Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [ 177 Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

Autor:	Hebert K; Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France., Santoro L; Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France., Monnier M; Biometry Unit, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France., Castan F; Biometry Unit, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France., Berkane I; Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France., Assénat E; Department of Medical Oncology, CHU de Montpellier, Université de Montpellier, Montpellier, France., Fersing C; Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.; Biometry Unit, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France.; Department of Medical Oncology, CHU de Montpellier, Université de Montpellier, Montpellier, France.; IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France; and., Gélibert P; Centre Hospitalier Métropole Savoie, Chambéry, France., Pouget JP; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France., Bardiès M; Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France., Kotzki PO; Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France., Deshayes E; Department of Nuclear Medicine, Institut du Cancer de Montpellier, Université de Montpellier, Montpellier, France; emmanuel.deshayes@icm.unicancer.fr.; Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Montpellier, France.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Jun 03; Vol. 65 (6), pp. 923-930. Date of Electronic Publication: 2024 Jun 03.
DOI:	10.2967/jnumed.123.267023
Abstrakt:	[ 177 Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from 177 Lu. The objective of this work was to explore how postinfusion [ 177 Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity. Methods: Patients with GEP-NETs treated with [ 177 Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measurement masked to the somatostatin receptor imaging uptake). For toxicity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients' health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models. Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1-9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor volume variation ( P < 0.001) 3 mo after treatment end, and it was a significant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. Conclusion: In patients treated with [ 177 Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management. (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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