Yttrium-90 Microsphere Radioembolization Research Articles

Current status of yttrium-90 microspheres radioembolization in primary and metastatic liver cancer

Liver malignancy, including primary liver cancer and metastatic liver cancer, has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy. Radioembolization with yttrium-90 (90Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy. The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with 90Y microspheres, from patient selection to follow up, both technically and clinically, are discussed in this paper. It describes the application and development of 90Y microspheres in the treatment of liver cancer.

Non Target Shunting of Tc-99m Macroaggregates of Albumin and Radiolabeled Yttrium-90 Microspheres into Hepatic Falciform Artery - Less Observed Arterial Variant not to be Overlooked.

Identification of nontarget arteries is crucial prior to Yttrium-90 microspheres radioembolization. We present a case where an uncommon nontarget artery, the hepatic falciform artery was identified during work up for radioembolization and necessary preventive measures were taken to minimize the complications.

Transradial versus transfemoral arterial access in Yttrium-90 microspheres radioembolization for hepatocellular carcinoma.

OBJECTIVETransradial access has become more popular in body intervention procedures but has not been ubiquitously adapted. This study assesses the efficacy of this approach in Yttrium-90 labeled microspheres radioembolization. To compare transradial to transfemoral access in hepatocellular carcinoma patients who underwent Yttrium-90 radioembolization.MATERIALS AND METHODSA total of 244 hepatocellular carcinoma patients underwent 337 radioembolization procedures at our institute from May 2014 to May 2020. The transradial access-group included 188 patients (252 procedures) while the transfemoral access group had 63 patients (85 procedures). The recovery time, fluoroscopy time, contrast volume, peak radiation dose, and equipment cost for each procedure were all reviewed to evaluate for statistical differences between the two groups.RESULTSThe transradial cohort recorded a significantly shorter (P < 0.01) mean recovery time (from the end of the procedure to discharge) and had a significantly shorter (P < 0.05) use of contrast volume versus the transfemoral group. In addition, the radiation dose and fluoroscopy time were lower in the transradial subset, although not statistically different. Furthermore, the overall cost for procedural equipment was significantly less (P < 0.01) in the transradial cohort than in the transfemoral. No major complications were reported in the transradial group, while one pseudoaneurysm was noted in the transfemoral group.CONCLUSIONWith respect to many pertinent parameters, transradial access was evaluated as being more advantageous than transfemoral access. The results of this study suggest that transradial access should be considered more often, whenever feasible, as an option in the Yttrium-90 treatment of hepatocellular carcinoma patients.

Measuring radiation exposure of operators engaged in the yttrium-90 microsphere radioembolization treatment of hepatocellular carcinoma patients

To validate the radiation safety norms for radiation operators, their exposure to radiation during the yttrium-90 radioembolization treatment of 20 hepatocellular carcinoma patients was measured and evaluated. The mean radioactivity of yttrium-90 used was 2.15 GBq, and the survey meter was placed between the radionuclide source and catheter at a distance of 50 cm. The radiation dose during fluoroscopy was measured for comparison. In addition, the total accumulated exposure to a radiation operator during a treatment was calculated. The results indicated that the mean radiation exposure during fluoroscopy was 459 μSv/h. The mean radiation exposures from the patient after the injection of yttrium-90 were 5.66 μSv/h at 1 min, 5.99 μSv/h at 3 min, 3.97 μSv/h at 5 min, 2.35 μSv/h at 10 min, and 1.98 μSv/h at 1 min. The total calculated accumulated radiation exposure to a operator during the treatment was 0.73 μSv. In conclusion, the radiation exposure to the administering operator was within the safe exposure range.

Outpatient Yttrium-90 microsphere radioembolization: assessment of radiation safety and quantification of post-treatment adverse events causing hospitalization.

Quantification of post-interventional adverse events of outpatient SIRT leading to hospitalization and quantification of radiation exposure. In this single-center, retrospective cohort study, we reviewed 212 patients treated with SIRT (90Y-microspheres) for primary and secondary liver malignancies. We searched for adverse events (AEs) and serious adverse events (SAEs), defined as AE's causing hospitalization. Additionally, radiation exposure was measured in 36 patients. Seven patients had an SAE (3.3%), four patients had AE without readmission/hospitalization (1.9%) and 201 patients had no complications (94.8%). The mean ambient dose rate at 1m distance from the source after administration of 90Y-microspheres was 1.88µSv/h ± 0.74 (± SD) with a range from 4.3 to 0.2µSv/h. Outpatient radioembolization with 90Y-microspheres is safe and requires hospitalization only in a very small number of patients. The mean dose rate was low and met the national conditions for outpatient treatment (< 5µSv/h).

