Resin Microsphere Radioembolization Research Articles

Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Treated by Yttrium-90 Resin Microsphere Radioembolization: A Retrospective Analysis Using Technetium-99m Macroaggregated Albumin SPECT/CT and Planning Software

PurposeTo characterize estimated mean absorbed tumor dose (ADT), objective response (OR), and estimated target dose of hepatocellular carcinoma (HCC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. Materials and MethodsIn this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between October 2015 and June 2022 was performed using a commercial software package and pretreatment technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT)/computed tomography (CT). In total, 101 patients with HCC underwent 102 treatments of 127 index tumors. Patients underwent imaging every 2–3 months after treatment to determine best response per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Best response was defined as the greatest response category per mRECIST and categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and progression-free survival using ADT. ResultsThe median follow-up period was 148 days (interquartile range [IQR], 92–273 days). The median ADT of OR was 141.9 Gy (IQR, 89.4–215.8 Gy) compared with the median ADT of NR treatments of 70.8 Gy (IQR, 42.0–135.3 Gy; P < .001). Only ADT was predictive of response (hazard ratio = 2.79 [95% confidence interval {CI}: 1.44–5.40]; P = .003). At 6 months, an ADT of 157 Gy predicted 90.0% (95% CI: 41.3%–98.3%) probability of OR. At 1 year, an ADT of 157 Gy predicted 91.6% (95% CI: 78.3%–100%) probability of progression-free survival. Partition modeling and delivered activity were predictive of progression (P = .021 and P = .003, respectively). ConclusionsFor HCC treated with resin microspheres, tumors receiving higher ADT exhibited higher rates of OR. An ADT of 157 Gy predicted 90.0% OR at 6 months.

Partition Dosimetry and Outcomes of Metastatic Neuroendocrine Tumors after Yttrium-90 Resin Microsphere Radioembolization

PurposeTo characterize estimated mean tumor-absorbed dose (ADT) and objective response of metastatic neuroendocrine tumor (NET) after resin microsphere yttrium-90 (90Y) hepatic radioembolization using partition dosimetry. Materials and MethodsIn this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between 2013 and 2022 involved the use of Sureplan (MIM Software, Cleveland, Ohio) and technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) combined with computed tomography. Thirty-six patients with NET underwent treatment of 56 index tumors. Patients underwent imaging every 3–6 months after treatment to determine best response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Responses were categorized as objective response (OR) or nonresponse (NR). Wilcoxon rank sum test evaluated differences in continuous variables, and Pearson χ2 test evaluated differences in categorical variables. ResultsMedian follow-up was 582 days (IQR, 187–1,227 days). Per RECIST 1.1, 27 patients (75%) experienced OR and 9 patients experienced (25%) NR. Of the 36 patients, 33 (92%) showed hypervascular, mRECIST-evaluable tumors. Among them, 28 patients (85%) showed mRECIST OR and 5 patients (15%) showed NR. The mRECIST OR group received a higher ADT than the NR group (median, 107 Gy; IQR, 95.1–154 Gy vs median, 70.4 Gy; IQR, 62.9–87.6 Gy; P = .048). All tumors receiving at least 120 Gy showed mRECIST OR. ConclusionsIn hypervascular metastatic NET treated by 90Y resin microsphere radioembolization, higher tumor dose was associated with better tumor response per mRECIST. Doses of ≥120 Gy led to OR.

Predictive Partition Dosimetry and Outcomes after Yttrium-90 Resin Microsphere Radioembolization of Colorectal Cancer Metastatic to the Liver: A Retrospective Analysis

