Mr Perfusion Imaging As A Potential Early Imaging Biomarker For Radiation Response In Brain Metastases

Brain metastases have poor prognoses, and there is substantial heterogeneity in their response following radiation. The aim of this study was to identify potential early imaging biomarkers of tumor response using T1-weighted dynamic contrast-enhanced (DCE) MRI (perfusion MRI). Nineteen patients receiving whole-brain radiation therapy (30 Gy in 10 fractions or 37.5 Gy in 15 fractions) for brain metastases participated in a prospective IRB-approved MR imaging study, in which they underwent DCE MRI before radiotherapy, at the completion of radiotherapy, and at 1 month following radiotherapy. Vascular volume and blood-tumor barrier (BTB) permeability were quantified from the DCE MRI. The pre-radiotherapy vascular volume and BTB permeability of brain metastases, as well as their changes during radiotherapy, were evaluated for association with subsequent volumetric response at 1 month after radiotherapy. All metastases were analyzed in patients with 1–3 lesions; the three largest metastases were analyzed in those patients with greater than 3 lesions. Thirty-five brain metastases were analyzed. Histologies included melanoma (n = 24), non–small-cell lung cancer (8), renal cell carcinoma (2), and squamous cell carcinoma of the head and neck (1). At 1 month following radiotherapy, 17 lesions (47%) demonstrated an increase in volume, consistent with progression; the remaining lesions were stable or decreased in volume. Volumetric changes at the end of radiotherapy were not significantly correlated with volumetric changes at 1 month following radiotherapy (p = 0.50). In contrast, increases in vascular volume at the end of radiotherapy (compared to pretreatment) were significantly associated with subsequent tumor growth at 1 month (p = 0.005). This association was greatest for metastases greater than 1 cc in volume (p < 0.002), in which every 10% increase in vascular volume at the end of radiotherapy resulted in a 9% growth in tumor volume at 1 month post-therapy on linear regression. Changes in BTB permeability, as well as pretreatment perfusion characteristics, were not correlated with tumor response. In this prospective MR imaging study, changes in the vascular volume of brain metastases at the completion of radiotherapy predicted for subsequent volumetric tumor response. While these findings need to be validated in a larger cohort, they suggest that DCE MRI may be used to improve assessment of treatment response. Imaging biomarkers may potentially select patients who may benefit from early treatment intensification via stereotactic RT boost or systemic chemotherapy.