Hepatic Flow Redistribution is Feasible in Patients with Hepatic Malignancies Undergoing Same-Day Work-Up Angiography and Yttrium-90 Microsphere Radioembolization.

To assess the feasibility of performing same-day vascular flow redistribution and Yttrium-90 radioembolization (90Y-RE) for hepatic malignancies. From November 2015 to February 2019, patients undergoing same-day hepatic flow redistribution during work-up angiography, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA) SPECT/CT and 90Y microsphere-RE, were recruited. Within 18h following the delivery of 90Y resin microspheres, an 90Y-PET/CT study was performed. According to patients' vascular anatomy, flow redistribution was performed by microcoil embolization of extrahepatic branches (group A), intrahepatic non-tumoral vessels (group B) and intrahepatic tumoral arteries (group C). The accumulation of 99mTc-MAA particles and microspheres in the redistributed areas was qualitatively evaluated using a 5-point visual scale (grade 1 = < 25% accumulation; grade 5 = 100% accumulation). Differences in the distribution of microspheres among groups were assessed with Mann-Whitney U test. Twenty-two patients were treated for primary (n = 17) and secondary (n = 5) hepatic malignancies. The MAA-SPECT/CT showed uptake in all the redistributed areas. Regarding the accumulation of microspheres within the redistributed segments in all the groups, perfusion patterns were classified as 2 in 1 case, 4 in 6 cases and 5 in 15 cases. No statistically significant differences were observed between groups A and B-C (U value = 34, p = 0.32) and between groups B and C (U value = 26, p = 0.7). Mean predicted absorbed doses by the tumoral and normal hepatic tissues were 163.5 ± 131.2Gy and 60.4 ± 69.3Gy, respectively. Mean total procedure time (from work-up angiography to 90Y delivery) was 401 ± 0.055min. Performing same-day redistribution of the arterial hepatic flow to the target and 90Y-microsphere delivery is feasible in the treatment of liver tumors. Clinical Trials Registry NCT03380130.

Validation of post-treatment PET-based dosimetry software for hepatic radioembolization of Yttrium-90 microspheres.

Yttrium-90 (90 Y) microsphere radioembolization enables selective internal radiotherapy for hepatic malignancies. Currently, there is no standard postdelivery imaging and dosimetry of the microsphere distribution to verify treatment. Recent studies have reported utilizing the small positron yield of 90 Y (32ppm) with positron emission tomography (PET) to perform treatment verification and dosimetry analysis. In this study, we validated a commercial dosimetry software, MIM SurePlan™ LiverY90 (MIM Software Inc., Cleveland, OH), for clinical use. A MATLAB-based algorithm for 90 Y PET-based dosimetry was developed in-house and validated for the purpose of commissioning the commercial software. The algorithm is based on voxel S values and dosimetry formalism reported in MIRD Pamphlet 17. We validated the in-house algorithm to establish it as the ground truth by comparing results from a digital point phantom and a digital uniform cylinder to manual calculations. Once we validated our in-house MATLAB-based algorithm, we used it to perform acceptance testing and commissioning of the commercial dosimetry software, MIM SurePlan, which uses the same dosimetry formalism. A 0.4cm/5% gamma test was performed on PET-derived dose maps from each algorithm of uniform digital and nonuniform physical phantoms filled with 90 Y chloride solution. Average dose (Davg ) and minimum dose to 70% (D70 ) of a given volume of interest (VOI) were compared for the digital phantom, the physical phantom, and five patient cases (27 tumor VOIs), representing different clinical scenarios. The gamma-pass rates were 97.26% and 97.66% for the digital and physical phantoms, respectively. The differences between Davg and D70 were 0.076% and 0.10% for the digital phantom, respectively, and <5.2% for various VOIs in the physical phantom. In the clinical cases, 96.3% of the VOIs had a difference <5% for Davg , and 88.9% of the VOIs had a difference <5% for D70 . Dose calculation results from MIM SurePlan were found to be in good agreement with our in-house algorithm. This indicates that MIM SurePlan performs as it should and, hence, can be deemed accepted and commissioned for clinical use for post-implant PET-based dosimetry of 90 Y radioembolization.

Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer: a large single-center experience.

Radioembolization (RE) is a promising treatment option for biliary tract cancers (BTC). We report here the largest series to date using this treatment modality. We retrospectively studied data from 64 patients treated outside prospective clinical trial at our institution. We studied baseline characteristics as potential prognostic factors. We studied dose delivered to the tumor as predictive factors of outcomes in patients not receiving concomitant chemotherapy. The Progression-Free Survival and Overall Survival (OS) were 7.6months [95% Confidence Interval (CI): 4.6-10.6] and 16.4months [95% CI: 7.8-25.0] in the whole cohort. The factors independently associated with OS in multivariable analysis were the primary localization of ICC (HR = 0.27, 95% CI: 0.11-0.68, p = 0.005) and a PS > 0 (HR = 2.21, 95% CI: 1.11-4.38, p = 0.024). During follow-up, 12 patients (19%) underwent surgery following downstaging, with a median OS of 51.9months. In patients not treated with concomitant chemotherapy (n = 31), OS was significantly higher in patients with a dose delivered to the tumor 260Gy or higher than in patients with a dose delivered to the tumor lower than 260Gy (median 28.2 vs 11.4months, log-rank p = 0.019). Our results confirm that RE is a promising treatment modality in BTC. A high proportion of patients could be downstaged to surgery, with promising long-term survival. Dose delivered to the tumor correlated with clinical outcomes when chemotherapy was not used concomitantly.

Radiation Gastritis Associated With Yttrium-90 Microsphere Radioembolization

Radioembolization of hepatic neoplasms (primary or secondary) using angiographically administered yttrium-90 (Y90) microspheres is an increasingly utilized ablative technique. We describe a patient with colon cancer metastatic to the liver, who developed biopsy confirmed radiation gastro-toxicity related to the Y90 radioembolization. A 66-year-old female with hepatic metastasis from colon cancer was treated with Y90 radioembolization to her liver. Prior to her first Y90 radioembolizaton, obliteration of her left gastric artery and gastroduodenal artery was performed using Gelfoam and coil embolization in order to prevent non-target embolization. Her first Y90 radioembolizaton was uneventful. One month later, she received her second Y90 radioembolization. Prior to her second Y90 radioembolization, prophylactic obliteration of her right gastric artery and supraduodenal artery was performed using Gelfoam and coil embolization. One day later, she complained of left upper quadrant abdominal pain, nausea, and vomiting. Upper endoscopy revealed antral erosive gastritis. Gastric biopsies showed chronic gastritis, superficial mucosal hemorrhage, lamina propria fibrosis, and intravascular microspheres consistent with Y90 microspheres used for radioemoblization treatment. She was treated with proton pump inhibitors, sucralfate, and ondansetron. She slowly recovered after a few weeks. Gastrointestinal toxicity due to inadvertent radioembolization to the gut has been described after Y90 radioembolization with an incidence ranging from 0-14%. Manifestations include gastric edema, gastritis, duodenitis, gastric ulcer, gastrointestinal bleeding, gastric outlet obstruction due to pyloric stricture, gastroparesis, esophagitis, pancreatitis, and hepatitis. Symptoms may occur from one day to a few months after radioembolization. Characteristic purple microspheres are seen in the lamina propria, as demonstrated in our case, in association with mucosal ulceration and epithelial/capillary changes. Physicians should be aware of gastrointestinal toxicities following Y90 radioembolization.2647_A Figure 1. Endoscopic image of radiation erosive gastritis.2647_B Figure 2. 100x magnification of gastric mucosa showing chronic inflammatory infiltrate in the lamina propria, foreign spherical-shaped purple particles, glandular dilatation, epithelial flattening and superficial mucosal hemorrhage.2647_C Figure 3. 400x magnification of gastric antral mucosa contains the foreign spherical-shaped purple particles.

Conversion therapy and suitable timing for subsequent salvage surgery for initially unresectable hepatocellular carcinoma: What is new?

