Treatment options for patients with neuroendocrine tumors (NETs) and other somatostatin receptor positive (sstr+) tumors include peptide receptor radionuclide therapy (PRRT) using high activities of beta-emitter and/or Auger electron-emitter radiopharmaceuticals; PRRT may induce renal impairment. The aim of this study is to evaluate renal function modifications at renal dynamic scintigraphy (RDS) with GFR estimation in NET patients treated with PRRT.
We retrospectively reviewed clinical records of 39 patients (17F and 22M) with a diagnosis of NET who were referred for PRRT. Histological diagnoses were: pancreatic neuroendocrine carcinoma (NEC) in 11, ileal NEC in 6, NEC of unknown origin in 5, duodenal NEC in 1, mediastinal NEC in 1, thymic NEC in 1, mesenterial NEC in 1, jugular chemodectoma in 1, lung carcinoid in 4, carcinoid of unknown origin in 2, pancreatic carcinoid in 1, ileal carcinoid in 1, medullary thyroid carcinoma in 1, radioiodine-negative sstr+ thyroid cancer in 1, and intracranial meningiomatosis in 2 patients.
All patients underwent PRRT with 111In-Pentetreotide (1-7 cycles, median 4 cycles, activity range per cycle 1.1-7.5 GBq, median activity per cycle 5.5 GBq, mean cumulative activity 16.2 GBq) and/or 90Y-DOTATOC/DOTATATE (1-7 cycles, median 3 cycles, activity range per cycle 0.74-2.6 GBq, median activity per cycle 1.9 GBq, mean cumulative activity 10.3 GBq) and/or 177Lu-DOTATATE (1-6 cycles, median 4 cycles, activity range per cycle 3.7-7.0 GBq, median activity per cycle 5.5 GBq, median cumulative activity 15.5 GBq). Each patient was treated with 1 to 13 PRRT cycles. To reduce tubular peptide uptake and minimize renal damage, intravenous aminoacids were always administered prior to PRRT. In 20 patients comorbility factors were present (diabetes, hypertension, dyslipidemia). Renal function was evaluated with RDS before each PRRT cycle; creatinine and azothemia serum levels were also recorded.
Baseline GFR ranged 46 to 129 ml/min/1.73 m2. GFR decrease ranged 4 to 63% (mean: 23%). A significant statistical correlation between the percentage of GFR reduction and cumulative administered activity was found only for 90Y-DOTATOC/DOTATATE (Spearman test: R=0.4818, P=0.0232), but not in the cases of 111In-Pentetreotide or 177Lu-DOTATATE PRRT. Oppositely, creatinine and azothemia values showed no statistical correlation with PRRT. The decrement in GFR values led to adjustment of the therapeutic activity and/or of the radiopharmaceutical used for PRRT in 11 patients (35.5%); interestingly, azothemia and/or creatinine serum levels were normal in 7 out of these 11 patients.
Our results show that neither creatinine nor azothemia serum concentration can be recommended for evaluation of renal function in patients undergoing PRRT. GFR evaluation with RDS is a reliable and simple method to evaluate renal function, which allows to manage PRRT for reaching the therapeutic purpose minimizing renal function impairment.