Influence of dosimetry accuracy on the correlation with treatment outcome in a preliminary PSMA radiopharmaceutical therapy study

Jiaxi Hu; Robert Seifert; Sofia Karkampouna; Carlos Vinicius Gomes; Song Xue; Ali Afshar-Ormieh; Axel Rominger; Kuangyu Shi

doi:10.1007/s00259-024-07010-3

Influence of dosimetry accuracy on the correlation with treatment outcome in a preliminary PSMA radiopharmaceutical therapy study

Eur J Nucl Med Mol Imaging. 2024 Dec 20. doi: 10.1007/s00259-024-07010-3. Online ahead of print.

Authors

Jiaxi Hu¹, Robert Seifert¹, Sofia Karkampouna^{2

3}, Carlos Vinicius Gomes¹, Song Xue^{1

4}, Ali Afshar-Ormieh¹, Axel Rominger¹, Kuangyu Shi⁵

Affiliations

¹ Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 20, 3010, Bern, Switzerland.
² Urology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland.
³ Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
⁵ Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 20, 3010, Bern, Switzerland. [email protected].

PMID: 39704811
DOI: 10.1007/s00259-024-07010-3

Abstract

Introduction: Despite the potential of dosimetry in optimizing personalized radiopharmaceutical therapy (RPT), its limited clinical implementation impedes the development of simplified protocols for routine adoption. However, simplifications may introduce errors in dosimetry, prompting questions about their impact on clinical practice.

Materials and methods: In this retrospective study, we analyzed data from 21 patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) who underwent multiple cycles of ¹⁷⁷Lu-PSMA-617 RPT treatment. Cumulative dosimetry of all the treatment cycles was calculated using both the standard multi-time point dosimetry (MTPD) method and the single time-point dosimetry (STPD, Hänscheid approximation) method for the same cohort. Their correlations with treatment outcome (PSA decline rate and overall survival, OS) and complication risk (anaemia grade) were investigated. The Fisher's Z-Transformed test was performed to statistically evaluate the difference between the correlations.

Results: STPD showed a non-significant difference in correlation with PSA decline rate, despite a mean percentage error (MPE) of up to 36.44% in tumor dosimetry compared to MTPD (MTPD: rho = -0.39, p < 0.001; STPD: rho = -0.46, p < 0.001; Z = 0.58, p = 0.56). Both STPD_total and MTPD_total demonstrated a significant impact on OS (STPD_total: Hazard Ratio = 1.05, p < 0.05, log-transformed MTPD_total: Hazard Ratio = 3.41, p < 0.05, log-transformed STPD_total: Hazard Ratio = 8.06, p < 0.05). Additionally, despite a MPE of up to -40.26% in bone marrow dosimetry, STPD showed a non-significant difference in correlation with anemia grade (MTPD: rho = 0.35, p < 0.001; STPD: rho = 0.40, p < 0.001; Z = -0.39, p = 0.70).

Conclusion: The preliminary findings from a small cohort indicate that the reduced accuracy of a clinically simplified protocol may not diminish the clinical therapy outcome predictive value of dosimetry. Future thorough systematic investigations may be needed to determine the clinically acceptable level of accuracy for dosimetry.

Keywords: 177Lu-PSMA-617; Dosimetry; Prostate cancer; Radionuclide therapy; Theranostics.