90Y Microspheres Research Articles

Multiscale Computational Fluid Dynamics Modeling for Personalized Liver Cancer Radioembolization Dosimetry.

Yttrium-90 (90Y) radioembolization is a minimally invasive procedure increasingly used for advanced liver cancer treatment. In this method, radioactive microspheres are injected into the hepatic arterial bloodstream to target, irradiate, and kill cancer cells. Accurate and precise treatment planning can lead to more efficient and safer treatment by delivering a higher radiation dose to the tumor while minimizing the exposure of the surrounding liver parenchyma. Treatment planning primarily relies on the estimated radiation dose delivered to tissue. However, current methods used to estimate the dose are based on simplified assumptions that make the dosimetry results unreliable. In this work, we present a computational model to predict the radiation dose from the 90Y activity in different liver segments to provide a more realistic and personalized dosimetry. Computational fluid dynamics (CFD) simulations were performed in a 3D hepatic arterial tree model segmented from cone-beam CT angiographic data obtained from a patient with hepatocellular carcinoma (HCC). The microsphere trajectories were predicted from the velocity field. 90Y dose distribution was then calculated from the volumetric distribution of the microspheres. Two injection locations were considered for the microsphere administration, a lobar and a selective injection. Results showed that 22% and 82% of the microspheres were delivered to the tumor, after each injection, respectively, and the combination of both injections ultimately delivered 49% of the total administered 90Y microspheres to the tumor. Results also illustrated the nonhomogeneous distribution of microspheres between liver segments, indicating the importance of developing patient-specific dosimetry methods for effective radioembolization treatment.

Yttrium-90 Portal Vein Radioembolization in Sprague-Dawley Rats: Dose-Dependent Imaging and Pathological Changes in Normal Liver.

Portal vein embolization (PVE) is an established neoadjuvant method to induce future liver remnant hypertrophy prior to surgical resection of hepatic tumors. The purpose of our study was to examine the feasibility of PVE with glass 90Y microspheres (Y90 PVE) in Sprague-Dawley rats. We tested the hypothesis that increased doses of Y90 PVE would increase target lobe fibrosis and atrophy. Twenty-two rats were assigned to four groups for Y90 PVE to the right median lobe: very high- (273.8MBq; n = 2), high- (99.9MBq; n = 10), medium- (48.1MBq; n = 5), and low-dose (14.8MBq; n = 5). An untreated control group included seven rats. 90Y PET/CT of 90Y distributions confirmed lobar targeting. MRI volumes were measured at baseline, 2-, 4-, 8- and 12-weeks. Explanted hepatic lobes were weighed, sectioned, and stained for H&E and immunohistochemistry. Digitized slides allowed quantitative measurements of fibrosis (20 foci/slide). Ex vivo measurements confirmed 91-97% activity was localized to the target lobe (n = 4). The percent growth of the target lobe relative to baseline was -5.0% (95% CI -17.0-6.9%) for high-, medium dose rats compared to + 18.6% (95% CI + 7.6-29.7%) in the low-dose group at 12-weeks (p = 0.0043). Radiation fibrosis increased in a dose-dependent fashion. Fibrotic area/microsphere was 22,893.5, 14,946.2 ± 2253.3, 15,304.5 ± 4716.6, and 5268.8 ± 2297.2μm2 for very high- (n = 1), high- (n = 4), medium- (n = 3), and low-dose groups (n = 5), respectively. Y90 PVE was feasible in the rat model, resulted in target lobe atrophy, and dose-dependent increases in hepatic fibrosis at 12weeks. The onset of imaging-based volumetric changes was 8-12weeks.

Estimation of Yttrium-90 Distribution in Liver Radioembolization using Computational Fluid Dynamics and Deep Neural Networks.

Yttrium-90 (90Y) radioembolization is a liver cancer therapy based on 90Y microspheres injected into the hepatic artery. Current dosimetry methods used to estimate the absorbed dose in order to prescribe the 90Y activity to inject are not accurate, which can affect the treatment effectiveness. A new dosimetry based on the hemodynamics simulation of the hepatic arterial tree, CFDose, aimed at overcoming some of the limitations of the current methods. However, due to the expensive computational cost of computational fluid dynamics (CFD) simulations, this method needs to be accelerated before it can be used in real-time during treatment planning. In this paper, we introduce a convolutional neural network model trained with the CFD results of a patient with hepatocellular carcinoma to predict the 90Y distribution under different downstream vasculature resistance conditions. The model performance was evaluated using two metrics, the mean squared error and prediction accuracy. The prediction accuracy showed that the average difference between the actual and predicted data was less than 1%. The proposed model could estimate the 90Y distribution significantly faster than a CFD simulation.

