Microsphere Selective Internal Radiation Therapy Research Articles

Expert consensus on the standardized procedure of selective internal radiation therapy with Yttrium-90 microspheres for liver malignancies (2024 edition)

Yttrium-90 microsphere selective internal radiation therapy (90Y-SIRT) has been used clinically for more than 50 years for liver malignancies, with confirmed safety and efficacy. Although it has been widely used for more than 20 years abroad, 90Y-SIRT is just getting started in China. The procedure of 90Y-SIRT is relatively complex, which need multidisciplinary teamwork and higher requirements for operators. Once the ectopic distribution of 90Y microspheres occurs, it may lead to relatively serious complications. Therefore, it does need to standardize the procedure of 90Y-SIRT to ensure its efficacy, reduce the incidence of complications, and promote the popularization and application in China. It is for these reasons that experts from Chinese College of Interventionalists and Society for Hepato-pancreato-biliary Surgery of Chinese Research Hospital Association formulate the Expert consensus based on the literature evidence and clinical practice, which including patient selection, preoperative imaging examination, aim of 90Y-SIRT, prescription dose calculation, 90Y-SIRT protocol, postoperative management, common adverse reactions and complications, etc.

Lung shunt fraction calculation using 99mTc-MAA SPECT/CT imaging for 90Y microsphere selective internal radiation therapy of liver tumors

Background99mTc-macroaggregated albumin (99mTc-MAA) scintigraphy is utilized in treatment planning for Yttrium-90 (90Y) Selective Internal Radiation Therapy (SIRT) of liver tumors to evaluate hepatopulmonary shunting by calculating the lung shunt fraction (LSF). The purpose of this study was to evaluate if LSF calculation using SPECT/CT instead of planar gamma camera imaging is more accurate and if this can potentially lead to more effective treatment planning of hepatic lesions while avoiding excessive pulmonary irradiation.ResultsLSF calculation was obtained using two different methodologies in 85 cases from consecutive patients intended to receive 90Y SIRT. The first method was based on planar gamma camera imaging in the anterior and posterior views with geometric mean calculation of the LSF from regions of interest of the liver and lungs. The second method was based on segmentation of the liver and lungs from SPECT/CT images of the thorax and abdomen. The differences in planar imaging versus SPECT/CT derived LSF values along with the estimated absorbed lung mean dose (LMD) were evaluated. The LSF values were higher in planar imaging versus SPECT/CT in 81/85 cases, with a mean value of 8.5% vs. 4.6% respectively; the difference was statistically significant using a paired t-test (alpha = 0.05). In those patients who received SIRT, the estimated absorbed LMD calculated with planar imaging was significantly higher than with SPECT/CT (t-test, P < 0.005). Repeated phantom experiments using an anthropomorphic torso phantom with variable 99mTc activity concentrations for the liver and lungs were performed with the standard patient protocol, demonstrated improved accuracy of the LSF calculation based on SPECT/CT than planar imaging (mean overestimated value of 6% vs. 26%).ConclusionsThis study demonstrates that LSF calculation using planar imaging can be significantly overestimated while calculation using SPECT/CT imaging and appropriate segmentation tools can be more accurate. Minimizing the errors in obtaining the LSF can lead to more effective 90Y SIRT treatment planning for hepatic tumors while ensuring the lung dose will not exceed the standard acceptable safety thresholds.

Yttrium-90 radioembolization of isolated hepatic adrenocortical carcinoma metastases with negative surgical pathology

