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

Remco Bastiaannet, Caren van Roekel, Maarten L J Smits, Sjoerd G Elias, Wouter A C van Amsterdam, Dan T Doan, Jip F Prince, Rutger C G Bruijnen, Hugo W A M de Jong, Marnix G E H Lam

Research output: Contribution to journalArticleAcademicpeer-review


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. Methods: 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-micro-sphere 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. Results: 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; n 5 32) and stable disease (147 Gy; 95% CI, 113-191 Gy; n 5 28) (P 5 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87-159 Gy; n 5 21) (P 5 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; n 5 13) and patients with progressive disease (116 Gy; 95% CI, 81-165 Gy; n 5 9) (P 5 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, P 5 0.01). Conclusion: These results confirm a significant absorbed dose-response relationship in 166Ho radioembolization. Treatment response is associated with a higher overall survival.

Original languageEnglish
Pages (from-to)608-612
Number of pages5
JournalJournal of Nuclear Medicine
Issue number4
Early online date10 Oct 2019
Publication statusPublished - 1 Apr 2020


  • radioembolization
  • holmium
  • dose–response
  • dosimetry
  • dose personalization
  • dose-response
  • Holmium
  • Dose-response
  • Dose personalization
  • Dosimetry
  • Radioembolization


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