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.

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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
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article

The NET Score: An Interpretable AI-Assisted Prognostic Score for Mortality Risk in Lung Neuroendocrine Tumors

Lorenzo Spaggiari, Nicola Fazio, Luca Bertolaccini, G Caffarena et al.
Endocrine Related Cancer
Neuroendocrine Tumor Research Advances
article

The NET Score: An Interpretable AI-Assisted Prognostic Score for Mortality Risk in Lung Neuroendocrine Tumors

Lorenzo Spaggiari, Nicola Fazio, Luca Bertolaccini, G Caffarena, Renato Lobrano, Francesca Spada, Juliana Guarize, Eleonora Pisa, Lavinia Benini, Nicola Fusco, Monica Casiraghi
article en

Abstract

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.

Endocrine Related Cancer
University of Milan (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), European Institute of Oncology (IT)
Openalex Percentile: Top 7%
Neuroendocrine Tumor Research Advances
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