PurposeTo characterize estimated absorbed tumor dose (ADT), objective response (OR), and estimated target dose of liver metastatic colorectal cancer (mCRC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. Materials and MethodsIn this retrospective, single-center study, multicompartment dosimetry of index tumors undergoing 90Y radioembolization from October 2013 to July 2022 was performed using MIM SurePlan and pretreatment technetium-99m macroaggregated albumin infusion data. Thirty-eight patients with mCRC underwent treatments for 59 index tumors. Patients were imaged every 2–3 months after treatment and then every 3–6 months after disease control to determine the best response per Response Evaluation Criteria in Solid Tumors 1.1. Responses were categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and local progression–free survival (LPFS) based on ADT. ResultsPatients had a median follow-up of 116 days (interquartile range [IQR], 69–231 days). The ADT was higher for OR patients than for NR patients (median, 130.8 [IQR, 85.6–239.0] vs 40.6 [IQR, 26.0–66.3] Gy; P < .001). A greater percentage of OR than NR patients were treated with activities calculated by partition modeling (54% vs 12%; P = .005). Only ADT predicted response (P = .032). At 6 months, an ADT of 120 Gy predicted a 55% (95% CI, 0.0%–89%) probability of OR. Only ADT (P = .010) and female sex (P = .014) predicted LPFS. At 1 year, an ADT of 120 Gy predicted a 70% (95% CI, 35%–100%) probability of LPFS. ConclusionsTumor dose was the strongest predictor of OR for mCRC. Administration of an estimated 120 Gy to mCRC predicted 55% OR with 90Y resin microspheres at 6 months.

Abstract No. 122 Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Following Liver Resin Microsphere Radioembolization

Abstract No. 122 Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Following Liver Resin Microsphere Radioembolization

Toxicity comparison of yttrium-90 resin and glass microspheres radioembolization.

To investigate the clinical, hematological and biochemical toxicity differences between glass and resin yttrium-90 (90Y)-microspheres radioembolization treatment of primary and metastatic liver disease. Between May 2014 and November 2016 all consecutive glass and resin 90Y microspheres radioembolization treatments were retrospectively analyzed. Biochemical, hematological and clinical data were collected at treatment day, two weeks, one month and three months follow-up. Post-treatment 90Y PET/CTs were assessed for the absorbed doses in non-tumorous liver volume (DNTLV) and tumor volume (DTV). Biochemical, hematological and clinical toxicity were compared between glass and resin using chi square tests and repeated ANOVA measures. Biochemical and clinical toxicity was correlated with DNTLV,total by means of Pearson correlation and independent T-tests. A total of 85 patients were included (n=44 glass, n=41 resin). Clinical toxicity the day after treatment (i.e. abdominal pain (p=0.000), nausea (p=0.000) and vomiting (p=0.003)) was more prevalent for resin. Biochemical and hematological toxicities were similar for both microspheres. The DNTLV,total was significantly higher in patients with REILD grade ≥3 in the resin group (43.5 versus 33.3 Gy (p=0.050)). A similar non-significant trend was seen in the glass group: 95.0 versus 69.0 Gy (p=0.144). The clinical, hematological and biochemical toxicity of radioembolization treatment with glass and resin is comparable, however, post-embolization syndrome related complaints are more common for resin.

Post-treatment three-dimensional voxel-based dosimetry after Yttrium-90 resin microsphere radioembolization in HCC

