AUTHOR=Mathew Annie , Kersting David , Fendler Wolfgang P. , Braegelmann Johanna , Fuhrer Dagmar , Lahner Harald 

TITLE=Impact of functionality and grading on survival in pancreatic neuroendocrine tumor patients receiving peptide receptor radionuclide therapy

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1526470

DOI=10.3389/fendo.2025.1526470

ISSN=1664-2392

ABSTRACT=BackgroundPeptide receptor radionuclide therapy (PRRT) is a well-established treatment option for neuroendocrine tumors (NET), yet randomized controlled trials have not provided data on its impact on overall survival. The real-world efficacy of PRRT and its association with tumor functionality and grading in pancreatic neuroendocrine tumors (PanNET) remains underexplored.MethodsA retrospective analysis of 166 patients with histologically confirmed metastatic PanNET was performed. Subgroup analyses examined progression-free survival (PFS) and overall survival (OS) following PRRT cycles, stratified by tumor grading, tumor functionality and bone metastases.ResultsOf 166 patients, 100 (60.2%) received PRRT with a median of four cycles. In the PRRT cohort, 68% of patients had deceased. PFS after four and eight consecutive cycles was 20 and 18 months, respectively (p=0.4). OS for the entire cohort was 79 months, with patients receiving 4+ cycles of PRRT having an OS of 87 months and those receiving 5+ cycles achieving an OS of 100 months. Patients with grade 1 or 2 tumors had a significantly longer median OS of 97 months compared to 74.5 months for grade 3 tumors (p = 0.0055). There was no significant difference in OS between functioning and non-functioning tumors after PRRT. Patients with bone metastases who received PRRT had a significantly shorter OS than those without (74 vs. 89 months, p = 0.013). In 19% of patients who received PRRT, therapy was discontinued due to progressive disease, toxicity or death.ConclusionsPatients receiving extended cycles of PRRT showed improved survival outcomes in metastatic PanNET, particularly in patients with lower tumor grades and without bone metastases. No survival difference was seen between functioning and non-functioning PanNET, while patients with grade 3 tumors and bone metastases had significantly shorter survival despite PRRT.