Factors affecting the response to Y-90 microsphere therapy in the cholangiocarcinoma patients.

The aim of this study was to assess the early therapy response in patients with unresectable CCA who received Y-90 microsphere therapy for CCA and define the factors related to therapy response. Data of 19 patients [extrahepatic (n: 6) and intrahepatic (n: 13)] who received 24 sessions of Y-90 microsphere therapy [glass (n: 13) and resin (n: 11)] were retrospectively evaluated. Tumor load, tumor size, therapy response evaluation by RECIST1.1 criteria (n: 13), tumor lesion glycolysis (TLG), metabolic tumor volume (MTV), and metabolic therapy responses were evaluated (n: 8) using PERCIST1.0 criteria. No significant relation was found between therapy response and tumor localization, treated liver lobe, type of Y90 microspheres, the presence of previous therapies, perfusion pattern on hepatic artery perfusion scintigraphy, or patient demographics. The mean overall survival (OS) was 11.9 ± 2.3months and was similar after both resin and glass Y90 microspheres; however, it was longer RECIST responders (p: 0.005). MTV and TLG values significantly decreased after therapy, and ΔMTV (- 45.4% ± 12.1) was found to be positively correlated with OS. No statistical difference was found between iCCA and eCCA, in terms of OS and response to therapy. Although not quantitatively displayed, better-perfused areas on HAPS images had a better metabolic response and less perfused areas were prone to local recurrences. Both resin and glass microsphere therapy can be applied safely to iCCA and eCCA patients. Early therapy response can be evaluated with both RECIST and PERCIST criteria. Both anatomical and metabolic therapy response evaluations give complementary information.

Long-term results of selective internal radioembolization (SIRT) to control progressive liver metastases of gastro-intestinal stromal tumors (GIST) beyond treatment with tyrosine kinase inhibitors (TKI).

11538 Background: Liver and peritoneum are the main area of metastatic spread in GIST. Liver resection does not play a role for hepatic metastases in comparison to f.e. colorectal cancer. If hepatic metastases are the only or major area of tumor progression and are resistant to available TKIs due to a missing mutation in KIT/PDGFRA/SDH ( ‘wildtype’) or after treatment with 1st/2nd/3rd/4th line therapy, interventional radioembolization with yttrium-90 (90Y) microspheres are promising treatment options, as radiation doses as high as 200Gy can be applied locally. We analyzed the long-term results of SIRT with respect to hepatic-progression-free survival (HEP-PFS) in a consecutive cohort of patients.. Methods: From 1/2008 to 1/2018, 25 pts (12f, 13m) with biopsy proven liver metastases of GIST which were the only (n = 13) or the dominant site of progression (n = 12) were treated by SIRT. Median age at GIST diagnosis had been 51.8 yrs and when receiving SIRT was 57.6yrs (range, 18–75yrs). The mutational status was ‘wildtype’ (n = 7, 2 NF-1), exon 11 (n = 7), exon 11+2nd mutation (n = 6), exon 9 (n = 3), exon 9+2ndmut (n = 1), and, exon 13 (n = 1). All patients except of two had prior TKI therapy: 1 line n = 3, 2 lines n = 11, 3-4 lines n = 9. Follow-up after SIRT was done via dynamic MRI and contrast-enhanced (CE)-CT, the median follow-up is 30.6 mos (range, 12-100mos) and all patients were followed until death. Results: The median hepatic-progression free survival (HEP-PFS) after SIRT was 17 months (range, 5-53+, 95%CI 11.8-22.1 mos). Of the patients with concomitant extrahepatic disease, the extraHEP-PFS was median 10 months. Twelve patients received next-line TKI therapy for progressive extrahepatic disease, whereas six patients required this for progressive liver metastases. When comparing the results according to the mutational status, patients with a ‘wildtype’ tumor showed a better median HEP-PFS of 19 mos (range, 12-53+, 95%CI 16.7-21.2 mos.) in comparison to KIT exon 9/11/13 mutated patients with only 14 months (range, 4-34 mos., 95%CI 6.5-21.4 mos), p < 0.11 (Wilcoxon). Conclusions: 90Y radioembolization (SIRT) offers a safe and effective treatment for patients with liver metastases of GISTs being the dominant site of tumor progression and with no drug treatment options available. In patients known to have no mutation in KIT/PDGFRA (wt, also NF-1 associated) it looks whether the results might be even more promising and SIRT could be used in early treatment lines.

