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Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, no 6, p. 970-988Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.

METHODS: Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%).

RESULTS: In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.

CONCLUSIONS: Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.

Place, publisher, year, edition, pages
2018. Vol. 45, no 6, p. 970-988
Keywords [en]
177Lu-DOTA-octreotate, Dosimetry, Neuroendocrine tumour, Outcome, PRRT, Toxicity
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-346995DOI: 10.1007/s00259-018-3945-zISI: 000430832400010PubMedID: 29497803OAI: oai:DiVA.org:uu-346995DiVA, id: diva2:1192664
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-11-12Bibliographically approved

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Garske, UlrikeSandström, MattiasFröss-Baron, KatarzynaLundin, LarsHellman, PerWelin, StaffanJohansson, SilviaKhan, Tanweera ShaheenaLundqvist, HansEriksson, BarbroSundin, AndersGranberg, Dan

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Garske, UlrikeSandström, MattiasFröss-Baron, KatarzynaLundin, LarsHellman, PerWelin, StaffanJohansson, SilviaKhan, Tanweera ShaheenaLundqvist, HansEriksson, BarbroSundin, AndersGranberg, Dan
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Radiology, Nuclear Medicine and Medical ImagingCancer and OncologyMedical and Health Sciences

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