In vivo detection of EGFRvIII in glioblastoma via perfusion magnetic resonance imaging signature consistent with deep peritumoral infiltration

The φ-index

Spyridon Bakas, Hamed Akbari, Jared Pisapia, Maria Martinez-Lage, Martin Rozycki, Saima Rathore, Nadia Dahmane, Donald M. O'Rourke, Christos Davatzikos

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4724-4734
Number of pages11
JournalClinical Cancer Research
Volume23
Issue number16
DOIs
StatePublished - Aug 15 2017
Externally publishedYes

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Magnetic Resonance Angiography
Glioblastoma
Epidermal Growth Factor Receptor
Perfusion
Edema
Neoplasms
Mutation
Therapeutics
Brain Neoplasms
Patient Selection
Area Under Curve
Research Design
Clinical Trials
Radiation
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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In vivo detection of EGFRvIII in glioblastoma via perfusion magnetic resonance imaging signature consistent with deep peritumoral infiltration : The φ-index. / Bakas, Spyridon; Akbari, Hamed; Pisapia, Jared; Martinez-Lage, Maria; Rozycki, Martin; Rathore, Saima; Dahmane, Nadia; O'Rourke, Donald M.; Davatzikos, Christos.

In: Clinical Cancer Research, Vol. 23, No. 16, 15.08.2017, p. 4724-4734.

Research output: Contribution to journalArticle

Bakas, S, Akbari, H, Pisapia, J, Martinez-Lage, M, Rozycki, M, Rathore, S, Dahmane, N, O'Rourke, DM & Davatzikos, C 2017, 'In vivo detection of EGFRvIII in glioblastoma via perfusion magnetic resonance imaging signature consistent with deep peritumoral infiltration: The φ-index', Clinical Cancer Research, vol. 23, no. 16, pp. 4724-4734. https://doi.org/10.1158/1078-0432.CCR-16-1871
Bakas, Spyridon ; Akbari, Hamed ; Pisapia, Jared ; Martinez-Lage, Maria ; Rozycki, Martin ; Rathore, Saima ; Dahmane, Nadia ; O'Rourke, Donald M. ; Davatzikos, Christos. / In vivo detection of EGFRvIII in glioblastoma via perfusion magnetic resonance imaging signature consistent with deep peritumoral infiltration : The φ-index. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 16. pp. 4724-4734.
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abstract = "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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AU - Pisapia, Jared

AU - Martinez-Lage, Maria

AU - Rozycki, Martin

AU - Rathore, Saima

AU - Dahmane, Nadia

AU - O'Rourke, Donald M.

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