90Y SIR-Spheres Activity Measurement with New SIROS D-Vial Delivery Kit.

A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate-to-activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit. Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified. Results: SIROS D-vial 90Y activity can be accurately and reliably estimated directly using setting 51 × 10 on both the CRC-15R and the CRC-55tR dose calibrators (errors within ±0.5%) and indirectly with an exposure-rate reading at 30 cm using conversion factor 0.664 ± 0.003 GBq/(mR/h) (R 2 = 0.985). Conclusion: Dose calibrator settings and exposure-rate-to-activity conversion factor for 90Y activity assays with new SIROS kit should be updated from legacy V-Vial parameters to avoid an approximately 10% underestimation.

Factors impacting survival after transarterial radioembolization in patients with hepatocellular carcinoma: Results from the prospective CIRT study.

Background & Aims: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is an established treatment option for patients with hepatocellular carcinoma (HCC). However, optimising treatment application and patient selection remains challenging. We report here on the effectiveness, safety and prognostic factors, including dosing methods, associated with TARE for HCC in the prospective observational CIRT study. Methods: We analysed 422 patients with HCC enrolled between Jan 2015 and Dec 2017, with follow-up visits every 3 months for up to 24 months after first TARE. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every 3-month follow-up visit. We used the multivariable Cox proportional hazard model and propensity score matching to identify independent prognostic factors for effectiveness outcomes. Results: The median OS was 16.5 months, the median PFS was 6.1 months, and the median hepatic PFS was 6.7 months. Partition model dosimetry resulted in improved OS compared to body surface area calculations on multivariable analysis (hazard ratio 0.65; 95% CI 0.46-0.92; p = 0.0144), which was confirmed in the exact matching propensity score analysis (hazard ratio 0.56; 95% CI 0.35-0.89; p = 0.0136). Other independent prognostic factors for OS were ECOG-performance status >0 (p = 0.0018), presence of ascites (p = 0.0152), right-sided tumours (p = 0.0002), the presence of portal vein thrombosis (p = 0.0378) and main portal vein thrombosis (p = 0.0028), ALBI grade 2 (p = 0.0043) and 3 (p = 0.0014). Adverse events were recorded in 36.7% of patients, with 9.7% of patients experiencing grade 3 or higher adverse events. Conclusions: This large prospective observational dataset shows that TARE is an effective and safe treatment in patients with HCC. Using partition model dosimetry was associated with a significant improvement in survival outcomes. Impact and implications: Transarterial radioembolization (TARE) is a form of localised radiation therapy and is a potential treatment option for primary liver cancer. We observed how TARE was used in real-life clinical practice in various European countries and if any factors predict how well the treatment performs. We found that when a more complex but personalised method to calculate the applied radiation activity was used, the patient responded better than when a more generic method was used. Furthermore, we identified that general patient health, ascites and liver function can predict outcomes after TARE. Clinical trial number: NCT02305459.

Posttreatment Exposure Rates for 90Y-Microsphere Patients: A Comparison of Products.

There has been a significant increase in the use of 90Y-microspheres in treating liver malignancies. This increase could be seen over the last 30 y, and Food and Drug Administration approval of 2 products-Sirtex SIR-Spheres and Boston Scientific TheraSphere-has helped in the proliferation of these treatments. As the increase in use of both products rose at our institution, there was a need to determine whether there should be special considerations for patients who receive one product compared with patients who receive the other product. This determination was made by measuring exposure rates for several regions of the patient before and after implantation. An independent-samples t test analysis (ɑ = 0.05) was performed for 50 patients (25 TheraSphere and 25 SIR-Spheres) to determine whether the products behaved similarly to the extent that exposure to others was minimized and that as-low-as-reasonably-achievable principles were kept. The results showed that the products exhibited no significant differences in exposure rates, suggesting that no special considerations are needed for the procedure for one product compared with the other.

