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Clinical Trial
. 2024 Sep 1;49(9):847-853.
doi: 10.1097/RLU.0000000000005330. Epub 2024 Jun 19.

177 Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors : Data From the Prospective Phase 2 LUMEN Study

Magdalena Mileva  1 , Camille Van Bogaert  2 , Gwennaëlle Marin  3 , Rachele Danieli  3 , Carlos Artigas  1 , Hugo Levillain  3 , Lieveke Ameye  4 , Loubna Taraji-Schiltz  1 , Konstantinos Stathopoulos  5 , Zéna Wimana, Alain Hendlisz  6 , Patrick Flamen  1 , Ioannis Karfis  1
Affiliations
Clinical Trial

177 Lu-DOTATATE PRRT Safety and Organ-at-Risk Dosimetry in Patients With Gastroenteropancreatic Neuroendocrine Tumors : Data From the Prospective Phase 2 LUMEN Study

Magdalena Mileva et al. Clin Nucl Med. .

Abstract

Purpose: The aim of this study was to assess the association among toxicity, dosimetry of organs-at-risk, and disease progression in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177 Lu-DOTATATE.

Patients and methods: Thirty-seven patients with GEP-NETs underwent 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in a single-arm, prospective, phase 2 study, where patients were followed up with blood tests, isotopic glomerular filtration rate (iGFR), and imaging examinations (CT/MRI and PET) every 6 months until disease progression. Adverse events (AEs) graded per CTCAEv4.03 and occurring during treatment were collected and followed up until resolution. Dosimetry, including biologically effective doses (BEDs) to kidneys, BED to bone marrow, and absorbed dose (AD) to spleen, was performed after each PRRT cycle. Statistical analyses explored associations among dosimetry, toxicity, and patient progression free-survival.

Results: The most common AEs were anemia and lymphopenia (65%), followed by thrombocytopenia and fatigue (each 51%), alopecia (46%), and nausea (41%). The most common grade ≥3 AE was lymphopenia (43%). There was no grade ≥3 nephrotoxicity. The median iGFR % decrease was 11% ( P < 0.001), at a median follow-up of 23 months. iGFR %decrease and renal BED did not correlate (Spearman ρ = -0.09). Similarly, no significant association was found between bone marrow BED or spleen AD and the grades of hematological toxicities. We observed no association between progression free-survival and either the decline of renal function or the occurrence of hematological toxicities during PRRT.

Conclusions: This study confirms the safety profile of 177 Lu-DOTATATE PRRT in patients with GEP-NETs irrespective of the dosimetry of organs at risk. Kidney, bone marrow, and spleen dosimetry measures were not associated with renal or hematological toxicity.

Trial registration: ClinicalTrials.gov NCT01842165.

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Conflict of interest statement

Conflicts of interest and sources of funding: none declared.

References

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    1. Bergsma H, van Lom K, Raaijmakers M, et al. Persistent hematologic dysfunction after peptide receptor radionuclide therapy with 177 Lu-DOTATATE: incidence, course, and predicting factors in patients with gastroenteropancreatic neuroendocrine tumors. J Nucl Med . 2018;59:452–458.
    1. Goncalves I, Burbury K, Michael M, et al. Characteristics and outcomes of therapy-related myeloid neoplasms after peptide receptor radionuclide/chemoradionuclide therapy (PRRT/PRCRT) for metastatic neuroendocrine neoplasia: a single-institution series. Eur J Nucl Med Mol Imaging . 2019;46:1902–1910.

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