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

Background: Yttrium-90 (Y90) radioembolization is a catheter-based therapy for hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; however, few have assessed long-term hepatic function. This study aimed to evaluate a clinical real-world experience of Y90 effectiveness and long-term impact on hepatic function. Methods: A single-center retrospective chart review was performed for patients with Child-Pugh (CP) class 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 on the day of treatment and 1, 3, 6, 12, and 24 months post-procedure. Results: Of the 134 patients included, the mean age was 60 years old and median overall survival (OS) from date of diagnosis was 28 months [95% confidence interval (CI): 22.21-38.05]. Patients with CP class A (85%) had a median progression-free survival (PFS) of 3 months (95% CI: 2.99-5.55) and median OS of 17 months (95% CI: 9.59-23.10) from date of Y90 treatment compared to a median PFS of 4 months (95% CI: 2.07-8.28) and OS of 8 months (95% CI: 4.60-15.64) for patients with CP class B. MELD scores were significantly higher post-treatment than pre-treatment, with significant recovery at 24 months. No significant differences were seen between cancer stage and OS, while PFS and cancer stage did show difference between cancer stage 1 and 3 with longer median PFS seen in stage 1. Conclusions: While our study supports the literature for OS in Y90-treated patients, we found a shorter PFS in this population. This may reflect the differences between the utilization of RECIST in clinical trials and clinical radiology practice in determining progression. Significant factors associated with OS were age, MELD, CP scores and portal vein thrombosis (PVT). For PFS, CP score and stage at diagnosis were significant. Increasing MELD scores over time likely reflected a combination of radioembolization-induced liver disease, liver decompensation or progression of HCC. The downtrend at 24 months is likely due to long term survivors with significant benefit from therapy with no long-term complications from Y90.

Role of Interventional Radiology in Pediatric Cancer Patients.

PURPOSE OF REVIEW: Pediatric interventional radiology (IR) is a growing subspecialty. Here, we review the current role of IR in children with cancer, which uses imaging such as ultrasound, fluoroscopy, and computed tomography to perform minimally invasive procedures. These include biopsy, needle localization, central venous access, thermal ablation, transarterial chemoembolization, transarterial radioembolization with yttrium-90, non-tunneled/tunneled drainage catheter placement, and lymphatic interventions. RECENT FINDINGS: Although locoregional therapies for the treatment of cancer in adults are common, they are less common in children, perhaps due to the relative rarity of cancer in children, their typically better performance status, and paucity of comorbidities. Preliminary results from small-scale studies for ablation, transarterial chemoembolization, and transarterial radioembolization with yttrium-90 used in the front-line armamentarium of curative therapy are encouraging. Pediatric IR offers an array of minimally invasive procedures intended to diagnose and treat pediatric cancer patients. However, more research is required to determine the efficacy of locoregional therapy in children and to define the clinical scenarios where benefit is likely to be optimized.

Radiation Segmentectomy for the Treatment of Primary Hepatic Malignancies of the Caudate Lobe: A Case Series.

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

Role of Radioembolization in Metastatic Neuroendocrine Tumors.

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

Clinical consensus statement: Selective internal radiation therapy with yttrium 90 resin microspheres for hepatocellular carcinoma in Asia.

BACKGROUND: Hepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia. MATERIALS AND METHODS: A systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine. RESULTS: The experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus. CONCLUSION: These recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations.

Narrative review of the role of yttrium-90 selective internal radiation therapy in the surgical management of colorectal liver metastases.

The management of colorectal liver metastasis (CRLM) is complicated and benefits from a multidisciplinary team approach. Liver-directed therapy has been emerging as a modality for better progression-free control. In its early years, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) was confined as an end-of-line therapy. However, literature has supported other roles including: a first-line treatment for CRLM alone or in combination with systemic chemotherapy; an adjunct to second or third-line chemotherapy; and a salvage treatment for chemo-refractory disease. Although future liver remnant (FLR) hypertrophy may take 3-12 months, the SIRT effect on loco-regional disease control has rendered it to be a useful tool in some pathologies with certain strategic goals. This paper reviews the use of SIRT with Y-90 in a surgical treatment pathway. This includes: (I) an element of multidisciplinary treatment of low-volume CRLMs, (II) convert an R1 to R0 resection by sterilizing the margins of tumor near critical structures, and (III) radiation lobectomy to induce contralateral hypertrophy in order to aid in a safer resection. There are many opportunities to validate the role of SIRT as a first-line therapy along with surgical resection including an umbrella clinical trial design.

