TY - JOUR
T1 - In vivo detection of EGFRvIII in glioblastoma via perfusion magnetic resonance imaging signature consistent with deep peritumoral infiltration
T2 - The φ-index
AU - Bakas, Spyridon
AU - Akbari, Hamed
AU - Pisapia, Jared
AU - Martinez-Lage, Maria
AU - Rozycki, Martin
AU - Rathore, Saima
AU - Dahmane, Nadia
AU - O'Rourke, Donald M.
AU - Davatzikos, Christos
N1 - Funding Information:
This work was primarily supported by two grants awarded from the NIH; (i) R01 grant on "Predicting brain tumor progression via multiparametric image analysis and modeling" (R01-NS042645), and (ii) U24 grant of "Cancer imaging phenomics software suite: application to brain and breast cancer" (U24-CA189523). It was also supported in part by a sponsored research grant from Celldex Therapeutics to the University of Pennsylvania (to D.M. O'Rourke).
Publisher Copyright:
©2017 AACR.
PY - 2017/8/15
Y1 - 2017/8/15
N2 - Purpose: The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma noninvasively, using routine clinically acquired imaging. Experimental Design: We found peritumoral infiltration and vascularization patterns being related to EGFRvIII 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 (n = 64) and validation (n = 78) cohorts, revealed the generalizability of this EGFRvIII imaging signature. Results: 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 (P = 4.0033 × 10-10, AUC = 0.8869). Findings indicated a highly infiltrative-migratory phenotype for EGFRvIII+ tumors, which displayed similar perfusion patterns throughout peritumoral edema. Contrarily, EGFRvIII- tumors displayed perfusion dynamics consistent with peritumorally confined vascularization, suggesting potential benefit from extensive peritumoral resection/radiation. Conclusions: This EGFRvIII 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 EGFRvIII for patient selection for targeted therapy, stratification into clinical trials, personalized treatment planning, and potentially treatment-response evaluation.
AB - Purpose: The epidermal growth factor receptor variant III (EGFRvIII) mutation has been considered a driver mutation and therapeutic target in glioblastoma, the most common and aggressive brain cancer. Currently, detecting EGFRvIII requires postoperative tissue analyses, which are ex vivo and unable to capture the tumor's spatial heterogeneity. Considering the increasing evidence of in vivo imaging signatures capturing molecular characteristics of cancer, this study aims to detect EGFRvIII in primary glioblastoma noninvasively, using routine clinically acquired imaging. Experimental Design: We found peritumoral infiltration and vascularization patterns being related to EGFRvIII 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 (n = 64) and validation (n = 78) cohorts, revealed the generalizability of this EGFRvIII imaging signature. Results: 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 (P = 4.0033 × 10-10, AUC = 0.8869). Findings indicated a highly infiltrative-migratory phenotype for EGFRvIII+ tumors, which displayed similar perfusion patterns throughout peritumoral edema. Contrarily, EGFRvIII- tumors displayed perfusion dynamics consistent with peritumorally confined vascularization, suggesting potential benefit from extensive peritumoral resection/radiation. Conclusions: This EGFRvIII 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 EGFRvIII for patient selection for targeted therapy, stratification into clinical trials, personalized treatment planning, and potentially treatment-response evaluation.
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U2 - 10.1158/1078-0432.CCR-16-1871
DO - 10.1158/1078-0432.CCR-16-1871
M3 - Article
C2 - 28428190
AN - SCOPUS:85028049395
SN - 1078-0432
VL - 23
SP - 4724
EP - 4734
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -