Pituitary Function after High-Dose [sup.177]Lu-DOTATATE Therapy and Long-Term Follow-Up

Introduction: The pituitary gland has a high expression of somatostatin receptors and is therefore a potential organ at risk for radiation-induced toxicity after [sup.177]Lu-DOTATATE treatment. Objective: To study changes in pituitary function in patients with neuroendocrine tumors (NETs) treated with dosimetry-based [sup.177]Lu-DOTATATE to detect possible late toxicity. Methods: 68 patients from a phase II clinical trial of dosimetry-based, individualized [sup.177]Lu-DOTATATE therapy were included in this analysis. Patients had received a median of 5 (range 3-9) treatment cycles of 7.4 GBq/cycle. Median follow-up was 30 months (range 11-89). The GH/IGF-1 axis, gonadotropins, and adrenal and thyroid axes were analyzed at baseline and on a yearly basis thereafter. Percent changes in hormonal levels over time were analyzed statistically using a linear mixed model and described graphically using box plots. The absorbed radiation dose to the pituitary was estimated based on post-therapeutic imaging, and the results analyzed versus percent change in IGF-1 levels over time. Results: A statistically significant decrease in IGF-1 levels was found (p < 0.005), which correlated with the number of treatment cycles (p = 0.008) and the absorbed radiation dose (p = 0.03). A similar decrease, although non-significant, was seen in gonadotropins in postmenopausal women, while in men there was an increase during the first years after therapy, after which the levels returned to baseline. No change was observed in the adrenal or thyroid axes. Conclusions: No signs of severe endocrine disorders were detected, although a significant decrease in the GH/IGF-1 axis was found, where dosimetric analyses indicated radiation-induced damage to the pituitary gland as a probable cause. Keywords: .sup.177Lu-DOTATATE, Peptide receptor radionuclide therapy, Pituitary, Radiotherapy, Neuroendocrine tumor