Assessment Of The Outcomes And Prognostic Factors Of Fractionated Stereotactic Radiation Therapy For Large Brain Metastases As Potential Alternative To Surgery

Abstract

Stereotactic radiation therapy (SRT) for brain metastases (BM) has been known for excellent local control with preservation of cognitive function. Recently, fractionated SRT(FSRT) has been shown to be superior to single fraction SRT in reducing the risk of radiation necrosis (RN), while maintaining or improving the rates of local control, especially in large BM. The purpose of this study was to clarify the outcomes and prognostic factors of FSRT for large BM and to evaluate whether FSRT could be an alternative to surgery. Patients who met the following criteria were retrospectively reviewed from our institutional database; 1) diagnosed with a BM by computed tomography or magnetic resonance imaging, 2) treated with FSRT, 3) no history of surgical resection for target lesion before FSRT and 4) maximum diameter of BM was 2 cm or greater. Local control (LC), intracranial control (ICC), overall survival (OS) and adverse events (AEs) were evaluated. AEs were evaluated based on Common Terminology Criteria for Adverse Events 5.0. Among 821 lesions, 131 lesions in 122 patients were selected from our database between February 2012 and December 2019 and the following data were extracted: median age, 67 (range, 39-93) years; performance status (PS), 0-1/2-4/unknown, 79/41/2; primary disease, lung/breast/colorectal/others, 81/13/10/18; median tumor maximum diameter, 25 (range, 20-50) mm; median tumor volume, 7.2 (range, 1.7-39.1) cm3; number of BM; 1/2 or more, 50/81; median prescription dose, 35 Gy in 3 fractions (range, 22.7-41.5 Gy in 3-5 fractions). Twenty-eight lesions (21.3%) with tumor diameter greater than 30 mm were included. Twenty-three lesions (17.6%) had a history of whole-brain radiation therapy (WBRT) before FSRT. The median follow-up after FSRT was 7 (range, 0-53) months. The 1-year LC rate, ICC rate and OS rate were 79.1%, 28.4% and 41.8%, respectively. In univariate analysis of LC, Dmax for planning target volume (PTV) calculated in biologically effective dose using α/β = 10 Gy (BED10) more than 135 Gy (p = 0.0032), Dmean for PTV calculated in BED10 more than 100 Gy (p = 0.019), PS 0-1 (p = 0.00083) and systemic therapy after FSRT (p = 0.0057) were associated with a significant better prognosis. The prescribed dose was not a significant factor for LC. In multivariate analysis, Dmax for PTV calculated in BED10 more than 135 Gy, PS 0-1 and systemic therapy after FSRT were independent prognostic factors. Seventeen lesions (12.9%) received WBRT following FSRT. Surgery for targeted lesion was performed in 3 lesions (2.9%) after FSRT. RN, including suspicious RN, were observed in 5 lesions (3.8%). Grade 2 intracranial hemorrhage were observed in 2 lesions (1.5%). FSRT for large BM has the potential to be an alternative to surgery, especially in patients with good PS who can receive systemic therapy following FSRT. FSRT with a higher maximum tumor dose might be improve LC.