BackgroundPost-therapy [90Y] PET/CT-based dosimetry is currently recommended to validate treatment planning as [99mTc] MAA SPECT/CT is often a poor predictor of subsequent actual [90Y] absorbed dose. Treatment planning software became available allowing 3D voxel dosimetry offering tumour-absorbed dose distributions and dose-volume histograms (DVH). We aim to assess dose–response effects in post-therapy [90Y] PET/CT dosimetry in SIRT-treated HCC patients for predicting overall and progression-free survival (OS and PFS) and four-month follow-up tumour response (mRECIST). Tumour-absorbed dose and mean percentage of the tumour volume (V) receiving ≥ 100, 150, 200, or 250 Gy and mean minimum absorbed dose (D) delivered to 30%, 50%, 70%, and 90% of tumour volume were calculated from DVH’s. Depending on the mean tumour -absorbed dose, treated lesions were assigned to a < 120 Gy or ≥ 120 Gy group.ResultsThirty patients received 36 SIRT treatments, totalling 43 lesions. Median tumour-absorbed dose was significantly different between the ≥ 120 Gy (n = 28, 207 Gy, IQR 154–311 Gy) and < 120 Gy group (n = 15, 62 Gy, IQR 49–97 Gy, p <0 .01). Disease control (DC) was found more frequently in the ≥ 120 Gy group (79%) compared to < 120 Gy (53%). Mean tumour-absorbed dose optimal cut-off predicting DC was 131 Gy. Tumour control probability was 54% (95% CI 52–54%) for a mean tumour-absorbed dose of 120 Gy and 90% (95% CI 87–92%) for 284 Gy. Only D30 was significantly different between DC and progressive disease (p = 0.04). For the ≥ 120 Gy group, median OS and PFS were longer (median OS 33 months, [range 8–33 months] and median PFS 23 months [range 4–33 months]) than the < 120 Gy group (median OS 17 months, [range 5–33 months] and median PFS 13 months [range 1–33 months]) (p < 0.01 and p = 0.03, respectively).ConclusionsHigher 3D voxel-based tumour-absorbed dose in patients with HCC is associated with four-month DC and longer OS and PFS. DVHs in [90Y] SIRT could play a role in evaluative dosimetry.

Yttrium-90 radioembolization using MIRD dosimetry with resin microspheres

To review the technical feasibility of resin microsphere (SIR-Spheres®) yttrium-90 radioembolization prescribed using the medical internal radiation dose (MIRD) model. All radioembolization procedures for hepatic malignancies using resin microspheres with MIRD model between November 2015 and February 2019 were included in this IRB-approved study (n = 60). Student's T test was used to compare prescribed activity based on MIRD and BSA models. Adverse events were assessed immediately, 30days, and 6months post-treatment. Sixty radioembolizations were performed in 54 patients (age 68 ± 9years, 48-87years, 35% female). Mean prescribed activity calculated by the MIRD model (target absorbed dose 120-200Gy for primary and 80-200Gy for metastatic liver cancers) was 1.7GBq (0.3-6.4) compared with 0.6GBq (0.12-2.1) if BSA had been used (p < 0.0001). The prescribed activity was successfully delivered in 93% (56/60) treatments. Prophylactic embolization and anti-reflux catheters were used in 20% (12/60) and 5% (3/60) treatments, respectively. No immediate post-procedural complications occurred. Abdominal pain was the most common clinical Grade 3 CTCAE in 30days (10%) and 6months (12%). Radiation pneumonitis occurred in 3 (5%) patients but no radiation-induced gastric ulcer or radiation-induced liver disease occurred. MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry with resin microspheres. MIRD prescribed activity with target absorbed doses up to 200Gy can be successfully administered without prophylactic embolization in selected patients. •MIRD dosimetry results in higher prescribed activity compared with BSA dosimetry for radioembolization. •MIRD dosimetry can be used for yttrium-90 resin microsphere radioembolization with acceptable safety profile.

The MAAPE score in intermediate and advanced hepatocellular carcinoma treated with Yttrium‐90 resin microsphere radioembolization

Yttrium-90 resin microsphere radioembolization (RE) is not recommended for routine use in intermediate or advanced hepatocellular carcinoma (HCC) by recent guidelines. This study aims to establish pre-treatment variables which predict survival in HCC patients treated with RE to identify those who will benefit most from it, and to inform patient selection for future trials. Single center, retrospective study of consecutive patients with HCC treated with RE from 2007 to 2018. Patients included if undergoing their first RE treatment for intermediate or advanced HCC; a Child-Pugh score of B7 or less; and a performance status of 1 or less. Multivariable Cox regression identified variables that were significantly associated with survival. A predictive score was developed based upon coefficients from the fitted Cox regression model, and cubic spline regression was used to identify prognostic groups. One hundred thirteen patients with intermediate (53.1%) and advanced HCC (45.1%) followed for a median of 13.2months were included. Variables associated with superior survival used to derive the MAAPE score were lower Model for End-Stage Liver Disease score (≤7), lower Alpha-fetoprotein (≤150IU/L), higher serum Albumin (>37g/L), absence of Portal vein tumor thrombus, and better performance status (Eastern Cooperative Oncology Group=0). Three survival prognostic groups were identified: good (median overall survival 25.0months), average (15.3months), and poor (6.3months) (overall log-rank test, P<0.001). The MAAPE score accurately identifies HCC patients in whom RE is safe and effective. This will allow for optimal patient selection for future trials of RE versus systemic therapy.