Abstract No. 562 Temporary reversal of hepatoenteric collaterals during Y90 planning and treatment

A serious complication of Y90 radioembolotherapy (Y90 RE) is nontarget embolization. Current conventional methods to prevent this include coil embolization of hepatoenteric arteries. Temporary redirection of blood towards the liver within these arteries using a balloon catheter in the common hepatic artery provides a safe alternative with prevention of nontarget deposition of Y90 microspheres. Between September 2010 to September 2015, 88 patients with diagnostic or treatment angiograms with attempted use of the balloon occlusion technique were catalogued. A balloon catheter was inflated in the common hepatic artery to temporarily redirect flow from hepatoenteric arteries toward the liver during both diagnostic Tc99m MAA (67 patients) and therapeutic Y90 RE (72 patients) delivery. SPECT/CT nuclear scintigraphy was performed after delivery of each radionuclide. Clinical and laboratory follow-up at 1, 3 and 6 months and imaging follow-up at 3 and 6 months were performed. 72 Y90 RE treatment sessions were performed with use of the balloon technique with either glass (21) or resin (51) microspheres. Tumor types included hepatocellular (26), neuroendocrine (26), colorectal (23), or other (13). Post Y90 RE scintigraphy confirmed no significant extrahepatic activity in any patient. Whole liver, right lobe, left lobe Y90 RE treatments were performed in 58, 15 and 5 sessions respectively. One grade 2 gastrointestinal ulcer was present at 90 day follow-up. Greater than 80% administration of the prescribed dose of was possible in 34/51 resin microsphere sessions and in 20/21 sessions of glass microspheres. Temporary occlusion of the common hepatic artery with a balloon-catheter is a reliable and reproducible alternative to conventional coil embolization of hepatoenteric arteries during both diagnostic Tc99m MAA and therapeutic Y90 RE delivery.

Feasibility of imaging 90 Y microspheres at diagnostic activity levels for hepatic radioembolization treatment planning.

PurposePrior to 90Y hepatic radioembolization, a dosage of 99mTc‐macroaggregated albumin (99mTc‐MAA) is administered to simulate the distribution of the 90Y‐loaded microspheres. This pretreatment procedure enables lung shunt estimation, detection of potential extrahepatic depositions, and estimation of the intrahepatic dose distribution. However, the predictive accuracy of the MAA particle distribution is often limited. Ideally, 90Y microspheres would also be used for the pretreatment procedure. Based on previous research, the pretreatment activity should be limited to the estimated safety threshold of 100 MBq, making imaging challenging. The purpose of this study was to evaluate the quality of intra‐ and extrahepatic imaging of 90Y‐based pretreatment positron emission tomography/computed tomography (PET/CT) and quantitative single photon emission computed tomography (SPECT)/CT scans, by means of phantom experiments and a patient study.MethodsAn anthropomorphic phantom with three extrahepatic depositions was filled with 90Y chloride to simulate a lung shunt fraction (LSF) of 5.3% and a tumor to nontumor ratio (T/N) of 7.9. PET /CT (Siemens Biograph mCT) and Bremsstrahlung SPECT/CT (Siemens Symbia T16) images were acquired at activities ranging from 1999 MBq down to 24 MBq, representing post‐ and pretreatment activities. PET/CT images were reconstructed with the clinical protocol and SPECT/CT images were reconstructed with a quantitative Monte Carlo‐based reconstruction protocol. Estimated LSF, T/N, contrast to noise ratio of all extrahepatic depositions, and liver parenchymal and tumor dose were compared with the phantom ground truth. A clinically reconstructed SPECT/CT of 150 MBq 99mTc represented the current clinical standard. In addition, a 90Y pretreatment scan was simulated for a patient by acquiring posttreatment PET/CT and SPECT/CT data with shortened acquisition times.ResultsAt an activity of 100 MBq 90Y, PET/CT overestimated LSF [+10 percentage point (pp)], underestimated liver parenchymal dose (−3 Gy/GBq), and could not detect the extrahepatic depositions. SPECT/CT more accurately estimated LSF (−0.7 pp), parenchymal dose (−0.3 Gy/GBq) and could detect all three extrahepatic depositions. 99mTc SPECT/CT showed similar accuracy as 90Y SPECT/CT (LSF: +0.2 pp, parenchymal dose: +0.4 Gy/GBq, all extrahepatic depositions visible), although the noise level in the liver compartment was considerably lower for 99mTc SPECT/CT compared to 90Y SPECT/CT. The patient’s SPECT/CT simulating a pretreatment 90Y procedure accurately represented the posttreatment 90Y microsphere distribution.ConclusionsQuantitative SPECT/CT of 100 MBq 90Y could accurately estimate LSF, T/N, parenchymal and tumor dose, and visualize extrahepatic depositions.

