Neuroendocrine Tumors Research Updates

Using real-world data from 647 advanced neuroendocrine tumor (NET) patients treated with [177Lu]Lu-DOTATATE, the authors developed and internally validated the NEPTUNE score—an accelerated failure time model incorporating 10 routine variables (including ECOG status, PRRT line, Ki67, metastatic sites, primary site, sex, Krenning grade, metastasis resection, liver metastases, and time from advanced diagnosis to PRRT) to predict progression-free survival. The model demonstrated good calibration and discrimination (Integrated Brier Score 0.201; bias-corrected C-index 0.702) and was converted into a nomogram and web calculator, with external validation noted as required before broader use.

In high-grade serous ovarian carcinoma (human datasets and chemoresistant murine metastatic HGSC models), chemotherapy increased tumor myeloid IL1β expression, neutrophil infiltration and neutrophil extracellular traps (NETs) in omental metastases compared with pre‑treatment or wild-type controls. Genetic disruption of the IL1β–IL1R1 axis or antibody-mediated neutrophil depletion reduced neutrophil/NET accumulation, increased effector-like CD8+ T cells and tumor control, and enhanced chemosensitivity; in vitro NETs (but not IL1β) reduced cancer cell chemosensitivity. Single-cell data implicated tumor-associated fibroblasts as IL1R1-expressing sources of CXCL2, and residual human post-chemotherapy HGSC showed increased neutrophils with a trend toward more NETs.

This case report describes a 68-year-old woman with metastatic functional pancreatic neuroendocrine tumor (VIPoma) who developed a temozolomide-associated hypermutated, microsatellite instability–high tumor after capecitabine-temozolomide treatment; subsequent pembrolizumab produced a robust clinical, biochemical, and radiographic response. The case highlights dynamic genomic evolution after alkylating chemotherapy and the potential value of serial molecular profiling to inform therapy selection.