BackgroundAdrenocortical carcinoma (ACC) is an uncommon malignancy with an estimated 15,400 new cases annually across the globe. The prognosis is generally poor as the disease is often already advanced at initial diagnosis due to non-specific symptoms. Even for local disease, recurrence after surgical resection is high. Treatment choices for advanced disease include mitotane, chemotherapy, ablation, chemoembolization, radioembolization, and external beam radiotherapy, with varying degrees of efficacy. To the best of our knowledge, there have only been two prior case studies of complete clinical and radiological response of stage 4 disease at 1 year and 2 years after yttrium-90 (90Y) microsphere selective internal radiation therapy (SIRT) of isolated hepatic metastases post-surgery and chemotherapy.Case presentationWe present a case of a 58-year-old man with metastatic ACC who was treated with 90Y resin microsphere (SIR-spheres) for local control of liver metastases leading to a surgically proven negative pathology after partial hepatectomy 7 months after SIRT. The patient was initially diagnosed with stage 1 ACC that progressed 6 years later to stage 4 disease with new liver metastases that were deemed unresectable at an outside institution. After review of the case at multidisciplinary tumor board, he was referred for liver directed therapy for local tumor control. Angiographic workup demonstrated partial extrahepatic supply to the tumors from the right inferior phrenic artery, which was successfully embolized on the day of SIRT for flow redistribution. As the patient was being treated with mitotane that suppresses steroid production, he developed post-SIRT adrenal crisis, which was successfully controlled with steroids, highlighting the need for pre SIRT stress dose steroids.ConclusionsThis case continues to add to the literature supporting 90Y radioembolization as an effective treatment for isolated hepatic ACC metastases. Our case is the first to demonstrate surgically proven negative pathology after radioembolization. Further prospective study is warranted to better establish efficacy as well as safety of SIRT for ACC liver metastases.

A MAA-based dosimetric study in patients with intrahepatic cholangiocarcinoma treated with a combination of chemotherapy and 90Y-loaded glass microsphere selective internal radiation therapy.

Selective internal radiation therapy (SIRT) appears to be an interesting treatment possibility for locally-advanced intrahepatic cholangiocarcinoma (ICC), yet the appropriate dosimetry has never been evaluated in this context. We retrospectively studied data from 40 patients treated at our institution with 90Y-loaded glass microsphere SIRT combined with chemotherapy for inoperable ICC as first-line treatment. Macroaggregated albumin (MAA)-based single-photon emission computed tomography (SPECT)/computed tomography (CT) quantitative analysis was used to calculate the tumor dose (TD), healthy-injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3months using the European Association for the Study of the Liver criteria. Factors associated with response and toxicity were analyzed using univariate analysis. We assessed a total of 35 patients (five excluded) receiving 55 injections. Mean TD was 322 ± 165Gy and mean HILD was 74 ± 24Gy for a mean ILD of 128 ± 28Gy. All but two lesions responded, with a minimal TD for responding lesions of 158Gy. Six Grade 3-4 permanent liver toxicities were observed. Mean HILD was not associated with liver toxicity (73.2 ± 25.8Gy for patients with liver toxicity and 77.8 ± 16.9Gy for patients without, ns). Only underlying Child-Pugh status (p = 0.0014) and underlying cirrhosis (p = 0.0021) were associated with liver toxicity. Median progression-free survival was 12.7months and median overall survival (OS) was 28.6months. Median OS was 52.7months for patients with Child-Pugh A5 status. When combined with chemotherapy, SIRT is highly effective, with a TD > 158Gy. Tolerance was good except for the few patients with cirrhosis or Child-Pugh status ≥A6, who exhibited some liver toxicity. Prospective studies are warranted to confirm.

Combined Yttrium-90 microsphere selective internal radiation therapy and external beam radiotherapy in patients with hepatocellular carcinoma: From clinical aspects to dosimetry.

PurposeSelective internal radiation therapy (SIRT) is an effective treatment strategy for unresectable hepatocellular carcinoma (HCC) patients. However, the prognoses of patients with portal vein thrombosis, extra-hepatic metastases, or residual tumors remain poor when treated with SIRT alone. In these patients, sequential external beam radiotherapy (EBRT) may offer a chance of salvage. Here, we reported the clinical outcomes and the detailed dosimetry analysis of 22 patients treated with combination therapy.MethodsBetween October 2011 and May 2015, 22 consecutive patients who underwent EBRT after yttrium-90 (90Y) SIRT were included in this study. The post-SIRT 90Y bremsstrahlung SPECT/CT of each patient was transferred to dose distribution by adopting the local deposition hypothesis. The patient-specific 3-dimensional biological effective dose distribution of combined SIRT and EBRT was generated. The overall survival and safety were evaluated. The relationship between dosimetric parameters and liver toxicity was analyzed.ResultsThe mean administered activity of SIRT was 1.50 GBq (range: 0.5–2.8). The mean prescribed dose of EBRT was 42.3 Gy (range: 15–63) in 14 fractions (range: 5–15) and was targeted to the residual liver tumor in 12 patients (55%), portal vein thrombosis in 11 patients (50%), and perihilar lymphadenopathies in 4 patients (18%). The overall 1-, 2-, and 3-year survival rates were 59.8%, 47.9%, and 47.9%, respectively. Overall, 8 patients (36%) developed > grade 2 liver toxicities, and the Child-Pugh score prior to EBRT strongly affected the toxicity risk. A dosimetry analysis restricted to 18 Child-Pugh A/B patients showed that the V100 (The fraction of normal liver exposed to more than 100 Gy) to V140 significance differed between patients who did or did not experience hepatotoxicity. The V110 was the strongest predictor of hepatotoxicity (18.6±11.6% vs 29.5±5.8%; P = 0.030).ConclusionCombined therapy is feasible and safe if patients are carefully selected. Specifically, 3-dimensional dosimetry is crucial for the evaluation of efficacy and toxicity. The normal liver V100 to V140 values of the combined dose should be as low as possible to minimize the risk of liver toxicity.

