Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors.

Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumours with (90)Y-DOTATOC and (177)Lu-DOTATATE is promising. The kidney is the critical organ and despite renal protection, function loss may become evident years later. The aim of this study was to analyse renal parameters in patients who had undergone dosimetry before PRRT. Among those in protocols at our institution, 28 patients were considered: 23 received (90)Y-DOTATOC (3.8-29.2 GBq, median 12.2) and five received (177)Lu-DOTATATE (20.7-29.2 GBq, median 23.2). Patients were followed up after therapy for creatinine and creatinine clearance loss (CCL) for 3-97 months (median 30). Renal doses and bio-effective doses (BED) were calculated (MIRD, LQ model). After (90)Y-DOTATOC toxicity on creatinine according to NCI criteria occurred in nine cases (seven grade 1, one grade 2, one grade 3), CCL at 1 year was >5% in 12 cases and >10% in eight. A 28-Gy BED threshold was observed in patients with risk factors (mainly hypertension and diabetes), while it was 40 Gy in patients without risk factors. Probably due to the low number of patients, despite the absence of severe toxicity after hyper-fractionated PRRT, clear correlations between fractionation and toxicity could not be found. After (177)Lu-DOTATATE, no toxicity occurred in 1-2 year follow-up; CCL at 1 year >5% occurred in three patients and >10% in two. Our results indicate the importance of clinical screening for risk factors: In this case, a BED <28 Gy is recommended. Fractionation of therapy is important in order to decrease toxicity, and further studies are needed to evaluate its clinical impact.