Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery

Abstract

Purpose Transarterial radioembolization (TARE) is a treatment for liver tumours based on injection of radioactive microspheres in the hepatic arterial system. It is crucial to achieve a maximum tumour dose for an optimal treatment response, while minimizing healthy liver dose to prevent toxicity. There is, however, no intraprocedural feedback on the dose distribution, as nuclear imaging can only be performed after treatment. As holmium-166 (166Ho) microspheres can be quantified with MRI, we investigate the feasibility and safety of performing 166Ho TARE within an MRI scanner and explore the potential of intraprocedural MRI-based dosimetry. Methods Six patients were treated with 166Ho TARE in a hybrid operating room. Per injection position, a microcatheter was placed under angiography guidance, after which patients were transported to an adjacent 3-T MRI system. After MRI confirmation of unchanged catheter location, 166Ho microspheres were injected in four fractions, consisting of 10%, 30%, 30% and 30% of the planned activity, alternated with holmium-sensitive MRI acquisition to assess the microsphere distribution. After the procedures, MRI-based dose maps were calculated from each intraprocedural image series using a dedicated dosimetry software package for 166Ho TARE. Results Administration of 166Ho microspheres within the MRI scanner was feasible in 9/11 (82%) injection positions. Intraprocedural holmium-sensitive MRI allowed for tumour dosimetry in 18/19 (95%) of treated tumours. Two CTCAE grade 3–4 toxicities were observed, and no adverse events were attributed to treatment in the MRI. Towards the last fraction, 4/18 tumours exhibited signs of saturation, while in 14/18 tumours, the microsphere uptake patterns did not deviate from the linear trend. Conclusion This study demonstrated feasibility and preliminary safety of a first in-human application of TARE within a clinical MRI system. Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE. This proof of concept yields unique possibilities to better understand microsphere distribution in vivo and to potentially optimize treatment efficacy through treatment personalization. Registration Clinicaltrials.gov, identifier NCT04269499, registered on February 13, 2020 (retrospectively registered).

Safety and efficacy of Holmium-166 selective internal radiotherapy of primary and secondary liver cancer confirmed by real-world data

“…Overall, the frequency of AEs reported in the present study is low compared to earlier 166 Ho studies and is probably underreported ( 12 , 13 , 15 , 21 ). Radioembolization induced liver disease (REILD) represents a rare but dangerous complication of SIRT and occurred in one patient (0.7%) with lethal outcome.…”

“…Furthermore, the element Holmium is a chemical lanthanide with paramagnetic properties, which enables quantification of hepatic 166 Ho dose via MRI ( 9 ). This offers the possibility of intraprocedural MRI-based dosimetry, which has recently shown to be feasible ( 12 ). Following the administration of the scout dose, SPECT imaging of the thorax and abdomen is conducted in order to detect unintended delivery to the lungs or upper abdominal organs.…”

Characterizing the voxel‐based approaches in radioembolization dosimetry with reDoseMC

“…However, $$^{166}{\rm {Ho}}$$ is still in its infancy and under development, especially regarding its imaging protocols 45 . Feasibility of $$^{166}{\rm {Ho}}$$ imaging with CT and MRI has been clinically demonstrated and preliminary absorbed dose estimates have been reported, but their dosimetry relation to current treatment plans are unknown 6,46 . Of note, CT imaging of $$^{90}{\rm {Y}}$$ microspheres was also shown to be feasible in preclinical settings 47 .…”

“…45 Feasibility of 166 Ho imaging with CT and MRI has been clinically demonstrated and preliminary absorbed dose estimates have been reported, but their dosimetry relation to current treatment plans are unknown. 6,46 Of note, CT imaging of 90 Y microspheres was also shown to be feasible in preclinical settings. 47 Pertinently, our study utilized Gaussian distributions to represent theoretical image resolutions.…”

Improving MRI‐based dosimetry for holmium‐166 transarterial radioembolization using a nonrigid image registration for voxelwise ΔR2∗$\Delta R_2^*$ calculation

“…The most important inclusion criteria were age ≥18 years, diagnosis of primary liver cancer (hepatocellular carcinoma or intrahepatic cholangiocarcinoma) or liver metastases (primary tumors: colorectal cancer, breast cancer, melanoma or neuro‐endocrine tumor) not amenable for other standard therapies than TARE, a life expectancy of 12 weeks or longer, and a WHO performance score of 0–1. Clinical results of the trial are published elsewhere 14 …”