Abstract
BACKGROUND: Optimizing the timing of repeat focal radiosurgery versus transition to whole-brain radiotherapy (WBRT) in patients with brain metastases remains unresolved. Traditional static indices like the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) may not fully capture evolving intracranial disease burden. We investigated whether dynamic growth metrics—cumulative Brain Metastasis Velocity (cBMV), volumetric Brain Metastasis Velocity (vBMV), and initial BMV (iBMV)—could better guide treatment sequencing. MATERIAL AND METHODS: In this single-center, retrospective cohort (2018-2024), 122 patients with a total of 817 brain metastases underwent ≥2 courses of stereotactic radiosurgery (SRS), hypofractionated SRS (HFSRT), or WBRT. We calculated cBMV (metastases/year), vBMV (cm³/year), and iBMV (first-interval growth rate) for each patient. Associations with overall survival (OS), intracranial progression-free survival (iPFS), and time to WBRT (WBFS) were assessed via Kaplan-Meier estimates, Cox proportional hazards, and competing-risks models. Discrimination was quantified using Harrell’s C-index, and clinical thresholds (<4, 4-13, >13 metastases/year) were applied to cBMV. RESULTS: Patients received a median of two radiotherapy courses (range 2-6). Low cBMV (<4/year) was linked to prolonged OS (median 35.4 months) compared with intermediate (16.2 months) and high (>13/year; 13.3 months) groups (p<0.001 for OS, iPFS, WBFS). vBMV similarly stratified outcomes (OS p<0.001; iPFS p=0.001; WBFS p=0.009). In contrast, iBMV did not predict any endpoint (all p>0.7). DS-GPA achieved modest discrimination for OS (C-index 0.552), whereas cBMV and vBMV outperformed it (C-index 0.742 and 0.731, respectively). CONCLUSION: Dynamic velocity metrics, particularly cBMV and vBMV, offer robust prognostic stratification in patients undergoing repeated SRS. These measures can identify those with slow progression who may safely continue focal treatments and those with rapid lesion accrual warranting earlier WBRT, thereby enabling more personalized radiotherapeutic decision-making.