Abstract
PurposeAfter peptide receptor radionuclide therapy (PRRT), renal toxicity may occur, particular in PRRT with 90Y-labelled somatostatin analogues. Risk factors have been identified for increased probability of developing renal toxicity after PRRT, including hypertension, diabetes and age. We investigated the renal function over time, the incidence of nephrotoxicity and associated risk factors in patients treated with PRRT with [177Lu-DOTA0,Tyr3]-Octreotate (177Lu-Octreotate). Also, radiation dose to the kidneys was evaluated and compared with the accepted dose limits in external beam radiotherapy and PRRT with 90Y-radiolabelled somatostatin analogues.MethodsThe annual decrease in creatinine clearance (CLR) was determined in 209 Dutch patients and the incidence of grade 3 or 4 renal toxicity (according to CTCAE v4.03) was evaluated in 323 patients. Risk factors were analysed using a nonlinear mixed effects regression model. Also, radiation doses to the kidneys were calculated and their association with high annual decrease in renal function were analysed.ResultsOf the 323 patients, 3 (1 %) developed (subacute) renal toxicity grade 2 (increase in serum creatinine >1.5 – 3.0 times baseline or upper limit of normal). No subacute grade 3 or 4 nephrotoxicity was observed. The estimated average baseline CLR (± SD) was 108 ± 5 ml/min and the estimated average annual decrease in CLR (± SD) was 3.4 ± 0.4 %. None of the risk factors (hypertension, diabetes, high cumulative injected activity, radiation dose to the kidneys and CTCAE grade) at baseline had a significant effect on renal function over time. The mean absorbed kidney dose in 228 patients was 20.1 ± 4.9 Gy.ConclusionNephrotoxicity in patients treated with 177Lu-octreotate was low. No (sub)acute grade 3 or 4 renal toxicity occurred and none of the patients had an annual decrease in renal function of >20 %. No risk factors for renal toxicity could be identified. Our data support the idea that the radiation dose threshold, adopted from external beam radiotherapy and PRRT with 90Y-labelled somatostatin analogues, does not seem valid for PRRT with 177Lu-octreotate.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-016-3382-9) contains supplementary material, which is available to authorized users.
Highlights
Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is increasingly being used in patients with neuroendocrine tumours
None of the risk factors at baseline had a significant effect on renal function over time
Noacute grade 3 or 4 renal toxicity occurred and none of the patients had an annual decrease in renal function of >20 %
Summary
Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is increasingly being used in patients with neuroendocrine tumours. A decrease in renal uptake can be achieved by coinfusion of amino acids during PRRT [7, 8]. Despite this renoprotection, there is still a significant radiation dose to the kidneys. According to new consensus guidelines, the limit for fractionated EBRT is set at 18 Gy that results in late radiation damage to the kidneys in 5 % of a treated population [10]. We analysed the association between known risk factors that have been indicated for PRRT with 90Y-based somatostatin analogues [2, 5] and change in renal function, including hypertension, diabetes, cumulative injected activity, age, previous therapies and poor renal function at baseline. Radiation doses to the kidneys were calculated and analysed
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