AIMTo review the conversion therapy for initially unresectable hepatocellular carcinoma (HCC) patients and the suitable timing for subsequent salvage surgery.METHODSA PubMed search was undertaken from 1987 to 2017 to identify articles using the keywords including “unresectable” “hepatocellular carcinoma”, ”hepatectomy”, ”conversion therapy”, “resection”, “salvage surgery” and “downstaging”. Additional studies were investigated through a manual search of the references from the articles. The exclusion criteria were duplicates, case reports, case series, videos, contents unrelated to the topic, comments, and editorial essays. The main and widely used conversion therapies and the suitable timing for subsequent salvage surgery were discussed in detail. Two members of our group independently performed the literature search and data extraction.RESULTSLiver volume measurements [future liver remnant (FLR)/total liver volume or residual liver volume/bodyweight ratio] and function tests (scoring systems and liver stiffness) were often performed in order to justify whether patients were suitable candidates for surgery. Successful conversion therapy was usually defined as downstaging the tumor, increasing FLR and providing subsequent salvage surgery, without increasing complications, morbidity or mortality. The requirements for performing salvage surgery after transcatheter arterial chemoembolization were the achievement of a partial remission in radiology, the disappearance of the portal vein thrombosis, and the lack of extrahepatic metastasis. Patients with a standardized FLR (sFLR) > 20% were good candidates for surgery after portal vein embolization, while other predictive parameters like growth rate, kinetic growth rate were treated as an effective supplementary. There was probably not enough evidence to provide a standard operation time after associating liver partition and portal vein ligation for staged hepatectomy or yttrium-90 microsphere radioembolization. The indications of any combinations of conversion therapies and the subsequent salvage surgery time still need to be carefully and comprehensively evaluated.CONCLUSIONConversion therapy is recommended for the treatment of initially unresectable HCC, and the suitable subsequent salvage surgery time should be reappraised and is closely related to its previous therapeutic effect.

Spectrum of findings in 99mTc-MAA SPECT/CT and their significance in treatment planning for Yttrium 90-microsphere radioembolization for hepatocellular carcinoma

Spectrum of findings in 99mTc-MAA SPECT/CT and their significance in treatment planning for Yttrium 90-microsphere radioembolization for hepatocellular carcinoma

37. 3D Personalized dosimetry for Yttrium-90 microsphere radioembolization of liver tumors: feedback and clinical cases

Introduction Today, dose computation for Selective internal radiation therapy (SIRT) is based on methods easy to apply clinically. Several studies highlight dose-effect relationship for SIRT. As a result, interest enhances for advanced calculations and dose analysis tools as the ones used in external beam radiation therapy (EBRT). The Nuclear Medicine department of Montpellier University Hospital (MUH) implemented a new system to meet this need. This study describes the methodology applied, its interest and the questions raised illustrated by some clinical cases. Methods For every patient treated by SIRT, the dosimetry referred as “standard” applied at MUH follows the method described by Garin et al. [1] . This is based on the partition model for which the volumes of interest are defined using Syngo® software (Siemens, Erlangen, Germany) on SPECT images acquired after the injection of macro-aggregates of albumin (MAA) labelled with 99Tcm. Recently, the implementation of a treatment planning system (TPS), PLANET® Dose (DOSIsoft, Cachan, France), allows to perform dosimetry at the voxel level. This is done through two major steps: predictive dosimetry based on MAA-SPECT images and in vivo control dosimetry using PET images acquired after the injection of yttrium-90 (90Y) microspheres ( Fig. 1 ). Dose distribution is especially evaluated for tumoral and non-tumoral liver delineated on the injected CT or MR images by the radiology team. Dose computation rests on a convolution method based on voxel S factors. Pre and post treatment dosimetries are analyzed by the mean dose to the volume, the dose-volume histograms (DVH) and the isodose curves. Results The comparison between both dosimetric approaches (standard and at the voxel level) pointed out some differences. This particularly allowed to highlight the TPS contribution according to various aspects that were observed through clinical cases. A first aspect is related to the volume definition (functional only vs. anatomical and/or functional) for which the TPS contribution is especially interesting for complex clinical cases (multiple tumor sites, heterogeneous or partially targeted lesions, liver failure). This kind of system then allows dose evaluation in any compartment (volume at risk, portal vein thrombosis, multiple lesions, viable tumor, etc.). Moreover, voxelized dosimetry allows to analyze dose distribution uniformity with advanced tools (isodoses, DVH, etc.) in order to better assess areas of over/under dosing. Finally, being able to perform post-treatment dosimetry in order to know the real delivered dose and to sum several treatment sessions can play an important role in the patient therapeutic care. Conclusion Integrating a TPS like the ones used in EBRT in the SIRT process allowed to increase the medical team confidence and accuracy in the prescription of the activity to administer and to better control the dose delivered during the treatment. Setting up these new tools open the way to a more advanced personalization of this therapy.

