Brain Metastasis Velocity: A Novel Prognostic Metric Predictive of Overall Survival and Freedom From Whole-Brain Radiation Therapy After Distant Brain Failure Following Upfront Radiosurgery Alone

Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):131-141. doi: 10.1016/j.ijrobp.2017.01.201. Epub 2017 Jan 26.


Purpose: Prior statistical models attempted to identify risk factors for time to distant brain failure (DBF) or time to salvage whole-brain radiation therapy (WBRT) to predict the benefit of early WBRT versus stereotactic radiosurgery (SRS) alone. We introduce a novel clinical metric, brain metastasis velocity (BMV), for predicting clinical outcomes after initial DBF following upfront SRS alone.

Methods and materials: BMV was defined as the cumulative number of new brain metastases that developed over time since first SRS in years. Patients were classified by BMV into low-, intermediate-, and high-risk groups, consisting of <4, 4 to 13, and >13 new metastases per year, respectively. Histology, number of metastases at the time of first SRS, and systemic disease status were assessed for effect on BMV.

Results: Of 737 patients treated at our institution with upfront SRS without WBRT, 286 had ≥1 DBF event. A lower BMV predicted for improved overall survival (OS) following initial DBF (log-rank P<.0001). Median OS for the low, intermediate, and high BMV groups was 12.4 months (95% confidence interval [CI], 10.4-16.9 months), 8.2 months (95% CI, 5.0-9.7 months), and 4.3 months (95% CI, 2.6-6.7 months), respectively. Multivariate analysis showed that BMV remained the dominant predictor of OS, with a hazard ratio of 2.75 for the high BMV group (95% CI, 1.94-3.89; P<.0001) and a hazard ratio of 1.65 for the intermediate BMV group (95% CI, 1.18-2.30; P<.004). A lower BMV was associated with decreased rates of salvage WBRT (P=.02) and neurologic death (P=.008). Factors predictive for a higher BMV included ≥2 initial brain metastases (P=.004) and melanoma histology (P=.008).

Conclusions: BMV is a novel metric associated with OS, neurologic death, and need for salvage WBRT after initial DBF following upfront SRS alone.

MeSH terms

  • Aged
  • Analysis of Variance
  • Brain Death
  • Brain Neoplasms / classification
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy*
  • Brain Neoplasms / secondary*
  • Breast Neoplasms
  • Carcinoma, Renal Cell / radiotherapy
  • Carcinoma, Renal Cell / secondary
  • Confidence Intervals
  • Cranial Irradiation / statistics & numerical data*
  • Female
  • Humans
  • Kidney Neoplasms
  • Lung Neoplasms
  • Male
  • Melanoma / radiotherapy
  • Melanoma / secondary
  • Middle Aged
  • Prognosis
  • Radiosurgery / methods*
  • Retrospective Studies
  • Risk Factors
  • Salvage Therapy / methods
  • Salvage Therapy / statistics & numerical data*
  • Time Factors
  • Treatment Outcome