Dose–Response and Dose–Toxicity Relationships for Glass ⁹⁰Y Radioembolization in Patients with Liver Metastases from Colorectal Cancer

Abstract

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.

Management of Liver Tumors during the COVID-19 Pandemic: The Added Value of Selective Internal Radiation Therapy (SIRT)

“…In fact, for HCC and in mCRC, the tumor response is strictly related to the tumor-absorbed dose, while the liver toxicity should be limited by preliminary assessment of the healthy liver-absorbed dose, which should not exceed certain thresholds [ 37 ].…”

Role of Resin Microsphere Y90 Dosimetry in Predicting Objective Tumor Response, Survival and Treatment Related Toxicity in Surgically Unresectable Colorectal Liver Metastasis: A Retrospective Single Institution Study

“…A prospective study conducted between 2011–2014 with 30 patients, which used the BSA model for treatment planning, reported a conservative estimate of at least 40–60 Gy tumor dose was predictive of metabolic response [ 25 ], and another study found 50 Gy (using modified BSA method) as threshold to achieve objective response [ 26 ], both using resin microspheres. A more recent 2021 retrospective study with 31 patients using glass microspheres found that median TD for complete responders was 196 Gy versus 177 Gy for partial responders [ 27 ]. This higher TD compared to our findings of 100 Gy can most likely be explained by their use of glass microspheres compared to our use of resin microspheres.…”

Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

“…The applied tumor dose is decisive for patient outcomes in RE. Previous studies have demonstrated the correlation of survival and absorbed tumor dose [ 6 , 7 , 8 , 9 , 10 ]. In addition, variations in response rates after RE indicate a medical need for optimizing dose prescriptions [ 11 ].…”