Radioembolization with 90Y Resin Microspheres of Neuroendocrine Liver Metastases After Initial Peptide Receptor Radionuclide Therapy

PurposePeptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT.MethodsPatients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected.ResultsForty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3–4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8–5.1 years] after radioembolization for the entire study population was found.ConclusionRadioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare.Level of Evidence4, case series.

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.

Ex Vivo Evaluation of Residual Activity and Infusion Dynamics in a Commercially Available Yttrium-90 Resin Microsphere Administration System

PurposeTo evaluate the infusion dynamics and residual yttrium-90 activity during and after resin microsphere radioembolization with different injection techniques and initial activities. To assess the distribution of residual activity in the administration systems to allow optimization of the procedure and the equipment. Materials and MethodsIn a setup similar to that in standard clinical practice, radioembolization procedures were performed ex vivo. The influence of different injection techniques was assessed by comparing pulsatile and continuous injections. The influence of the absolute amount of activity to the residual activity was assessed by comparing pulsatile 0.5-GBq- with 1.0-GBq-procedures. Continuous dose rate measurements were performed. Activity distribution was determined by positron-emission tomography (PET)/CT. ResultsFifteen procedures were performed: 5 pulsatile 0.5-GBq-, 5 continuous 0.5-GBq-, and 5 pulsatile 1.0-GBq-procedures. Mean residual activity was 4.0% ± 1.7% (range 1.2%–6.6%), without statistically significant differences between injection techniques (P = .841) or between prescribed activities (P = .222). Dose-rate measurements revealed an exponential decrease of the activities in the vials with high variability. Activity fell rapidly to 32% ± 7.9% (range 23%–55%) after injection of 4 of 20 mL 5% dextrose solution. Residual activity accumulations were identified at the 3-way stopcock (100% of procedures), in the C-line (80%), at the microcatheter connector (20%), and in the A-line (6.7%), but not in the vials. ConclusionsResidual activity in a commercial administration system for resin microsphere radioembolization is variable and does not systematically depend on initial yttrium-90 activity or on injection technique. Predilection sites for residual activity were identified, which should receive special attention when performing resin transarterial radioembolization procedures, and for further administration system developments.

90Y TOF-PET based EUD reunifies patient survival prediction in resin and glass microspheres radioembolization of HCC tumours

Clinical studies reported a twofold ratio between the efficacies per Gy of resin versus glass spheres. Our aim is to investigate whether this difference could result from the different degrees of heterogeneity in sphere distribution between the two medical devices. The 90Y TOF-PET based equivalent uniform doses (EUD) was used for this purpose.58 consecutive HCC radioembolizations were retrospectively analyzed. Absorbed doses D and Jones–Hoban EUD in lesions were computed. Radioembolization efficacy was assessed using Kaplan–Meier survival curves.In order to match together the glass and resin spheres survival curves using a 40 Gy-threshold, an efficacy factor of 0.73 and 0.36 has to be applied on their absorbed dose, respectively. Using EUD, a nice matching between glass and resin survival curves was obtained with a better separation of the responding and not responding survival curves.The results clearly support the fact that the activity heterogeneity observed in 90Y TOF-PET post radioembolization does not only result from statistical noise, but also reflects the actual heterogeneity of the spheres distribution. Use of EUD reunifies the efficacy of the two medical devices.

