A Foundation Model Based CT Biomarker for Non-Invasive Prediction of Response to Neoadjuvant Immunochemotherapy in Non-Small Cell Lung Cancer.
Authors
Affiliations (9)
Affiliations (9)
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Department of Radiology, Shanghai Pulmonary Hospital, Shanghai, China.
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Shanghai Institute of Medical Imaging, Shanghai, China.
- Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Radiology, Stanford University, Stanford, California, USA.
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing, China.
Abstract
Predicting pathological complete response (pCR) to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) is clinically important yet remains challenging. Here, we introduce a foundation model-derived computed tomography (CT) imaging biomarker established from a multi-center cohort of 702 patients. Specifically, we developed and validated a non-invasive baseline CT-based model for risk stratification of pathological response. To address scanner and protocol heterogeneity, we first built a 3D Vision Mamba-based CT super-resolution model trained on 2494 cases for image standardization. We then fine-tuned a lung cancer-specific CT foundation model from a pretrained 3D model (VoCo) using 6643 chest CT scans. Finally, we constructed a multi-task Swin Transformer that jointly performs risk stratification and segments tumors to generate the imaging biomarker. Across five centers, the model achieved consistently strong generalization (AUC: 0.75-0.87) for pCR prediction. Genomic analysis revealed that the biomarker was independent of tumor mutational burden but significantly associated with TP53 mutations, suggesting an association with a radiogenomic phenotype related to this alteration. Together, these results demonstrate a generalizable and biologically meaningful foundation model-based biomarker for non-invasive risk stratification of pathological response in NSCLC.