Pseudoprogression, radionecrosis, inflammation or true tumor progression? challenges associated with glioblastoma response assessment in an evolving therapeutic landscape

Abstract

The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and active or passive immunotherapies, all may alter aspects of vascular permeability within the tumor and/or normal parenchyma. These alterations manifest as changes in the degree of contrast enhancement or T2-weighted signal hyperintensity on standard anatomic MRI scans, posing a potential challenge for accurate radiographic response assessment for identifying anti-tumor effects. The current review highlights the challenges that remain in differentiating true disease progression from changes due to radiation therapy, including pseudoprogression and radionecrosis, as well as immune or inflammatory changes that may occur as either an undesired result of cytotoxic therapy or as a desired consequence of immunotherapies.

Keywords: Glioblastoma; Imaging; Pseudoprogression; Radiation necrosis.

Fig 1.

Example of a 45-year-old male MGMT methylated glioblastoma patient exhibiting transient increases in contrast enhancement followed by subsequent resolution, indicative of pseudoprogression, following treatment with concurrent radiation therapy and temozolomide followed by adjuvant temozolomide.