Background/Objectives: Peptide receptor radionuclide therapy (PRRT) is an established treatment for metastatic neuroendocrine tumors (NETs), yet long-term disease control occurs only in a subset of patients. Predicting progression-free survival (PFS) could support individualized treatment planning. This study evaluates laboratory, imaging, and multimodal deep learning models for PFS prediction in PRRT-treated patients. Methods: In this retrospective, single-center study 116 patients with metastatic NETs undergoing [177Lu]Lu-DOTATOC were included. Clinical characteristics, laboratory values, and pretherapeutic somatostatin receptor positron emission tomography/computed tomographies (SR-PET/CTs) were collected. Seven models were trained to classify low- vs. high-PFS groups, including unimodal (laboratory, SR-PET, or CT) and multimodal fusion approaches. Performance was assessed via repeated 3-fold cross-validation with area under the receiver operating characteristic curve (AUROC) and area under the precision–recall curve (AUPRC). Explainability was evaluated by feature importance analysis and gradient based saliency maps. Results: Forty-two patients (36%) displayed short PFS (≤1 year) and 74 patients displayed long PFS (>1 year). Groups were similar in most characteristics, except for higher baseline chromogranin A (p = 0.003), elevated $\gamma$-GT (p = 0.002), and fewer PRRT cycles (p < 0.001) in short-PFS patients. The Random Forest model trained only on laboratory biomarkers reached an AUROC of 0.59 ± 0.02. Unimodal three-dimensional convolutional neural networks using SR-PET or CT performed worse (AUROC 0.42 ± 0.03 and 0.54 ± 0.01, respectively). A multimodal fusion model integrating laboratory values, SR-PET, and CT—augmented with a pretrained CT branch—achieved the best results (AUROC 0.72 ± 0.01, AUPRC 0.80 ± 0.01). Explainability analyses provided insights into model predictions, with explainability patterns in the fusion model appearing physiologically plausible and predominantly tumor-focused. Conclusions: Multimodal deep learning combining SR-PET, CT, and laboratory biomarkers outperformed unimodal approaches for PFS prediction after PRRT. Upon external validation, such models may support risk-adapted follow-up strategies.

Reliable uncertainty quantification is crucial for trustworthy decision-making and the deployment of AI models in medical imaging. While prior work has explored the ability of neural networks to quantify predictive, epistemic, and aleatoric uncertainties using an information-theoretical approach in synthetic or well defined data settings like natural image classification, its applicability to real life medical diagnosis tasks remains underexplored. In this study, we provide an extensive uncertainty quantification benchmark for multi-label chest X-ray classification using the MIMIC-CXR-JPG dataset. We evaluate 13 uncertainty quantification methods for convolutional (ResNet) and transformer-based (Vision Transformer) architectures across a wide range of tasks. Additionally, we extend Evidential Deep Learning, HetClass NNs, and Deep Deterministic Uncertainty to the multi-label setting. Our analysis provides insights into uncertainty estimation effectiveness and the ability to disentangle epistemic and aleatoric uncertainties, revealing method- and architecture-specific strengths and limitations.