Beyond single-run metrics with CP-fuse: A rigorous multi-cohort evaluation of clinico-pathological fusion for improved survival prediction in TCGA
Bibliographic record
Abstract
Accurate prediction of progression-free survival (PFS) is critical for precision oncology. However, most existing multimodal survival studies rely on single fusion strategies, one-off cross-validation runs, and focus solely on discrimination metrics, leaving gaps in systematic evaluation and calibration. We evaluated multimodal fusion approaches combining histopathology whole-slide images (via Hierarchical Image Pyramid Transformer) and clinical variables (via Feature Tokenizer-Transformer) across five TCGA cohorts: bladder cancer (BLCA), uterine corpus endometrial carcinoma (UCEC), lung adenocarcinoma (LUAD), breast cancer (BRCA), and head and neck squamous cell carcinoma (HNSC) (N=2,984). Three intermediate (marginal, cross-attention, Variational Autoencoder or VAE) and two late fusion strategies (trainable-weight, meta-learning) were trained end-to-end with DeepSurv. Our 100-repetition 10-fold cross-validation (CV) framework mitigates the variance overlooked in single-run CV evaluations. VAE fusion achieved superior PFS prediction (Concordance-index) in BLCA (0.739±0.019), UCEC (0.770±0.021), LUAD (0.683±0.018), and BRCA (0.760±0.021), while meta-learning was best for HNSC (0.686±0.022). However, Integrated Brier Score values (0.066–0.142) revealed calibration variability. Our findings highlight the importance of multimodal fusion, combined discrimination and calibration metrics, and rigorous validation for clinically meaningful survival modelling. • VAE-based fusion outperforms unimodal models across most cancer types. • Both discrimination and calibration are vital for survival modeling. • Single cross-validation splits can lead to misleading performance claims. • We provide a public benchmark for multimodal survival analysis using clinical variables and biopsy whole slide images. • Our framework promotes reproducible and robust AI in medicine.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.023 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".