In Vivo Detection of EGFRvIII in Glioblastoma via Perfusion Magnetic Resonance Imaging Signature Consistent with Deep Peritumoral Infiltration: The φ -Index

• Published in: Clinical cancer research Vol. 23; no. 16; pp. 4724 - 4734
• Main Authors: Bakas, Spyridon, Akbari, Hamed, Pisapia, Jared, Martinez-Lage, Maria, Rozycki, Martin, Rathore, Saima, Dahmane, Nadia, O'Rourke, Donald M, Davatzikos, Christos
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.08.2017
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Brain; Brain Neoplasms - diagnosis; Brain Neoplasms - diagnostic imaging; Brain Neoplasms - genetics; Cancer; Cancer therapies; Clinical trials; Cohort Studies; Edema; Epidermal growth factor; ErbB Receptors - genetics; Experimental design; Female; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - diagnostic imaging; Glioblastoma - genetics; Heterogeneity; Humans; Image acquisition; In vivo methods and tests; Infiltration; Magnetic Resonance Angiography - methods; Magnetic resonance imaging; Male; Medical research; Metastases; Middle Aged; Mutation; Neuroimaging; Noninvasive evaluation; Perfusion; Radiation; Reproducibility of Results; Sensitivity and Specificity; Spatial heterogeneity; Tissue analysis; Tumors; Vascularization; Young Adult
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-16-1871

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. .