Objectives:

To report clinical outcomes and identify predictive factors associated with improved treatment results in Linac-based Stereotactic Radiosurgery (SRS) and fractionated Stereotactic Radiosurgery (fSRS) for single and multiple brain metastases (BM).

Methods:

Between March 2020 and June 2022, 70 patients for a total of 129 BM with at least one month of clinical and MRI follow-up were retrospectively included. Patients received either 15-21 Gy in a single fraction (n=59) or 27 Gy in three fractions (n=11) using single-isocenter coplanar FFF-VMAT technique. Post-treatment MRI scans were used to assess local control (LC) according to the RECIST (Response Evaluation Criteria in Solid Tumors) scale. Kaplan-Meier analysis was performed to evaluate in-field progression-free survival (ifPFS), brain progression-free survival (bPFS), and overall survival (OS) rates. Log-rank test and logistic regression analyses were carried out to identify predictive factors associated with better outcomes.

Results:

The population consisted of 33 females and 37 males, with a median age of 66 years [range, 30-85]. Lung (44%) and visceral (47%) were the most frequent tumor histology and extracranial metastases site, respectively. The median follow-up period was 9 months [range, 1-41]. The 1-year and 2-year LC rates for all lesions were 94% and 90%, respectively, with 13 (19%) patients experiencing local recurrence in at least one treated BM. The median ifPFS was 7.8 months, while the corresponding 1-year and 2-year rates were 80% and 72%, respectively. Thirty-six (51%) patients experienced brain progression (in- or extra-field). The median bPFS was 3.9 months, with 1-year and 2-year bFPS rates of 40% and 20%, respectively. The same features for OS were 13 months, 52%, and 29%, respectively. At the time of analysis, 17 (24%) patients were still alive. Lung primary tumor histology and extracranial controlled disease were significantly associated with increased OS (log-rank P=0.050 and P=0.015, respectively) and bPFS (log-rank P= 0.017 and P=0.015, respectively). No statistically significant differences (P>0.05) in clinical outcomes were found for number of treated lesions, total target volume, BM minimum dose and systemic therapy. Patient age and gender showed borderline significant correlations with bPFS (P=0.055) and ifPFS (P=0.060), respectively. Extended bPFS was observed in younger than 66 years patients (mean, 9.9 vs 6.4 months), while female patients had superior ifPFS (mean, 11.6 vs 9.1 months). At multivariate analysis, lung primary tumor histology was independently related to brain progression (OR, 0.35; 95% CI, 0.12–0.98; P=0.043).

Conclusion(s):

Linac-based SRS/fSRS treatments with single-isocenter coplanar FFF-VMAT technique were feasible and resulted in encouraging LC outcomes, comparable to other treatment approaches involving multiple non-coplanar arcs or dedicated machines. Patient prognosis remains unfavorable, mostly dependent on histology and extracranial disease status, rather than on the radiation treatment. Further analyses on a larger patient population are currently underway to confirm these findings and to investigate additional significant predictive factors.