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. 2024 Jul 14;14(7):747.
doi: 10.3390/jpm14070747.

Clinical Results of Holmium-166 Radioembolization with Personalized Dosimetry for the Treatment of Hepatocellular Carcinoma

Christian Kühnel  1 , Alexander Köhler  1 , Tim Brachwitz  1 , Philipp Seifert  1 , Falk Gühne  1 , René Aschenbach  2 , Robert Freudenberg  3 , Martin Freesmeyer  1 , Robert Drescher  1
Affiliations

Clinical Results of Holmium-166 Radioembolization with Personalized Dosimetry for the Treatment of Hepatocellular Carcinoma

Christian Kühnel et al. J Pers Med. .

Abstract

Transarterial radioembolization (TARE) with 166Ho-loaded microspheres is an established locoregional treatment for hepatocellular carcinoma (HCC), introduced in 2010. This study evaluates the clinical outcome of patients with HCC who underwent 166Ho-TARE with personalized dosimetry. Twenty-seven patients with 36 TARE procedures were analyzed. Treatment planning, execution, and evaluation was possible without complications in all cases. At the 3-month follow-up, disease control in the treated liver was achieved in 81.8% of patients (complete remission, partial remission, and stable disease in 36.4%, 31.8%, and 13.6%, respectively). The median overall survival (OS) was 17.2 months, and progression-free survival (PFS) in the treated liver was 11 months. Statistically significant positive correlations were observed between the achieved radiation dose for the tumor and both PFS (r = 0.62, p < 0.05) and OS (r = 0.48, p < 0.05), suggesting a direct dose-response relationship. The calculated achieved dose was 8.25 Gy lower than the planned dose, with relevant variance between planned and achieved doses in individual cases. These results confirm the efficacy of the 166Ho-TARE holmium platform and underscore the potential of voxel-based, personalized dosimetry to improve clinical outcomes.

Keywords: HCC; SIRT; TARE; dosimetry; holmium platform; holmium-166; microspheres; radioembolization.

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Conflict of interest statement

R.D. is a consultant for Boston Scientific and Terumo. C.K. is a consultant for Boston Scientific. No other potential conflict of interest relevant to this article exist.

Figures

Figure 1
Figure 1
Bilobar sequential TARE treatment of an 83-year-old man with HCC stage IB (singular 9.5 cm lesion involving segments IVa, IVb, V, and VIII). Left lobar planning (A,B) and treatment (C,D) with QuiremScout and QuiremSpheres microspheres from the left hepatic artery (green arrows). Planned tumor/healthy target doses of 164 Gy/19 Gy, prescribed activity of 3.9 GBq 166Ho. Achieved doses of 208 Gy (+27%) and 19 Gy (=). Right lobar planning (E,F) and treatment (G,H) from the right hepatic artery (green arrows) after coil embolization of the cystic artery (E, black arrow). Planned tumor/healthy target doses of 137 Gy/38 Gy, prescribed activity of 3.1 GBq 166Ho. Achieved doses of 171 Gy (+25%) and 37 Gy (−3%). Strong tumor blushes during both injections confirmed hypervascularity of the tumor (A,G, blue arrowheads), resulting in high tumor-to-healthy-target ratios for both treatments.
Figure 2
Figure 2
Correlations between planned and achieved doses in 36 TARE procedures (dashed lines: mean, upper/lower limits of agreement).
Figure 3
Figure 3
Discrepancy between planning and treatment procedures in a 65-year-old woman with HCC stage IIIA. QuiremScout microspheres were injected into the left hepatic artery (A, green arrow). SPECT/CT showed satisfactory activity deposition in the tumor in the liver segment IVa (B, red arrow; planned tumor/healthy target doses of 164 Gy/55 Gy). A total of 0.8 GBq QuiremSpheres microspheres were injected (C). Post-therapeutic imaging showed a different microsphere distribution with higher activity in non-tumor tissue (D, mean tumor/healthy target doses of 86 Gy/57 Gy), possibly due to a slightly more distal catheter position and a segment IV branch (A,C, red arrows) arising distally but opposite to the microcatheter tip (C, green arrow).
Figure 4
Figure 4
Progression-free and overall survival after 166Ho-TARE. Progression in the liver segments treated by 166Ho-TARE was detected in seven of 24 patients who underwent an imaging follow-up. Progression in the untreated liver, equivalent to the appearance of new HCC lesions, occurred earlier and more frequently.
Figure 5
Figure 5
Complete remission after bilobar sequential TARE treatment of a 68-year-old man with HCC stage IIIA, MR imaging (A,B; T1-weighted fat-saturated sequence with contrast enhancement) shows multiple hypervascular lesions with a diameter of up to 5.3 cm (A, arrow). A follow-up CT scan 3 months after TARE revealed complete remission of all lesions according to the mRECIST criteria (C, arrowheads), the largest lesion measuring 2.8 cm. Further shrinkage was observed after another 4 months (D). The hyperdense areas in the regions of highest microsphere density are a typical finding after 166Ho-TARE.
Figure 6
Figure 6
Correlations between dose delivered to the tumor and PFS in the treated liver (upper row; patients with LTx excluded) and between dose delivered to the tumor and OS (lower row) suggest a positive dose–response relationship.
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