a widely performed locoregional treatment for primary and metastatic liver lesions not amenable to resection. Our case is unique because the patient’s duodenal ulcer was likely ischemia-induced from mechanical occlusion of and direct injury to the gastroduodenal artery from the embolization coils. It is imperative that clinicians caring for patients who have received radioembolization therapy be familiar with the many gastrointestinal complications associated with this therapy. There is increasing awareness of radiation-induced mucosal injury in the literature. However, providers should also know that despite the presence of multiple collaterals in the gastroduodenal territory, chronic coil-induced ischemia can also form ulcers as a complication of selective embolization of the gastroduodenal artery.

734P - Selection of patients with hepatocellular carcinoma for selective internal radiation therapy based on tumour burden and liver function: A post-hoc analysis of the SARAH trial

BackgroundThe most recent ESMO (2018) and EASL Clinical Practice Guidelines (2018) for the treatment of hepatocellular carcinoma (HCC) recommend considering liver function and tumour burden when selecting patients for intra-arterial therapy, such as selective internal radiation therapy (SIRT). The SARAH randomised trial did not show a statistically significant benefit of SIRT using yttrium-90 (Y-90) resin microspheres over sorafenib 400mg bid in terms of overall survival (OS) in the overall trial population of European patients with HCC. In this post-hoc analsis we explored the comparative effectivenes of these treatments in a subgroup of patients with low tumour burden (≤25% of total liver volume) and good liver function (ALBI grade 1). MethodsA Cox proportional hazards survival regression was conducted in the intention to treat (ITT) population of the SARAH trial to explore treatment effect modification including low tumour burden/good liver function as an interaction effect with treatment. ResultsAmong the ITT population, 37 (16%) patients in the SIRT arm and 48 (22%) patients in the sorafenib arm had a tumour burden ≤25% and an ALBI grade of 1. The interaction effect estimate from the Cox regression was 0.609 (95% CI: 0.344 to 1.079, p=0.089) indicating that SIRT was relatively more effective in this subgroup. In the low tumour burden/good liver function subgroup the HR for SIRT vs sorafenib was 0.73 (95% CI: 0.44 to 1.21). Median OS was 21.9 months (95% CI: 15.2 to 32.5) for SIRT vs 17.0 months (95% CI: 11.6 to 20.8) for sorafenib. Subsequent curative therapy was more frequent after SIRT than sorafenib (14% vs 2%). The drop-out rate from randomisation to SIRT treatment was lower in the subgroup than in the overall ITT population (8% vs 22%). ConclusionsThe analysis suggests that it may be possible to select patients with HCC and a low tumour burden/good liver function, who would derive a meaningful benefit from treatment with SIRT compared to sorafenib. Further prospective validation is required. Clinical trial identificationNCT01482442. Legal entity responsible for the studySirtex Medical UK Ltd. FundingSirtex Medical UK Ltd. DisclosureD.H. Palmer: Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: Sirtex. N.S. Hawkins: Research grant / Funding (institution), Travel / Accommodation / Expenses: Sirtex. V. Vilgrain: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sirtex. P.J. Ross: Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Shire; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sirtex; Honoraria (self), Travel / Accommodation / Expenses: Servier; Research grant / Funding (institution): Sanofi. All other authors have declared no conflicts of interest.

Refractory Duodenal Ulcer and Upper Gastrointestinal Bleeding Following Yttrium-90 Transarterial Radioembolization

Abstract Transarterial radioembolization (TARE) with Yttrium-90 (Y90) is widely used for management of primary or secondary liver malignancies that are not amenable to surgery. Nevertheless, complications of Y90 treatment, including rare events of gastric and duodenal ulceration and cirrhosis, may be critical. Here we report a case of a 79-year-old man who received Y90 TARE for metastatic neuroendocrine tumor to liver from bronchial primary and developed multiple iatrogenic GI complications. Following TARE, a gastroduodenal artery (GDA) coil was instituted to prevent migration of Y90 beads. One year following TARE, the patient presented with cirrhosis of unknown etiology, thrombocytopenia, and multiple episodes of upper gastrointestinal bleeding (UGB). Endoscopy demonstrated GDA coil eroding into duodenum through mucosal ulcer base. Three years following TARE, an emergent esophagogastroduodenoscopy was performed due to upper GI bleeding. The histopathologic examination of stomach and duodenum revealed mucosal hemorrhage, submucosal and serosal fibrosis, and chronic inflammation associated with Y90 intravascular beads. A cholecystectomy was performed for fibrotic gallbladder that showed chronic cholecystitis with cholelithiasis and intravascular Y90 beads. GDA coil was removed, which showed attached food material, bacterial colonies, and Candida spp. A subsequent liver biopsy showed previously treated area with Y90 beads, inflammation, and fibrosis in adjacent parenchyma. Due to rich vascularity, TARE is considered an ideal treatment choice for neuroendocrine tumor. GI ulceration is the most common complication, which occurs in less than 4% patients, and usually can be managed with proton pump inhibitor. A surgery should be performed upon failure of medical treatment. Radiation-associated fibrosis has been reported mainly in hepatocellular carcinoma patients, who often have cirrhosis before the procedure. To conclude, this is the first case report of Y90 TARE complications in multiple GI organs in a metastatic NET patient.

Calculation of beta radiation dose of a circular Y-90 skin patch: Analytical and simulation methods

Beta radiation therapy of superficial skin tumors using a radioactive patch can be an interesting treatment, mainly when the lesion is near sensitive targets, for example, close to the eye or bone. Due to their short range and rapid dose fall-off, beta radiation from a skin patch deposits its energy within the first layers of the skin. This property may lead to the protection of sensitive structures located right beneath the skin lesion during the radiation therapy procedure. To create and use individual and personalized radiation patches the distribution of the beta radiation dose needs to be known. An accurate and realistic calculation is needed to determine the amount of radioisotope required and the duration of the radiation therapy procedure to deliver the prescribed dose in a certain depth from the surface. In this paper, the theoretical model for a dose distribution calculation from a radioactive skin patch loaded with Yttrium-90 (Y-90) in different depths of skin tissue is presented. The calculation was based on the Loevinger beta-point source dose function, which is a numerical method for dosimetry of beta-emitting isotopes. Results of the calculation were also compared with that of Monte Carlo simulation methods to assess the reliability of the application of the Loevinger method in dosimetry of a beta-emitting radioactive patch.

Safety and efficacy of radioembolization with glass microspheres in hepatocellular carcinoma patients with elevated lung shunt fraction: analysis of a 103-patient cohort.

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

Safety of Transarterial Y90 Radioembolization in Management for Unresectable-Intermediate and Locally Advanced-HCC

AbstractBackground: Egypt has the highest prevalence of HCV worldwide and has rising rates of hepatocellular carcinoma (HCC). Many have adopted the Barcelona Clinic Liver Cancer (BCLC) staging classification, which links the stage of the disease to a specific treatment strategy. More controversial than the prognostic scoring system is the treatment algorithm that is a part of the BCLC. TACE is usually recommended as the standard treatment of BCLC-B patients, yet it is a relatively contraindicated in BCLC-C1 patients. Radioembolization with yttrium-90 (Y90) is a recently introduced liver-directed therapy, it is a is a sort of internal brachytherapy by arterially injected yttrium-90 (Y90) microspheres for the treatment of HCC. Growing data suggest that (Y90) radioembolization has a potent anticancer effect with negligible adverse events if appropriate pretreatment evaluations. It can be used in BCLC-B and BCLC-C1 in an manner. In contrast toTACE, the rate of adverse effects after such unselective application, as performed over a lobar branch of the hepaticartery, is not significantly increased as compared to segmental or even subsegmental microsphere application, although the tumor response rate may vary.Aim of Study: This study aims to present and discuss the efficacy and clinical outcome of Y90 radioembolization using Y90 microsphere for management of patients with intermediate and locally advanced (BCLC-B and BCLC-C1) Hepato-Cellular Carcinoma (HCC).Patients and Methods: This is a prospective study carried out between June 2014 and May 2016 for patients with hepatocellular carcinoma and liver restricted disease. All patients underwent treatment by Y90 microsphere radioem-bolization (SIR-Tex). A total number of 20 patients with intermediate and locally hepatocellular carcinoma and liver restricted disease, not eligible for curative treatment.Results: Assessment was done according to RECIST and mRECIST guidelines. We found good therapeutic response in patients treated with Y90 radioembolization. The complete response, partial response, stable disease and disease progres-sion rates for the study sample after 3 months using the conventional RECIST criteria was 0%, 55%, 30% and 10%, while after 6 months it became 0, 50%, 20% and 25% respec-tively.Conclusion: Y90 microspheres radioembolization for patients with intermediate and advanced HCC is an effective treatment which can be utilized even in patients with compro-mised liver function.

Current State of Liver-Directed Therapies and Combinatory Approaches with Systemic Therapy in Hepatocellular Carcinoma (HCC).

