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

Abstract

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 (90)Y radioembolization treatment for CRLM.

Methods: Thirty patients with unresectable chemorefractory CRLM were treated with resin (90)Y-microspheres in a prospective phase II clinical trial. Tumor-absorbed dose was quantified on (90)Y PET. Metabolic tumor activity, defined as tumor lesion glycolysis (TLG*) on (18)F-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* 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* (P < 0.01). The effective tumor-absorbed dose was conservatively estimated at a minimum of 40-60 Gy.

Conclusion: A strong dose-response relationship exists for the treatment of CRLM with resin microsphere (90)Y 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.

Keywords: 90Y PET; CRLM; dose-response relationship; metabolic tumor response; radioembolization.