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Dose–response relationship after yttrium-90-radioembolization with glass microspheres in patients with neuroendocrine tumor liver metastases

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Abstract

Background

In radioembolization, response is achieved through the irradiation and damaging of tumor DNA. For hepatic metastases of neuroendocrine tumors, a dose–response relationship has not been established yet. This study assesses whether increasing tumor-absorbed doses lead to increased response rates.

Methods

We included all patients who underwent yttrium-90 (90Y) glass microspheres radioembolization in our center if both pre- and post-treatment contrast-enhanced CT and post-injection PET/CT were available. Up to five hepatic tumors and the healthy hepatic tissue were delineated, and absorbed dose was quantified using post-injection PET/CT. Response was measured according to RECIST 1.1 on patient and tumor level. Linear mixed models were used to study the relationship between absorbed dose and response on tumor level. Logistic regression analysis was used on patient level to study dose–response and hepatic dose-toxicity relationships.

Results

A total of 128 tumors in 26 patients (31 procedures) were included in the response analysis. While correcting for confounding by tumor volume, a significant effect of response on dose was found (p = 0.0465). Geometric mean of absorbed dose for responding tumors was 170 Gy, for stable disease 101 Gy, and for progressive disease 67 Gy. No significant dose-toxicity relationship could be identified.

Conclusion

In patients with neuroendocrine tumor liver metastases, treated with 90Y-radioembolization, a clear dose–response relationship was found. We propose to perform 90Y-radioembolization with an absolute minimum planned tumor-absorbed dose of 150 Gy.

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Data availability

The data that support the findings of this study and the code used to perform analyses are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, ENETS Center of Excellence, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Sander C. Ebbers, Caren van Roekel, Manon N. G. J. A. Braat, Maarten W. Barentsz, Marnix G. E. H. Lam & Arthur J. A. T. Braat

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  1. Sander C. Ebbers
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  2. Caren van Roekel
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Contributions

ML and AB were in charge of medical care of the treated patients. AB and SE were responsible for data collection. SE and CR performed data analysis. Data analysis was supervised by MWB and AB. MNB reviewed patient’s imaging. SE is the main author of this manuscript; all authors reviewed the manuscript and gave consent for publication of the final version.

Corresponding author

Correspondence to Arthur J. A. T. Braat.

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By the retrospective and anonymous nature of the study, the need for approval by an ethics committee was waived.

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The authors declare no competing interests.

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Ebbers, S.C., van Roekel, C., Braat, M.N.G.J.A. et al. Dose–response relationship after yttrium-90-radioembolization with glass microspheres in patients with neuroendocrine tumor liver metastases. Eur J Nucl Med Mol Imaging 49, 1700–1710 (2022). https://doi.org/10.1007/s00259-021-05642-3

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