Multi-institutional Normal Tissue Complication Probability (NTCP) Prediction Model for Mandibular Osteoradionecrosis: Results from the PREDMORN Study
Bibliographic record
Abstract
Abstract Background Mandibular osteoradionecrosis (ORN) is a severe late complication affecting patients with head and neck cancer (HNC) treated with radiotherapy that significantly impacts patients’ quality of life and can require costly interventions. While radiation dose is a key factor, other clinical and demographic risk factors influence ORN development. Previous predictive models have primarily been single-institutional, limiting their generalizability. The PREDMORN Consortium was established to address these limitations. In this first analysis, we have aimed to reproduce existing statistical association and modelling analyses on the largest and most diverse mandibular ORN cohort worldwide to allow comparison with previous studies. As such, we have developed, tested and externally validated a multi-institutional normal tissue complication probability (NTCP) model for mandibular ORN. Methods This retrospective multi-institutional study included 1,184 HNC patients (389 ORN cases) from seven institutions. Clinical, demographic, and dosimetric (DVH) variables were analysed to develop a prediction model (any grade of ORN vs. no ORN) using forward stepwise logistic regression with correlation-based variable pre-selection. The ORN NTCP model was developed on 80% of data from six institutions, tested on the remaining unseen 20%, and externally validated on the seventh institution’s dataset. Results Key predictors of ORN were D30%, V70Gy, pre-RT dental extractions, and smoking status. The ORN NTCP model demonstrated good calibration and predictive performance, with AUCs of 0.69 for internal testing and external validation, which improved when tested on a sub-cohort of oropharyngeal and locally advanced larynx/hypopharynx cancer cases (AUCs of 0.75). Conclusion The PREDMORN NTCP model is the largest multi-institutional effort to predict ORN risk in HNC patients. We provide guidance on how to adjust the NTCP predicted probabilities for differences in target population baseline ORN risk to facilitate application of the model. Future research will focus on incorporating imaging-based spatial data and further external validation to enhance clinical applicability.
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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 | 0.015 | 0.021 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".