Accepted for/Published in: JMIR Medical Informatics
Date Submitted: Oct 31, 2025
Open Peer Review Period: Oct 30, 2025 - Dec 25, 2025
Date Accepted: Jul 15, 2026
(closed for review but you can still tweet)
Integrating Lymph Node Metastasis and PD-L1 Prediction in NSCLC from a Single PET/CT Scan: A Multicenter Radiomics Study
ABSTRACT
Background:
Preoperative stratification for non-small cell lung cancer (NSCLC) necessitates the separate evaluation of lymph node metastasis (LNM) to guide surgical decisions and PD-L1 expression to inform immunotherapy. This fragmented approach depends on invasive procedures and fails to provide a comprehensive preoperative profile.
Objective:
Our aim was to develop and validate an integrated diagnostic solution that can simultaneously predict both LNM and PD-L1 expression status from a single, standard-of-care 18F-FDG PET/CT scan.
Methods:
In a retrospective multicenter study, we segmented primary tumors and peritumoral regions from preoperative PET/CT scans of 273 patients (for LNM prediction) and 242 patients (for PD-L1 prediction). A total of 7868 radiomic features were extracted. Following rigorous feature selection, two independent models were developed using machine learning and validated on an external test cohort (n=45). Model performance was benchmarked against clinicopathological models and nuclear medicine physicians.
Results:
The integrated model for LNM prediction (PT-IPT-LR) achieved an area under the curve (AUC) of 0.845 in the external test, outperforming physicians in sensitivity (0.813 vs. 0.628) and accuracy. The model for PD-L1 expression (PT-IPT-SVM) achieved an AUC of 0.776, surpassing clinicopathological benchmarks. Decision curve analysis (DCA) confirmed the clinical utility of both models. Critically, we found no significant correlation between the radiomic signatures of LNM and PD-L1, biologically validating our two-model approach.
Conclusions:
We present a robust, multicenter-validated radiomics framework that noninvasively integrates the prediction of two critical therapeutic targets—LNM and PD-L1—from a single preoperative PET/CT scan. This tool enables comprehensive preoperative stratification, potentially optimizing both surgical and systemic treatment planning for NSCLC patients in a single step. Clinical Trial: None
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