AUTHOR=Ren Jingyi , Lu Jinbo , Shi Xun , Cheng Yuexin TITLE=The significance of PET/CT combined with machine learning models for the classification of lymphoma involvement and metastases in enlarged lymph nodes JOURNAL=Frontiers in Oncology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1643924 DOI=10.3389/fonc.2025.1643924 ISSN=2234-943X ABSTRACT=ObjectiveAccurate differentiation between lymphoma involvement and lymph node metastasis poses significant diagnostic challenges due to overlapping imaging characteristics. This study evaluates the discriminative capacity of PET/CT metabolic profiling integrated with machine learning for nodal pathology classification.MethodsWe analyzed 247 lymph nodes from patients with diffuse large B-cell lymphoma (DLBCL, n=39) and solid tumor metastases (n=46). Multivariable logistic regression identified key PET/CT biomarkers, including metabolic parameters and anatomical features. Three machine learning models—Random Forest (RF), Support Vector Machine (SVM), and Artificial Neural Network (ANN)—were trained using these predictors.ResultsLymphomatous nodes exhibited significantly elevated metabolic activity (SUVmax median: 16.0 vs. 10.0, P<0.001), larger short-axis diameters (13 mm vs. 11 mm, P<0.001), and concurrent splenic hypermetabolism (spleen SUVmax 3.1 vs. 2.8, P<0.001). The RF model demonstrated exceptional performance with an AUC of 0.942, accuracy of 93.88%, and 100% specificity, outperforming SVM (AUC = 0.850) and ANN (AUC = 0.824). Splenic metabolic parameters significantly enhanced model discrimination.ConclusionIntegration of PET/CT-derived SUVmax and splenic metabolic features with machine learning, particularly RF algorithms, provides a potential framework for distinguishing lymphoma-involved from metastatic nodes. This approach holds promise for optimizing biopsy decisions and refining pretreatment risk stratification in clinical oncology.