THINKERS-X: multisequence MRI radiomics in a mixture-of-experts model for outcome prediction and exploratory dose-scenario evaluation in lung cancer brain metastases treated with radiosurgery.

We developed THINKERS-X: Lung, the eXtended multimodal evolution of THINKERS-Lung, to determine whether multisequence MRI radiomics provides incremental value for lesion-specific outcome prediction and exploratory dose-scenario evaluation after Gamma Knife radiosurgery (GKRS) for lung cancer brain metastases. We performed a retrospective single-center study of 767 patients with 3,728 lung cancer brain metastases treated with GKRS. THINKERS-X preserved the original mixture-of-experts and discrete-time survival architecture while adding a dedicated computational neuroradiology expert. Approximately 2,400 radiomic features per metastasis were extracted from pretreatment FSPGR/T1-weighted postcontrast, T2-weighted, and SWAN MRI. Validation used patient-grouped 5-fold cross-validation and a completely closed patient-grouped internal holdout cohort. In grouped cross-validation, THINKERS-X achieved a mean AUC12 of 0.919 ± 0.021 versus 0.876 for THINKERS-Lung (paired difference, 0.043; 95% CI 0.026-0.061; p < 0.001). In the internal holdout cohort, AUC12 improved from 0.863 to 0.929 (95% CI 0.895-0.958), with a paired difference of 0.066 (95% CI 0.031-0.101; p < 0.001). Mean absolute error decreased from 1.26 to 0.84 months. The calibrated Brier score was 0.039, calibration slope 0.94, and intercept 0.04. Radiomics altered model-derived dose-response profiles in 30.0% of metastases and the model-ranked candidate dose in 23.9%. THINKERS-X improved lesion-specific longitudinal prediction, temporal accuracy, and probabilistic calibration beyond THINKERS-Lung while materially altering exploratory dose-scenario evaluation in a subset of metastases. External multicenter and prospective validation are required before clinical implementation.