Comparison of the Uptake of Hepatocellular Carcinoma on Pre-Therapeutic MDCT, CACT, and SPECT/CT, and the Correlation with Post-Therapeutic PET/CT in Patients Undergoing Selective Internal Radiation Therapy.

(1) Background: To comparatively analyze the uptake of hepatocellular carcinoma (HCC) on pre-therapeutic imaging modalities, the arterial phase multi-detector computed tomography (MDCT), the parenchymal phase C-arm computed tomography (CACT), the Technetium99m-macroaggregates of human serum albumin single-photon emission computed tomography/computed tomography (SPECT/CT), and the correlation to the post-therapeutic Yttrium90 positron emission tomography/computed tomography (PET/CT) in patients with selective internal radiation therapy (SIRT). (2) Methods: Between September 2013 and December 2016, 104 SIRT procedures were performed at our institution in 74 patients with HCC not suitable for curative surgery or ablation. Twenty-two patients underwent an identical sequence of pre-therapeutic MDCT, CACT, SPECT/CT, and post-therapeutic PET/CT with a standardized diagnostic and therapeutic protocol. In these 22 patients, 25 SIRT procedures were evaluated. The uptake of the HCC was assessed using tumor-background ratio (TBR). Therefore, regions of interest were placed on the tumor and the adjacent liver tissue on MDCT (TBRMDCT), CACT (TBRCACT), SPECT/CT (TBRSPECT/CT), and PET/CT (TBRPET/CT). Comparisons were made with the Friedman test and the Nemenyi post-hoc test. Correlations were analyzed using Spearman's Rho and the Benjamini-Hochberg method. The level of significance was p < 0.05. (3) Results: TBR on MDCT (1.4 ± 0.3) was significantly smaller than on CACT (1.9 ± 0.6) and both were significantly smaller compared to SPECT/CT (4.6 ± 2.0) (pFriedman-Test < 0.001; pTBRMDCT/TBRCACT = 0.012, pTBRMDCT/TBRSPECT/CT < 0.001, pTBRCACT/TBRSPECT/CT < 0.001). There was no significant correlation of TBR on MDCT with PET/CT (rTBRMDCT/TBRPET/CT = 0.116; p = 0.534). In contrast, TBR on CACT correlated to TBR on SPECT/CT (rTBRCACT/TBRSPECT/CT = 0.489; p = 0.004) and tended to correlate to TBR on PET/CT (rTBRCACT/TBRPET/CT =0.365; p = 0.043). TBR on SPECT/CT correlated to TBR on PET/CT (rTBRSPECT/CT/TBRPET/CT = 0.706; p < 0.001) (4) Conclusion: The uptake assessment on CACT was in agreement with SPECT/CT and might be consistent with PET/CT. In contrast, MDCT was not comparable to CACT and SPECT/CT, and had no correlation with PET/CT due to the different application techniques. This emphasizes the value of the CACT, which has the potential to improve the dosimetric assessment of the tumor and liver uptake for SIRT.

Management of Intrahepatic Cholangiocarcinoma.

Cholangiocarcinoma is a tumor that arises as a result of differentiation of the cholangiocytes and can develop from anywhere in the biliary tree. Subtypes of cholangiocarcinoma are differentiated based on their location in the biliary tree. If diagnosed early these can be resected, but most cases of intrahepatic cholangiocarcinoma present late in the disease course where surgical resection is not an option. In these patients who are poor candidates for resection, a combination of chemotherapy, locoregional therapies like ablation, transarterial chemo and radioembolization, and in very advanced and metastatic disease, external radiation are the available options. These modalities can improve overall disease-free and progression-free survival chances. In this review, we will discuss the risk factors and clinical presentation of intrahepatic cholangiocarcinoma, diagnosis, available therapeutic options, and future directions for management options.