The increasing set of liver-directed therapies (LDT) have become an integral part of hepatocellular carcinoma (HCC) treatment. These range from percutaneous ablative techniques to arterial embolization, and varied radiotherapy strategies. They are now used for local disease control, symptom palliation, and bold curative strategies. The big challenge in the face of these innovative and sometimes overlapping technologies is to identify the best opportunity of use. In real practice, many patients may take benefit from LDT used as a bridge to curative treatment such as resection and liver transplantation. Varying trans-arterial embolization strategies are used, and comparison between established and developing technologies is scarce. Also, radioembolization utilizing yttrium-90 (Y-90) for locally advanced or intermediate-stage HCC needs further evidence of clinical efficacy. There is increasing interest on LDT-led changes in tumor biology that could have implications in systemic therapy efficacy. Foremost, additional to its apoptotic and necrotic properties, LDT could warrant changes in vascular endothelial growth factor (VEGF) expression and release. However, trans-arterial chemoembolization (TACE) used alongside tyrosine-kinase inhibitor (TKI) sorafenib has had its efficacy contested. Most recently, interest in associating Y-90 and TKI has emerged. Furthermore, LDT-led differences in tumor immune microenvironment and immune cell infiltration could be an opportunity to enhance immunotherapy efficacy for HCC patients. Early attempts to coordinate LDT and immunotherapy are being made. We here review LDT techniques exposing current evidence to understand its extant reach and future applications alongside systemic therapy development for HCC.

Novel design and development of a 3D-printed conformal superficial brachytherapy device for the treatment of non-melanoma skin cancer and keloids

BackgroundSkin tumors are the most predominant form of cancer in the United States. Radiation therapy, particularly high dose-rate (HDR) brachytherapy, provides an effective form of cancer control when surgery is not possible or when surgical margins are incomplete. The treatment of superficial skin cancers on irregular surfaces, such as the nose, lips or ears, present challenges for treatment. To address this issue, we designed and constructed a novel conformal superficial brachytherapy (CSBT) device prototype to improve patient-specific treatment for complex sites. The device is mounted on an automated remote after-loader, providing limited radiation exposure to operating personnel, is inexpensive to construct, and offers a unique method of conformal surface radiation therapy.ResultsA prototype of the CSBT device was successfully manufactured. A computed tomography (CT) scan of a Rando phantom was used to plan the target treatment area. The CSBT device has a hexagonal lattice array of retractable rods with radioactive seeds placed at the tip of each rod. A 3D-printed conformal shape insert with a hexagonal array of cylindrical projections of varying length is driven into the rods by a single linear actuator. The rods are displaced to conform to the patient’s skin. This elegant device design permits the delivery of radiation to complex targets using readily available beta-emitting radionuclides, such as Yttrium-90 (Y-90) or Strontium-90 (Sr-90).ConclusionA working prototype of a novel CSBT device was built using 3D-printing technology that provides a safe and economically attractive means of improving radiation delivery to complex treatment sites.

Predictors of survival in chemorefractory colorectal liver metastases treated with Y90 radioembolization.

e15044 Background: The aim of the study was to evaluate molecular signatures and timing of yttrium-90 (Y90) as prognostic factors of survival following Y90 radioembolization (RE) in patients with chemorefractory colorectal liver metastases (CRLM). Methods: In a retrospective single-institution study, patients with unresectable, chemorefractory CRLM who had undergone genomic analysis prior to Y90 RE from 2013 to 2018 were identified. Timing of Y90 (following failure of first line vs following multiple lines of chemotherapy) and oncogenic mutation status (MAPK and PI3K pathways) were evaluated as predictors of survival length following Y-90. Survival was measured from first Y90 using Kaplan-Meier estimation and predictors of outcome were identified using log-rank analysis. Results: Overall, 58 patients with chemorefractory CRLM who underwent genomic analysis prior to Y-90 were identified. Of these, 26 (44.8%) had MAPK mutations, and 2 (3.5%) had PI3K mutations. Median survival after first Y-90 RE was 12.9 months. There was significantly prolonged overall survival (OS) in patients receiving Y90 immediately following failure of the first line of chemotherapy (FOLFOX ± bevacizumab) versus patients who underwent multiple lines of chemotherapy prior to Y90 (median OS of 16.9 vs 11.4 months for others; p = 0.023). When stratifying the cohort based on the timing of Y90, patients with WT-MAPK (n = 8) had prolonged OS if they underwent Y-90 following failure of the first line of chemotherapy (median OS of 22.3 vs 12.9 mo; p = 0.019). Patients with WT-PI3K (n = 19) had prolonged OS if they underwent Y90 following failure of the first line of chemotherapy (median OS of 16.9 vs 12 mo; p = 0.037). When analyzing the entire cohort non-stratified by timing of Y90, genetic mutation was not found to be a predictor of prolonged OS. Conclusions: Y90 RE after failure of first line of chemotherapy in CRLM appears to confer prolonged survival specifically for WT-MAPK and WT-PI3K oncogenes. Conversely, the prognosis of more favorable genetic status appears to be negated if Y90 RE is performed after failure of second or third line chemotherapies.

