Insights into the Dose-Response Relationship of Radioembolization with Resin 90Y-Microspheres: A Prospective Cohort Study in Patients with Colorectal Cancer Liver Metastases

Randomized controlled trials are investigating the benefit of hepatic radioembolization added to systemic therapy in the first- and second-line treatment of patients with colorectal liver metastases (CRLM). Remarkably, administered activity may still be suboptimal, because a dose-response relationship has not been defined. The purpose of this study was to characterize the relationship between tumor-absorbed dose and response after Y-90 radioembolization treatment for CRLM. Methods: Thirty patients with unresectable chemorefractory CRLM were treated with resin Y-80-microspheres in a prospective phase II clinical trial. Tumor-absorbed dose was quantified on Y-80 PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG(star)) on F-18-FDG PET, was measured at baseline and 1 mo after treatment. The relationship between tumor-absorbed dose and posttreatment metabolic activity was assessed per metastasis with a linear mixed-effects regression model. Results: Treated metastases (n = 133) were identified. The mean tumor absorbed dose was 51 +/- 28 Gy (range, 7-174 Gy). A 50% reduction in TLG(star) was achieved in 46% of metastases and in 11 of 30 (37%) patients for the sum of metastases. The latter was associated with a prolonged median overall survival (11.6 vs. 6.6 mo, P = 0.02). A strong and statistically significant dose-response relationship was found (P < 0.001). The dose effect depended on baseline TLG(star) (P < 0.01). The effective tumor-absorbed dose was conservatively estimated at a minimum of 40-60 Gy. Cohclusion: A strong dose-response relationship exists for the treatment of CRLM with resin microsphere Y-90 radioembolization. Treatment efficacy is, however, still limited, because the currently used pretreatment activity calculation methods curb potentially achievable tumor-absorbed dose values. A more personalized approach to radioembolization is required before concluding on its clinical potential.