Purpose Radioembolization based on personalized treatment planning requires established doseresponse and dose-toxicity relationships. The aim of this study was to investigate dose-response and dose-toxicity relationships in patients with colorectal liver metastases (CRLM) treated with glass yttrium-90 ( 90 Y)-microspheres. Methods All CRLM patients treated with glass 90 Y-microspheres in our institution were retrospectively analyzed. The tumor-absorbed dose was calculated for each measurable metastasis (i.e., 18 F-FDG-positive and >5 mL tumor volume) on post-treatment 90 Y-PET. Metabolic tumor response was determined on 18 F-FDG-PET/CT by measuring the total lesion glycolysis at baseline and at three months post-treatment. The relationship between tumor-absorbed dose and metabolic response was determined on a per lesion and per patient basis using a linear mixed-effects regression model. Clinical and laboratory toxicity were correlated with healthy liver-absorbed dose. Results Thirty-one patients were included. The median tumor-absorbed dose of 85 measurable metastases was 133 Gy (range 20-1001 Gy). Per response category this was 196 Gy for complete response (CR), 177 Gy for partial response (PR), 72 Gy for stable disease, and 95 Gy for progressive disease (PD). A significant dose-response relationship was found on a tumor level with a significantly higher tumor-absorbed dose in metastases with CR (+94%) and PR (+74%) compared to metastases with PD, p<0.001. A similar relationship was found on a patient level, with PR having a higher tumor-absorbed dose compared to PD (+58%, p=0.044). A tumor-absorbed dose of >139 Gy predicted three-month metabolic response with the greatest accuracy (89% specificity, 77% sensitivity), while a tumor-absorbed dose of >189 Gy predicted response with 97% specificity and 45% sensitivity. The median healthy liver-absorbed dose was 63 Gy (range: 24-113 Gy).Toxicity was mostly limited to grade 1-2, with one case of radioembolization-induced liver disease who received the highest healthy liver-absorbed dose. A positive trend was seen for most laboratory parameters in our dose-toxicity analysis. Conclusion A significant relation was observed between dose and response in CRLM patients treated with glass 90 Y-radioembolization.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pretreatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments.

Introduction Distribution of microspheres after radioembolization can be accurately visualized using PET/CT. In this pictorial essay, we aim to demonstrate the value of 90 Y-PET/CT after radioembolization. Methods 90 Y-PET/CT imaging was routinely performed after radioembolization at our institute. Patients were scanned the same day or the day after treatment, using a scanner with time-of-flight technology. We retrospectively reviewed all 90 Y-PET/ CTs from patients treated with radioembolization (both glass and resin microspheres) between January 2011 and January 2019. Five cases were selected that are illustrative of the added value of PET/CT after radioembolization. Results 90 Y-PET/CT allows for distribution assessment and dosimetry of 90 Y-microspheres. It was used for the assessment of treatment success by visualization of tumor targeting, quantification of the absorbed dose, prediction of complications such as radioembolization-induced liver disease, and determining the required dosage for retreatment. Conclusion PET/CT is an excellent modality for post-treatment imaging of 90 Y-microspheres and could lead to improved dose planning and more personalized treatment.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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