First Evidence for a Dose-Response Relationship in Patients Treated with ¹⁶⁶Ho Radioembolization: A Prospective Study.

Abstract

¹⁶⁶Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose-response relationship and its association with overall survival for ¹⁶⁶Ho radioembolization in patients with liver metastases. <b>Methods:</b> Patients treated in the HEPAR I and II studies who underwent an ¹⁸F-FDG PET/CT scan at baseline, a posttreatment ¹⁶⁶Ho SPECT/CT scan, and another ¹⁸F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment ¹⁶⁶Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo-based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose-response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. <b>Results:</b> Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178-303 Gy; <i>n</i> = 32) and stable disease (147 Gy; 95% CI, 113-191 Gy; <i>n</i> = 28) (<i>P</i> = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87-159 Gy; <i>n</i> = 21) (<i>P</i> = 0.0008). This constitutes a robust absorbed dose-response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161-274 Gy; <i>n</i> = 13) and patients with progressive disease (116 Gy; 95% CI, 81-165 Gy; <i>n</i> = 9) (<i>P</i> = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, <i>P</i> = 0.01). <b>Conclusion:</b> These results confirm a significant absorbed dose-response relationship in ¹⁶⁶Ho radioembolization. Treatment response is associated with a higher overall survival.