Y(III) ion substituted 2D anionic clay (I); in-vitro cytotoxicity and intercellular uptake behavior

Radiotherapeutic yttrium-90 (Y-90) is known to be a pure β-emitter with few environmental radiation restrictions, and therefore, it is considered to be suitable for use in the irradiation of large solid tumors due to its high energy (2280 keV) and long particle traveling range (12 mm). To develop a novel radio-therapeutic system based on Y-90, we have prepared nonradioactive Y(III) incorporated hydrotalcite nanoparticles (YHN) as the proof of concept. Confirmed as a drug delivery carrier, hydrotalcite nanoparticles (HN) with the size of ~100 nm could target not only tumor tissues but also tumor cells due to their superior intercellular permeability thanks to the clathrin-mediated endocytosis. Therefore, YHN, [Mg2.17Al0.89Y0.11(OH)6.34(CO3)0.5∙nH2O], was prepared by co-precipitation method and by subsequent hydrothermal treatment. The as-prepared YHN was determined to have an average size of ~100 nm with a plate-like morphology, and their cellular uptake efficiency in the mouse liver cancer cells was found to be 2.5 times higher than that in the normal ones. The YHN showed very low cytotoxicity with no significant decrease in cell proliferation at the concentration below 100 μg/mL, implying that the present YHN could potentially be used in theranostic applications.

Is hepatectomy safe following Yttrium-90 therapy? A multi-institutional international experience

BackgroundSingle institution reports demonstrate variable safety profiles when liver-directed therapy with Yttrium-90 (Y-90) is followed by hepatectomy. We hypothesized that in well-selected patients, hepatectomy after Y90 is feasible and safe. MethodsNine institutions contributed data for patients undergoing Y90 followed by hepatectomy (2008–2017). Clinicopathologic and perioperative data were analyzed, with 90-day morbidity and mortality as primary endpoints. ResultsForty-seven patients were included. Median age was 59 (20–75) and 62% were male. Malignancies treated included hepatocellular cancer (n = 14; 30%), colorectal cancer (n = 11; 23%), cholangiocarcinoma (n = 8; 17%), neuroendocrine (n = 8; 17%) and other tumors (n = 6). The distribution of Y-90 treatment was: right (n = 30; 64%), bilobar (n = 14; 30%), and left (n = 3; 6%). Median future liver remnant (FLR) following Y90 was 44% (30–78). Resections were primarily right (n = 16; 34%) and extended right (n = 14; 30%) hepatectomies. The median time to resection from Y90 was 196 days (13–947). The 90-day complication rate was 43% and mortality was 2%. Risk factors for Clavien-Dindo Grade>3 complications included: number of Y-90-treated lobes (OR 4.5; 95% CI1.14–17.7; p = 0.03), extent of surgery (p = 0.04) and operative time (p = 0.009). ConclusionsThese data demonstrate that hepatectomy following Y-90 is safe in well-selected populations. This multi-disciplinary treatment paradigm should be more widely studied, and potentially adopted, for patients with inadequate FLR.

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes

IntroductionSelective internal radiotherapy (SIRT) with yttrium-90 (Y-90) is an intra-arterial therapy for hepatic malignancy in patients who are unsuitable for surgical resection. This treatment is considered palliative, although some patients can demonstrate a response that is adequate to facilitate surgical resection with curative intent.MethodsAll patients who underwent liver resection post SIRT were reviewed. Data gathered included patient demographics, tumor type, surgical details, and post-operative outcomes.ResultsTwelve patients underwent SIRT followed by liver resection (7 males and 5 females). Pathologies were hepatocellular carcinoma (n = 5), metastatic colorectal cancer (n = 5), and neuroendocrine tumor (n = 2). Lesional response (size, volume, and RECIST (response evaluation criteria in solid tumors)) was calculated and where appropriate functional liver remnant (FLR) is presented. Mean FLR increase was 264cm3 (range − 123 to 909), and all cases demonstrated a partial response according to RECIST with a mean largest lesion volume reduction of 475cm3 (range 14–1632). No post-SIRT complications were noted. Hepatectomy occurred at a mean of 322 days from SIRT treatment. Ninety-day morbidity was 67% (n = 6), complications post-surgery were analyzed according to the Clavien-Dindo classification scale; a total of 15 events occurred in 6 patients. Ninety-day mortality of 11% (n = 1).ConclusionIn selected cases, liver resection is possible post SIRT. As this can represent a potentially curative option, it is important to reconsider resection in the follow-up of patients undergoing SIRT. Post-operative complications are noted following major and extended liver resection. Therefore, further studies are needed to improve patient selection.