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. 2021 Nov;48(12):3776-3790.
doi: 10.1007/s00259-021-05340-0. Epub 2021 Apr 10.

To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer

Joey Roosen  1 , Nienke J M Klaassen #  1 , Lovisa E L Westlund Gotby #  1 , Christiaan G Overduin  1 , Marcel Verheij  2 , Mark W Konijnenberg  1   3 , J Frank W Nijsen  4
Affiliations

To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer

Joey Roosen et al. Eur J Nucl Med Mol Imaging. 2021 Nov.

Abstract

Purpose: To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and secondary liver cancer.

Methods: A standardized search was performed in PubMed (MEDLINE), Embase, and the Cochrane Library in order to identify all published articles on dose-response evaluation in SIRT. In order to limit the results, all articles that investigated SIRT in combination with other therapy modalities (such as chemotherapy) were excluded.

Results: A total of 3038 records were identified of which 487 were screened based on the full text. Ultimately, 37 studies were included for narrative analysis. Meta-analysis could not be performed due to the large heterogeneity in study and reporting designs. Out of 37 studies, 30 reported a 'mean dose threshold' that needs to be achieved in order to expect a response. This threshold appears to be higher for hepatocellular carcinoma (HCC, 100-250 Gy) than for colorectal cancer metastases (CRC, 40-60 Gy). Reported thresholds tend to be lower for resin microspheres than when glass microspheres are used.

Conclusion: Although the existing evidence demonstrates a dose-response relationship in SIRT for both primary liver tumours and liver metastases, many pieces of the puzzle are still missing, hampering the definition of standardized dose thresholds. Nonetheless, most current evidence points towards a target mean dose of 100-250 Gy for HCC and 40-60 Gy for CRC. The field would greatly benefit from a reporting standard and prospective studies designed to elucidate the dose-response relation in different tumour types.

Keywords: Dosimetry; Holmium; Radioembolization; SIRT; TARE; Yttrium.

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Conflict of interest statement

JFW Nijsen is a co-founder and part-time scientific director of Quirem Medical which has been acquired by Terumo Europe NV in July 2020. Nijsen is entitled to certain milestone payments from Terumo which are related to Quirem’s financial, operational, and regulatory performance in the future. Furthermore, Nijsen is an inventor on the patents related to radioactive microspheres that are assigned to the University Medical Center Utrecht Holding BV, Quirem Medical or BASF Corp. The activities of JFW Nijsen within Quirem Medical are approved of and supported by the board of directors of the Radboudumc. The other authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow chart of the search strategy and inclusion/exclusion process
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