Initial Brain Metastasis Velocity: Does the Rate at Which Cancers First Seed the Brain Affect Outcomes?

Abstract

Brain metastasis velocity (BMV) is a novel metric used to describe the rate of development of new brain metastases (BM) after initial stereotactic radiosurgery (SRS). BMV, as defined in a previous publication, is a valuable tool to help guide the decision for WBRT vs SRS for salvage therapy. A limitation in the application of BMV is that it requires the number of metastases at time of treatment failure after initial SRS. By investigating patient characteristics at time of first SRS, we developed initial brain metastasis velocity (iBMV), a new metric that takes into account factors that influence the BMV prior to treatment failure. Particularly, it incorporates the rate at which cancer seeds the brain from time of initial cancer diagnosis. We retrospectively reviewed patients with BM treated at our institution from 2000-2013 with upfront SRS without WBRT. BMV for each patient was calculated as the cumulative number of new metastases from initial SRS divided by units of years. We defined iBMV, a new metric for patients who were diagnosed with BM after their primary cancer diagnosis. iBMV was calculated as the number of BM at the time of initial SRS over the unit of years from initial diagnosis to first SRS. Thus, representing a rate that the primary cancer seeded the brain. We performed a linear regression to assess the relationship of iBMV to BMV and overall survival (OS) after first SRS to death and other oncologic outcomes. iBMV was not calculated for patients who presented with stage IV disease with BM or for patients who developed BM <2 months from initial diagnosis. From 2000-2013, 736 patients were treated at our institution with upfront SRS without WBRT. Median OS was 8.6 mos (IQR 7.9-9.6). The presence or absence of BM at initial cancer diagnosis was not predictive of survival after first SRS, neurologic death, or BMV and the median number of BM at first SRS was similar (median BM = 1.0, IQR = 1-3, P = 0.71). Four hundred forty-three (60%) patients developed BM ≥2 months after initial diagnosis. In these 443 patients, the median time to first SRS from time of initial diagnosis was 27.2 mos (IQR = 24.7-31.4). Median iBMV was 0.73 (IQR = 0.30-1.74). Lung histology was associated with a higher iBMV compared to breast (β = 0.09 SE = 0.02, P < 0.001). Renal cell, melanoma, and other histologies did not have significantly different iBMV rates compared to breast. The iBMV was predictive of both BMV after treatment (β = 23.87, SE 6.92, P<0.001) and OS (HR = 1.11; CI: 1.03-1.20, P = 0.006). The iBMV was not significant for predicting neurologic death (HR = 1.07; CI 1.00-1.15 P = 0.07) or time to WBRT (P = 0.18). The iBMV ≥4 metastases/year was predictive of distant brain failure per Gray’s test (P = 0.02). The iBMV is a metric that predicts for BMV and OS. A higher iBMV was associated with a worse OS and numerically higher BMV. Lung histology was associated with a higher iBMV than breast. The presence or absence of BM at time of initial cancer diagnosis was not predictive for survival, as calculated from time of first SRS to death.