Pitfalls in le neuroimaging of glioblastoma in le era of antiangiogenic and immuno/targeted therapy - detecting illusive disease, defining response

被引:109
作者
Huang, Raymond Y. [1 ]
Neagu, Martha R. [1 ]
Reardon, David A. [1 ]
Wen, Patrick Y. [1 ]
机构
[1] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA
关键词
glioblastoma; pseudoprogression; pseudoresponse; antiangiogenic therapy; Immunotherapy; imaging techniques; POSITRON-EMISSION-TOMOGRAPHY; APPARENT DIFFUSION-COEFFICIENT; CEREBRAL BLOOD-VOLUME; HIGH-GRADE GLIOMAS; MAGNETIC-RESONANCE-SPECTROSCOPY; PROTON MR SPECTROSCOPY; T-2-ASTERISK-DOMINANT EXTRAVASATION CORRECTION; RECURRENT BRAIN-TUMORS; FDG-PET; RADIATION NECROSIS;
D O I
10.3389/fneur.2015.00033
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Glioblastoma, the most common malignant primary brain tumor in adults is a devastating diagnosis with an average survival of 14-16 months using the current standard of care treatment. The determination of treatment response and clinical decision making is based on the accuracy of radiographic assessment. Notwithstanding, challenges exist in the neuroimaging evaluation of patients undergoing treatment for malignant glioma. Differentiating treatment response from tumor progression is problematic and currently combines long-term follow-up using standard magnetic resonance imaging (MRI), with clinical status and corticosteroid-dependency assessments. In the clinical trial setting, treatment with gene therapy, vaccines, immunotherapy, and targeted biologicals similarly produces MRI changes mimicking disease progression. A neuroimaging method to clearly distinguish between pseudoprogression and tumor progression has unfortunately not been found to date. With the incorporation of antiangiogenic therapies, a further pitfall in imaging interpretation is pseudoresponse. The Macdonald criteria that correlate tumor burden with contrast-enhanced imaging proved insufficient and misleading in the context of rapid blood brain barrier normalization following antiangiogenic treatment that is not accompanied by expected survival benefit. Even improved criteria, such as the RANO criteria, which incorporate non-enhancing disease, clinical status, and need for corticosteroid use, fall short of definitively distinguishing tumor progression, pseudoresponse, and pseudoprogression. This review focuses on advanced imaging techniques including perfusion MRI, diffusion MRI, MR spectroscopy, and new positron emission tomography imaging tracers. The relevant image analysis algorithms and interpretation methods of these promising techniques are discussed in the context of determining response and progression during treatment of glioblastoma both in the standard of care and in clinical trial context.
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