The number of microspheres in Y90 radioembolization directly affects normal tissue radiation exposure.

In Y90 radioembolization, the number of microspheres infused varies by more than a factor of 20 over the shelf-life of the glass radioembolization device. We investigated the effect of the number of Y90 microspheres on normal liver tissue. Healthy pigs received lobar radioembolization with glass Y90 microspheres at 4, 8, 12, and 16 days post-calibration, representing a > 20× range in the number of microspheres deposited per milliliter in tissue. Animals were survived for 1-month post-treatment and the livers were explanted and scanned on a micro CT system to fully characterize the microscopic distribution of individual microspheres. A complete 3D microdosimetric evaluation of each liver was performed with a spatially correlated analysis of histopathologic effect. Through whole-lobe microscopic identification of each microsphere, a consistent number of microspheres per sphere cluster was found at 4, 8, and 12 days postcalibration, despite an 8-fold increase in total microspheres infused from days 4 to 12. The additional microspheres instead resulted in more clusters formed and, therefore, a more homogeneous microscopic absorbed dose. The increased absorbed-dose homogeneity resulted in a greater volume fraction of the liver receiving a potentially toxic absorbed dose based on radiobiologic models. Histopathologic findings in the animals support a possible increase in normal liver toxicity in later treatments with more spheres (i.e., ≥ day 12) compared to early treatments with less spheres (i.e., ≤ day 8). The microdosimetric evidence presented supports a recommendation of caution when treating large volumes (e.g., right lobe) using glass 90Y microspheres at more than 8 days post-calibration, i.e., after "2nd week" Monday. The favorable normal tissue microscopic distribution and associated low toxicity of first week therapies may encourage opportunities for dose escalation with glass microspheres and could also be considered for patients with decreased hepatic reserve.

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers.

Radioembolization using 90Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope 90Y is a β-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of 90Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.

Catheter-Directed Computed Tomography Hepatic Angiography for Yttrium-90 Selective Internal Radiotherapy of Hepatocellular Carcinoma Reduces Prophylactic Embolization of Extrahepatic Vessels.

To determine the rate of prophylactic embolization of extrahepatic vessels in patients undergoing yttrium-90 selective internal radiotherapy (90Y SIRT) for hepatocellular carcinoma (HCC) with the use of catheter-directed computed tomography hepatic angiography (CD-CTHA). This retrospective study included 186 HCC patients who received 90Y SIRT from May 2010 to June 2015 in a single institution. All procedures were performed in a hybrid angiography-CT suite equipped with digital subtraction angiography (DSA) and CD-CTHA capabilities. CD-CTHA was performed during pre-treatment hepatic angiography. 90Y SIRT was administered approximately 2weeks later. Selective prophylactic embolization of extrahepatic vessels was performed if extrahepatic enhancement was seen on CD-CTHA or if an extrahepatic vessel opacified on DSA/CD-CTHA despite the final microcatheter position for 90Y microsphere delivery being beyond the origin of this vessel. Thirty-five patients (18.8%) required selective embolization of extrahepatic vessels. Technical success of 90Y SIRT was 99.5%. Two patients (1.1%) developed radiation-induced gastrointestinal ulceration, and one (0.54%) developed radiation-induced pneumonitis. Extrahepatic uptake of 90Y microspheres was seen in the gallbladder of one patient without significant complications. The use of CD-CTHA in 90Y SIRT of HCC was associated with a low rate of prophylactic embolization of extrahepatic vessels while maintaining a high technical success rate of treatment and low rate of complications. Level 4, case series.

Yttrium-90 selective internal radiation therapy: Are patient radiation protection contact restrictions necessary?

