Can clinicians predict individual patient outcomes in neuroendocrine tumors treated with [177Lu]Lu-DOTATATE?

Abstract

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has become a cornerstone in the management of neuroendocrine tumors (NETs), yet optimal sequencing and patient selection remain unsettled. This study aimed to develop and internally validate the NEPTUNE score to predict progression-free survival (PFS) in advanced NETs patients receiving [177Lu]Lu-DOTATATE. MATERIALS AND METHODS: Real-world data from the nationwide SEPTRALU registry and the Jules Bordet Institute included patients with advanced NETs treated with [177Lu]Lu-DOTATATE. Predictors of PFS were identified using an accelerated failure time model and combined into the NEPTUNE score. Internal validation was performed using bootstrap resampling. This tool was subsequently transformed into a nomogram and an interactive web-based calculator to enhance its integration into routine clinical practice. RESULTS: The cohort comprised 647 patients with diverse NET subtypes: pancreatic (39%), midgut (30%), bronchopulmonary (9%), pheochromocytoma/paraganglioma (3%), other gastroenteropancreatic (11%), and other non-gastroenteropancreatic (8%). The NEPTUNE score incorporates ten routinely available variables: ECOG performance status, PRRT line, Ki67 index, number of metastatic sites, primary tumor site, sex, Krenning grade, surgical resection of metastases, presence of liver metastases, and time from advanced tumor diagnosis to PRRT. The score demonstrated strong performance, with an Integrated Brier Score of 0.201 and a bias-corrected C-index of 0.702, indicating good calibration and discrimination. CONCLUSIONS: The NEPTUNE score is a promising tool for predicting individual PFS in patients with advanced NETs treated with [177Lu]Lu-DOTATATE. By integrating readily available clinical variables, it may support clinical decision-making. However, external validation is required before broader clinical implementation.