Clin Cancer Res 2017 Aug 20;23(16):4724-4734. Epub 2017 Apr 20.
Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
The epidermal growth factor receptor variant III () mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting requires postoperative tissue analyses, which are and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of imaging signatures capturing molecular characteristics of cancer, this study aims to detect in primary glioblastoma noninvasively, using routine clinically acquired imaging. We found peritumoral infiltration and vascularization patterns being related to status. We therefore constructed a quantitative within-patient peritumoral heterogeneity index (PHI/φ-index), by contrasting perfusion patterns of immediate and distant peritumoral edema. Application of φ-index in preoperative perfusion scans of independent discovery ( = 64) and validation ( = 78) cohorts, revealed the generalizability of this imaging signature. Analysis in both cohorts demonstrated that the obtained signature is highly accurate (89.92%), specific (92.35%), and sensitive (83.77%), with significantly distinctive ability ( = 4.0033 × 10, AUC = 0.8869). Findings indicated a highly infiltrative-migratory phenotype for tumors, which displayed similar perfusion patterns throughout peritumoral edema. Contrarily, tumors displayed perfusion dynamics consistent with peritumorally confined vascularization, suggesting potential benefit from extensive peritumoral resection/radiation. This signature is potentially suitable for clinical translation, since obtained from analysis of clinically acquired images. Use of within-patient heterogeneity measures, rather than population-based associations, renders φ-index potentially resistant to inter-scanner variations. Overall, our findings enable noninvasive evaluation of for patient selection for targeted therapy, stratification into clinical trials, personalized treatment planning, and potentially treatment-response evaluation. .