Dosimetric Analysis of Individual Liver Metastases from Colorectal Cancer Following 90 y Microsphere Selective Internal Radiation Therapy

Colorectal cancer (CRC) is a common cause of cancer-related deaths (12.2% overall mortality, GLOBOCAN 2012 v1.0). Approximately half of CRC patients develop or present with metastasis (mCRC) to the liver. Selective internal radiation therapy (SIRT) involves injection of yttrium-90 (90Y) radiolabelled microspheres into the arterial blood supply of tumours in the liver. Radioactivity prescription for 90Y SIRT is currently based on a body surface area (BSA) formula. The purpose of this study was to conduct a lesion-by-lesion analysis to establish a dose-response relationship. A retrospective review of 24 patients (99 lesions) treated with resin 90Y microspheres was conducted. All patients had inoperable liver metastases refractory to standard chemotherapies. Single photon emission computed tomography (SPECT) images were transformed into dose maps using an in-house MATLAB script and the direct deposition dosimetry method. The 90Y S-value was generated by Monte Carlo-simulation using the EGSnrc/EGS++ code. Baseline and follow-up CT scans were segmented to derive liver and lesion volumes. Mean, median, and D70 (minimum dose to 70% of lesion volume) values derived from dose maps were correlated to change in lesion volume and RECIST 1.1 outcome using linear and logistic regression, respectively. The median administered radioactivity was 1513 MBq (range 847-2185) for lobar and bilobar administrations. The median uniform normal liver dose was 26.3 Gy (range 15.4-41.3, IQR 22.3-30.6) and median lesion dose was 32.8 Gy (range 2.3-90.0, IQR 23.4-48.2). Stable disease or partial response was observed in 17 (71%) patients. Median survival from the date of administration was 313 days. Radiation absorbed dose correlated with lesion response (i.e. a 1 Gy increase in mean, median, and D70 dose resulted in reduction in lesion volume by 2.7%, 2.7%, and 2.3%, respectively, p < 0.02). Higher doses were associated with a decrease in total (combined) lesion volume (by 2.3% and 1.9% for a 1 Gy increase in mean and D70 doses respectively, p < 0.04). Higher lesion doses were associated with a higher probability of RECIST response (odds ratio of 1.05, 1.05, and 1.04 for a 1 Gy increase in mean, median, and D70 doses, respectively, p < 0.2). Higher mean, median, and D70 doses are associated with a decrease in lesion volume and an increased probability of RECIST response. The type of analysis presented here will allow suboptimally treated liver lesions to be managed by a multi-modality approach.

Treating hepatocellular carcinoma with 90Y-bearing microspheres: a review.

Hepatocellular carcinoma (HCC) is a disease usually diagnosed in its advanced-stage, and is frequently not amenable to curative surgical treatment. Also, HCC is resistant to chemotherapy and less vulnerable to radiation therapy compared to normal hepatic parenchyma. Both of these facts render the efficacy of adjuvant and palliative treatments problematic. Selective internal radiation therapy (SIRT) with 90Y-bearing microspheres is characterized by preferentially delivering substantially high doses of radiation to a liver tumor dose simultaneously limiting the damage to its non-tumorous cells, providing an opportunity for effective local tumor control and even tumor regression therapy. The current article reviews the specific characters, dosimetry, possible applications, and special considerations toward the pre-existing radiation therapy of 90Y microsphere SIRT in treating HCC.