Mapping angiography and transarterial technetium macroaggregated albumin particle simulation of recurrent atypical intracranial meningioma: feasibility for potential vascular brachytherapy.

Atypical meningioma (AM) (WHO-II) has a recurrence rate of 28% after gross total resection (GTR) with limited salvage options. Transarterial therapies may provide treatment opportunities in AM patients who exhausted standard-of-care therapy. In cases where favorable tumor vasculature and particle simulation demonstrate acceptable target dose, Yttrium-90 trans-arterial radioemobilization (TARE) could theoretically provide salvage therapy. A 67-year-old man presented with recurrent AM post gross total resection with adjuvant radiotherapy in 2012, 2014, and 2016. The patient was deemed a poor candidate for additional therapies. Tumor vasculature mapping was performed to determine TARE candidacy. Super-selective angiography and contrast-enhanced cone-beam computed tomography angiosomes demonstrated predominant pial collaterals and minor supply from a middle meningeal artery branch. Particle simulation was performed by infusing 0.3 mCi of 99mTc-macroaggregated albumin (99mTc-MAA). SPECT/CT-MRI fusion demonstrated conformal activity solely within the tumor volume perfused by the middle meningeal artery branch with a lung shunt fraction of 54.7%. The patient subsequently received off-label Nivolumab (PD-1 inhibitor). Mapping angiography for AM using 99mTc-MAA is feasible. It may identify candidates for TARE and potential AM patients with favorable blood supply. The potential for conformal intracranial vascular brachytherapy is intriguing, however, altered arterial supply in recurrent tumors is challenging.

Neoadjuvant transarterial radiation lobectomy for colorectal hepatic metastases: a small cohort analysis on safety, efficacy, and radiopathologic correlation.

Colorectal cancer patients have a high incidence of liver metastasis (ml-CRC). Surgical resection is the gold standard for treatment of hepatic metastasis but only a small percent of patients are traditional candidates based on disease extent and adequate size of the future liver remnant (FLR). Interventions such as portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) are performed to increase FLR for operative conversion. Limitations to PVE include intrahepatic disease progression, portal vascular invasion, and utilization with concurrent chemotherapy. ALPPS is associated with a high morbidly and mortality. Radiation lobectomy (RL) with yttrium-90 (Y-90) delivers transarterial ablative brachytherapy to the future hepatectomy site which generates FLR hypertrophy similar or greater than PVE. Early results indicate that RL is safe, effective, and may offer unique benefits by providing cytoreduction of hepatic metastases which extends FLR hypertrophy time and allows FLR surveillance to gauge disease biology. A retrospective analysis of four patients with ml-CRC treated with RL prior to hepatectomy was performed to evaluate initial safety, efficacy, FLR hypertrophy, and radiopathologic correlation. Adverse events after RL and hepatectomy were evaluated. Imaging findings were analyzed for efficacy defined as FLR hypertrophy and disease control. Radiopathologic correlation was performed after histologic analysis. RL was well tolerated without major adverse events or hepatic decompensation. FLR hypertrophy ranged from 24.9% to 119% at mean follow-up of three months. The majority of complications were related to surgical instrumentation of the FLR due to upstaging at time of surgery. Hepatectomy specimen histology demonstrated complete pathologic response in 50% of patients, 50% radiopathologic concordance rate, and no significant hepatic fibrosis. Initial experience with neoadjuvant RL for ml-CRC is safe and provides both durable disease control and FLR hypertrophy with concurrent chemotherapy. A 50% complete pathologic response rate raises the possibility of definitive chemoradiation in poor surgical candidates. Prospective investigation is required.

Pretreatment albumin may aid in patient selection for intrahepatic Y-90 microsphere transarterial radioembolization (TARE) for malignancies of the liver.

