Efficacy of radioembolization with holmium-166 microspheres in salvage patients with liver metastases: a phase 2 study.

Abstract

Rationale: Radioembolization of liver malignancies with holmium-166 (166Ho) microspheres has been shown safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy of 166Ho radioembolization. Methods: In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. Radioembolization was performed with a projected average absorbed dose of 60 Gy to the liver (equal to 3.8 GBq/kg liver tissue). The primary outcome was tumor response of two target lesions on triphasic liver CT scans, 3 months after therapy using RECIST 1.1 criteria. Secondary outcomes included overall tumor response, response on ¹⁸F-FDG-PET/CT, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI. Results: Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27/37 (73%) patients, the target lesions showed complete response, partial response or stable disease (disease control) at three months (95% confidence interval [CI], 57 to 85%). Disease control in the whole liver was achieved in 18/37 (49%) of patients (95% CI, 33 to 64%). The median overall survival was 14.5 months (95% CI, 8.6 to 22.8 months). For colorectal cancer patients (n = 23), the median overall survival was 13.4 months (95% CI, 8.2 - 15.7 months). Grade 3 or 4 toxic events after treatment (according to CTCAE v4.03 criteria) included abdominal pain (in 18% of patients), nausea (8%), ascites (3%), fatigue (3%), gastric stenosis (3%), hepatic failure (3%), liver abscesses (3%), paroxysmal atrial tachycardia (3%), thoracic pain (3%), upper gastrointestinal hemorrhage (3%), and vomiting (3%). On SPECT/CT, 166Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3±7.1% in the liver. Conclusion: Radioembolization with 166Ho microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.