Is Deformable Image Registration Ready for Brain Metastasis Reirradiation Dose Accumulation? A Longitudinal MRI Benchmark of Registration Accuracy

Dose accumulation is increasingly important in adaptive radiation therapy and reirradiation, but its clinical validity depends on the performance of deformable image registration (DIR). Reirradiation of brain metastases (BMs) with stereotactic radiosurgery (SRS) provides a controlled but clinically meaningful DIR test case: intra-subject brain deformation is usually limited after rigid alignment, yet recurrent lesions can undergo substantial local shape and volume changes that rigid registration cannot capture and can affect dose accumulation. We benchmarked a wide range of learning-based and optimization-based DIR methods on 87 manually screened longitudinal contrast-enhanced T1-weighted MRI lesion pairs from an institutional BM SRS retreatment cohort. Learning-based methods pretrained on healthy-brain MRI were evaluated zero-shot and after instance-specific optimization (ISO) or tumor-proximity target-specific optimization (TSO). Registration was assessed using lesion overlap (Dice), surface distance metrics (HD95 and sASD), target-volume recovery, and runtime and memory. Pretrained learning-based methods showed variable zero-shot performance, while ISO/TSO improved all tested learning-based families. However, optimization-based methods remained the best-performing approach while maintaining reasonable runtime. These findings suggest that even state-of-the-art DIR methods do not yet provide sufficiently accurate and consistent registration for unmonitored use in brain metastasis reirradiation dose accumulation. Because accurate registration is a prerequisite for deformable dose accumulation, clinical application will require case-level quality control and direct assessment of how registration uncertainty affects downstream dose metrics.