329. Personalized dosimetric approach in advanced HCC patients treated with 90Y resin microspheres

Purpose Radioembolization with 90Y resin microspheres is becoming an effective therapeutic option for advanced HCC patients. Dosimetric methods are compared to standard ones to highlight the relevance of a personalized approach. Methods The study was conducted on 42 HCC patients undergoing 90Y resin-microspheres radioembolization. The optimal activity was calculated on pre-treatment 99mTc-MAA CT-SPECT images with dosimetric approaches (Voxel and MIRD methods with the following dose treatment’s goals: whole healthy liver (NL) 120 Gy) and it was compared to the activity obtained with standard methods (BSA, fixed method). On 10 SPECT-CT images (IT_AC or IT_NOAC) the influence of CT attenuation correction was investigated: mean doses (T, NL) as well as DVH curves (D100, D95, D20, D2) were compared (using t-test). Results 77% of patients received a mean administered activity (1.42 ± 0.52, range 0.70 ÷ 2.63 GBq) lower than the BSA activity (up to −1.3 GBq) and only in 23% of cases the activity was higher (+0.8 GBq). Similar results with bigger discrepancies were observed comparing the activity calculated with dosimetric and fixed method: 84% of patients received a lower activity than the one suggested by the fixed method (up to −1.7 GBq), 16% were administered with higher activity (up to 0.8 GBq). If the doses to NL were rescaled to BSA and fixed activity values, they would be significantly higher, exceeding the 30 Gy constraint in 54.2% of patients (BSA) and 70.8% (fixed). Mean T doses were 172 ± 145 Gy (IT_AC) and 181 ± 168 Gy (IT_NOAC) and mean scintigraphic NL doses 38 ± 23 Gy (IT_AC) and 30 ± 12 Gy (IT_NOAC) without statistical differences as well as in DVHs comparisons. NL IT_NOAC DVH points were in mean lower than IT_AC while higher discrepancies between the reconstructions were found in doses calculated to tumours. The results are shown in Fig. 1. Conclusions A dosimetric approach is mandatory in 90Y radioembolization because it is required by EU 2013/59 Directive but also to avoid under or over treatments; an accurate dosimetry can also be achieved on SPECT images without CT correction, which is useful, however, for volumes definition. Download : Download high-res image (141KB) Download : Download full-size image

Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma

PurposeTo identify predictive factors of tumor response, progression-free survival (PFS), overall survival (OS), and toxicity using three-dimensional (3D) voxel-based dosimetry in patients with intermediate and advanced stage hepatocellular carcinoma (HCC) treated by yttrium-90 (90Y) resin microspheres radioembolization (RE). Materials and MethodsFrom February 2012 to December 2015, 45 90Y resin microspheres RE procedures were performed for HCC (Barcelona Clinic Liver Cancer stage B/C; n = 15/30). Area under the dose-volume histograms (AUDVHs) were calculated from 3D voxel-based dosimetry to measure 90Y dose deposition. Factors associated with tumor control (ie, complete/partial response or stable disease on Modified Response Evaluation Criteria in Solid Tumors) at 6 months were investigated. PFS and OS analyses were performed (Kaplan-Meier). Toxicity was assessed by occurrence of radioembolization-induced liver disease (REILD). ResultsTumor control rate was 40.5% (17/42). Complete tumor targeting (odds ratio = 36.97; 95% confidence interval, 1.83–747; P < .001) and AUDVHtumor (odds ratio = 1.027; 95% confidence interval, 1.002–1.071; P = .033) independently predicted tumor control. AUDVHtumor ≥ 61 Gy predicted tumor control with 76.5% sensitivity and 75% specificity. PFS and OS in patients with incomplete tumor targeting were significantly shorter than in patients with complete tumor targeting (median PFS, 2.7 months [range, 0.8–4.6 months] vs 7.9 months [range, 2.1–39.5 months], P < .001; median OS, 4.5 months [range, 1.4–23 months] vs 19.2 months [range, 2.1–46.9 months], P < .001). Patients with incomplete tumor targeting and AUDVHtumor < 61 Gy, incomplete tumor targeting and AUDVHtumor > 61 Gy, complete tumor targeting and AUDVHtumor < 61 Gy, and AUDVHtumor > 61 Gy had median PFS of 2.7, 1.8, 6.3, and 12.1 months (P < .001). REILD (n = 4; 9.5%) was associated with higher dose delivered to normal liver (P = .04). ConclusionsComplete tumor targeting and 90Y dose to tumor are independent factors associated with tumor control and clinical outcomes.