Trans-arterial radio-embolization: a new chance for patients with hepatocellular cancer to access liver transplantation, a world review.

Liver transplantation (LT) for hepatocellular carcinoma (HCC) within the Milan criteria (MC) is nowadays a curative procedure. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. The aim of this work is to offer a view on the publications which report on the use of Y90-RE as bridge or downstaging prior to LT. Twenty articles have been considered for this world review. About 178 LT in patients were treated with Y90-RE prior to LT. Most of patients had a downstaging strategy. In all series alpha-fetoproteins decreased between Y90-RE and LT. Therefore, Y90-RE may have an important role in the bridge and downstaging treatments.

Duodenal Ulceration as a Complication of Yttrium-90 Microsphere Radioembolization of Intrahepatic Cholangiocarcinoma

Yttrium-90 (Y-90) microsphere radioembolization (RE) can be an effective regional treatment for primary hepatobiliary malignancies. RE with Y-90 has been described as safe for patients with intrahepatic cholangiocarcinoma (ICC)1. However, gastrointestinal ulceration is a rarely reported complication of Y-90 microsphere RE2. Given the increasing incidence of primary hepatobiliary tumors and an expected rise in use of Y-90 RE, we present a case of Y-90 RE-associated duodenal ulceration. A 76-year-old woman presented to the hospital with lower abdominal pain and was evaluated with a CT scan which revealed an ill-defined liver mass adjacent to the gallbladder which was diagnosed as stage IV intrahepatic cholangiocarcinoma involving segment 4 of the liver. She was treated with Y-90 RE with the intent of tumor down-sizing prior to resection. As part of the treatment application, the gastroduodenal artery was densely packed with coils with complete stasis of flow achieved. Through the medial branch of the left hepatic artery, the Y-90 spheres were super-selectively deployed through a micro-catheter. Two months after the radioembolization, she experienced mid-epigastric abdominal pain, not responsive to proton pump inhibitor. Upper endoscopy revealed two non-bleeding superficial duodenal ulcers with no stigmata of bleeding in the duodenal bulb. Pathology from biopsies of the ulcer bed revealed the presence of Y-90 beads in the lamina propria, consistent with radiation-induced duodenitis. She is currently being treated with high dose proton pump inhibitor (PPI) therapy by mouth twice daily, with good response. This case highlights a potential complication associated with radioactive microsphere embolization. Given the increasing use of this treatment modality, gastroenterologists should recognize this entity, and its delayed occurrence in particular. New-onset, or change in abdominal discomfort or pain should prompt endoscopic evaluation in patients with prior Y-90 RE. We suggest high dose PPI therapy as initial management, but the optimal treatment strategy to treat gastrointestinal ulceration as a complication of RE should be further investigated.

Hepatocellular carcinoma with macrovascular invasion treated with yttrium-90 radioembolization prior to transplantation.

Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. According to the staging system of the Barcelona Clinic Liver Cancer (BCLC), patients with macrovascular invasion are staged as BCLC-C. This paper comprises a presentation of the results following application of the procedure. From January 2002 to December 2015, 367 patients were transplanted at the San Camillo Hospital Center. One hundred and forty-three patients were transplanted for hepatocellular carcinoma (HCC) and in 22 cases patients were treated with Y90-RE before liver transplantation (LT), of them 4 with macrovascular invasion were included in this study. The four patients had a complete response for the thrombosis, and were included in the waiting list within the Milan criteria. Means interval time between Y90-RE and LT was 15.86 months. No patient death was observed at Y90-RE procedure or at LT. We obtain a free-survival of 39.1 (range, 6-76) months. In all four cases the complete thrombosis regression was observed. We reported a short series of patients transplanted after Y90-RE in patients with BCLC stage C. In our experience we achieved acceptable overall and disease-free survival. Eventually, Y90-RE seems to have a place in the downstaging strategy for LT candidates.

