Efficacy of Radioembolization with ¹⁶⁶Ho-Microspheres in Salvage Patients with Liver Metastases: A Phase 2 Study

Abstract

Radioembolization of liver malignancies with Ho-microspheres has been shown to be safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy ofHo radioembolization. In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. The primary outcome was a response by 2 target lesions on triphasic liver CT scans 3 mo after therapy, as assessed using RECIST, version 1.1. Secondary outcomes included overall tumor response, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI. Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27 (73%) of 37 patients, the target lesions showed complete response, partial response, or stable disease (disease control) at 3 mo (95% confidence interval [CI], 57%-85%). The median overall survival was 14.5 mo (95% CI, 8.6-22.8 mo). For colorectal cancer patients ( = 23), the median overall survival was 13.4 mo (95% CI, 8.2-15.7 mo). Grade 3 or 4 toxic events after treatment (according to the Common Terminology Criteria for Adverse Events, version 4.03) 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, Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3% ± 7.1% in the liver. Radioembolization with Ho-microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.

The superior predictive value of 166Ho-scout compared with 99mTc-macroaggregated albumin prior to 166Ho-microspheres radioembolization in patients with liver metastases

“…Again, injection position(s) of the treatment-planning procedures were mimicked. Total treatment activity was planned based on an aimed whole liver absorbed dose of 20, 40, 60, and 80 Gy for patients who were treated in the phase 1 HEPAR study and 60 Gy for patients in the phase 2 HEPAR study [10,11]. The total number of microspheres injected was the same for all patients (i.e., 600 mg; approximately 30 million microspheres).…”

Quality of life in patients with liver tumors treated with holmium-166 radioembolization

“…The maximum tolerated dose was found to be 60 Gy and its safety and efficacy was established in the HEPAR II study. A more detailed description of the study designs and the main study results have been published elsewhere [29][30][31].…”

“…The second angiography was planned in the morning, during which patients received a scout dose of 166 Ho-microspheres, directly followed by SPECT and MRI. The treatment dose of 166 Ho-microspheres was administered that same afternoon and was followed by SPECT and MR image acquisition 3-5 days later [30,31]. Patients received the questionnaires at baseline, 6 weeks and 3 months after treatment.…”

“…Follow-up in the HEPAR II study was longer, so those patients also received the questionnaires at 6, 9 and 12 months after treatment. The last included 26 patients of the HEPAR II study received an extra questionnaire 1 week after treatment to better reflect patients' transient symptoms shortly after treatment [30,31].…”

Simultaneous 166Ho/99mTc dual-isotope SPECT with Monte Carlo-based downscatter correction for automatic liver dosimetry in radioembolization

“…To bring pre-treatment dosimetry to a higher level, a more practical imaging protocol and a more predictive particle are needed. In previous studies, the use of a small amount of 166 Ho microspheres with an activity of 250 MBq, was determined to be safe and superior to 99m Tc-MAA [15][16][17][18][19]. Thus the main aim of this study was to investigate the technical feasibility of a dual-isotope protocol combining 166 Ho microspheres and 99m Tc sulfur colloid.…”