3:27 PM Abstract No. 124 MIRD-based activity calculation may improve outcomes over body surface area for resin microsphere radioembolization of metastatic colorectal carcinoma

To compare clinical outcomes of resin microsphere Y90 radioembolization (RE) using standard Body Surface Area (BSA) activity prescription versus Medical Internal Radiation Dose (MIRD) prescription for treatment of metastatic colorectal carcinoma (mCRC). Patients with mCRC treated with resin microsphere RE between 2004-2015 were retrospectively reviewed. Standard BSA activity prescription was used from 2004-2012. Starting 2013, MIRD-based activity prescription was substituted, with treated region absorbed doses ranging from 40-65 Gy depending on performance status, liver function, volume of treatment, hypervascularity, and previous treatment history. Radiographic, biochemical, and clinical outcomes were compared. 109 patients (61 M/48 F), median age 60, underwent 118 treatment sessions (96 BSA/ 22 MIRD). 77 underwent whole liver treatment, either single session (72) or staged (5). In the MIRD group, 7 (36%) patients had activity prescribed >10% greater and 3 (15%) had activity >10% lower than what would have been prescribed by BSA. Disease control rate (DCR) by RECIST 1.1 showed a trend favoring MIRD over BSA (71% vs 53%, p = 0.1). MIRD patients showed more mild laboratory toxicity changes at 90 days (CTCAE 4.03, ≤ 2 grade change from baseline) (28% vs 18%, p = NS), but slightly less moderate and severe toxicity changes than BSA patients (>2 grade change from baseline) (0% vs 3%, p = NS). Median changes in serum carcinoembryonic antigen (CEA) in MIRD and BSA groups at 8 weeks after RE were -16% and -8%, (p = NS). Differences in median hepatic progression-free survival did not reach statistical significance (MIRD 150 days vs BSA 90 days, p = 0.5). Likewise, the study was underpowered to show a difference in overall survival (210 vs 321 days, p = 0.4). Using MIRD rather than BSA for activity calculation for resin microsphere Y90 RE of mCRC resulted in increase in dose in 36% and decrease in 15% of patients. Although additional statistical power is needed, consideration of the target liver volume rather than body surface area is a promising approach to increase the efficacy and decrease the toxicity of resin microsphere RE.

3:27 PM Abstract No. 264 PI3K pathway mutations predict response on PET/CT after radioembolization as salvage therapy for heavily pretreated patients with breast cancer liver metastases

Transarterial radioembolization (RE) is an emerging treatment for patients with hepatic metastasis due to breast cancer. This single-center retrospective review was conducted to identify factors predicting favorable outcomes and survival after RE. Thirty-one heavily pretreated female patients underwent RE between January 2011 and September 2017 (9 with glass and 22 with resin microspheres). Of these, 24 also underwent next-generation genetic sequencing with MSK-IMPACT or Sequenom, and 26 had PET/CTs available to document imaging response performed on average 38 ± 35 before and 80 ± 33 days after RE. Response was categorized as complete response when the SUVmax in the targeted liver segments decreased by >80%, partial response when SUVmax decreased by 30-80%, stable disease when a change in by normalized SUVmax between -30% and 30%, and progressive disease when normalized SUVmax increased by more than 30%. Kaplan-Meier survival analysis demonstrated a median survival after RE of 10.8 months. Complete or partial response was achieved in 18/26 (69%). PI3K pathway mutations were associated with imaging response (p = 0.006) but not survival (p = 0.58). Imaging response predicted longer survival (p = 0.005). Trends for lower bilirubin levels (p = 0.15), lower preprocedure neutrophil-to-lymphocyte ratio (p = 0.06), younger age (p = 0.15), and lower total bilirubin level (p = 0.06) to predict improved survival were not significant. Mutations in TP53, the MAPK-ERK pathway, hormonal status, and preradioembolization imaging variables (lung shunt fraction, arterial enhancement fraction, or tumor burden) did not correlate with imaging response (p>0.05). Three (9.6%) patients had major adverse events after resin microsphere-radioembolization, including two with gastric ulcers managed conservatively and one with liver failure and death 26 days after the first lobar treatment. These preliminary observations confirm the prognostic relevance of early interval follow-up imaging after RE to survival. Furthermore, these data suggest that genomic profiling may help predict which metastatic breast cancer patients could benefit most from RE.

