Treatment of metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) with peptide receptor radionuclide therapy (PRRT) is effective in retarding tumor growth. Renal dysfunction, anemia, and thrombocytopenia are well-described treatment-related toxicities. However, hepatotoxicity is not well recognized.

We performed a retrospective cohort study of consecutive patients with GEP-NETs seen in a tertiary NET clinic from January 2010 to September 2013 (n = 211) with the primary study cohort being patients with metastatic disease to the liver (n = 93). The study exposure was PRRT, and the primary outcome of interest was hepatotoxicity. Hepatotoxicity was defined as a grade 2 or greater injury according to the Common Terminology Criteria for Adverse Events version 3.0 of the National Cancer Institute.

Seventeen (18%) of 93 patients with liver metastases received PRRT after radiographic confirmation of disease progression despite receipt of other traditional therapies. Peptide receptor radionuclide therapy patients were similar to the unexposed patient population in terms of sex, age, baseline laboratory values, prior treatment exposure, and duration of disease. In the unexposed group, 23 (30%) of 76 patients had hepatotoxicity related to traditional GEP-NET therapy. In the exposed group, 10 (59%) of 17 patients had an episode of hepatotoxicity. Ascites developed in 59% of the PRRT group versus 6.6% in the unexposed group (P < 0.001). The calculated relative risk of hepatotoxicity related to PRRT exposure in metastatic GEP-NET patients was 1.94 (95% confidence interval, 1.15-3.28).

Hepatotoxicity after PRRT for metastatic GEP-NET is more common than previously reported.