Yttrium-90 (90Y) microspheres are used for selective internal radiation therapies (SIRTs) to treat patients with hepatocellular carcinoma (HCC) or metastatic colon cancer to the liver, with doses of up to 150 Gy delivered per treatment. 90Y is a pure beta emitter with a decay energy of 0.94 MeV and half-life of 64.2 h. While external beta exposure from the patient is negligible, there can be a considerable associated Bremsstrahlung radiation exposure component. Previous studies in the US, towards establishing radiation dose rates from patients, have deemed radiation protection precautions post-therapy to be unnecessary in most cases; however, the question remains as to whether precautions are necessary within the EU, where more conservative dose constraints are employed. Accordingly, dose rates from 28 patients, treated over a three year period (2016–2018) were measured post therapy at distances of 0.3 m and 1 m, and in contact with the patients’ upper abdomen. Dose rates were compared with theoretical predictions and used as model inputs for calculating radiation doses received by family members and carers based on interaction patterns previously described in the literature. The work demonstrated restrictions to be advisable considering the dose constraints employed within the EU. Indeed, while this study examined dose rates for 90Y Therasphere patients, another 90Y therapeutic pharmaceutical, namely SIRSpheres, require reportedly similar treatment activities, leading to similar Bremsstrahlung radiation dose rates. Thus, in accordance with EU dose constraints, radiation protection precautions are necessary for those individuals in regular contact with patients having undergone SIRT procedures.

Y90-radioembolization via variant hepatic arteries: Is there a relevant risk for non-target embolization?

BACKGROUNDThe hepatic arterial anatomy is highly variable, with the two most common variants being a replaced right hepatic artery (RHA) originating from the superior mesenteric artery (SMA) and a left hepatic artery (LHA) originating from the left gastric artery (LGA). These anatomical variants could potentially increase the risk for non-target embolization during Y90-Radioembolization due to the close proximity between hepatic and enteric vessel branches.AIMTo evaluate the safety of Yttrium-90 radioembolization (90Y-RE) with resin microspheres in patients with a variant hepatic arterial anatomy.METHODSIn this retrospective single-center observational study, 11 patients who underwent RE with 90Y-resin microspheres via a LHA originating from the LGA, and 13 patients via a RHA originating from the SMA were included. Patient and treatment data were reviewed regarding clinical and imaging evidence of non-target embolization of 90Y-resin microspheres to the GI tract. Positioning of the tip of the microcatheter in relationship to the last hepatoenteric side branch was retrospectively analyzed using angiographic images, cone-beam CT and pre-interventional CT-angiograms.RESULTSNone of the 24 patients developed clinical symptoms indicating a potential non-target embolization to the GI tract within the first month after 90Y-RE. On the postinterventional 90Y-bremsstrahlung images and/or 90Y-positron emission tomographies, no evidence of extrahepatic 90Y-activity in the GI tract was noted in any of the patients. The mean distance between the tip of the microcatheter and the last enteric side branch during delivery of the 90Y microspheres was 3.2 cm (range: 1.9-5 cm) in patients with an aberrant LHA originating from a LGA. This was substantially shorter than the mean distance of 5.2 cm (range: 2.9-7.7 cm) in patients with an aberrant right hepatic originating from the SMA.CONCLUSION90Y-RE via aberrant hepatic arteries appears to be safe; at least with positioning of the microcatheter tip no less than 1.9 cm distal to the last hepatoenteric side branch vessel.

PET-CT post therapy dosimetry in radioembolization with resin 90Y microspheres: Comparison with pre-treatment SPECT-CT 99mTc-MAA results

