Dose-effect relationships in neuroendocrine tumour liver metastases treated with [166Ho]-radioembolization

K Ramdhani; J Beijer-Verduin; S C Ebbers; R van Rooij; M L J Smits; R C G Bruijnen; H W A M de Jong; M G E H Lam; A J A T Braat

doi:10.1007/s00259-024-06645-6

Dose-effect relationships in neuroendocrine tumour liver metastases treated with [¹⁶⁶Ho]-radioembolization

Eur J Nucl Med Mol Imaging. 2024 Feb 19. doi: 10.1007/s00259-024-06645-6. Online ahead of print.

Authors

K Ramdhani¹, J Beijer-Verduin², S C Ebbers², R van Rooij², M L J Smits², R C G Bruijnen², H W A M de Jong², M G E H Lam², A J A T Braat²

Affiliations

¹ Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, Huispostnummer E01.132, Utrecht, The Netherlands. K.ramdhani@umcutrecht.nl.
² Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, Huispostnummer E01.132, Utrecht, The Netherlands.

PMID: 38369678
DOI: 10.1007/s00259-024-06645-6

Abstract

Purpose: Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([¹⁶⁶Ho]-radioembolization).

Materials and methods: Single center, retrospective study included patients with NELM that received [¹⁶⁶Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (D_t) and whole liver healthy tissue (D_h) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS).

Results: Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 - 82 months). Mean D_t in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a D_t of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1-2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached.

Conclusion: This study confirms the safety and efficacy of [¹⁶⁶Ho]-radioembolization in NELM in a real-world setting. A clear dose-response relationship was demonstrated and future studies should aim at a D_t of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established.

Keywords: Holmium-166; Neuroendocrine liver metastases; Neuroendocrine tumour; Radioembolization; SIRT.