Calibración de PET/TC para adquisición de estudio de cuerpo estándar postratamiento con esferas de resina de ytrio-90 / PET/CT calibration for post-treatment standard body scan acquisition with yttrium-90 Resin Micro-SPHERES

Introducción Entre los objetivos en los tratamientos con esferas marcadas con ytrio-90 figura demostrar que se consigue la dosis tumoricida y que se evitan dosis hepatotóxicas, así como que no existe deposición extrahepática. Material y métodos Utilizamos diferentes cantidades de ytrio y un maniquí NEMA NU2-2007 para comprobar si el tomógrafo mantiene una respuesta que permita hacer cálculos dosimétricos reales. Resultados El tomógrafo Gemini responde de manera lineal en un rango amplio de actividades con una R2=0,9983. Conclusión La capacidad de detección del equipo PET nos permite realizar estudios de cuerpo estándar con finalidad dosimétrica con tiempos de 5min por BED, que además hacen posible verificar la ausencia de deposición extrahepática de cantidades significativas de esferas de ytrio-90 (AU)

Introduction Among the objectives in treatments with yttrium-90 spheres is to demonstrate that the tumoricidal dose is achieved and that hepatotoxic doses are avoided, as well as that there is no extrahepatic deposition. Material and methods We use different amounts of yttrium-90 resin micro-spheres and a NEMA NU2-2007 phantom to check if the scanner maintains a response that allows real dosimetric calculations. Results The Gemini tomograph responds linearly in a wide range of activities with R2=0.9983. Conclusion The detection capacity of the PET equipment allows us to carry out standard body studies with dosimetric purposes with times of five minutes per BED. It also make possible to verify the absence of extrahepatic deposition of significant amounts of yttrium 90 spheres (AU)

PET/CT calibration for post-treatment standard body scan acquisition with yttrium-90 resin micro-SPHERES.

INTRODUCTION: Among the objectives in treatments with yttrium-90 spheres, is to demonstrate that the tumoricidal dose is achieved and that hepatotoxic doses are avoided, as well as that there is no extrahepatic deposition. MATERIAL AND METHODS: We use different amounts of yttrium-90 resin micro-spheres and a NEMA NU2-2007 phantom to check if the scanner maintains a response that allows real dosimetric calculations. RESULTS: The Gemini tomograph responds linearly in a wide range of activities with R2 = 0.9983. CONCLUSION: The detection capacity of the PET equipment allows us to carry out standard body studies with dosimetric purposes with times of five minutes per bed. It also make possible to verify the absence of extrahepatic deposition of significant amounts of yttrium 90 spheres.

Transarterial Radioembolization Versus Atezolizumab-Bevacizumab in Unresectable Hepatocellular Carcinoma: A Matching-Adjusted Indirect Comparison of Time to Deterioration in Quality of Life.

INTRODUCTION: Given the relatively short life expectancy of patients with hepatocellular carcinoma (HCC), quality of life (QOL) plays a significant role in treatment selection. This analysis aimed to compare time to deterioration (TTD) in QOL with transarterial radioembolization (TARE) and atezolizumab-bevacizumab, as well as sorafenib, in advanced and unresectable HCC. METHODS: Patient-level data from SARAH (TARE using SIR-Spheres® Y-90 resin microspheres [SIR-Spheres] versus sorafenib) and aggregate data from IMbrave150 (atezolizumab-bevacizumab versus sorafenib) randomized controlled trials were used to conduct an anchored matching-adjusted indirect comparison (MAIC). Patients with a Child-Pugh score B in SARAH were excluded to align with exclusion criteria in IMbrave150. To identify potential effect modifiers for adjustment, the literature was searched and multivariate Cox proportional hazards models were implemented using SARAH data. Patients from SARAH were then weighted to balance with baseline characteristics from IMbrave150. Median TTD in QOL and hazard ratios (HRs) were calculated. RESULTS: Four potential effect modifiers were identified and used for adjustment: cause of disease (viral/non-viral), macrovascular invasion, Eastern Cooperative Oncology Group performance score, and alpha-fetoprotein level. The MAIC included 217 patients from SARAH (TARE = 94; sorafenib = 123). Median TTD in QOL was 11.23 and 8.64 months for atezolizumab-bevacizumab and TARE, respectively (HR = 1.06; 95% confidence interval [CI] 0.75-1.50; p = 0.725). A sensitivity analysis was conducted adjusting for cause of disease defined as hepatitis B/hepatitis C/non-viral: median TTD in QOL was higher for TARE compared with atezolizumab-bevacizumab (19.88 vs 11.23 months; HR = 0.66; 95% CI 0.36-1.19; p = 0.163). Sorafenib resulted in the shortest TTD in QOL, with statistically significant differences in both base case and sensitivity analyses. CONCLUSION: TARE using SIR-Spheres may achieve similar TTD in QOL compared with atezolizumab-bevacizumab, as the analyses found no statistically significant differences between these two interventions. Both TARE using SIR-Spheres and atezolizumab-bevacizumab seem to be more efficacious than sorafenib in maintaining QOL.

