Abstract
BackgroundTo explore if early perfusion-weighted magnetic resonance imaging (PWI) may be a promising imaging biomarker to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS).MethodsThis is a prospective pilot study of adult brain metastasis patients who were treated with SRS and imaged with PWI before and 1 week later. Relative cerebral blood volume (rCBV) parameter maps were calculated by normalizing to the mean value of the contralateral white matter on PWI. Cox regression was conducted to explore factors associated with time to LR, with Bonferroni adjusted p<0.0006 for multiple testing correction. LR rates were estimated with the Kaplan-Meier method and compared using the log-rank test.ResultsTwenty-three patients were enrolled from 2013 through 2016, with 22 evaluable lesions from 16 patients. After a median follow-up of 13.1 months (range: 3.0–53.7), 5 lesions (21%) developed LR after a median of 3.4 months (range: 2.3–5.7). On univariable analysis, larger tumor volume (HR 1.48, 95% CI 1.02–2.15, p = 0.04), lower SRS dose (HR 0.45, 95% CI 0.21–0.97, p = 0.04), and higher rCBV at week 1 (HR 1.07, 95% CI 1.003–1.14, p = 0.04) had borderline association with shorter time to LR. Tumors >2.0cm3 had significantly higher LR than if ≤2.0cm3: 54% vs 0% at 1 year, respectively, p = 0.008. A future study to confirm the association of early PWI and LR of the high-risk cohort of lesions >2.0cm3 is estimated to require 258 patients.ConclusionsPWI at week 1 after SRS may have borderline association with LR. Tumors <2.0cm3 have low risk of LR after SRS and may be low-yield for predictive biomarker studies. Information regarding sample size and potential challenges for future imaging biomarker studies may be gleaned from this pilot study.
Highlights
Brain metastases occur in approximately 10–35% of adult cancer patients [1]
Larger tumor volume (HR 1.48, 95% CI 1.02–2.15, p = 0.04), lower SRS dose (HR 0.45, 95% CI 0.21–0.97, p = 0.04), and higher Relative cerebral blood volume (rCBV) at week 1 (HR 1.07, 95% CI 1.003–1.14, p = 0.04) had borderline association with shorter time to local recurrence (LR)
A future study to confirm the association of early perfusion-weighted magnetic resonance imaging (PWI) and LR of the high-risk cohort of lesions >2.0cm3 is estimated to require 258 patients
Summary
For patients with a limited number of brain metastases, stereotactic radiosurgery (SRS) rather than whole brain radiation therapy (WBRT) has increasingly become the preferred treatment [1, 2]. Four randomized trials have collectively demonstrated that SRS alone has superior neurocognitive profile and quality of life than SRS plus WBRT without jeopardizing overall survival (OS) [3,4,5,6,7]. Biomarkers of tumor response to SRS, ideally within the first weeks after treatment, may aid in identifying high-risk patients who could benefit from additional HA-WBRT or other local salvage therapies such as laser interstitial thermal therapy (LITT) or staged SRS boost [9, 10]. To explore if early perfusion-weighted magnetic resonance imaging (PWI) may be a promising imaging biomarker to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS)
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