Resin microspheres radioembolization is an effective treatment for liver tumors when the surgical option is not feasible. Doses delivered to tumor and normal liver can be assess in the pre-therapy phase by means of a 99mTc-MAA SPECT-CT simulation and after the treatment with 90Y PET-CT acquisition. The optimal therapeutic 90Y activity is determined on 99mTc-MAA SPECT-CT dose results in order to avoid healthy parenchyma toxicity and to effectively irradiate the tumor. The assumption of identical radiopharmaceutical distribution between simulation and verification is still under debate and literature data showed controversial results. In this study 10 HCC patient’s dosimetry performed on 99mTc SPECT-CT and 90Y PET-CT were compared. Patients were selected when a good agreement between the pre and post-therapy distribution was observed in order to investigate the intrinsic dosimetric variations between the two imaging modalities. Mean doses (MIRD and Voxel approaches) showed a good correlation (Pearson’s coefficient r > 0.90) both for tumor and normal liver. Dose Volume Histogram curves were compared with a good agreement particularly for normal liver (D50). Goal doses were achieved for 90% of patients. Bland-Altman analysis indicates lower variations for healthy parenchyma than for tumor (1.96 SD equal to 9.1 Gy and 68 Gy respectively) confirming the robustness of the dose-toxicity approach. PET-CT dosimetry well correlates with SPECT-CT doses (under assumption of same catheter position and 90Y activity). Better agreement was showed for 7/10 and 8/10 patients for T and NL respectively, confirming dosimetry as effective tool to optimize and individualize the treatment.

A pooled analysis of transarterial radioembolization with yttrium-90 microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma.

Purpose: The aim of this pooled analysis was to evaluate the clinical efficacy and safety of transarterial radioembolization (TARE) with yttrium-90 (90Y) microspheres for the treatment of unresectable intrahepatic cholangiocarcinoma (ICC).Methods: We searched the Cochrane Library, Embase, PubMed, SCI with the English language from inception to October 2018. A pooled analysis was conducted using Stata software.Results: There were 16 eligible studies included in this pooled analysis. The pooled median overall survival (OS) from 12 studies was 14.3 (95% CI: 11.9–17.1) months. Based on Response Evaluation Criteria in Solid Tumors (RECIST), no complete response was reported, and the median of partial response, stable disease and progressive disease were 11.5% (range: 4.8–35.3%), 61.5% (range: 42.9–81.3%) and 22.7% (range: 12.5–52.4%) respectively. The pooled disease control rate (DCR) from nine studies was 77.2% (95% CI: 70.2–84.2%). According to the type of microspheres, subgroup analysis was performed, the median OS in the glass microspheres group was 14.0 (95% CI: 9.1–21.4) months, and 14.3 (95% CI: 11.5–17.8) months in the resin microspheres group. The DCR was 77.3% (95% CI: 63.5–91.1%) and 77.4% (95% CI: 66.8–87.9%) in the glass and resin microspheres groups respectively. Most of the side effects reported in the included studies were mild and did not require intervention.Conclusion: TARE with 90Y microspheres is safe and effective for patients with unresectable ICC with acceptable side effects. And it seems that the type of microsphere has no influence on therapeutic efficacy.

Early metabolic response assessment of breast cancer liver metastases: 4-week posttreatment FDG PET predicts survival after 90Y microsphere radioembolization.

To evaluate the feasibility of early metabolic response assessment with 18F-FDG PET/CT in patients with breast cancer liver metastases 4 weeks after radioembolization with Yttrium-90 labeled microspheres. 25 patients (mean age 58y, range 40-74) with advanced stage liver metastases of breast cancer were treated with 1.9 ± 0.4 GBq of 90Y-microspheres in the salvage setting and underwent 18F-FDG PET/CT at baseline and 4 weeks post-radioembolization. 14 patients (56 %) had an excessive hepatic tumor burden (> 50 % of total liver volume), 21 patients (84 %) had extrahepatic disease. Liver lesions with the highest SUVmax were selected as target lesions and a cut-off was set at 50 % reduction to separate responders from non-responders. The predictive impact of metabolic response on overall survival (OS) was investigated along with other prognostic factors. The median OS in this highly advanced metastatic cohort was 7 months (95 % CI, 5-9). All patients had a reduction in SUVmax (mean ΔSUVmax: -49 ± 26 %) at 4 weeks post-treatment. Patients with > 50 % SUVmax reduction survived longer (median OS 13 mo, 95 % CI 8-18) than the remaining patients (median OS 4 mo, 95 % CI 2-6; p = 0.001). From all investigated baseline factors including age, performance status, and presence of extra-hepatic disease, only the hepatic tumor burden had a significant impact on OS (p = 0.02). This is the first preliminary evidence in breast cancer that early post-radioembolization molecular response assessment of treated liver metastases - as early as 4 weeks posttreatment - may predict survival. If confirmed by larger series, FDG PET/CT could be considered for early response-adapted treatment modifications.