Tumor Dose Response in Yttrium-90 Resin Microsphere Embolization for Neuroendocrine Liver Metastases: A Tumor-Specific Analysis with Dose Estimation Using SPECT-CT

PurposeTo evaluate dose-response relationship in yttrium-90 (90Y) resin microsphere radioembolization for neuroendocrine tumor (NET) liver metastases using a tumor-specific dose estimation based on technetium-99m–labeled macroaggregated albumin (99mTc MAA) single photon emission computed tomography (SPECT)-CT. Materials and MethodsFifty-five tumors (mean size 3.9 cm) in 15 patients (10 women; mean age 57 y) were evaluated. Tumor-specific absorbed dose was estimated using a partition model. Initial (median 2.3 months) follow-up data were available for all tumors; last (median 7.6 months) follow-up data were available for 45 tumors. Tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors (mRECIST) on follow-up CT. Tumors with complete or partial response were considered responders. Mean tumor absorbed dose was 231.4 Gy ± 184.3, and mean nontumor liver absorbed dose was 39.0 Gy ± 18.0. ResultsThirty-six (65.5%) and 30 (66.7%) tumors showed response at initial and last follow-up, respectively. Mean absorbed doses in responders and nonresponders at initial and last follow-up were 285.8 Gy ± 191.1 and 128.1 Gy ± 117.1 (P = .0004) and 314.3 Gy ± 195.8 and 115.7 Gy ± 117.4 (P = .0001). Cutoff value of ≥ 191.3 Gy for tumor-specific absorbed dose predicted tumor response with 93% specificity, whereas < 72.8 Gy predicted nonresponse with 100% specificity at last follow-up. Estimated mean absorbed tumor dose per patient was significantly higher in responders versus nonresponders over the follow-up period (224.5 Gy ± 90.3 vs 70.0 Gy ± 28.0; P = .007). ConclusionsTumor-specific absorbed dose, estimated with a partition model, was significantly associated with tumor response in NET liver metastases. An estimated dose ≥ 191.3 Gy predicted treatment response with high sensitivity and specificity.

Yttrium-90 Radioembolization with Resin Microspheres without Routine Embolization of the Gastroduodenal Artery

PurposeTo evaluate safety of resin microsphere radioembolization (RE) without prophylactic embolization of the gastroduodenal artery (GDA). Materials and MethodsBetween July 2013 and April 2015, all patients undergoing RE with resin microspheres for liver-dominant metastatic disease were treated without routine embolization of the GDA. Selective embolization of distal hepaticoenteric vessels was performed if identified by digital subtraction angiography, cone-beam computed tomography, or technetium-99m macroaggregated albumin scintigraphy. Resin microspheres were administered using 5% dextrose flush distal to the origin of the GDA in lobar or segmental fashion, with judicious use of an antireflux microcatheter in recognized high-risk situations. Gastrointestinal toxicity was evaluated by the performing physician for at least 3 months. ResultsRE with resin microspheres was performed in 62 patients undergoing 69 treatments. During planning angiography, embolization of 0 or 1 vessel (median, 1; range, 0–4) was performed in 86% of patients, most commonly the right gastric and supraduodenal arteries. Prophylactic embolization of the GDA was performed in only 2 patients (3%). In 6 treatments (9%), adjunctive embolization was required immediately before RE, and an antireflux microcatheter was used in 14% of treatments. Clinical follow-up was available in 60 of 62 patients (median, 134 d; range, 15–582 d). No signs or symptoms of gastric or duodenal ulceration were observed. ConclusionsRE using resin microspheres without embolization of the GDA can be performed safely.

