Structured Proxy Features for Multimodal NSCLC Survival Prediction from Pretreatment CT

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.

Distribution-based deep multiple instance learning for tumor proportion scoring in NSCLC

Accurate assessment of tumor proportion score (TPS) in non-small cell lung cancer (NSCLC) is critical for treatment planning and prognosis. Key challenges include the tedious manual work required to annotate each slide, combined with the limited number of experts certified for this task. Multiple instance learning (MIL) has proven to be an effective approach for predicting TPS scores at the slide level; however, existing methods struggle with non-expressive (zero class) images. Our approach involves two models: (1) an embedding-extraction and multiclass-classification network that captures the histopathological features of individual patches, and (2) a MIL model that aggregates these embeddings to predict zero-inflated beta (ZIBeta) parameters representing the overall TPS probability distribution for the entire slide. Using only slide-level TPS scores as labels, we demonstrate how this end-to-end framework can leverage a novel distribution-based architecture to improve prediction accuracy and explainability. ZIBeta modeling significantly outperforms baseline linear and ridge regression while capturing expected accuracy through distribution concentration.

A Deployment Audit of Release-Side Risk in Conformal Triage under Prevalence Shift

Conformal triage converts predictive scores into deployment actions that either release a case, flag it for urgent attention, or defer it to human review. Under prevalence shift, however, the usual summaries of marginal coverage and human-review rate can miss the safety-critical question of whether patients who truly experience the target event are released without review. To address this gap, we introduce a leakage-aware deployment audit for release-side conformal triage. It first assigns target subjects to three non-overlapping roles: prevalence correction, conformal calibration, and held-out release-safety evaluation. This separation then lets the audit evaluate release directly: how many event-positive patients are cleared without review, whether the pilot has enough event labels for calibration, and how the safety-review trade-off shifts. Applying this audit to a retrospective NSCLC pilot shows why lower review can be misleading: after prevalence correction, the pooled conformal branch lowers review by releasing more patients, some of whom are event-positive. Within the audit, the classwise branch acts as a scarcity diagnostic: the pilot has too few event labels to certify safe low-review release.