For patients with hepatocellular carcinoma, as well as physicians treating hepatocellular carcinoma, the quality of life that different treatments can offer represents an increasingly important aspect to consider when choosing treatments. Transarterial radioembolization and atezolizumab­bevacizumab are two potential treatments for advanced and unresectable hepatocellular carcinoma, but no clinical trials have directly compared the outcomes of these two therapeutic options. With the data available (patient-level data from a clinical trial of transarterial radioembolization using SIR-Spheres^® Y-90 resin microspheres [SIR-Spheres] versus sorafenib and data from a trial of atezolizumab­bevacizumab versus sorafenib from the literature), this study indirectly compared the time to deterioration of quality of life (i.e., how long quality of life is maintained) after treatment with transarterial radioembolization and atezolizumab­bevacizumab. The study showed that quality of life may be preserved over a similar time period with transarterial radioembolization using SIR-Spheres and atezolizumab­bevacizumab; also, both transarterial radioembolization using SIR-Spheres and atezolizumab­bevacizumab seem to maintain patients' quality of life over a longer period of time compared with sorafenib. These results are expected to enrich the existing evidence on which patients and physicians can base their decisions, allowing them to choose the most appropriate treatment by assessing the treatments' characteristics as a whole.

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.

Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

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

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

Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France.

PURPOSE: Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondary effectiveness outcomes, will be published later. Overall, CIRT-FR is aiming to support French authorities in the decision making on reimbursement considerations for this treatment. METHODS: Data on patients enrolled in CIRT-FR from August 2017 to October 2019 were analysed. The interim analysis describes clinical practice, baseline characteristics, safety (adverse events according to CTCTAE 4.03) and quality of life (according to EORTC QLQ C30 and HCC module) aspects after TARE. RESULTS: This cohort included 200 patients with hepatocellular carcinoma (114), metastatic colorectal cancer (mCRC; 38) and intrahepatic cholangiocarcinoma (33) amongst others (15). TARE was predominantly assigned as a palliative treatment (79%). 12% of patients experienced at least one adverse event in the 30 days following treatment; 30-day mortality was 1%. Overall, global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%). CONCLUSION: This interim analysis demonstrates that data regarding safety and quality of life generated by randomised-controlled trials is reflected when assessing the real-world application of TARE. TRIAL REGISTRATION: Clinical Trials.gov NCT03256994.

Selective internal radiation therapies for unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma: systematic review, network meta-analysis and economic evaluation.

