2678 - A Single-Center Randomized Trial Comparing the Outcomes of Hypofractionated Stereotactic Radiotherapy in Different Regimens for Large Brain Metastases

Purpose/Objective(s): Objective of the study was to assess the outcomes in patients with large brain metastases (LBMs) after stereotactic radiotherapy (SRT) with different regimens (24 Gy in 3, 30 Gy in 5, 35 Gy in 7 fractions), and to determine the equivalence of fractionation schemes regarding local control and the risk of radiation necrosis.

Materials/Methods: 115 patients with LBMs (diameter greater than 2 cm) were included in the study at National Medical Research Center for Neurosurgery named after Academician N.N. Burdenko in the 2013-2019 period. Non-inclusion criteria were cases exceeding 10 metastases, presence of leptomeningeal disease, small cell lung cancer metastases, poor general condition, and prior brain radiotherapy. Mean target volume was 8.3 ccm (3.4-46.3 ccm). Patients were randomized into 3 groups according to fractionation scheme: 24 Gy in 3fr; 30 Gy in 5fr; 35 Gy in 7fr (36/39/40 patients, respectively; 41/45/45 LBMs, respectively). Other metastases less than 2 cm were treated radiosurgically (according to RTOG 90-05). Treatment was performed using 6 MeV Linacs from four different companies. Follow-up MRI and clinical evaluations were performed every 3 months. 18F-FET PET/CT or perfusion studies were performed to differentiate recurrence and radionecrosis.

Results: Of 115, 5 patients died before the first follow-up (2 due to comorbidities; 2 - extracranial progression; 1 - neurologic deterioration). Overall survival did not differ between the groups (p=0.505). OS for 3 groups composed 12.3 months. 24 months were survived by 11/10/10 patients in the 24Gy in 3fr; 30Gy in 5fr; 35Gy in 7fr groups, respectively. At 12 months, the cumulative incidence of leptomeningeal progression was 11%. The risk in the groups was comparable (p=0.876).The 12-month local recurrence-free survival rates were 71%, 61,2%, 74,4% in the 24Gy in 3fr; 30Gy in 5fr; 35Gy in 7fr groups with no difference between 3 groups (p=0.905). The volume of the irradiated target was a significant factor for local recurrence, at 12 months the cumulative incidence was 36% versus 15.5% in lesions greater than or less than 7 ccm, respectively (p=0.05). Cumulative incidence of radiation necrosis of 2-3 degree in 12 months was 28% in group of 24Gy in 3fr, 22% in group of 30Gy in 5 fractions and 17% in group of 35Gy in 7 fr. The 35 Gy in 7fr regimen was a factor for the risk reduction of radiation necrosis, with no statistical significance (p = 0.10).

Conclusion: The results of the study support the hypothesis that the regimens 24 Gy in 3fr; 30 Gy in 5fr; 35 Gy in 7fr are equivalent regarding local tumor growth control. The 35 Gy in 7fr regimen may be associated with a lower risk of radiation necrosis, which requires further study to achieve statistical significance.