Survival and Failure Outcomes Predicted by Brain Metastasis Volumetric Kinetics in Melanoma Patients Following Upfront Treatment with Stereotactic Radiosurgery Alone

Introduction The roles of early whole brain radiotherapy (WBRT) and upfront stereotactic radiosurgery (SRS) alone in the treatment of melanoma patients with brain metastasis remain uncertain. We investigated the volumetric kinetics of brain metastasis development and associations with clinical outcomes for melanoma patients who received upfront SRS alone. Methods Volumetric brain metastasis velocity (vBMV) was defined as the volume of new intracranial disease at the time of distant brain failure (DBF) for the first DBF (DBF1) and second DBF (DBF2) averaged over the time since initial or most recent SRS. Non-volumetric brain metastasis velocity (BMV) was calculated for comparison. Results Median overall survival (OS) for all patients was 7.7 months. Increasing vBMV(DBF1) was associated with worsened OS (hazard ratio (HR): 1.10, confidence interval (CI): 1.02 - 1.18, p = .01). Non-volumetric BMV(DBF1) was not predictive of OS after DBF1 (HR: 1.00, CI: 0.97 - 1.02, p = .77). Cumulative incidence of DBF2 at three months after DBF1 was 50.0% for vBMV(DBF1) > 4 cc/yr versus (vs) 15.1% for vBMV(DBF1) ≤ 4 cc/yr, (Gray’s p-value = .02). Cumulative incidence of salvage WBRT at three months after DBF1 was 50.0% for vBMV(DBF1) > 4 cc/yr vs 2.3% for vBMV(DBF1) ≤ 4 cc/yr (Gray’s p-value < .001). Conclusion In melanoma patients with brain metastasis, volumetric BMV was predictive of survival, shorter time to second DBF, and the need for salvage WBRT. Non-volumetric BMV, however, did not predict for these outcomes, suggesting that vBMV is a stronger predictor in melanoma.