Radiation-Induced Vascular Malformations Mimicking Tumor in MRI-Based Treatment Response Assessment Maps (TRAMs)

Abstract

We have recently presented MRI-based TRAMs enabling efficient separation between tumor (contrast clearance >1-hour post injection, blue) and treatment-effects (TEs, contrast accumulation, red), validated histologically in 51 resected patients reaching 92%/100% PPV/sensitivity to morphologically active tumor. This high selectivity stems from the ability of viable vessels in blue/tumor regions to efficiently clear contrast by 1hour, while damaged lumens in red/TEs regions are unable to, resulting in contrast accumulation. Approximately 400 adult patients have been recruited to our studies in Israel since 2010. As the TRAMs cannot differentiate blood vessels from active tumor (both appearing blue), we studied whether radiation-induced cavernoma-like vascular malformations (RICMs) may mimic tumors in the TRAMs. Cases in which the pre-surgical TRAMs were found false-positive for tumor were re-reviewed. For comparison, 2 patients with newly diagnosed cavernomas and 4 with treated AVMs were scanned by the TRAMs. One AVM underwent TRAMs-guided biopsies. Four cases of false-positive TRAMs showing RICMs in histology were found between 2010-2017: GBM post Stupp followed by bevacizumab +rindopepimut, breast and NSCLC metastases post SRS, and resected NSCLC post SRS to the surgery site. The pre-surgical TRAMs of the GBM and post-resection NSCLC showed 2-3mm blue masses within larger thin blue rims. The metastases depicted thin blue rims surrounding red regions. Histology revealed clusters of connective tissue with multiple vessel-channels in all 4 cases, consistent with RICMs at various stages of tissue re-organization. The treated AVMs TRAMs showed mixed blue/red regions. Biopsies taken from blue regions revealed large vessels, some showing re-organization; red regions showed TEs. The cavernomas were depicted blue in the TRAMs. The TRAMs reliability in differentiating tumor from TEs has been validated histologically reaching PPV=92%. The presented findings suggest that RICMs, as other vascular-malformations, may mimic tumor (blue) in the TRAMs, thus explaining false-positive cases.