The NET Score: An Interpretable AI-Assisted Prognostic Score for Mortality Risk in Lung Neuroendocrine Tumors
Background: Lung neuroendocrine tumors (NETs), including typical and atypical carcinoids, show heterogeneous outcomes. Existing nomograms are often complex and insufficiently validated, limiting their bedside use. A simple, reproducible model based on routine pathology is therefore needed. This study aimed to develop and internally validate the NET Score, an interpretable, AI-assisted tool to estimate individualized mortality risk. Methods: In a retrospective cohort of resected pulmonary carcinoids, candidate predictors were screened using LASSO regression to reduce overfitting and identify key variables: nodal status, mitotic index (>2 per 2 mm2), necrosis, and Ki-67 (>5%). Selected variables were incorporated into a logistic regression model to generate a point-based score (0-8). The model estimates cumulative mortality risk across follow-up, not fixed-time survival. Internal validation included bootstrap and cross-validation to assess discrimination and calibration. Results: The final model included LODDS > -0.5 (3 points), mitotic index >2 (2 points), necrosis (2 points), and Ki-67 (1 point). Discrimination was moderate (bootstrap-corrected AUC 0.70). Risk groups were defined as low (0-2 points, ≤5%), intermediate (3-4 points, 8-12%), and high (≥5 points, ≥18%). Kaplan-Meier curves demonstrated progressive survival stratification across risk groups. Conclusion: The NET Score is a practical and interpretable prognostic tool for lung NETs. It supports risk communication and clinical decision-making while maintaining transparency. External validation is required. Combining AI-based variable selection with a simple scoring system represents a pragmatic approach to prognostic modeling in rare thoracic malignancies.
Authors
- Lorenzo Spaggiari (ORCID: https://orcid.org/0000-0002-1068-3541)
- Nicola Fazio (ORCID: https://orcid.org/0000-0001-6869-0704)
- Luca Bertolaccini (ORCID: https://orcid.org/0000-0002-1153-3334)
- G Caffarena
- Renato Lobrano (ORCID: https://orcid.org/0000-0002-4603-6426)
- Francesca Spada (ORCID: https://orcid.org/0000-0003-3642-0798)
- Juliana Guarize (ORCID: https://orcid.org/0000-0002-1695-1375)
- Eleonora Pisa
- Lavinia Benini
- Nicola Fusco
- Monica Casiraghi
Institutions
- University of Milan (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- European Institute of Oncology (IT)
Publication Details
- Journal
- Endocrine Related Cancer
- Published
- 2026-06-16
- DOI
- https://doi.org/10.1530/erc-26-0164
- Primary Topic
- Neuroendocrine Tumor Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 0.00