Clinical and volumetric predictors of local control after robotic stereotactic radiosurgery for cerebral metastases: active systemic disease may affect local control in the brain

Abstract

Background: The aim of the study was to assess the association between physical and biological dose normalized to volume of the metastatic tumor as well as clinical factors with local control in patients with brain metastases who underwent robotic stereotactic radiosurgery.

Patients and methods: A cohort of 69 patients consecutively treated with robotic radiosurgery between 2011 and 2016 was analyzed. The patients were treated with either single fraction radiosurgery or hypofractionated regimens. Biologically effective dose (BED) was calculated assuming alpha/beta value = 10 and both physical dose and BED were normalized to the tumor volume to allow dose-volume effect evaluation. Moreover, clinical and treatment-related variables were evaluated to asses association with local control.

Results: A total of 133 tumors were irradiated and their volumes ranged between 0.001 and 46.99 cm3. Presence of extracranial progression was associated with worse local control whereas higher total dose, BED₁₀ > 59 Gy and single metastasis predicted statistically significantly better local outcome. BED₁₀/cm³ > 36 Gy, and BED₂ > 60 Gy negatively affected local control in univariate analysis. In multivariate analysis performed on all these variables, presence of a single metastasis, BED₁₀ > 59 Gy and extracranial progression retained their significance. Excluding a priori the BED₂/ cm³ parameter resulted with a Cox model confirming significance of all remaining variables.

Conclusions: Hypofractionated treatment schemes have similar efficiency to single fraction treatment in terms of local control and the effect depends on BED irrespective of fractionation schedule. Effective control of extracranial sites of the disease is associated with higher probability of local control in the brain which in turn is consistently lower in patients with multiple lesions.

Keywords: brain metastases; local control; radiobiology; radiosurgery.

Figure 1

Local progression-free survival according to biologically effective dose (BED)₁₀. Doses above 59 Gy₁₀ (red, dashed line) were associated with significantly longer local progression-free survival (LPFS) (median 7.5 vs. 18.4 months).

Figure 2

Local progression-free survival according to number of metastases. Presence of a single metastasis (blue, solid line) was a favorable prognostic factor.

Figure 3

Local progression-free survival according to systemic disease status. Extracranial progression (red, dashed line) was an adverse prognostic factor.

Figure 4

Local progression-free survival according to biologically effective dose (BED)₁₀ normalized to tumor volume. Exceeding the threshold value of 36 Gy₁₀/cm³ (red, dashed line) was associated with reduced chances of maintaining local control.