ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026
Interpretable deep learning model of circulating genomics for quantitative survival prediction in advanced non-small cell lung cancer.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Liquid Biopsy in Colorectal Cancer: Future Perspectives Through the Lens of Artificial Intelligence-A Comprehensive Review of Novel Literature.International journal of molecular sciences · 2026Review
- Application of deep learning in prognostic prediction of non-small cell lung cancer.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
10 authors.
Funding
Abstract
purposeAccurate quantitative survival prediction in advanced non-small cell lung cancer (NSCLC) remains an unmet clinical need. While liquid biopsy is widely used, single circulating tumor DNA (ctDNA) shows limited predictive power. We developed an interpretable deep-learning model to quantitatively predict outcomes. METHODS/PATIENTS: We integrated data from 1373 advanced NSCLC patients profiled by two ultra-deep ctDNA sequencing assays (MSK-ACCESS and ctDx Lung). Features associated with overall survival (OS) were incorporated into a deep-learning network (DeepSurv), which estimates time-to-event survival probabilities. Model performance was evaluated by time-dependent area under the curve (AUC). SHapley Additive exPlanations (SHAP) were employed to interpret model output.
resultsA total of 1373 patients were analyzed, with 1012 using MSK-ACCESS (discovery) and 361 using ctDx Lung (validation). Among over 40 clinicopathological features, ctDNA status, cell-free DNA (cfDNA) concentration, age, blood-based TP53, EGFR, PIK3CA, ARID1A, STK11 and MET mutations significantly predicted OS. In ctDNA-positive patients, TP53/PIK3CA/ARID1A/STK11/MET-mutated patients had significantly inferior OS compared with wildtype patients (P < 0.001). Using above variables, DeepSurv was trained and tested in the MSK-ACCESS cohort (12-month AUC = 0.75), outperforming single cfDNA (AUC = 0.66) or ctDNA (AUC = 0.59), and externally validated in the ctDx Lung cohort. Compared with high-risk patients, DeepSurv-identified low-risk patients had significantly longer OS in both discovery (12-month OS 87.8% vs 53.8%, HR 0.32, P < 0.001) and validation cohorts (73.2% vs 48.4%, HR 0.42, P < 0.001). SHAP revealed TP53 and cfDNA concentration > 4.8 ng/mL had the most important contributions.
conclusionsThe interpretable DeepSurv model, integrating multimodal features, enables quantitative survival prediction and risk stratification in advanced NSCLC, facilitating personalized decision-making.
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