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Clinical Trial
. 2025 Feb;52(3):993-1003.
doi: 10.1007/s00259-024-06940-2. Epub 2024 Oct 29.

Holmium-166 radioembolisation dosimetry in HCC

Margot T M Reinders  1 , Arthur J A T Braat  1 , Karel J van Erpecum  2 , Joep de Bruijne  2 , Rutger C G Bruijnen  1 , Dave Sprengers  3 , Rob de Man  3 , Erik Vegt  4 , Jan N M IJzermans  5 , Sjoerd G Elias  6 , Marnix G E H Lam  1 , Maarten L J Smits  7
Affiliations
Clinical Trial

Holmium-166 radioembolisation dosimetry in HCC

Margot T M Reinders et al. Eur J Nucl Med Mol Imaging. 2025 Feb.

Abstract

Purpose: To evaluate dosimetry, dose-response and dose-toxicity relationships for holmium-166 (166Ho) radioembolisation in patients with hepatocellular carcinoma (HCC).

Methods: Thirty-one patients with hepatocellular carcinoma were included in the HEPAR Primary study (NCT03379844, registered on December 20th, 2017) and underwent 166Ho-microspheres radioembolisation. Linear mixed models assessed the association between tumour absorbed doses and response based on mRECIST both on tumour and patient level. Preliminary tumour absorbed dose thresholds were estimated based on predictive value. Linear regression models assessed the association between non-tumour absorbed dose and Common Terminology Criteria for Adverse Events version 4.03.

Results: Median tumour absorbed dose (tumour level) was 95.5 Gy (range 44-332 Gy). Median non-tumour absorbed dose based on whole liver volume was 19 Gy (range 3 - 48 Gy) and based on target liver volume was 30 Gy (range 13 - 54 Gy). There was a significant association between non-tumour absorbed dose and toxicity. Tumours with partial response/complete response (PR/CR, responders) received a 41% higher absorbed dose than tumours with progressive disease/stable disease (PD/SD, non-responders) (95%CI: 2%-93%, p = 0.04). A predictive value of 90% for tumour response was observed at a tumour absorbed dose threshold of 155 Gy, 100% predictive value was achieved at 184.5 Gy.

Conclusion: This study confirms a positive relationship between tumour absorbed dose and response and between non-tumour absorbed dose and toxicity. Dose thresholds found in this study can serve as a basis for personalized dosimetry in HCC patients treated with 166Ho-microspheres.

Keywords: Biodistribution; Dosimetry; Hepatocellular carcinoma; Holmium; Personalised treatment planning; Radioembolisation.

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Conflict of interest statement

Declarations. Ethics approval: This clinical study was approved by the Medical Ethics Committee of University Medical Centre Utrecht and Erasmus Medical Centre and by the institutional radiation protection committee. Furthermore, this study was performed in concordance with Good Clinical Practice and the declaration of Helsinki. Consent to participate: All participants provided written, informed consent before undergoing any study-specific activity. Conflicts of interest: Margot Reinders-Hut is currently employed by Genmab B.V., acted as a speaker for Boston Scientific. Marnix Lam acts as a consultant for Terumo, Quirem Medical and Boston Scientific, receives research support from Terumo, Quirem Medical and Boston Scientific. Maarten Smits and Arthur Braat are consultants for Terumo. The department of Radiology and Nuclear Medicine of the University Medical Centre Utrecht receives royalty payments from Quirem Medical.

Figures

Fig. 1
Fig. 1
A Receiver operating characteristic curves (ROCs) showing discriminative value of tumour absorbed dose for response based on SPECT; AUC is 0.72 (95% CI: 0.58–0.85). B Ability of mean tumour absorbed dose per patient to discriminate between patients with complete or partial response and progressive or stable disease-based AUC is 0.76 (95% CI: 0.58–0.93). ROCs are not based on clustered data analysis, but area-under-the-curves (AUCs) are
Fig. 2
Fig. 2
Relationship between (mean) tumour absorbed dose and best response according to mRECIST assessment on (A) tumour level (p for trend test is 0.0395) and (B) patient level (p for trend test is 0.0493). Average absorbed doses are indicated with white dot and black vertical lines represent 95% confidence intervals. PD progressive disease, SD stable disease, PR partial response, CR complete response
Fig. 3
Fig. 3
Association between change in laboratory values and non-tumour absorbed dose based on whole liver volume (NTD). Regression lines in blue and grey areas indicating 95% confidence intervals. AST aspartate aminotransferase, ALT alanine aminotransferase, ALP alkaline phosphatase, GGT gamma-glutamyl transferase
Fig. 4
Fig. 4
Overall survival of patients in HEPAR Primary study, median 14.9 months (95% CI: 10.4–24.9 months)
See this image and copyright information in PMC

References

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