BACKGROUND: Hepatic malignancies are common including primary malignancies and metastases. Transarterial radioembolization (TARE) is an important treatment option. We reviewed safety and efficacy of (TARE) in our patients to identify factors that may impact treatment outcomes in a heterogeneous population. METHODS: All patients that received TARE at the Medical University of South Carolina from March 2006 through May of 2014 were included. Kaplan-Meier estimates on overall survival (OS) from date of first procedure are reported. Potential prognostic factors for OS were evaluated using log rank tests and Cox proportional hazards models. RESULTS: In the 114 patients that received TARE at our institution, median follow-up was 6.4 months (range, 0-86 months) with the following histologies: colorectal (CR) n=55, hepatocellular (HC) n=20, cholangiocarcinoma (CC) n=16, neuroendocrine (NE) n=12, breast (BR) n=6, other n=5. At least 1 line of prior systemic therapy was noted in 79% of patients. Median OS was significantly better with NE and BR histology, and in those with normal albumin levels. With an albumin >3.4 median OS was 10.3 months, but was only 3.1 months with an albumin <3 g/dL. Grade ≥2 toxicity was observed in 22 patients (19.3%) including 9 (7.9%) with Grade 3 and 1 (0.9%) with Grade 4 toxicity. CONCLUSIONS: TARE is a relatively safe and effective treatment for intrahepatic malignancies. Patients with NE and BR histology as well as those with better hepatic synthetic function were associated with significantly better survival. Our data suggest that patients with albumin below 3 g/dL may not derive significant benefit from TARE.

Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience.

BACKGROUND: Neuroendocrine tumors (NETs) metastatic to the liver are treated with transarterial radioembolization (TARE) using yttrium-90 (Y-90) microspheres or transarterial chemoembolization (TACE). However the criteria for patient selection are not well defined. We sought to determine if Ki67 score could help select patients for one therapy over the other in the management of hepatic neuroendocrine metastases. METHODS: Single institution analysis of patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 staining. Data were analyzed using multivariate association for survival outcomes. RESULTS: Amongst 72 patients (male: 39, female: 33, median age: 57 years) with metastatic NET, the most common site of origin was small bowel (n=35, 49%), while pancreas constituted 32% (n=23). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) with TACE. Within Y-90 group, there was greater use of Sandostatin (95% vs. 75%, P=0.02) and less number of total treatments completed (89% vs. 46%, P<0.001). There was no significant difference in overall survival (OS) between Y-90 and TACE when used without selection (median, 69 vs. 82 months, P=0.47). When adjusted for Ki67, patients with Ki67 score ≥3% had better OS with Y-90 compared to TACE (HR, 0.1; CI, 0.01-0.9), however for Ki67 <3%, OS was better when treated with TACE compared to Y-90 (HR, 13.5; CI, 1.22-148.87). CONCLUSIONS: There is significant interaction between Ki-67 score and liver-directed treatment benefit in patients with hepatic neuroendocrine metastases. Ki-67 score ≥3% predicts greater benefit with Y-90 and a Ki-67 score <3% predicts greater benefit with TACE.

Transarterial Radioembolization with Yttrium-90 for the Treatment of Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cause of worldwide mortality. Transarterial radioembolization (TARE) with yttrium-90 (Y90), a transcatheter intra-arterial procedure performed by interventional radiology, has become widely utilized in managing HCC. METHODS: The following is a focused review of TARE covering its commercially available products, clinical considerations of treatment, salient clinical trial data establishing its utility, and the current and future roles of TARE in the management of HCC. RESULTS: TARE is indicated for patients with unresectable, intermediate stage HCC. The two available products are glass and resin microspheres. All patients undergoing TARE must be assessed with a history, physical examination, clinical laboratory tests, imaging, and arteriography with macroaggregated albumin. TARE is safe and effective in the treatment of unresectable HCC, as it has a safer toxicity profile than chemoembolization, longer time-to-progression, greater ability to downsize and/or bridge patients to liver transplant, and utility in tumor complicated by portal vein thrombosis. TARE can also serve as an alternative to ablation and chemotherapy. CONCLUSION: TARE assumes an integral role in the management of unresectable HCC and has been validated by numerous studies.