Yttrium-90 Radioembolization for Hepatocellular Carcinoma Prior to Liver Transplantation.

Liver transplantation (LT) is a well-established procedure for hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres radioembolization (Y90-RE) has shown to be an effective and safe treatment of primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in patients with HCC prior to LT. From January 2002 to December 2015, 365 patients were transplanted at the San Camillo Hospital Center. One hundred forty-three patients were transplanted for HCC, and in 22 cases the patients were treated with Y90-RE before LT. Three patients were treated with Y90-RE within the Milan criteria, and 19 patients were out of criteria before Y90-RE. Four patients had an increasing MELD score between Y90-RE and LT. On the other hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient death was observed in Y90-RE procedure or at LT. In 78.9% of cases, a successful downstaging was observed, and in 100% of cases bridging was achieved. From Y90-RE treatment overall survival was 43.9months. From LT, overall mean survival was 30.2months with a free survival of 29.6months. The overall survival after LT analysis between the patients treated with Y90-RE and patients without was not significant (p=0.113). Free survival analysis was not significant (p=0.897) between the two populations. We successfully performed LT in patients after Y90-RE treatment both as bridging and downstaging for HCC and obtained a similar overall and free survival of LT for HCC within Milan criteria. Y90-RE becomes a real option to provide curative therapy for patients who traditionally are not considered eligible for surgery.

Planning Arteriography for Yttrium-90 Microsphere Radioembolization.

Yttrium-90 radioembolization (Y RE) is a contemporary transcatheter locoregional therapy for primary and secondary hepatic malignancies that is commonly utilized in modern Interventional Radiology (IR) practice.1 Unlike other targeted endovascular therapies, such as transarterial chemoembolization (TACE) and transarterial embolization (TAE), the current standard of care protocol for Y RE treatment of liver tumors involves a two-stage treatment process consisting of a planning arteriography procedure followed by the therapeutic Y RE, typically performed 1 to 2weeks later. The diagnostic planning procedure has threefold intent: (1) to delineate hepatic and tumor vascular anatomy relevant to Y microsphere dosimetry and administration; (2) to identify and possibly embolize extrahepatic vessels at risk for nontarget microsphere deposition; and (3) to quantify the degree of hepatopulmonary shunting using technetium-99mmacroaggregated albumin (Tc-MAA) scanning.2 Given the multifactorial basis for performance of mapping arteriography, and despite some literature guidelines outlining procedure methodology,3,4 this procedure is often technically challenging, labor intensive, and time consuming. This article aims to present a simple overview of a single operator’s technical approach to planning arteriography performed prior to Y RE—including tips, tricks, and pitfalls—based on experience gained in having performed hundreds of hepatic arteriography procedures. Technical details of Y RE dosimetry and microsphere administration are beyond the scope of the current topic, and will not be discussed.

Yttrium-90 Glass-Based Microsphere Radioembolization in the Treatment of Hepatocellular Carcinoma Secondary to the Hepatitis B Virus: Safety, Efficacy, and Survival

