Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors
Abstract
Purpose Peptide receptor radionuclide therapy (PRRT) with (90)Y and (177)Lu provides objective responses in neuroendocrine tumours, and is well tolerated with moderate toxicity. We aimed to identify clinical parameters predictive of long-term renal and haematological toxicity (myelodysplastic syndrome and acute leukaemia).Methods Of 807 patients studied at IEO-Milan (1997-2013), 793 (98 %) received (177)Lu (278, 34.4 %), (90)Y (358, 44.4 %) or (177)Lu and (90)Y combined (157. 19.5 %), and 14 (2 %) received combinations of PRRT and other agents. Follow-up was 30 months (1-180 months). The parameters evaluated included renal risk factors, bone marrow toxicity and PRRT features. Data analysis included multiple regression, random forest feature selection, and recursive partitioning and regression trees.Results Treatment with (90)Y and (90)Y + (177)Lu was more likely to result in nephrotoxicity than treatment with (177)Lu alone (33.6 %, 25.5 % and 13.4 % of patients, respectively; p < 0.0001). Nephrotoxicity (any grade), transient and persistent, occurred in 279 patients (34.6 %) and was severe (grade 3 + 4) in 12 (1.5 %). In only 20-27 % of any nephrotoxicity was the disease modelled by risk factors and codependent associations (p < 0.0001). Hypertension and haemoglobin toxicity were the most relevant factors. Persistent toxicity occurred in 197 patients (24.3 %). In only 22-34 % of affected patients was the disease modelled by the clinical data (p < 0.0001). Hypertension (regression coefficient 0.14, p < 0.0001) and haemoglobin toxicity (regression coefficient 0.21, p < 0.0001) were pertinent factors. Persistent toxicity was associated with shorter PRRT duration from the first to the last cycle (mean 387 vs. 658 days, p < 0.004). Myelodysplastic syndrome occurred in 2.35 % of patients (modelled by the clinical data in 30 %, p < 0.0001). Platelet toxicity grade (2.05 ± 1.2 vs. 0.58 ± 0.8, p < 0.0001) and longer PRRT duration (22.6 ± 24 vs. 15.5 ± 9 months, p = 0.01) were relevant. Acute leukaemia occurred in 1.1 % of patients (modelled by the clinical data in 18 %, p < 0.0001).Conclusion Identified risk factors provide a limited (<30 %) risk estimate even with target tissue dosimetry. These data strongly suggest the existence of unidentified individual susceptibilities to radiation-associated disease.
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Bodei reported a 2.35% frequency of myelodysplastic syndrome.
“Bodei reported a 2.35% frequency of MDS ( 103 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [103]
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- Authors
- Bodei, L., Kidd, M., Paganelli, G., Grana, C. M., Drozdov, I., Cremonesi, M., Lepensky, C., Kwekkeboom, D. J., Baum, R. P., Krenning, E. P., & Modlin, I. M.
- Affiliations
- European Institute of Oncology (IT)
- Yale University (US)
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT)
- Erasmus MC (NL)
- Zentralklinik Bad Berka (DE)
- Corresponding author
- Bodei, Lisa
- ORCID
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2014-10-02
- Volume
- 42
- Issue
- 1
- Pages
- 5-19
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- OpenAlex
- W1969170786
- Cited by
- 465
- References
- 31
- Citations by year
- 2026: 26 · 2025: 30 · 2024: 55 · 2023: 47 · 2022: 48 · 2021: 52 · 2020: 40 · 2019: 37 · 2018: 40 · 2017: 40 · 2016: 26 · 2015: 21 · 2014: 2
- FWCI
- 22.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- peptide receptor radionuclide therapy, neuroendocrine tumors, yttrium-90, lutetium-177, nephrotoxicity, hematologic toxicity, myelodysplastic syndrome, acute leukemia, hypertension, predictive factors, treatment tolerability
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Lutetium, Male, Middle Aged, Myelodysplastic Syndromes, Radiation Dosage, Yttrium Radioisotopes, Octreotide, Leukemia, Myeloid, Acute, Receptors, Peptide, Neuroendocrine Tumors, Radiopharmaceuticals
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