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Purpose: There are no published data on organ doses following intra‐hepatic‐arterial administration of 99mTc‐macroaggregated‐albumin (IHA 99mTc‐MAA) routinely used in 90Y‐radioembolization treatment planning to assess intra‐ and extra‐hepatic depositions and calculate lung‐shunt‐fraction (LSF). We propose a method to model the organ doses following IHA 99mTc‐MAA that incorporates three in vivo constituent biodistributions, the 99mTc‐MAA that escape the liver due to LSF, and the 99mTc‐MAA dissociation fraction (DF). Methods: The potential in vivo biodistributions for IHA 99mTc‐MAA are: Liver‐Only MAA with all activity sequestered in the liver (LSF = 0&DF = 0), Intravenous MAA with all activity transferred intravenously as 99mTc‐MAA (LSF = 1&DF = 0), and Intravenous Pertechnetate with all activity is transferred intravenously as 99mTc‐pertechnetate (LSF = 0&DF = 1). Organ doses for Liver‐Only MAA were determined using OLINDA/EXM 2.2, where liver was modeled as the source organ containing 99mTc‐MAA, while those for Intravenous MAA and Intravenous Pertechnetate were from ICRP 128. Organ doses for the general case can be determined as a weighted‐linear‐combination of the three constituent biodistributions depending on the LSF and DF. The maximum‐dose scenario was modeled by selecting the highest dose rate for each organ amongst the three constituent cases. Results: For Liver‐Only MAA, the liver as source organ received the highest dose at 98.6 and 126 mGy/GBq for the adult male and adult female phantoms, respectively; all remaining organs received <27 and <32 mGy/GBq. For Intravenous MAA, the lung as source organ received the highest dose at 66 and 97 mGy/GBq; all remaining organs received <16 and <21 mGy/GBq. The organ with the highest dose for Intravenous Pertechnetate was the upper‐large‐intestinal wall at 56 and 73 mGy/GBq; all remaining organs received <26 and <34 mGy/GBq. The liver and lung doses for the maximum‐dose scenario with 5 mCi (185 MBq) 99mTc‐MAA were estimated at 18.2 and 12.2 mGy, and 23.3 and 17.9 mGy, for the adult male and adult female phantoms, respectively. Conclusion: Organ dose estimates following IHA 99mTc‐MAA based on constituent biodistribution models and patient‐specific LSF and DF values have been derived. Liver and lung were the organs with highest dose, receiving at most 15–25 mGy in the maximum‐dose scenario, following 5 mCi IHA 99mTc‐MAA. [ABSTRACT FROM AUTHOR]

Purpose: 99mTc‐MAA‐SPECT/CT may be used in 90Y‐glass microsphere radioembolization treatment planning to assess perfused liver volumes and absorbed dose distributions. The partition model (PM) offers a more detailed planning dosimetry option beyond the single‐compartment model more traditionally used in 90Y radioembolization. As 90Y radioembolization treatments shift toward activities and doses that aim to achieve tumor control, accurate and reliable treatment planning dosimetry for both tumors and normal liver (NL) becomes more critical. In this work, we explore the accuracy and precision of 90Y dosimetry predictions from pretherapy 99mTc‐MAA and PM. Methods: Both PM and voxel dosimetry models were used to calculate tumor and NL mean doses using both planning 99mTc‐MAA and verification 90Y‐SPECT/CT in this retrospective analysis of hepatocellular carcinoma cases treated with glass microspheres (NCT01900002, n = 32). Linear regression models were developed at first access, and then later correct, the estimates by (a) 99mTc‐MAA for 90Y voxel dosimetry and (b) 99mTc‐MAA PM for voxel dosimetry, separately for both tumors and NL. Bland‐Altman analysis was then used to evaluate the accuracy and precision of the regression model predictions with the mean bias and 95% prediction intervals (PI, ±1.96σ). Two categories of cases were stratified (catheter matched vs catheter unmatched) by establishing the level of 99mTc‐MAA and 90Y catheter position alignment. Only catheter‐matched cases were included in the 99mTc‐MAA vs 90Y voxel dosimetry comparison, while all cases were used to compare dosimetry models (PM vs voxel). Results: Half (16/32) of cases were deemed catheter matched. 99mTc‐MAA could reliably predict NL doses in catheter‐matched cases after application of the linear model, with mean bias (PI) of −1% (±31%). PM was equivalent to voxel dosimetry for NL doses with mean bias (PI) of 0% (±1%). Even among catheter‐matched cases, 99mTc‐MAA planning for 90Y tumor voxel doses was poor, overestimating dose by an average of nearly 40%. Upon application of the linear model, 99mTc‐MAA predictions for 90Y tumor voxel dose were only minimally biased (−4%) but possessed very large PI (±104%). PM predictions for tumor voxel dose using the linear model also showed small bias (−6%) but maintained similarly high PI of ±90%. Cases with tumors representing a large majority (>80%) of the total tumor volume demonstrated the best scenarios for 99mTc‐MAA and PM tumor dose predictions, with mean biases (PI) of −3% (±53%) and −4% (±21%), respectively. Conclusion: The unconditional use of 99mTc‐MAA to predict 90Y dosimetry across all cases is not recommended due to: (a) demonstrated the risk of unmatched catheter positions between procedures, and (b) large bias and uncertainty in 99mTc‐MAA predictions in cases with matched catheter locations. However, NL voxel dose predictions with 99mTc‐MAA are clinically viable and either PM or voxel dosimetry can be used to produce equivalent predictions. Both 99mTc‐MAA and PM can provide tumor dose predictions with potential clinical utility, but only in catheter‐matched cases and with tumors comprising a clear majority (>80%) of the total tumor volume. These findings stratify the predictive fidelity of 99mTc‐MAA‐ and PM‐based treatment planning for 90Y dosimetry in improving treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Peptide 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.Methods: Patients 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.Results: Forty-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.Conclusion: Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare.Level Of Evidence: 4, case series. [ABSTRACT FROM AUTHOR]