PurposeTo evaluate outcomes of yttrium-90 radioembolization performed with glass-based microspheres in the treatment of hepatocellular carcinoma (HCC) secondary to the hepatitis B virus (HBV). Materials and MethodsA total of 675 patients treated between January 2006 and July 2014 were reviewed, of which 45 (age 62 y ± 10; 91% male) received glass-based radioembolization for HCC secondary to HBV. All patients were stratified according to previous therapy (naive, n = 14; 31.1%), Child–Pugh class (class A, n = 41; 91%), Eastern Cooperative Oncology Group (ECOG) performance status (PS; < 1, n = 21; 47%), solitary (n = 26; 58%) and unilobar (n = 37; 82%) tumor distribution, tumor size < 5 cm (n = 29; 64%), portal vein thrombosis (n = 14; 31%), α-fetoprotein level > 400 ng/mL (n = 17; 38%), and Barcelona Clinic Liver Cancer stage (A, n = 8; B, n = 9; C, n = 28). ResultsA total of 50 radioembolization treatments were performed, with a 100% technical success rate (median target dose, 120 Gy). Clinical toxicities included pain (16%), fatigue (12%), and nausea (4%). Grade 3/4 laboratory toxicities included bilirubin (8%) and aspartate aminotransferase (4%) toxicities. Observed toxicities were independent of treatment dose. The objective response rates were 55% per modified Response Evaluation Criteria In Solid Tumors and 21% per World Health Organization criteria, and the disease control rate was 63%. Disease progression was secondary to new, nontarget HCC in 45% of cases. Median time to progression and overall survival were 6.0 mo (95% confidence interval [CI], 4.4–8.0 mo) and 19.3 mo (95% CI, 11.2–22.7 mo), respectively. Multivariate analysis demonstrated ECOG PS ≥ 1 and AFP level > 400 ng/mL to be independent predictors of inferior overall survival. ConclusionsGlass-based radioembolization for HCC secondary to HBV can be safely performed, with favorable target lesion response and overall survival.

Serious hepatic complications of selective internal radiation therapy with yttrium-90 microsphere radioembolization for unresectable liver tumors.

Selective internal radiation therapy with yttrium-90 microsphere radioembolization has been used to treat unresectable liver tumors and its acute toxicity has been well described. Subacute and long-term hepatic complications related to radioembolization however may be underreported in the literature. This retrospective study describes the incidence and sequelae of serious hepatic complications in patients who underwent radioembolization for unresectable liver tumors. A retrospective review of clinical notes of patients who received radioembolization for unresectable liver tumors from 2001 to 2011 at two Australian institutions was performed to identify those who developed clinically significant hepatic complications. Relevant clinical data were obtained and analyzed to determine their incidence and sequelae. A total of 205 patients were identified, of whom 10 (4.9%) developed serious hepatic complications with 7 (3.4%) attributable to radioembolization-induced liver disease. None had preexisting underlying liver disease or progressive hepatic metastases at the time of developing hepatic complication. The median time to the onset of hepatic complications was 3.5 months (range 1-67 months); six patients had a complete resolution eventually, including one patient who subsequently underwent hepatic metastasectomy safely. Three patients died as a result of fulminant hepatic failure. Selective internal radiation therapy with radioembolization was associated with serious hepatic complications with an incidence of 4.9% and a mortality rate of 1.5% in 205 patients from two Australian institutions. The risk of serious hepatic toxicity therefore needs to be discussed when counseling patients regarding this potential treatment option.

Multimodality therapy and liver transplantation for hepatocellular carcinoma: a 14-year prospective analysis of outcomes.

Hepatocellular carcinoma is a major cause of death among patients with cirrhosis. A standardized approach of multimodality therapy with intent-to-treat by transplantation for all patients with hepatocellular carcinoma was instituted at our transplant center in 1997. Data were prospectively collected to evaluate the impact of multimodality therapy on posttransplant patient survival, tumor recurrence, and patient survival without transplantation. All patients with hepatocellular carcinoma were eligible for multimodality therapy. Multimodality therapy consisted of hepatic resection, radiofrequency ablation, transarterial chemoembolization, transarterial chemoinfusion, yttrium-90 microsphere radioembolization, and sorafenib. Approximately 715 patients underwent multimodality therapy; 231 patients were included in the intent-to-treat with transplantation arm, and 484 patients were treated with multimodality therapy or palliative therapy because of contraindications for transplantation. A 60.2% transplantation rate was achieved in the intent-to-treat with transplantation arm. Posttransplant survivals at 1 and 5 years were 97.1% and 72.5%, respectively. Tumor recurrence rates at 1, 3, and 5 years were 2.4%, 6.2%, and 11.6%, respectively. Patients with contraindications to transplant had increased 1- and 5-year survival from diagnosis with multimodality therapy compared with those not treated (73.1% and 46.5% versus 15.5% and 4.4%, P<0.0001). Using multimodality therapy before liver transplantation for hepatocellular carcinoma achieved low recurrence rates and posttransplant survival equivalent to patients with primary liver disease without hepatocellular carcinoma. Multimodality therapy may help identify patients with less active tumor biology and result in improved disease-free survival and organ utilization.