Abstract
Aims and Objectives: Assessment of renal toxicity profile of 177Lu-DOTATATE based Peptide Receptor Radionuclide therapy (PRRT) in patients of Metastatic Neuroendocrine tumor (NET) with a single functioning kidney. Materials and Methods: This was a retrospective analysis of NET patients, who had undergone PRRT with 177Lu-DOTATATE at a large tertiary care centre. The patients selected for the study fulfilled the following criteria: (i) all patients were cases of somatostastin receptor (SSTR) positive neuroendocrine tumours who had received at least 3 cycles of PRRT with 177Lu-DOTATATE and (ii) had a documented single functioning kidney. The selected patients were analyzed under the following parameters: (i) the patient characteristics, (ii) associated metastatic burden, (iii) renal parameters at diagnosis and during the course of therapy, (iv) evaluation of associated nephrotoxic factors. For renal assessment, following parameters were studied before each PRRT cycle: (i) glomerular filtration rate (GFR) estimated by 99mTc-DTPA renogram study, (ii) Effective Renal Plasma Flow (ERPF) by 99mTc-EC renogram study, (iii) blood urea and serum creatinine levels. Renal toxicity was evaluated using Common Terminology Criteria for Adverse Events v4.0 (NCI-CTCAE score). The percentage reduction in the GFR and ERPF for all patients was also assessed. Calculation of filtration fraction (FF) was undertaken to clarify whether there has been a relatively greater reduction in one of the two indices of renal function compared to the other. Results: At the time of analysis, six patients with single functioning kidney with metastatic NET received PRRT with 177Lu-DOTATATE between 3-5 cycles and cumulative activity of 16.6 GBq to 36.2 GBq. Duration of follow-up ranged from 12 - 56 months. Overall toxicity profile (as per the NCI-CTCAE score) showed no patients had any acute renal toxicity. Three patients had no overall chronic renal toxicity; one patient had grade II chronic renal toxicity and two patients had grade I chronic renal toxicity level . All the patients who showed overall chronic renal toxicity showed compromised renal function at the onset (baseline chronic renal toxicity). Interestingly, the two patients with resultant grade I chronic renal toxicity level post-PRRT had grade II chronic renal toxicity before commencement of PRRT with gradual improvement over the subsequent cycles. One patient had grade II chronic renal toxicity before commencement of PRRT with transient worsening to grade III toxicity after first cycle PRRT with gradual improvement and return to basal levels post second cycle of PRRT (values revert back to the grade II toxicity grade). Only two patients showed reduction in GFR (one patient had 5.3% reduction whereas one patient had 13.84% reduction). Four patients showed a reduction in the ERPF (with one patient showing maximum reduction in ERPF it being 31.39% from basal ERPF) and all the four demonstrated rise in filtration fraction signifying that tubular parameters are more affected compared to the glomerular parameters. Conclusion: The preliminary results of this analysis show the feasibility of 177-Lu DOTATATE based PRRT in patients of NET with single functioning kidney, along with proper renal protection and dose fractionation. Further studies are required to assess the long term renal consequences of the changes in ERPF and FF parameters in these patients.