# Explainable artificial intelligence for personalized prognosis in pancreatic cancer: A nationwide study from Taiwan

**Authors:** Dai-Rong Tsai, Chun-Ju Chiang, Pei-Chun Hsieh, Chi-Yen Huang, Wen-Chung Lee, Henry Horng-Shing Lu, Minh Le, Henry Horng-Shing Lu

PMC · DOI: 10.1371/journal.pdig.0001296 · PLOS Digital Health · 2026-03-19

## TL;DR

This study uses explainable AI with nationwide data to predict pancreatic cancer survival and identify key factors affecting prognosis.

## Contribution

The novel contribution is developing an interpretable AI model using large-scale national registry data to reveal prognostic factors, interactions, and non-linear effects in pancreatic cancer.

## Key findings

- XGBoost outperformed other models in predicting pancreatic cancer survival.
- Adenocarcinoma had the highest mortality risk, while neuroendocrine and acinar cell carcinomas had lower risks.
- Chemotherapy and surgery showed treatment-specific survival benefits depending on tumor subtype and stage.

## Abstract

Pancreatic cancer is highly aggressive with poor outcomes; current artificial intelligence (AI) prognostic models often lack interpretability and underutilize large-scale data. This study develops an explainable AI prognostic model for pancreatic cancer survival using Taiwan’s national registry data, aiming to identify key prognostic factors, their interactions, non-linear relationships, and patient-specific survival variability. We analyzed 8,864 pancreatic cancer cases diagnosed between 2013 and 2021 from the Taiwan Cancer Registry. We developed three classes of prognostic models using regression-based, machine learning, and deep learning methods. The models were evaluated using nested cross-validation and time-dependent metrics, with Shapley additive explanations enhancing interpretability. XGBoost outperformed random survival forest and deep learning models in predicting pancreatic cancer survival. Key determinants included surgery, histological type, chemotherapy, tumor stage, and their interactions. Adenocarcinoma was associated with the highest mortality risk, whereas acinar cell and neuroendocrine carcinomas had lower risks (hazard ratios 0.768 and 0.660, respectively, vs adenocarcinoma). Chemotherapy showed the greatest mortality risk reduction in adenocarcinoma, while surgery was most strongly associated with reduced mortality in neuroendocrine tumors and adenocarcinoma, particularly in early-stage disease. The mortality reduction associated with chemotherapy increased in advanced stages and with age, plateauing around 65 years. Mortality risk rose faster with age in neuroendocrine carcinoma. Non-linear relationships emerged for age, smoking duration, and BMI: mortality increased gradually (0.69% per year) before age 65, rapidly afterward (2.41% per year); risk increased with longer smoking duration but plateaued between 10 and 30 years; and BMI exhibited a U-shaped risk, lowest at 26. This study demonstrates the potential of explainable AI for predicting pancreatic cancer survival by identifying key prognostic factors, nonlinear relationships, interactions, and patient-level variability, thereby revealing substantial heterogeneity in prognosis.

Artificial intelligence (AI)-based models have been developed for pancreatic cancer prognosis, but they often lack interpretability, overlook feature interactions and non-linear effects, and are based on limited or single-institution datasets. This study develops an explainable AI prognostic model using Taiwan’s nationwide cancer registry, identifying key prognostic factors, non-linear effects, and interactions—especially between treatments and tumor subtypes—while highlighting variability in patient-specific risk. The findings illustrate how explainable AI can be integrated with population-based cancer registry data to improve prognostic assessment and risk stratification in pancreatic cancer, thereby informing the future development of transparent, scalable prognostic tools and methodologies in oncology research and clinical practice.

## Linked entities

- **Diseases:** pancreatic cancer (MONDO:0005192), adenocarcinoma (MONDO:0004970), acinar cell carcinoma (MONDO:0004965), neuroendocrine carcinoma (MONDO:0002120)

## Full-text entities

- **Genes:** SHROOM4 (shroom family member 4) [NCBI Gene 57477] {aka MRXSSDS, SHAP, shrm4}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845] {aka 'C-K-RAS, C-K-RAS, CFC2, K-RAS2A, K-RAS2B, K-RAS4A}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}
- **Diseases:** breast cancer (MESH:D001943), stage (MESH:D062706), ACC (MESH:D004476), frailty (MESH:D000073496), diabetes (MESH:D003920), MISSING BIOMARKERS IMPACT ASSESSMENT (MESH:D004834), Pancreatic Cancer (MESH:D010190), chronic inflammation (MESH:D007249), cachexia (MESH:D002100), Adenocarcinoma (MESH:D000230), MAJOR ISSUES (MESH:D004830), AI (MESH:C538142), advanced (MESH:D020178), acinar cell and neuroendocrine carcinomas (MESH:D018267), Neuroendocrine tumor (MESH:D018358), metabolic dysfunction (MESH:D008659), Diseases (MESH:D004194), neuroendocrine carcinoma (MESH:D018278), metastasis (MESH:D009362), carcinoma in situ (MESH:D002278), death (MESH:D003643), Tumor (MESH:D009369)
- **Chemicals:** alcohol (MESH:D000438), CA19 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Full text

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## Figures

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## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC13001956/full.md

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Source: https://tomesphere.com/paper/PMC13001956