04:12 PM Abstract No. 333 How does number of microspheres affect absorbed-dose uniformity in Y90 radioembolization? An in vivo 3D evaluation in a porcine model

To characterize the effect of the number of Y90 microspheres on the microscopic dosimetry and absorbed-dose uniformity in a porcine model. Four healthy pigs received lobar infusions of Y90 glass microspheres at 4, 8, 12 and 16 days post-calibration. The administration dates resulted in the specific activity per microsphere of approximately 855, 302, 106, and 38 Bq at 4, 8, 12 and 16 days, respectively. CBCT was used to evaluate the perfused tissue volume at the time of delivery and the activity was selected to deliver a consistent absorbed dose of 50-60 Gy. After a 1 month survival, livers were explanted, fixed in formalin and gross pathologic evaluation performed. The embolized lobes were scanned on a Bruker MicroCT with a 9 um3 resolution. A blob-detection algorithm was used to identify all microspheres and a complete microdosimetric evaluation was performed. Twelve and 16-day pigs demonstrated focally distributed areas of necrosis on gross exam at organ harvest. Average lobar absorbed-doses were 50.9, 48.7, 53.5 and 50.0 Gy in the 4, 8, 12 and 16 day pigs, as calculated based on MicroCT identification of individual spheres. 3D analysis of microsphere deposition patterns showed average number of microspheres per cluster was 2.3, 3.4, 5.8 and 8.6 in 4, 8, 12 and 16 day pigs, with 4%, 7%, 11% and 14% of clusters in each pig containing >10 spheres, respectively. The percentage of liver tissue receiving more than 40Gy was 32%, 47%, 52% and 58% (days 4, 8, 12, 16), suggesting that microsphere number increases the fraction of normal tissue receiving a higher absorbed dose (p<.01). An analysis of absorbed dose to individual lobules shows higher maximum lobular dose (3501 Gy) in the 4 day pig compared to the 12 day pig (766 Gy, p<.01), but with lower median lobular dose in the 4 day pig (23 Gy) vs the 12 day pig (40 Gy, p<.01). While average organ doses were comparable, earlier treatments (i.e., 4 days post calibration) resulted in a greater fraction of liver receiving lower absorbed-doses (<40 Gy) compared to treatments at 12 or 16 days post calibration. These data suggest that treatments closer to calibration (higher specific activity/sphere) may be less hepatotoxic.

Right hepatectomy after down staging by Y90 microspheres radioembolization

Right hepatectomy after down staging by Y90 microspheres radioembolization

Impact of 90Y PET gradient-based tumor segmentation on voxel-level dosimetry in liver radioembolization

BackgroundThe purpose was to validate 90Y PET gradient-based tumor segmentation in phantoms and to evaluate the impact of the segmentation method on reported tumor absorbed dose (AD) and biological effective dose (BED) in 90Y microsphere radioembolization (RE) patients. A semi-automated gradient-based method was applied to phantoms and patient tumors on the 90Y PET with the initial bounding volume for gradient detection determined from a registered diagnostic CT or MR; this PET-based segmentation (PS) was compared with radiologist-defined morphologic segmentation (MS) on CT or MRI. AD and BED volume histogram metrics (D90, D70, mean) were calculated using both segmentations and concordance/correlations were investigated. Spatial concordance was assessed using Dice similarity coefficient (DSC) and mean distance to agreement (MDA). PS was repeated to assess intra-observer variability.ResultsIn phantoms, PS demonstrated high accuracy in lesion volumes (within 15%), AD metrics (within 11%), high spatial concordance relative to morphologic segmentation (DSC > 0.86 and MDA < 1.5 mm), and low intra-observer variability (DSC > 0.99, MDA < 0.2 mm, AD/BED metrics within 2%). For patients (58 lesions), spatial concordance between PS and MS was degraded compared to in-phantom (average DSC = 0.54, average MDA = 4.8 mm); the average mean tumor AD was 226 ± 153 and 197 ± 138 Gy, respectively for PS and MS. For patient AD metrics, the best Pearson correlation (r) and concordance correlation coefficient (ccc) between segmentation methods was found for mean AD (r = 0.94, ccc = 0.92), but worsened as the metric approached the minimum dose (for D90, r = 0.77, ccc = 0.69); BED metrics exhibited a similar trend. Patient PS showed low intra-observer variability (average DSC = 0.81, average MDA = 2.2 mm, average AD/BED metrics within 3.0%).Conclusions90Y PET gradient-based segmentation led to accurate/robust results in phantoms, and showed high concordance with MS for reporting mean tumor AD/BED in patients. However, tumor coverage metrics such as D90 exhibited worse concordance between segmentation methods, highlighting the need to standardize segmentation methods when reporting AD/BED metrics from post-therapy 90Y PET. Estimated differences in reported AD/BED metrics due to segmentation method will be useful for interpreting RE dosimetry results in the literature including tumor response data.

