Journal Article Ahead of print
PubMed: 42551638 DOI: 10.1016/j.radonc.2026.111715
Interpretable AI to predict anal cancer local failure at 3 years with the FFCD Anabase prospective multicentric cohort.
Radiother Oncol
Authors: C Raynaud, V Vendrely, L Quero, C Lemanski, P Pommier, K Le Malicot, A Saint, E Rivin Del Campo, P Regnault, N Baba-Hamed, P Ronchin, G Crehange, D Tougeron, E Menager-Tabourel, O Diaz, M Hummelsberger, M Minsat, F Drouet, A Larrouy, D Peiffert, A Lievre, X Zasadny, V Hautefeuille, F Mornex, C Lepage, J-E Bibault
Affiliations
- Radiation Oncology Department European Hospital Georges Pompidou, Paris, France.
- Department of Radiation Oncology, CHU Bordeaux, France.
- Department of Radiation Oncology, Radiotherapy Saint-Louis Hospital, AP-HP Paris, France.
- Department of Radiation Oncology, Montpellier Cancer Institute (ICM), France.
- Radiation Oncology, Institut Curie, Paris, France.
- Fédération Francophone de Cancérologie Digestive, EPICAD INSERM LNC-UMR 1231, University of Burgundy (Biostatistics), France.
- Department of Radiation Oncology, Antoine Lacassagne Cancer Center, Nice, France.
- Department of Radiation Oncology, Tenon University Hospital, AP-HP, Sorbonne University, Paris, France.
- Radiotherapy, Tivoli Clinic, Bordeaux, France.
- Oncology Department, Saint-Joseph Hospital Group, Paris, France.
- Radiotherapy Department, Azuréen Cancer Center, Mougins, France.
- Hepatology and Gastroenterology Department, Poitiers University Hospital, France.
- Medical Oncology, Departmental Hospital of Vendée, La Roche-sur-Yon, France.
- Radiotherapy Department, Daniel Hollard Institute, Grenoble, France.
- Radiotherapy Department, Radiotherapy and Medical Oncology Center, Béziers, France.
- Radiation Oncology, Institut Curie, Saint-Cloud, France.
- Mutualité Clinical Estuary, Saint-Nazaire, France.
- Medical Oncology, Cancer Institute North Paris, France.
- Department of Radiaton Oncology, Lorraine Cancer Center, Vandoeuvre-Les-Nancy, France.
- Gastroenterology Department, Rennes University Hospital, Rennes 1 University, Inserm U1242 COSS (Chemistry Oncogenesis Stress Signaling), Rennes, France.
- Oncology Radiotherapy Department, Limoges Polyclinic François Chenieux, Limoges, France.
- Medical Oncology, CHU Amiens, Amiens, France.
- Université Claude Bernard Lyon1, 69008 LYON, France.
- Department of Hepato-gastroenterology, University Hospital of Dijon, Dijon, France.
- Radiation Oncology Department European Hospital Georges Pompidou, Paris, France.
Abstract
PURPOSE
Machine learning (ML) has transformed oncological risk prediction by enabling personalized therapeutic strategies. Local tumor control remains a critical endpoint in anal cancer management. This study aimed to develop and validate an explainable ML model for predicting local recurrence at 3 years in patients with anal cancer.
METHODS AND MATERIALS
We analyzed data from the prospective multicentric FFCD-Anabase cohort, comprising 1,015 patients with anal cancer treated with chemoradiotherapy across 60 French centers between January 2015 and April 2020. The endpoint was local recurrence at 3 years. An extreme gradient boosting model with an Accelerated Failure Time extension was developed to handle time-to-event data. Model inputs combined routinely available clinical, biological, and treatment variables, selected on the training set only. Model development incorporated cross-validation for hyperparameter optimization, followed by calibration to ensure reliable probability estimates. Performance was assessed on an independent test set using discrimination, calibration metrics, and clinical utility measures, with right-censored patients retained through inverse-probability-of-censoring weighting. Model interpretability was enhanced using Shapley Additive exPlanations values, providing global feature importance and individual patient-level prediction explanations.
RESULTS
The model demonstrated a C-index of 0.735 (95 % CI 0.65-0.82) and a time-dependent AUC at 3 years of 0.755 (0.66-0.85). The model achieved a sensitivity of 64 % and specificity of 74 %, with positive and negative predictive values of 39 % and 89 %, respectively. All 3-year classification metrics were computed on the full test set using inverse-probability-of-censoring weighting, so that censored patients were not discarded. Overall accuracy was 72 % with an F1-score of 0.49. Calibration performance was assessed using Brier score (0.135) and integrated Brier score (0.131). Calibration plots demonstrated good agreement between predicted and observed probabilities. Decision curve analysis revealed net clinical benefit across a range of threshold probabilities, with optimal risk stratification at a 37 % probability threshold for distinguishing low- and high-risk patients. Kaplan-Meier survival analysis confirmed statistically significant differences between risk groups (p = 2.78 × 10⁻5). Model interpretability analysis using SHAP value (SHapley Additive exPlanations, a method that quantifies each feature's contribution to a model's prediction) identified World Health Organization (WHO) performance status as the most influential predictor, followed by tumor size and age.
CONCLUSION
Our model yielded good performances on real-world data to predict the risk of local recurrence at 3 years for anal cancer.
MeSH
Radiotherapy, Anus Neoplasms, Probability, Neoplasms, Therapeutics, Artificial Intelligence