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Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial

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Abstract

Purpose

Peptide receptor radionuclide therapy (PRRT) is mostly administered using a fixed injected activity (IA) per cycle. This empiric regime results in highly variable absorbed doses to the critical organs and undertreatment of the majority of patients. We conceived a personalized PRRT protocol in which the IA is adjusted to deliver a prescribed absorbed dose to the kidney, with the aim to safely increase tumour irradiation. We herein report on the initial results of our prospective study of personalized PRRT, the P-PRRT Trial (NCT02754297).

Methods

PRRT-naïve patients with progressive and/or symptomatic neuroendocrine tumour (NET) were scheduled to receive a four-cycle induction course of 177Lu-octreotate with quantitative SPECT/CT-based dosimetry. The IA was personalized according to the glomerular filtration rate and the body surface area for the first cycle, and according to the prior renal Gy/GBq for the subsequent cycles. The prescribed renal absorbed dose of 23 Gy was reduced by 25–50% in case of significant renal or haematological impairment. Responders were allowed to receive consolidation or maintenance cycles, for each of which 6 Gy to the kidney were prescribed. We simulated the empiric PRRT regime by fixing the IA at 7.4 GBq per cycle, with the same percentage reductions as above. Radiological, molecular imaging, biochemical, and quality of life responses, as well as safety, were assessed.

Results

Fifty-two patients underwent 171 cycles. In 34 patients who completed the induction course, a median cumulative IA of 36.1 (range, 6.3–78.6) GBq was administered, and the median cumulative kidney and maximum tumour absorbed doses were 22.1 (range, 8.3–24.3) Gy and 185.7 (range: 15.2–443.1) Gy respectively. Compared with the simulated fixed-IA induction regime, there was a median 1.26-fold increase (range, 0.47–2.12 fold) in the cumulative maximum tumour absorbed dose, which was higher in 85.3% of patients. In 39 assessable patients, the best objective response was partial response in nine (23.1%), minor response in 14 (35.9%), stable disease in 13 (33.3%) and progressive disease in three patients (7.7%). In particular, 11 of 13 patients (84.6%) with pancreatic NET had partial or minor response. The global health status/quality of life score significantly increased in 50% of patients. Acute and subacute side-effects were all of grade 1 or 2, and the most common were nausea (in 32.7% of patients) and fatigue (in 30.8% of patients) respectively. Subacute grade 3 or 4 toxicities occurred in less than 10% of patients, with the exception of lymphocytopenia in 51.9% of patients, without any clinical consequences however. No patient experienced severe renal toxicity.

Conclusions

Personalized PRRT makes it possible to safely increase tumour irradiation in the majority of patients. Our first results indicate a favourable tolerance profile, which appears similar to that of the empiric regime. The response rates are promising, in particular in patients with NET of pancreatic origin.

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Acknowledgements

We thank Anna Celler, Ph.D. (Physicist, University of British Columbia, Vancouver, Canada) and her students for their ongoing collaboration on quantitative SPECT and dosimetry methods. We are grateful to the nurses and nuclear medicine technologists at the CHU de Québec – Université Laval who provided care for our patients, as well as to the Gastrointestinal Oncology Multidisciplinary Team at CHU de Québec – Université Laval for supporting our PRRT program, in particular to Dr. Jean-François Ouellet (Surgeon) and Dr. Félix Couture (haematologist-oncologist). Finally, we would like to thank all our referring physicians for their trust, in particular Dr. Daniel Rayson (Medical Oncologist, Dalhousie University, Halifax, Canada).

Funding

M.D.P. was supported by a Merit Scholarship for Foreign Students from the Ministère de l’éducation et de l’enseignement supérieur du Québec. J.M.B. is supported by a Clinical Research Scholarship from the Fonds de recherche du Québec – Santé. This work was funded by the Canadian Institutes of Health Research (CIHR) operating grant MOP-142233 to J.M.B.

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Correspondence to Jean-Mathieu Beauregard.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Del Prete, M., Buteau, FA., Arsenault, F. et al. Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial. Eur J Nucl Med Mol Imaging 46, 728–742 (2019). https://doi.org/10.1007/s00259-018-4209-7

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