Advanced imaging to assess longitudinal vascular changes in brain metastases treated with immune checkpoint inhibition.

Abstract

2529 Background: Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) for melanoma and lung cancer. This breakthrough has prompted interest in evaluating ICI in BM of other histologies. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot distinguish pseudoprogression from true tumor progression. To shed light on potential biomarkers of response, we prospectively use perfusion MRI to identify characteristic vascular signatures in a BM-specific trial of ICI. Methods: As part of an ongoing phase II study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology, patients underwent advanced MRI that includes tumor volume measurements and perfusion imaging with dynamic susceptibility contrast MRI. To calculate volumetric radiographic response, all enhancing voxels were summated. A volumetric increase of >40% was categorized as progressive disease (PD), a decrease of >60% as partial response (PR), and stable disease (SD) as between -60% and +40%. Results: 53 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) and volumetric response to patient outcome and standardized response criteria (iRANO) are ongoing. Conclusions: Pembrolizumab likely has anti-tumor efficacy in BM. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to illustrate mechanisms of efficacy for ICI and biomarkers of response in this patient population.