Radiomic Model Associated with Tumor Microenvironment Predicts Immunotherapy Response and Prognosis in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.
Authors
Affiliations (11)
Affiliations (11)
- Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
- Medical AI Lab, The First Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, Hebei, China.
- Hebei Provincial Engineering Research Center for AI-Based Cancer Treatment Decision-Making, The First Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, Hebei, China.
- Department of Oncology, The First Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, Hebei, China.
- Department of Radiology, Hainan Affiliated Hospital of Hainan Medical University (Hainan General Hospital), Haikou, Hainan, China.
- Department of Medical Imaging, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
- Department of Radiology, Hainan Cancer Hospital, Haikou, Hainan, China.
- Department of Radiology, The Third Bethune Hospital of Jilin University, Changchun, Jilin, China.
- Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
- Department of Radiology, The Affiliated Panyu Central Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
- Department of Radiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Abstract
<b>Background:</b> No robust biomarkers have been identified to predict the efficacy of programmed cell death protein 1 (PD-1) inhibitors in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). We aimed to develop radiomic models using pre-immunotherapy MRI to predict the response to PD-1 inhibitors and the patient prognosis. <b>Methods:</b> This study included 246 LANPC patients (training cohort, <i>n</i> = 117; external test cohort, <i>n</i> = 129) from 10 centers. The best-performing machine learning classifier was employed to create the radiomic models. A combined model was constructed by integrating clinical and radiomic data. A radiomic interpretability study was performed with whole slide images (WSIs) stained with hematoxylin and eosin (H&E) and immunohistochemistry (IHC). A total of 150 patient-level nuclear morphological features (NMFs) and 12 cell spatial distribution features (CSDFs) were extracted from WSIs. The correlation between the radiomic and pathological features was assessed using Spearman correlation analysis. <b>Results:</b> The radiomic model outperformed the clinical and combined models in predicting treatment response (area under the curve: 0.760 vs. 0.559 vs. 0.652). For overall survival estimation, the combined model performed comparably to the radiomic model but outperformed the clinical model (concordance index: 0.858 vs. 0.812 vs. 0.664). Six treatment response-related radiomic features correlated with 50 H&E-derived (146 pairs, |<i>r</i>|= 0.31 to 0.46) and 2 to 26 IHC-derived NMF, particularly for CD45RO (69 pairs, |<i>r</i>|= 0.31 to 0.48), CD8 (84, |<i>r</i>|= 0.30 to 0.59), PD-L1 (73, |<i>r</i>|= 0.32 to 0.48), and CD163 (53, |<i>r</i>| = 0.32 to 0.59). Eight prognostic radiomic features correlated with 11 H&E-derived (16 pairs, |<i>r</i>|= 0.48 to 0.61) and 2 to 31 IHC-derived NMF, particularly for PD-L1 (80 pairs, |<i>r</i>|= 0.44 to 0.64), CD45RO (65, |<i>r</i>|= 0.42 to 0.67), CD19 (35, |<i>r</i>|= 0.44 to 0.58), CD66b (61, |<i>r</i>| = 0.42 to 0.67), and FOXP3 (21, |<i>r</i>| = 0.41 to 0.71). In contrast, fewer CSDFs exhibited correlations with specific radiomic features. <b>Conclusion:</b> The radiomic model and combined model are feasible in predicting immunotherapy response and outcomes in LANPC patients. The radiology-pathology correlation suggests a potential biological basis for the predictive models.