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[Preprint]. 2025 Oct 28:2025.10.26.25338837. [Version 1] doi: 10.1101/2025.10.26.25338837

Multiregional CT Features Improve Prediction of Immunotherapy Response in Advanced Melanoma

Grant Kokenberger, Jatin Singh, Drew Hurd, Tong Yu, Xin Meng, Madison Nguyen, Walter J Storkus, William McKay, Jason J Luke, Yana G Najjar, John M Kirkwood, Hassane M Zarour, Diwakar Davar, Jiantao Pu
PMCID: PMC12636632  PMID: 41282802

Abstract

Objective

Immunotherapy has improved outcomes for advanced-stage melanoma, however, predictive biomarkers remain limited. We evaluated whether computed tomography (CT) features from multiple anatomical regions could predict immunotherapy response.

Materials and Methods

This study included 157 advanced cutaneous melanoma patients (mean age: 63.3 years; 65.6% male) treated with PD-1 immune checkpoint inhibitor (ICI) singly or in combination with LAG-3 or CTLA-4 ICIs. The primary outcome was 1-year progression-free survival (PFS ≥12 months). Available artificial intelligence (AI) algorithms were applied to pretreatment CT scans to extract and quantify three-dimensional (3D) body composition and thoracic features across abdominal, chest, pelvic regions, and spinal vertebrae. Feature relationship to PFS was assessed. Machine learning (ML) models were used to predict PFS, utilizing only the most important five features to mitigate overfitting. Prediction performance was evaluated using the area under the receiver operating curve (AUROC) with stratified 10-fold cross-validation.

Results

Multiple CT features are significantly associated with immunotherapy response. Body tissues at the L5 spinal vertebrae emerged as key predictors. A random forest classifier (RFC) trained on three CT features (L5 bone volume, L5 subcutaneous adipose tissue volume, pelvis visceral adipose tissue density) and two clinical variables achieved a mean AUROC of 0.83 (95% CI: 0.72–0.94). A logistic regression model using the same features yielded an AUROC of 0.82 (95% CI: 0.74–0.91), significantly outperforming a clinical-only model (AUROC 0.65; 95% CI: 0.56–0.74; p=0.006).

Conclusion

Integrating imaging features from multiple anatomical regions can improve the prediction of immunotherapy response in advanced melanoma.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


Articles from medRxiv are provided here courtesy of Cold Spring Harbor Laboratory Preprints

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