Radioembolization with Yttrium-90 microspheres for patients with unresectable hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is aggressive primary malignancy of the liver that most commonly presents late in the disease course. As a result, the majority of patients are not candidates for curative therapies. Locoregional therapies including Yttrium-90 (Y-90) radioembolization play an important role in management of the vast majority of patients with HCC. METHODS: Patients with unnresectable HCC (n=17) treated with Y-90 radioembolization from 2005 to 2014 were evaluated retrospectively. Data was abstracted from medical records including patient charts, laboratory data, and imaging. Toxicities were recorded using Common Terminology Criteria 3.0. Response was recorded according to modified RECIST (mRECIST) criteria. RESULTS: Seventeen patients received 33 treatments with Y-90 radioembolization. A majority (65%) received TheraSphere with a minority (35%) receiving SIR-Spheres. The median treatment activity delivered was 1.725 gBq (range, 1.4-2.5 gBq). The median treatment dose delivered was 100 Gy (range, 90-120 Gy). The median lung shunt fraction was 2.02% (range, 1.5-4.1%). The most common clinical toxicity among all patients was nausea and vomiting (59%), primarily grade 1 and 2. Other post-treatment findings included abdominal pain (29%), fatigue (53%), and weight loss (18%). One patient developed a grade 5 gastric ulcer after the treatment. A clinical benefit, defined as patients achieving complete response (CR), partial response (PR) or stable disease (SD), was seen in 48% of patients. PR was seen in 24% of cases; progressive disease (PD) was noted in 35%. Patients survived for a median of 8.4 months (range, 1.3 to 21.1 months) after the first radioembolization treatment. Median survival after Y-90 treatment was 8.4 months among patients treated TheraSphere as compared with 7.8 months in patients treated with SIR-Spheres. The mean overall survival from the time of diagnosis was 11.7 months (range, 3.4 to 43.2 months). CONCLUSIONS: For patients with unresectable HCC, Y-90 radioembolization is a safe and well-tolerated procedure. Our experience suggests that a significant percentage of patients achieve clinical benefit including many with PR. Survival after treatment from this single-center, transplant center is in line with prior reports. Prospective, randomized data is required to compare radioembolization with other therapies including chemoembolization and systemic therapy with sorafenib.

Emerging trends in hepatocellular carcinoma: focus on diagnosis and therapeutics.

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide and one of the deadliest. Patients with chronic liver disease are at the highest risk for developing this tumor. This link provides an opportunity for developing preventive strategies and surveillance that aims at early detection of this tumor and possibly improving outcomes. In this review, we will discuss the latest developments in surveillance strategies, diagnosis, and treatment of this tumor. HCC is the sixth most common cancer in the world, with 782,000 new cases occurring in 2012 worldwide. In 2012, there were 746,000 deaths from liver cancer.1 HCC is the third most fatal cancer in the world.2 The distribution of HCC, which varies geographically, is related to the prevalence of hepatotropic virus. The burden of the disease is the highest in Eastern Asia, sub-Saharan Africa, and Melanesia where hepatitis B (HBV) infection is endemic. Meanwhile, in Japan, United States, and Europe, hepatitis C (HCV) infection is prevalent, and subsequently, is the major risk factor for acquiring HCC in these regions.1,3 It is estimated that the incidence of HCC in Europe and United States will peak at 2020-there will be 78,000 new HCC cases in Europe and 27,000 in the United States-and decline thereafter.1 Indeed, in Japan, the incidence of HCC had already plateaued and started to slowly fall.4 Cirrhosis is the most important risk factor for HCC regardless of etiology and may be caused by chronic viral hepatitis (mainly HBV and HCV), alcoholic liver disease, autoimmune disease, Stage 4 primary biliary cirrhosis, and metabolic diseases such as hereditary hemochromatosis, alpha-1 antitrypsin deficiency, and non-alcoholic fatty liver disease. In the Western hemisphere, HCC occurs in a background of cirrhosis in 90% of the cases.5 Before concentrating on diagnosis and therapeutics, it is important to discuss surveillance for this tumor.