Purpose: The aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (¹⁶⁶Ho-MS), when administered as adjuvant therapy after RFA of HCC 2–5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of ≥ 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume). Methods: In this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2–5 cm, RFA was followed by (super-)selective infusion of ¹⁶⁶Ho-MS on day 5–10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of ¹⁶⁶Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of ≥ 120 Gy in 9/10 patients within a cohort. Results: Twelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3–71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1–4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127–145]). No local recurrences were found within 1-year follow-up. Conclusion: Adjuvant (super-)selective infusion of ¹⁶⁶Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of ≥ 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2–5 cm. Trial registration: Clinicaltrials.gov NCT03437382.

Purpose: Navigational strategies create a scenario whereby percutaneous needle-based interventions of the liver can be guided using both pre-interventional 3D imaging datasets and dynamic interventional ultrasound (US). To score how such technologies impact the needle placement process, we performed kinematic analysis on different user groups. Methods: Using a custom biopsy phantom, three consecutive exercises were performed by both novices and experts (n = 26). The exercise came in three options: (1) US-guidance, (2) US-guidance with pre-interventional image-registration (US + Reg) and (3) US-guidance with pre-interventional image-registration and needle-navigation (US + Reg + Nav). The traveled paths of the needle were digitized in 3D. Using custom software algorithms, kinematic metrics were extracted and related to dexterity, decision making indices to obtain overall performance scores (PS). Results: Kinematic analysis helped quantifying the visual assessment of the needle trajectories. Compared to US-guidance, novices yielded most improvements using Reg (PS_avg(US) = 0.43 vs. PS_avg(US+Reg) = 0.57 vs. PS_{avg(US+Reg+Nav)} = 0.51). Interestingly, the expert group yielded a reversed trend (PS_avg(US) = 0.71 vs PS_avg(US+Reg) = 0.58 vs PS_{avg(US+Reg+Nav)} = 0.59). Conclusion: Digitizing the movement trajectory allowed us to objectively assess the impact of needle-navigation strategies on percutaneous procedures. In particular, our findings suggest that these advanced technologies have a positive impact on the kinematics derived performance of novices.