A delta-based multi-omics model to predict adaptive radiotherapy benefit in patients with non-small cell lung cancer during carbon-ion radiotherapy.

[OBJECTIVE] Patients with non-small cell lung cancer (NSCLC) treated with carbon-ion radiotherapy (CIRT) are potential candidates for adaptive radiotherapy (ART). However, ART is time- and resource-intensive. This study aimed to develop a decision-support tool to estimate ART demand before treatment.

[APPROACH] This retrospective study included 69 patients with NSCLC treated with CIRT. Baseline clinical characteristics, dose-volume histogram (DVH) parameters, and radiomic and dosiomic features from the plan-computed tomography (CT) (1-2 weeks before treatment) and confirm-CT (1-2 days before treatment) were collected, and relative change rates in features (ΔDVH, Δradiomics, and Δdosiomics) were calculated. Feature selection involved univariable testing, correlation analysis, least absolute shrinkage and selection operator regression, and stepwise regression with 1000 bootstrap resamples. A multivariable logistic regression model was constructed and validated using 200 iterations of five-fold cross-validation.

[MAIN RESULTS] ART was triggered in 32 (46.4%) patients. A five-feature delta-omic model (one ΔDVH, two Δradiomic, and two Δdosiomic features) achieved a validated median area under the curve of 0.897 (interquartile range, 0.833-0.950) with good calibration. At a high-sensitivity threshold (0.11), the model identified all ART candidates while potentially reducing the frequency of weekly-CT evaluations in 21.4% of patients; at the maximum-Youden threshold (0.41), the median accuracy reached 78.6%, with up to 50.0% classified as low ART demand.

[SIGNIFICANCE] A delta-omic model predicting ART demand in patients with NSCLC receiving CIRT was developed. The model may help optimize resource allocation and streamline ART workflows, although prospective validation in larger cohorts is warranted before widespread clinical adoption.