Abstract:Objective: This study explores a semi-supervised learning (SSL), pseudo-labeled strategy using diverse datasets to enhance lung cancer (LCa) survival predictions, analyzing Handcrafted and Deep Radiomic Features (HRF/DRF) from PET/CT scans with Hybrid Machine Learning Systems (HMLS). Methods: We collected 199 LCa patients with both PET & CT images, obtained from The Cancer Imaging Archive (TCIA) and our local database, alongside 408 head&neck cancer (HNCa) PET/CT images from TCIA. We extracted 215 HRFs and 1024 DRFs by PySERA and a 3D-Autoencoder, respectively, within the ViSERA software, from segmented primary tumors. The supervised strategy (SL) employed a HMLSs: PCA connected with 4 classifiers on both HRF and DRFs. SSL strategy expanded the datasets by adding 408 pseudo-labeled HNCa cases (labeled by Random Forest algorithm) to 199 LCa cases, using the same HMLSs techniques. Furthermore, Principal Component Analysis (PCA) linked with 4 survival prediction algorithms were utilized in survival hazard ratio analysis. Results: SSL strategy outperformed SL method (p-value<0.05), achieving an average accuracy of 0.85 with DRFs from PET and PCA+ Multi-Layer Perceptron (MLP), compared to 0.65 for SL strategy using DRFs from CT and PCA+ K-Nearest Neighbor (KNN). Additionally, PCA linked with Component-wise Gradient Boosting Survival Analysis on both HRFs and DRFs, as extracted from CT, had an average c-index of 0.80 with a Log Rank p-value<<0.001, confirmed by external testing. Conclusions: Shifting from HRFs and SL to DRFs and SSL strategies, particularly in contexts with limited data points, enabling CT or PET alone to significantly achieve high predictive performance.