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Stereotactic radiosurgery (SRS) has revolutionized the initial management of patients with brain metastases. It delivers focused, highly conformal, ionizing radiation to a target delineated using high-resolution imaging with minimal toxicity to adjacent brain structures. The most common late-delayed radiation effect of SRS is the development of brain radionecrosis (RN), which is often associated with the presence of different degrees of neurologic deficits. MF-SRS (2-5 fx) has been used as an alternative to SF-SRS, with the aim to reduce the incidence of late radiation induced toxicity while maintaining high LC rates. The aim of this retrospective study was to evaluate the acute toxicity, local control and incidence of RN in patients who received SF-SRS or MF-SRS for brain metastases.

In this mono-institutional analysis, 90 consecutive patients with 1 or 2 brain metastases treated with SF or MF-SRS, were included. Endpoints of the analysis were radiation-induced brain necrosis and local control (LC), progression-free survival (PFS) in SF and MF-SRS.

90 patients were eligible and treated with SRS from June 2017 to June 2020 and retrospectively analysed.  63 patients had lung cancer, 18 breast cancer, 5 renal cancer and 4 other cancer. Metastases were treated with Linac based radiotherapy, using VMAT tecnique. A total of 98 lesions were treated: 82 patients had 1 metastasis, while 8 patients had 2 metastases. Patients' median age was  65 years (range 40-80). Median follow up was 20 months (range 8-36 months). Patients were divided into two groups. Group A (35 patients) received a single fraction with a dose ranged from 21 Gy to 24 Gy; Group B (55 patients) received 3 fractions with a dose ranged from 24 Gy to 27 Gy. Size limits were metastases <2cm in longest diameter, largest tumor <4 ml in volume (Group A range 0.6-1.4cm; Group B range 0.6-2cm). 6 patients (7%) experienced toxicity grade 1 on the RTOG scale, without medications. 2 patients (2%) experienced toxicity grade 2 requiring home care and medication, including steroids. Every patient undergoing to perfusion and spectroscopic MRI before SRS and then every 3 months. At first follow up (3 months) 70% of patients had  CR and 30% had SD, no PD. The 1-year local control rates were 76% in the SF-SRS group and 89% in the MF-SRS group. The 1-year local PFS cumulative rate was 84%, 83% in the group A and 84% in the group B. 7 patients (20%) undergoing SF-SRS and 5 (9%) subjected to MF-SRS experienced brain RN; the 1-year incidence rate of RB was 17% and 8%, respectively. Pretreatment prognostic factors associated with improved OS were female, age <65 years, KPS>80%, absence of extracranial metastases.

MF-SRS at a dose of 27 Gy or 24 Gy in 3 daily fractions seems to be an effective and safety treatment modality for brain metastases, associated with better local control and a reduced risk of radiation-induced RN as compared with SF-SRS at dose ranged from 21 Gy to 24 Gy.