Quantitative comparison of pre-therapy 99mTc-macroaggregated albumin SPECT/CT and post-therapy PET/MR studies of patients who have received intra-arterial radioembolization therapy with 90Y microspheres

ObjectiveThe aim of our study was to compare yttrium -90 (90Y) dosimetry obtained from pre-therapy 99mTc-macroaggregated albumin (MAA) SPECT/CT versus post-therapy PET/MRI imaging among patients with primary or metastatic hepatic tumors. Materials and methodsPrior to 90Y radioembolization (RE), 32 patients underwent a scan using MAA mimicking 90Y distribution. After RE with 90Y microspheres, the patients were imaged on a PET/MRI system. Reconstructed images were transferred to a common platform and used to calculate 90Y dosimetry. The Passing-Bablok regression scatter diagram and the Bland and Altman method were used to analyze the difference between dosimetry values. ResultsFor MAA and PET/MRI modalities, the mean liver doses for all 32 subjects were 43.0 ± 20.9 Gy and 46.5 ± 22.7 Gy, respectively, with a mean difference of 3.4 ± 6.2 Gy. The repeatibility coefficient was 12.1 (27.0% of the mean). The Spearman rank correlation coefficient was high (ρ = 0.92). Although, there was a substantial difference in the maximum doses to the liver between the modalities, the mean liver doses were relatively close, with a difference of 24.0% or less. ConclusionsThe two main contributors to the difference between dosimetry calculations using MAA versus 90Y PET/MRI can be attributed to the changes in catheter positioning as well as the liver ROIs used for the calculations. In spite of these differences, our results demonstrate that the dosimetry values obtained from pre-therapy MAA SPECT/CT scans and PET/MRI post-therapy 90Y studies were not significantly different.

Selective Internal Radiation Therapy Using Yttrium-90 Radioembolization for Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. It is the sixth most common cancer worldwide with an incidence of 626,000 new patients a year, and the third most common cause of cancer related death. Secondary or metastatic liver are more common than primary tumor. The most common sites of primary tumor are breast, lung, and colorectal cancer with the majority of secondary liver cancers are metastases from colorectal cancer. Several locoregional catheter-based therapies options are available such as transarterial chemoembolism (TACE), drug eluting bead chemo-embolism and 90Y radioembolization for treatment of choice for unresectable HCC. Aim: To assess the effectiveness, safety and cost-effectiveness of selective internal radiation therapy (SIRT) using 90Y microspheres for the treatment of hepatocellular carcinoma. Methods: Electronic databases searched through the Ovid interface using MEDLINE (R) In-Process and Other Non-Indexed Citations and Ovid MEDLINE (R) 1946 to present. Additional articles were identified from reviewing the references of retrieved articles. Last search was conducted on 25th February 2016. Results: Seventeen articles related to SIRT using 90Y microspheres for HCC were included in this report in term of safety and effectiveness. For primary HCC, limited fair level of retrievable evidence to demonstrate that yttrium-90 radioembolization increased clinical response rates, improve survival and downstaging tumor for resection or transplant in unresectable primary HCC. For liver metastatic disease in colorectal cancer, limited fair level of retrievable evidence to demonstrate improvement in clinical response rates, longer median time to liver progression and overall survival when used in combination with first, second or third line chemotherapy as well as salvage treatment of chemotherapy refractory disease. For liver metastasis in neuroendocrine tumor, limited low level of retrievable evidence to suggest the use of 90Y radioembolization improved clinical response rates and median overall survival. Sufficient fair level of retrievable to suggest that 90Y radioembolization is a safe and well-tolerated procedure with some radioembolization specific complications. No retrievable evidence on cost-effectiveness. Conclusion: SIRT using 90Y microspheres may be used for unresectable primary hepatocellular carcinoma (HCC) and liver metastasis from colorectal cancer (mCRC). Strict criteria should be applied for patient selection and treatment shall be delivered through multidisciplinary team approach. However, SIRT is not recommended for unresectable metastatic liver disease of neuroendocrine tumor (mNET).