Metabolic tumor volume and total lesion glycolysis on FDG-PET/CT can predict overall survival after 90Y radioembolization of colorectal liver metastases: A comparison with SUVmax, SUVpeak, and RECIST 1.0

PurposeTo compare the performance of 4 metrics of metabolic response on FDG-PET/CT against RECIST 1.0 for determining response and predicting overall survival (OS) following 90Y resin microspheres radioembolization of colorectal liver metastases (CLM). MethodsWe conducted an IRB-waived retrospective review of our radioembolization database to identify patients with unresectable CLM treated between December 2009 and December 2013. We included patients who had both PET/CT and contrast enhanced CT (CECT) available at baseline and on the first follow-up post-radioembolization. On baseline CECT up to five target tumors were chosen per patient according to RECIST 1.0. Four metrics of FDG-avidity (SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) on PET/CT were measured for the same target tumors. Using RECIST 1.0, patients were classified as no progression (partial response or stable disease) and progression. For each PET metric, a cut-off point of ≥30% decrease was chosen to define response. OS was calculated from the time of radioembolization using Kaplan-Meier methodology. The log-rank test was used for univariate analysis to identify predictors of OS. ResultsThe study enrolled 49 patients with 119 target tumors; a median of 2 (range: 1–5) tumors were selected per patient. Median OS was 12.7 months (95%CI: 7.2-16.7). Response by MTV (P=0.035) and TLG (P=0.044) reached statistical significance in predicting OS. Response by SUVmax (P=0.21), SUVpeak (P=0.20) or no progression by RECIST 1.0 (P=0.44) did not predict OS. ConclusionMetabolic response based on changes in MTV and TLG can predict OS post-radioembolization of CLM.

A descriptive analysis of remnant activity during (90)Y resin microspheres radioembolization of hepatic tumors: technical factors and dosimetric implications.

Activity planning for (90)Y radioembolization aims to maximize the effect of the treatment while keeping toxicity acceptably low. Our aim was to describe the amount of residual activity in post-treatment v-vials and tubing and analyze the possible factors affecting it (total activity administered, number of split activity injection(s), previous treatments, administration artery and microcatheter size), as these may influence dosimetric planning and treatment. This was a retrospective review using case records of patients who received (90)Y-radioembolization for hepatic tumors at a single tertiary center. From August 2013 to September 2015, seventy-seven out of one hundred and fifty patients who received radioembolization with (90)Y resin microspheres due to inoperable Hepatocellular Carcinoma (HCC) or liver metastases were included. The rest were mainly excluded due to incomplete data sets. The number of split activities (injections) for the radioembolization could be: one single injection, two or three. The remnant activity in post-treatment v-vials and tubing were measured for every patient. The administration arteries evaluated were: proper hepatic artery (PHA), right hepatic artery (RHA), middle hepatic artery (MHA), left hepatic artery (LHA) and small caliber branch arteries. The sizes of the microcatheters (2.2 or 2.7 Fr) used to administer the dose were also evaluated. In total, 77 out of 150 patients were included in the final analysis. There were 59 men of median age 64.0 years old. The total median dose loss was 0.10 GBq. The total dose loss increased 0.244 GBq [95 % CI = (0.169, 0.318)] when three split activities were given compared to single activity injection. Activity loss for each injection increased 0.0297 GBq [95 % CI = (0.0151, 0.0443)] for every 1.0 GBq increase of split activity injection. There were no significant statistical differences in the rest of patient characteristics. There is significant loss of activity observed during radioembolization, which can have a major dosimetric impact. The total administered activity and the number of split injections during radioembolization are the main influencing factors. Further prospective studies as well as measures of clinical outcome are warranted.