Individualized dosimetry-based activity reduction of 90Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy
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Assessment of kidney function evolution after 90Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney.
In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq 111In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose–toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using 51Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL).
Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33 % was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT.
Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for 90Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.
KeywordsPRRT Dosimetry Renal function 90Y-DOTATOC
The project was funded by Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie in Vlaanderen (IWT) (http://www.iwt.be) with grant “Innovatie door Wetenschap en Technologie-Toegepast Biomedisch onderzoek met een primair Maatschappelijke finaliteit project no. 0707181”. S.V.B. is a beneficiary of an Emmanuel van der Schueren grant of the Vlaamse Liga tegen Kanker. C.M.D. is a postdoctoral fellow of the Clinical Research Fund of the UZ Leuven. This study was partially funded within the framework of ORAMED for which funding was received from the European Community’s Seventh Framework Program (FP7/2007/2011) under grant agreement no. 211361.
Conflict of interest
The authors declare that they have no conflict of interest.
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