Association of Progressive PPFE and Mortality in Lung Cancer Screening Cohorts

Accurate prediction of overall survival (OS) from positron emission tomography/computed tomography (PET/CT) can support personalized treatment and follow-up strategies in oncology. However, the impact of temporal modeling on imaging-based survival prediction remains insufficiently explored. We investigate how different temporal formulations influence survival prediction by developing two complementary approaches: Attention-guided Time-Conditioned Survival (ATCS) and Multi-Time Survival (MTS). We retrospectively analyzed pre-treatment PET/CT images from 848 patients with non-small cell lung cancer (NSCLC), including 556 for model development and 292 for held-out testing. A previously proposed Time-Conditioned Survival (TCS) model was used as a baseline. Models were trained using 5-fold cross-validation and evaluated on the test set using time-dependent area under the curve (AUC) at 6-month intervals from 0.5 to 5 years. Both ATCS and MTS outperformed the baseline TCS model, achieving mean AUCs of 0.794 and 0.793, respectively, compared to 0.767. ATCS performed better at earlier time points (0.5-3 years), whereas MTS performed better at later intervals (3.5-5 years). Combining tumor-specific and tissue-wise PET/CT features improved performance over either input alone. Finer temporal discretization improved short-term prediction, while coarser intervals provided more stable long-term estimates. These findings demonstrate that temporal modeling and input design influence PET/CT-based survival prediction. The proposed approaches enable time-specific survival estimation from pre-treatment imaging and may support improved risk stratification and clinical decision-making.

Lung cancer results in roughly 1.8 million fatalities annually worldwide, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Despite advancements in treatment, survival stratification remains challenging due to intratumoral heterogeneity inadequately captured by conventional descriptors. Standard radiomic and deep learning techniques regard imaging features as independent quantities, overlooking structured interactions between tumor characteristics. We evaluate whether structured proxy features can enhance multimodal NSCLC survival prediction by augmenting pretreatment computed tomography (CT) representations, radiomics, and clinical variables with six simulation-derived features designed to capture interactions between heterogeneity and morphology. A radiomic-parameterized cellular automaton generates growth-rate and necrosis-ratio proxy features from baseline CT by using entropy and sphericity to compute low-dimensional proxy parameters. The imaging backbone is a Transformer-based Masked Autoencoder (TMAE), which was chosen after a systematic evaluation with alternative encoders within the same pipeline and provides attention-based visualizations that highlight tumor regions receiving higher model attention. On the public Lung1 cohort (n = 390), the primary four-modality fusion attained a C-index of 0.641 (iAUC 0.731, log-rank p < 0.001). The primary result compares favorably with prior multimodal results on Lung1 (C-index 0.631; iAUC 0.592 [15]) under a comparable evaluation protocol, while a separate exploratory coefficient-optimization analysis achieved a best observed C-index of 0.662 (iAUC 0.748). These results indicate that, in addition to conventional radiomic, deep, and clinical representations within the Lung1 benchmark, simulation-derived proxy features may provide complementary predictive information within this fixed Lung1 benchmark.

Purpose: Automated medical image-based prediction of clinical outcomes, such as overall survival (OS), has great potential in improving patient prognostics and personalized treatment planning. We developed a deep regression framework using tissue-wise FDG-PET/CT projections as input, along with a temporal input representing a scalar time horizon (in days) to predict OS in patients with Non-Small Cell Lung Cancer (NSCLC). Methods: The proposed framework employed a ResNet-50 backbone to process input images and generate corresponding image embeddings. The embeddings were then combined with temporal data to produce OS probabilities as a function of time, effectively parameterizing the predictions based on time. The overall framework was developed using the U-CAN cohort (n = 556) and evaluated by comparing with a baseline method on the test set (n = 292). The baseline utilized the ResNet-50 architecture, processing only the images as input and providing OS predictions at pre-specified intervals, such as 2- or 5-year. Results: The incorporation of temporal data with image embeddings demonstrated an advantage in predicting OS, outperforming the baseline method with an improvement in AUC of 4.3%. The proposed model using clinical + IDP features achieved strong performance, and an ensemble of imaging and clinical + IDP models achieved the best overall performance (0.788), highlighting the complementary value of multimodal inputs. The proposed method also enabled risk stratification of patients into distinct categories (high vs low risk). Heat maps from the saliency analysis highlighted tumor regions as key structures for the prediction. Conclusion: Our method provided an automated framework for predicting OS as a function of time and demonstrates the potential of combining imaging and tabular data for improved survival prediction.