Comparing voxel-based absorbed dosimetry methods in tumors, liver, lung, and at the liver-lung interface for (90)Y microsphere selective internal radiation therapy.

BackgroundTo assess differences between four different voxel-based dosimetry methods (VBDM) for tumor, liver, and lung absorbed doses following 90Y microsphere selective internal radiation therapy (SIRT) based on 90Y bremsstrahlung SPECT/CT, a secondary objective was to estimate the sensitivity of liver and lung absorbed doses due to differences in organ segmentation near the liver-lung interface.MethodsInvestigated VBDM were Monte Carlo (MC), soft-tissue kernel with density correction (SKD), soft-tissue kernel (SK), and local deposition (LD). Seventeen SIRT cases were analyzed. Mean absorbed doses ( overline{AD} ) were calculated for tumor, non-tumoral liver (NL), and right lung (RL). Simulations with various SPECT spatial resolutions (FHWMs) and multiple lung shunt fractions (LSs) estimated the accuracy of VBDM at the liver-lung interface. Sensitivity of patient RL and NL overline{AD} on segmentation near the interface was assessed by excluding portions near the interface.ResultsSKD, SK, and LD were within 5 % of MC for tumor and NL overline{AD} . LD and SKD overestimated RL overline{AD} compared to MC on average by 17 and 20 %, respectively; SK underestimated RL overline{AD} on average by −60 %. Simulations (20 mm FWHM, 20 % LS) showed that SKD, LD, and MC were within 10 % of the truth deep (>39 mm) in the lung; SK significantly underestimated the absorbed dose deep in the lung by approximately −70 %. All VBDM were within 10 % of truth deep (>12 mm) in the liver. Excluding 1, 2, and 3 cm of RL near the interface changed the resulting RL overline{AD} by −22, −38, and −48 %, respectively, for all VBDM. An average change of −7 % in the NL overline{AD} was realized when excluding 3 cm of NL from the interface. overline{AD} was realized when excluding 3 cm of NL from the interface.ConclusionsSKD, SK, and LD are equivalent to MC for tumor and NL overline{AD} . SK underestimates RL overline{AD} relative to MC whereas LD and SKD overestimate. RL overline{AD} is strongly influenced by the liver-lung interface.

The relationship between the percentage of lung shunting on Tc-99m macroaggregated albumin (Tc-99m MAA) scan and the grade of hepatocellular carcinoma vascularity

BackgroundHepatocellular carcinoma (HCC) stands for the majority of primary liver malignancy. HCC has variable grade of vascularity according to the histological tumor grade and underlying liver damage. Yttrium-90 radioembolization is a promising catheter-based hepatic intra-arterial therapy for HCC that necessitates proper planning. Technetium-99m macroaggregated albumin (Tc-99m MAA), a simulation of the treatment, is used to identify the shunting of microspheres to the lungs or gastrointestinal tract. ObjectiveTo evaluate the relationship between the percentage of lung shunting on Tc-99m MAA scan performed in treatment planning of Yttrium-90 (Y-90) microsphere selective internal radiation therapy (SIRT) for HCC and the grade of tumor vascularity shown on digital subtraction hepatic angiography. Materials and methodsThis study was conducted on 19 patients diagnosed to have HCC, based on typical computed tomography (CT) criteria and/or elevated alpha-fetoprotein (AFP) ⩾200ng/ml, and planned for Y-90 therapy. They were injected by Tc-99m MAA into the hepatic arterial territory with prior digital subtraction angiography. Tc-99m MAA scan was reviewed for extrahepatic shunting within the abdomen. Additionally, the hepatopulmonary shunt (HPS) fraction or the lung shunting (LS) percentage was calculated and further evaluated in relation to the grade of tumor vascularity shown on digital subtraction hepatic angiography. ResultsThere was no extrahepatic accumulation of Tc-99m MAA related to umbilical, gastroduodenal or splenic shunting. The LS percentage assorted among patients and ranged between 0.8% and 42.9% with a median of 5.5%. LS more than 20% occurred in only 1 patient. Subsequent therapy plan was changed accordingly in 5% of patients. The more vascular the lesion was, the higher lung shunting percentage was detected. ConclusionTc-99m MAA scan is fundamental prior to Y-90 microsphere SIRT as it minimizes the risk of post-radioembolization complications, hence, enhancing the safety of Y-90 microsphere subsequent administration. Moreover, the percentage of lung shunting varies considerably among patients with HCC relying on the grade of tumor vascularity.