BACKGROUND: Hepatocellular carcinoma is the most common type of primary liver cancer. Treatment choice is dependent on underlying liver dysfunction and cancer stage. Treatment options include conventional transarterial therapies for patients with intermediate-stage disease and systemic therapy [e.g. sorafenib (Nexavar®; Bayer plc, Leverkusen, Germany)] for patients with advanced-stage disease. Selective internal radiation therapies deliver radiation to liver tumours via microspheres that are injected into the hepatic artery. There are three selective internal radiation therapies: TheraSphere™ [BTG Ltd, London, UK (now Boston Scientific, Marlborough, MA, USA)], SIR-Spheres® (Sirtex Medical Ltd, Woburn, MA, USA) and QuiremSpheres® (Quirem Medical BV, Deventer, the Netherlands). OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of selective internal radiation therapies for treating patients with unresectable early-, intermediate- or advanced-stage hepatocellular carcinoma. METHODS: A search was undertaken to identify clinical effectiveness literature relating to selective internal radiation therapies and relevant comparators for the treatment of hepatocellular carcinoma. Studies were critically appraised and summarised. The network of evidence was mapped to estimate the relative effectiveness of the different selective internal radiation therapies and comparator treatments. An economic analysis evaluated the cost-effectiveness. RESULTS: Twenty studies were included in the clinical effectiveness review. Two large randomised controlled trials rated as having a low risk of bias [SARAH: Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled Phase 3 trial. Lancet Oncol 2017;18:1624-36; and SIRveNIB: Chow PKH, Gandhi M, Tan SB, Khin MW, Khasbazar A, Ong J, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 2018;36:1913-21] found no significant difference in overall survival or progression-free survival between SIR-Spheres and sorafenib (systemic therapy) in an advanced population, despite greater tumour response in the SIR-Spheres arm of both trials. There were some concerns regarding generalisability of the SARAH and SIRveNIB trials to UK practice. All other studies of SIR-Spheres, TheraSphere or QuiremSpheres were either rated as being at a high risk of bias or caused some concerns regarding bias. A network meta-analysis was conducted in adults with unresectable hepatocellular carcinoma who had Child-Pugh class A liver cirrhosis and were ineligible for conventional transarterial therapies. The analysis included the SARAH and SIRveNIB trials as well as a trial comparing lenvatinib (Kisplyx®; Eisai Ltd, Tokyo, Japan) (systemic therapy) with sorafenib. There were no meaningful differences in overall survival between any of the treatments. The base-case economic analysis suggested that TheraSphere may be cost-saving relative to both SIR-Spheres and QuiremSpheres. However, incremental cost differences between TheraSphere and SIR-Spheres were small. In a fully incremental analysis, which included confidential Patient Access Scheme discounts, lenvatinib was the most cost-effective treatment and dominated all selective internal radiation therapies. In pairwise comparisons of sorafenib with each selective internal radiation therapy, sorafenib also dominated all selective internal radiation therapies. LIMITATIONS: The existing evidence cannot provide decision-makers with clear guidance on the comparative effectiveness of treatments in early- and intermediate-stage hepatocellular carcinoma or on the efficacy of TheraSphere or QuiremSpheres. CONCLUSIONS: In the advanced-stage hepatocellular carcinoma population, two large randomised trials have shown that SIR-Spheres have similar clinical effectiveness to sorafenib. None of the selective internal radiation therapies was cost-effective, being more costly and less effective than lenvatinib, both at list price and with Patient Access Scheme discounts. FUTURE WORK: Future studies may wish to include early- and intermediate-stage hepatocellular carcinoma patients and the low tumour burden/albumin-bilirubin 1 subgroup of advanced-stage patients. Future high-quality studies evaluating alternative selective internal radiation therapies would be beneficial. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019128383. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 48. See the NIHR Journals Library website for further project information.

