Assessment of Glioblastoma Response in the Era of Bevacizumab: Longstanding and Emergent Challenges in the Imaging Evaluation of Pseudoresponse

Glioblastoma is the deadliest primary malignant brain neoplasm, and despite the availability of many treatment options, its prognosis remains somber. Enhancement detected by magnetic resonance imaging (MRI) was considered the best imaging marker of tumor activity in glioblastoma for decades. However, its role as a surrogate marker of tumor viability has changed with the appearance of new treatment regimens and imaging modalities. The antiangiogenic therapy created an inflection point in the imaging assessment of glioblastoma response in clinical trials and clinical practice. Although BEV led to the improvement of enhancement, it did not necessarilymean tumor response. The decrease in the enhancement intensity represents a change in the permeability properties of the blood brain barrier, and presumably, the switch of the tumor growth pattern to an infiltrative non-enhancing phenotype. New imaging techniques for the assessment of cellularity, blood flow hemodynamics, and biochemistry have emerged to overcome this hurdle; nevertheless, designing tools to assess tumor response more accurately, and in so doing, improve the assessment of response to standard of care (SOC) therapies and to novel therapies, remains challenging.