Brain metastases treated with hypofractionated stereotactic radiotherapy: 8 years experience after Cyberknife installation.

Background: Hypofractionated stereotactic radiotherapy (HFSRT) is indicated for large brain metastases (BM) or proximity to critical organs (brainstem, chiasm, optic nerves, hippocampus). The primary aim of this study was to assess factors influencing BM local control after HFSRT. Then the effect of surgery plus HFSRT was compared with exclusive HFSRT on oncologic outcomes, including overall survival.
Materials and Methods: Retrospective study conducted in Léon Bérard Cancer Center, included patients over 18 years-old with BM, secondary to a tumor proven by histology and treated by HFSRT alone or after surgery. Three different dose-fractionation schedules were compared: 27 Gy (3 × 9 Gy), 30 Gy (5 × 6 Gy) and 35 Gy (5 × 7 Gy), prescribed on isodose 80%. Primary endpoint were local control (LC). Secondary endpoints were overall survival (OS) and radionecrosis (RN) rate.
Results: A total of 389 patients and 400 BM with regular MRI follow-up were analyzed. There was no statistical difference between the different dose-fractionations. On multivariate analysis, surgery (p = 0.049) and size (< 2.5 cm) (p = 0.01) were independent factors improving LC. The 12 months LC was 87.02% in the group Surgery plus HFSRT group vs 73.53% at 12 months in the group HFSRT. OS was 61.43% at 12 months in the group Surgery plus HFSRT group vs 50.13% at 12 months in the group HFSRT (p < 0.0085). Prior surgery (OR = 1.86; p = 0.0028) and sex (OR = 1.4; p = 0.0139) control of primary tumor (OR = 0.671, p = 0.0069) and KPS < 70 (OR = 0.769, p = 0.0094) were independently predictive of OS. The RN rate was 5% and all patients concerned were symptomatic.
Conclusions: This study suggests that HFSRT is an efficient and well-tolerated treatment. The optimal dose-fractionation remains difficult to determine. Smaller size and surgery are correlated to LC. These results evidence the importance of surgery for larger BM (> 2.5 cm) with a poorer prognosis. Multidisciplinary committees and prospective studies are necessary to validate these observations.