Evaluation of Liver and Renal Toxicity in Peptide Receptor Radionuclide Therapy for Somatostatin Receptor Expressing Tumors: A 2-Year Follow-Up

Abstract

Background: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin receptor (SSR) analogs is now an established systemic treatment for neuroendocrine tumors (NET). However, more short- and long-term data about renal and hepatotoxicity is needed. Here we present our experience in this clinical scenario.

Methods: Eighty-six patients with progressive SSR-expressing malignancies underwent PRRT with Lu-177 Dotatate and were followed up for up to 2 years. Laboratory tests were done 1 week before each cycle and every 2 months at follow-up. Hepatic and renal toxicity was determined based on NCI CTCAE V5.0.

Results: 55/86 (64%) patients completed all 4 cycles of PRRT; 18/86 (20.9%) are currently being treated; 13/86 (15.1%) had to discontinue PRRT: 4/13 (31%) due to hematologic toxicity, 9/13 (69%) due to non-PRRT-related comorbidities. Out of the patients who finished treatment, only transient grade 2 toxicities were observed during PRRT: hypoalbuminemia in 5.5% (3/55), and renal toxicity (serum creatinine and estimated glomerular filtration rate) in 1.8% (1/55). No grade 3 or 4 liver and renal toxicity occurred. Patients presenting with impaired liver or renal function prior to PRRT, either improved or had stable findings. No deterioration was observed.

Conclusion: Peptide receptor radionuclide therapy does not have a negative impact on liver and renal function, even in patients with pre-existing impaired parameters. No grade 3 or 4 hepatic or renal toxicity was identified. Only transient grade 2 hypoalbuminemia in 5.5% and nephrotoxicity in 1.8% of patients were seen during PRRT.

Keywords: Lu-177 dotatate; hepatotoxicity; neuroendocrine tumors; peptide receptor radionuclide therapy; renal toxicity.

Figure 1.

Forty-nine-year-old man with G2 small bowel NET presenting with hyperbilirubinemia (1.5 mg/dL) and elevated aminotransferases at baseline. Maximal intensity projection (MIP) images from Ga-68 Dotatate PET at baseline: diffuse metastatic infiltration of the whole liver and multiple bone lesions (A), after 2 cycles: stable disease (B), after completion of PRRT: stable disease (C), 4 months after PRRT: stable disease (D), 7 months after PRRT: stable disease but ascites with sudden increase of bilirubin to 5.5 mg/dL and carcinoid symptomatology, concerning for disease progression (E), 10 months after PRRT and 3 months after chemotherapy: stable disease with progressing ascites; symptomatology and bilirubin improved (F).

Figure 2.

Sixty-seven-year-old woman with G2 NET of unknown origin and status post TACE twice, presented for PRRT with elevated ALP (460 U/L). She developed transient grade 1 toxicity (elevated AST and ALT) during treatment. Aspartate aminotransferase and ALT recovered 6 months after last PRRT cycle. Maximal intensity projection images from Ga-68 Dotatate PET prior to PRRT: multiple hepatic, osseous, mediastinal, and retroperitoneal lymph node metastases (A), and 8 months after completion of PRRT: treatment response with decreased number, size, and avidity of known metastases (B).

Figure 3.

Creatinine development during PRRT and follow-up in patients with CKD (n = 4).