Pre- and post-treatment image-based dosimetry in 90Y-microsphere radioembolization using the TOPAS Monte Carlo toolkit

Objective: To evaluate the pre-treatment and post-treatment imaging-based dosimetry of patients treated with 90Y-microspheres, including accurate estimations of dose to tumor, healthy liver and lung. To do so, the Monte Carlo (MC) TOPAS platform is in this work extended towards its utilization in radionuclide therapy. Approach: Five patients treated at the Massachusetts General Hospital were selected for this study. All patients had data for both pre-treatment SPECT-CT imaging using 99mTc-MAA as a surrogate of the 90Y-microspheres treatment and SPECT-CT imaging immediately after the 90Y activity administration. Pre- and post-treatment doses were computed with TOPAS using the SPECT images to localize the source positions and the CT images to account for tissue inhomoegeneities. We compared our results with analytical calculations following the voxel-based MIRD scheme. Main results: TOPAS results largely agreed with the MIRD-based calculations in soft tissue regions: the average difference in mean dose to the liver was 0.14 Gy/GBq (2.6%). However, dose distributions in the lung differed considerably: absolute differences in mean doses to the lung ranged from 1.2 Gy/GBq to 6.3 Gy/GBq and relative differences from 153% to 231%. We also found large differences in the intra-hepatic dose distributions between pre- and post-treatment imaging, but only limited differences in the pulmonary dose. Significance: Doses to lung were found to be higher using TOPAS with respect to analytical calculations which may significantly underestimate dose to the lung, suggesting the use of MC methods for 90Y dosimetry. According to our results, pre-treatment imaging may still be representative of dose to lung in these treatments.

Yttrium-90 Microspheres for Intermediate- or Advanced-Stage Hepatocellular Carcinoma

Transarterial radioembolization using yttrium-90 (90Y) microspheres is a therapeutic option for patients with intermediate- or advanced-stage hepatocellular carcinoma, including those with recurrent or inoperable hepatocellular carcinoma. Overall, the evidence suggests that patients treated with 90Y-based transarterial radioembolization may experience no difference in overall survival, progression-free survival, and tumour response when compared to patients who received transarterial chemoembolization therapies or systemic treatment with sorafenib or lenvatinib. Patients treated with transarterial radioembolization generally experienced similar rates of adverse events compared to those treated with transarterial chemoembolization, although there were some instances where treatment with transarterial radioembolization led to increased or decreased risks of specific adverse events. The comparative safety of transarterial radioembolization versus systemic treatment with sorafenib was unclear as the included studies did not statistically compare the risks of experiencing adverse events. Evidence regarding the cost-effectiveness of 90Y microspheres for treating hepatocellular carcinoma is conflicting. Three economic evaluations suggest treatment with transarterial radioembolization is likely to be cost-effective or dominant — less costly and more effective — compared to transarterial chemoembolization or systemic therapies, while a single economic study suggested treatment with sorafenib or lenvatinib is most likely to be cost-effective or dominant compared to transarterial radioembolization.

Molecular and Metabolic Imaging of Hepatic Neuroendocrine Tumors Following Radioembolization with 90Y-microspheres

Liver is the predominant site of metastatization for neuroendocrine tumors (NETs). Up to 75% of patients affected by intestinal NETs present liver metastases at diagnosis. For hepatic NET, surgery represents the most effective approach but is often unfeasible due to the massive involvement of multifocal disease. In such cases, chemotherapy, peptide receptor radionuclide therapy and loco-regional treatments may represent alternative therapeutic options. In particular, radioembolization with 90Y-microspheres has been introduced as a novel technique for treating hepatic malignant lesions, combining the principles of embolization and radiation therapy. In order to evaluate the response to 90Y-radioembolization, standard radiologic criteria have been demonstrated to present several limitations. 18Fluoro-deoxyglucose (FDG) Positron Emission Tomography (PET) is routinely used for monitoring the response to therapy in oncology. Nevertheless, NETs often present low glycolytic activity thus the conventional 18FDG PET may not be adequate for these tumors. For many years, somatostatin receptor scintigraphy (SRS) with 111In-pentetreotide has been used for diagnosis and staging of NETs. More recently, three 68Ga-DOTA-compounds have been developed and introduced for the imaging of NETs with PET technology. The aim of the present paper was to review the existing literature concerning the application of different metabolic and molecular probes for the imaging evaluation of hepatic NETs following 90Y-RE.

Contralateral Liver Hypertrophy and Oncological Outcome Following Radioembolization with 90Y-Microspheres: A Systematic Review

Radioembolization with 90Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the present systematic review was to summarize the evidence of contralateral liver hypertrophy and oncological outcome following unilateral treatment with radioembolization. A systematic literature search using the MEDLINE, EMBASE, and Cochrane libraries for studies published between 2008 and 2020 was performed. A total of 16 studies, comprising 602 patients, were included. The median kinetic growth rate per week of the contralateral liver lobe was 0.7% and declined slightly over time. The local tumor control was 84%. Surgical resection after radioembolization was carried out in 109 out of 362 patients (30%). Although the available data suggest that radioembolization prior to major hepatectomy is safe with a promising oncological outcome, the definitive role of radioembolization requires assessment within controlled clinical trials.