Hepatocellular carcinoma is the most common type of liver cancer. The choice of treatment depends on the extent of the cancer and liver function. Selective internal radiation therapies deliver radiation directly to liver tumours via tiny beads injected into the main blood vessel into the liver. There are three selective internal radiation therapies: TheraSphere™ [BTG Ltd, London, UK (now Boston Scientific, Marlborough, MA, USA)], SIR-Spheres^® (Sirtex Medical Ltd, Woburn, MA, USA) and QuiremSpheres^® (Quirem Medical BV, Deventer, the Netherlands). Our aim was to assess the clinical effectiveness of selective internal radiation therapies for patients with hepatocellular carcinoma that is not treatable by surgery, and to assess whether or not these therapies represent good value for money. There was no meaningful difference between SIR-Spheres and sorafenib (Nexavar^®; Bayer plc, Leverkusen, Germany), which is a cancer drug for advanced hepatocellular carcinoma. Studies of other selective internal radiation therapies and studies in patients with less advanced disease were generally of poor quality, so their results may not be reliable. We could not assess whether or not selective internal radiation therapies are beneficial to patients with early- or intermediate-stage hepatocellular carcinoma, or whether or not TheraSphere and QuiremSpheres are beneficial. Compared with sorafenib or lenvatinib (Kisplyx^®; Eisai Ltd, Tokyo, Japan) (another systemic cancer drug), none of the selective internal radiation therapies were good value for money for treating patients with advanced hepatocellular carcinoma. We found that TheraSphere might be cheaper than SIR-Spheres and QuiremSpheres, but differences between TheraSphere and SIR-Spheres were small. There was not enough evidence for patients with early or intermediate disease to say whether or not selective internal radiation therapy is good value for treating these patients. Future studies in these populations, alongside any studies comparing the selective internal radiation therapies against each other, would be helpful.

Complete Pathological Response Noted in Explanted Liver After Y90-SIR-Spheres Therapy for Hepatocellular Carcinoma.

In the treatment of hepatocellular carcinoma, achieving complete pathological response (CPR) in explanted liver specimens following any locoregional treatments is associated with reduced recurrence rates and better posttransplant survival compared to the incomplete response. Here, we present the imaging findings of a patient who achieved CPR in the explanted liver following Y-90 SIR-Spheres® therapy.

Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study.

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

90Y Resin Microspheres Radioembolization for Colon Cancer Liver Metastases Using Full-Strength Contrast Material.

OBJECTIVES: To assess safety and efficacy of 90Y resin microspheres administration using undiluted non-ionic contrast material (UDCM) {100% Omnipaque-300 (Iohexol)} in both the "B" and "D" lines. MATERIALS AND METHODS: We reviewed all colorectal cancer liver metastases patients treated with 90Y resin microspheres radioembolization (RAE) from 2009 to 2017. As of April 2013, two experienced operators started using UDCM (study group) instead of standard sandwich infusion (control group). Occurrence of myelosuppression (leukopenia, neutropenia, erythrocytopenia or/and thrombocytopenia), stasis, nontarget delivery (NTD), median fluoroscopy radiation dose (FRD), median infusion time (IT), liver progression-free (LPFS) and overall survivals (OS) was evaluated. Complications within 6 months post-RAE were reported according to CTCAE v3.0 criteria. RESULTS: Study and control groups comprised 23(28%) and 58(72%) patients, respectively. Median follow-up was 9.1 months. There was no statistically significant difference in myelosuppression incidence within 6 months post-RAE between groups. Median FRD and IT for study and control groups were 44.6 vs. 97.35 Gy/cm2 (p = 0.048) and 31 vs. 39 min (p = 0.006), respectively. A 38% lower stasis incidence in study group was not significant (p = 0.34). NTD occurred in 1/27(4%) study vs. 5/73(7%) control group procedures (p = 1). Grade 1-2 and grade 3-4 toxicities between study and control group patients were 36%(8/22) vs. 45%(26/58), p = 0.61 and 9%(2/22) vs. 16%(9/58), p = 0.72, respectively. There was no difference in LPFS and OS between groups. CONCLUSION: Administration of 90Y resin microspheres using UDCM in both lines is safe and effective, resulting in lower fluoroscopy radiation dose and shorter infusion time, without evidence of myelosuppression or increased stasis incidence.

