Peptide Receptor Radionuclide Therapy-Induced Hepatotoxicity in Patients With Metastatic Neuroendocrine Tumors.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Hepatotoxicity after PRRT for metastatic GEP-NET is more common than previously reported.
From the *Division of Gastroenterology, †Department of Radiology, and ‡Division of Medical Oncology, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; §Clinic of Radiology and Nuclear Medicine, Division of Nuclear Medicine, University Basel Hospital, Basel, Switzerland.
Brian P
BP
Riff
Yu-Xiao
YX
Yang
Michael C
MC
Soulen
Daniel A
DA
Pryma
Bonita
B
Bennett
Damian
D
Wild
Guillaume
G
Nicolas
Ursina R
UR
Teitelbaum
David C
DC
Metz
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000453:epidemiology; D059248:Chemoradiotherapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000473:pathology / Q000628:therapy*; D015282:Octreotide / Q000009:adverse effects* / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000009:adverse effects* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*
D018931:Antineoplastic Agents, Hormonal; D019275:Radiopharmaceuticals; D015282:Octreotide