Purpose: Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature.Materials: 244 NEN patients with different NEN grades were included.Methods: Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities.Results: Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3-4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in < 4%. In symptomatic patients, improvement and resolution of symptoms occurred in 44% and 34%, respectively. Median overall survival from first radioembolization was 3.7, 2.7 and 0.7 years for G1, G2 and G3, respectively. Objective response is independent of NEN grade or primary tumour origin. Significant prognostic factors for survival were NEN grade/Ki67 index, ≥ 75% intrahepatic tumour load, the presence of extrahepatic disease and disease control rate according to RECIST 1.1.Conclusion: Safety and efficacy of radioembolization in NEN patients was confirmed with a high disease control rate of 91% in progressive patients and alleviation of NEN-related symptoms in 79% of symptomatic patients.Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Purpose: 90Y‐microsphere selective internal radiation therapy (90Y‐SIRT or 90Y‐radioembolization) is used in the management of unresectable liver tumors. 90Y‐SIRT presents a unique situation where the total 90Y activity inside the liver can be determined with high accuracy (> 95%). 90Y bremsstrahlung single‐photon emission computed tomography (SPECT)/computed tomography (CT) can be self‐calibrated to provide quantitative images that facilitate voxel‐level absorbed dose calculations. We investigated the effects of different approaches for 90Y‐SPECT self‐calibration on the quantification of absorbed doses following 90Y‐SIRT. Methods: 90Y bremsstrahlung SPECT/CT images of 31 patients with hepatocellular carcinoma, collected following 90Y‐SIRT, were analyzed, yielding 48 tumor and 31 normal liver contours. We validated the accuracy of absorbed doses calculated by a commercial software against those calculated using Monte Carlo‐based radiation transport. The software package was used to analyze the following definitions of SPECT volume of interest used for 90Y‐SPECT self‐calibration: (a) SPECT field‐of‐view (FOV), (b) chest‐abdomen contour, (c) total liver contour, (d) total liver contour expanded by 5 mm, and (e) total liver contour contracted by 5 mm. Linear correlation and Bland–Altman analysis were performed for tumor and normal liver tissue absorbed dose volume histogram metrics between the five different approaches for 90Y‐SPECT self‐calibration. Results: The mean dose calculated using the commercial software was within 3% of Monte Carlo for tumors and normal liver tissues. The tumor mean dose calculated using the chest‐abdomen calibration was within 2% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 68%, 47%, and 107%, respectively, of doses calculated using the SPECT FOV. The normal liver tissue mean dose calculated using the chest‐abdomen contour was within 1.3% of that calculated using the SPECT FOV, whereas the doses calculated using the total liver contour, expanded total liver contour, and contracted total liver contour were within 73%, 50%, and 114%, respectively, of doses calculated using the SPECT FOV. Conclusions: The mean error of < 3% for commercial software can be considered clinically acceptable for 90Y‐SIRT dosimetry. Absorbed dose quantification using 90Y‐SPECT self‐calibration with the chest‐abdomen contour was equivalent to that calculated using the SPECT FOV, but self‐calibration with the total liver contour yielded substantially higher (~70%) dose values. The large biases revealed by our study suggest that consistent absorbed dose calculation approaches are essential when comparing 90Y‐SIRT dosimetry between different clinical studies. [ABSTRACT FROM AUTHOR]

Background: Selective internal radiation therapy (SIRT) with yttrium-90 (90Y) resin microspheres is an established locoregional treatment option for unresectable hepatocellular carcinoma (HCC), which delivers a lethal dose of radiation to hepatic tumors, while sparing surrounding healthy tissue. DOORwaY90 is a prospective, multicenter, open-label, single arm study, designed to evaluate the safety and effectiveness of 90Y resin microspheres as first-line treatment in patients with unresectable/unablatable HCC. It is unique in that it is the first study with resin microspheres to utilize a personalized 90Y dosimetry approach, and independent review for treatment planning and response assessment.Methods: Eligibility criteria include unresectable/unablatable HCC, Barcelona Clinic Liver Cancer stage A, B1, B2, or C with a maximal single tumor diameter of ≤ 8 cm, and a sum of maximal tumor diameters of ≤ 12 cm, and at least one tumor ≥ 2 cm (long axis) per localized, modified Response Evaluation Criteria in Solid Tumors. Partition model dosimetry is used to determine the optimal dose; the target mean dose to tumor is ≥ 150 Gy. Patients are assessed at baseline and at regular intervals up until 12 months of treatment for response rates, safety, and quality of life (QoL). Post-treatment dosimetry is used to assess dose delivered to tumor and consider if retreatment is necessary. The co-primary endpoints are best objective response rate and duration of response. Secondary endpoints include grade ≥ 3 toxicity, QoL, and incidence of liver resection and transplantation post SIRT. Target recruitment is 100 patients.Discussion: The results of this trial should provide further information on the potential use of SIRT with 90Y resin microspheres as first-line therapy for unresectable HCC.Trial Registration: Clinicaltrials.gov; NCT04736121; date of 1st registration, January 27, 2021, https://clinicaltrials.gov/ct2/show/NCT04736121 . [ABSTRACT FROM AUTHOR]