Yttrium-90 resin microspheres and their use in the treatment of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a severe and rapidly progressive hepatic tumor. Surgery is often impracticable due to locally advanced presentation. On the other hand, chemotherapy has demonstrated only limited effectiveness. For these reasons, liver-directed therapies have been successfully applied for treating ICC. In particular, radioembolization with Yttrium-90 (90Y)-labeled spheres has been reported to be a promising therapeutic approach for this neoplasia. Two commercial forms of 90Y-labeled spheres are available: glass (TheraSphere®) and resin (SIR-Spheres®) microspheres. The aim of the present paper is to review the existing literature on the use of the resin microspheres for the treatment of unresectable and chemorefractory ICC, focusing on the methodology, clinical applications and side effects.

A single institute retrospective trial of concurrent chemotherapy with SIR-Spheres® versus SIR-Spheres® alone in chemotherapy-resistant colorectal cancer liver metastases.

BACKGROUND: The use of selective internal radiation therapy with yttrium 90 resin microspheres (SIR-Spheres®) in chemotherapy-resistant colorectal cancer liver metastases has been associated with favorable progression-free survival (PFS) and overall survival when given alone or concurrently with chemotherapy. We conducted a single institute retrospective trial to explore the potential impact of SIR-Spheres® with concurrent chemotherapy vs. SIR-Spheres® alone on liver PFS in patients with colorectal liver metastases (CRLM). METHODS: Patients with 5-fluorouracil-refractory CRLM treated with SIR-Spheres® between 2009 and 2014 were identified. Patients were excluded if they received any chemotherapy/targeted regimen following radioembolization on which they did not previously progress. This strategy was adopted to minimize the impact of post-SIR-Spheres® systemic therapy bias on PFS. RESULTS: Twenty-seven patients satisfied inclusion criteria and were included in this analysis. Patients' demographics were similar between the two treatment arms, except for the median number of prior therapies. No associated ≥ grade 3 toxicities were noted. Liver disease control rates were 84% and 14% on the SIR-Spheres® plus chemotherapy arms and SIR-Spheres® alone arms, respectively (P=0.001). Median PFS in the liver was 176 days in the SIR-Spheres® plus chemotherapy group vs. 91 days in the SIR-Sphere® alone group (P=0.0009). Median overall survival was 212 days in the SIR-Spheres® plus chemotherapy group vs. 154 days in the SIR-Spheres® alone group (P=0.1023). CONCLUSIONS: In patients with 5-fluorouracil-refractory disease, SIR-Spheres® plus chemotherapy is associated with an increased liver disease control rate and a prolonged liver PFS in comparison with SIR-Spheres® alone.

Treatment options for unresectable HCC with a focus on SIRT with Yttrium-90 resin microspheres.

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the second leading cause of cancer-related deaths across the globe. Only a small percentage of HCC patients (~20%-30%) are diagnosed at an early stage when first-line treatment options may be effective. The majority of HCC patients (>70%) are diagnosed with unresectable disease and given a poor overall prognosis. Current treatment guidelines recommend locoregional therapy with transarterial chemoembolisation (TACE) and systemic therapy with sorafenib as first-line treatment for patients with intermediate and advanced stage HCC. However, multiple factors including contraindications, technical considerations and treatment-related toxicities pose significant challenges in achieving favourable treatment outcomes, underscoring the need for a paradigm shift in managing these patients. In 2002, yttrium-90 (Y-90) resin microspheres was approved by the U.S. Food and Drug Administration (FDA) for the treatment of unresectable metastatic colorectal cancer to the liver with adjuvant floxuridine chemotherapy. However, thousands of patients with unresectable HCC have also been treated with resin Y-90. For over two decades, several small-scale prospective trials and retrospective studies have investigated and reported on the efficacy of locoregional selective internal radiation therapy (SIRT) with Y-90 microspheres in treating unresectable HCC. Although it is currently a treatment option for intermediate-stage HCC patients, mainstream clinical application of resin Y-90 has been largely limited because of the lack of sufficient clinical data from a randomised controlled trial. This could change with the imminent announcement of results from the phase 3 Sorafenib vs Radioembolization in Advanced Hepatocellular carcinoma (SARAH) trial. To provide the foundation and context for interpreting results from the SARAH trial, this article provides an overview of treatment modalities and current challenges in managing unresectable HCC. There is also a review of key prospective and retrospective studies evaluating the use of Y-90 SIRT, specifically Y-90 resin microspheres in unresectable HCC, which led to the development of the SARAH trial. METHODS: To identify relevant publications, the PubMed database was queried using one or more of the following search terms alone or in combination with Boolean operators: epidemiology, hepatocellular, hepatocellular cancer, hepatocellular carcinoma, unresectable, radioembolisation, selective internal radiation therapy, SIR-Spheres, yttrium 90, TACE, and sorafenib. The results were sorted or filtered by "Author", "Publication dates" or "Article types" to identify articles relevant to each section of the review. To ensure that information on ongoing clinical trials involving Y-90 resin was included, we conducted a search on "ClinicalTrials.gov", by combining the search terms "HCC" OR "hepatocellular carcinoma" with "Y 90" OR "yttrium 90" OR "radioembo", and screened for studies that involved treatment with Y-90 resin microspheres.

Recommendations for SIR-Spheres Y-90 resin microspheres in chemotherapy-refractory/intolerant colorectal liver metastases.

A Spanish expert panel reviewed current evidence for the use of SIR-Spheres Y-90 resin microspheres in patients with chemotherapy refractory/intolerant unresectable colorectal liver metastases. Substantial evidence for its efficacy and safety is available from a randomized controlled study, retrospective comparative studies and several single arm studies. Clinical evidence data obtained from more than 1500 patients have led to the inclusion of selective internal radiation therapy in the 2016 ESMO Clinical Guidelines as third-line treatment. This publication results from an expert panel meeting, where published evidence and author's experiences were shared to position SIR-Spheres Y-90 resin microspheres in Spain for the treatment of chemotherapy refractory/intolerant unresectable colorectal liver metastases, and second, to define the patient subgroup that will benefit the most with this treatment.

Selective internal radiation therapy with SIR-Spheres in hepatocellular carcinoma and cholangiocarcinoma.

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) often present at stages where patients have limited treatment options. Use of selective internal radiation therapy (SIRT) with yttrium-90 (Y-90) resin microspheres has progressed as data increasingly speak to its utility in patients with both intermediate and late stage disease in these cancers. In anticipation of the pending completion of several prospective randomized controlled multicenter studies exploring the use of Y-90 resin microspheres in primary liver cancers, this article outlines mechanisms involved in SIRT administration and reviews key efficacy and safety data that are currently available in the literature involving use of this therapy in both HCC and ICC.

Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review.

To compare the safety profiles of TheraSphere® (glass) and SIR-Spheres® (resin) Y90 microspheres for the treatment of hepatocellular carcinoma. A systematic review was conducted using the databases MEDLINE, Embase, and Cochrane Trials Register to identify all relevant studies. Baseline characteristics and adverse events of all grades related to gastrointestinal, hepatobiliary, and respiratory systems were collected along with commonly reported outcomes related to post-embolization syndrome. For all outcomes, data from each study were tabulated for each intervention. Adverse events and patients were summed across studies on TheraSphere® and SIR-Spheres®, respectively, and the resulting proportion of patients experiencing an outcome for both interventions was calculated. Thirty-one observational studies were included in the review. In the adverse events of all grades, more patients treated with resin microspheres reported gastric ulcers, hepatic encephalopathy, cholecystitis, hepatic failure, and pleural effusion. Patients treated with resin microspheres also had more hepatobiliary adverse events of grade 3 or higher. In the events related to post-embolization syndrome, glass microspheres exhibited a similar safety profile compared to resin microspheres. Ascites and nausea grade 3 or higher were recorded more frequently with glass microsphere treatment. Based on this review of the published literature, glass microspheres exhibit a safety profile with fewer gastrointestinal and pulmonary adverse events compared to resin microspheres in the treatment of hepatocellular carcinoma.