The prognostic value of functional tumor volume and total lesion glycolysis in patients with colorectal cancer liver metastases undergoing 90Y selective internal radiation therapy plus chemotherapy

Functional tumor volume (FTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images. These parameters could potentially have clinical value in response to treatment evaluation and disease prognostication. The objectives of this study were to investigate the relationship between functional tumor parameters (FTV and TLG) and clinical outcomes in patients with colorectal cancer liver metastases (CRCLM) undergoing (90)Y-resin microsphere selective internal radiation therapy (SIRT) (SIR-Spheres®, Sirtex Medical Limited, Lane Cove, NSW, Australia). FDG PET/CT studies of 20 patients with unresectable CRCLM who underwent (90)Y SIRT under a phase II clinical trial were analyzed. FTV and TLG were calculated using PET VCAR (GE Healthcare, Milwaukee, WI, USA) on pretreatment and 4-week posttreatment scans. The effects of pretreatment and posttreatment functional tumor activity on patient survival were evaluated using Kaplan-Meier survival curves. The median survival in the study group was 14.8 months (range 2.0-27.7 months). The median survival for patients with pretreatment FTV values of above and below 200 cc were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment FTV values of above and below 30 cc were 10.9 and 26.9 months, respectively (p < 0.05). The median survival for patients with pretreatment TLG values of above and below 600 g were 11.2 and 26.9 months, respectively (p < 0.05). The median survival for patients with 4-week posttreatment TLG values of above and below 100 g were 10.9 and 26.9 months, respectively (p < 0.05). Pretreatment and posttreatment FTV and TLG showed very strong association with survival. These values can be useful quantitative criteria for patient selection and disease prognostication when (90)Y SIRT is contemplated in patients with CRCLM.

Phase II trial of multiagent chemotherapy combined with Y-90 microsphere selective internal radiation therapy (chemo-SIRT) in patients with colorectal cancer liver metastases

15011 Background: Concurrent chemotherapy and radiation in colorectal cancer(CRC) can improve outcome of local or regional disease. This study is an attempt to derive a similar benefit using chemotherapy and a novel method of radiation therapy for patients with CRC metastatic to liver. Yttrium-90 (Y-90) microsphere selective internal radiation treament (SIRT) has proven to be a safe and effective mode of radiation delivery technique in patients (pts) with CRCLM as a single modality and with 5-FU and FUDR. This is a phase II trial of Y-90 microspheres and concurrent multiagent chemotherapy for management of CRCLM. This study is designed to measure response using updated methods of measurements based on pet scan and computer modeling as well as common criteria. Assessment of toxicity, especially hepatotoxicity and myelotoxicity, is the second major objective. Methods: 20 patients with disease limited predominantly to the liver were recruited for the study. Pre-treatment studies included a liver-protocol PET-CT, angiogram and 99mTc-MAAA (macroaggregaated albumin) imaging. Chemotherapy (Fol-Fox or Fol-Firi) was planned every 2 weeks for 8 cycles. SIRT with Y-90 resin microspheres (Sirtex Medical, Wilmington, MA) was administered on day 2 of the first chemotherapy course either lobar or whole-liver fashion. Administered activity of Y-90 microspheres ranged from 0.2 to 3.8 GBq (mean 1.8 GBq). CEA levels, tumor anatomic volume (VA) and functional volume (VF) by FDG-PET/CT were used to determine tumor response. Results: 20 patients have been treated and 19 are evaluable. 13 patients were chemo-naive, 7 had prior chemo. 3 received whole liver, 16 received lobar, one segmental SIRT. 16/19 patients had a VF decrease of >90% and the average decrease for 3 was 56%. 15/16 pts with an elevated cea had >50% decline. 12/19 pts had > 50% reduction in VA. 4 patients have undergone surgery subsequent to chemo-SIRT. 4 pts required hospitalization due to SAE, 1 with neutropenic fever. 2 pts had grade 3 sphere-induced gi ulcer. Conclusions: Chemo-SIRT with modern chemotherapy results in a high objective response rate with acceptable toxicity and deserves further study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Sirtex Medical Inc Sirtex Medical Inc