Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Clinical Neuroradiology
Published in: Clinical Neuroradiology 2/2015

01-06-2015 | Original Article

Pretreatment Dynamic Susceptibility Contrast MRI Perfusion in Glioblastoma: Prediction of EGFR Gene Amplification

Authors: A. Gupta, MD, R. J. Young, MD, A. D. Shah, MD, A. D. Schweitzer, MD, J. J. Graber, MD, W. Shi, MS, Z. Zhang, PhD, J. Huse, MD, A. M. P. Omuro, MD

Published in: Clinical Neuroradiology | Issue 2/2015

Login to get access

Abstract

Background and Purpose

Molecular and genetic testing is becoming increasingly relevant in GBM. We sought to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion imaging could predict EGFR-defined subtypes of GBM.

Materials and Methods

We retrospectively identified 106 consecutive glioblastoma (GBM) patients with known EGFR gene amplification, and a subset of 65 patients who also had known EGFRvIII gene mutation status. All patients underwent T2* DSC MRI perfusion. DSC perfusion maps and T2* signal intensity time curves were evaluated, and the following measures of tumor perfusion were recorded: (1) maximum relative cerebral blood volume (rCBV), (2) relative peak height (rPH), and (3) percent signal recovery (PSR). The imaging metrics were correlated to EGFR gene amplification and EGFRvIII mutation status using univariate analyses.

Results

EGFR amplification was present in 44 (41.5 %) subjects and absent in 62 (58.5 %). Among the 65 subjects who had undergone EGFRvIII mutation transcript analysis, 18 subjects (27.7 %) tested positive for the EGFRvIII mutation, whereas 47 (72.3 %) did not. Higher median rCBV (3.31 versus 2.62, p = 0.01) and lower PSR (0.70 versus 0.78, p = 0.03) were associated with high levels of EGFR amplification. Higher median rPH (3.68 versus 2.76, p = 0.03) was associated with EGFRvIII mutation.

Conclusion

DSC MRI perfusion may have a role in identifying patients with EGFR gene amplification and EGFRvIII gene mutation status, potential targets for individualized treatment protocols. Our results raise the need for further investigation for imaging biomarkers of genetically unique GBM subtypes.
Literature
1.
Essock-Burns E, Lupo JM, Cha S, et al. Assessment of perfusion MRI-derived parameters in evaluating and predicting response to antiangiogenic therapy in patients with newly diagnosed glioblastoma. Neuro Oncol. 2011;13:119–31.PubMedCentralPubMedCrossRef
2.
Law M, Yang S, Wang H, et al. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol. 2003;24:1989–98.PubMed
3.
Barajas RF Jr, Phillips JJ, Parvataneni R, et al. Regional variation in histopathologic features of tumor specimens from treatmentnaive glioblastoma correlates with anatomic and physiologic MR imaging. Neuro Oncol. 2012;14:942–54.PubMedCentralPubMedCrossRef
4.
Young RJ, Gupta A, Shah AD, et al. MRI perfusion in determining pseudoprogression in patients with glioblastoma. Clin Imaging. 2013;37:41–9.PubMedCrossRef
5.
Barajas RF Jr, Chang JS, Segal MR, et al. Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology. 2009;253:486–96.PubMedCentralPubMedCrossRef
6.
Young RJ, Gupta A, Shah AD, et al. Potential utility of conventional MRI signs in diagnosing pseudoprogression in glioblastoma. Neurology. 2011;76:1918–24.PubMedCentralPubMedCrossRef
7.
Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.PubMedCrossRef
8.
Vitucci M, Hayes DN, Miller CR. Gene expression profiling of gliomas: merging genomic and histopathological classification for personalised therapy. Br J Cancer. 2011;104:545–53.PubMedCentralPubMedCrossRef
9.
Jain R, Poisson L, Narang J, et al. Genomic mapping and survival prediction in glioblastoma: molecular subclassification strengthened by hemodynamic imaging biomarkers. Radiology. 2013 Apr;267(1):212–20. doi: 10.1148/radiol.12120846. Epub 2012 Dec 13.
10.
Jain R, Poisson L, Narang J, et al. Correlation of perfusion parameters with genes related to angiogenesis regulation in glioblastoma: a feasibility study. AJNR Am J Neuroradiol. 2012;33:1343–8.PubMedCrossRef
11.
Huang PH, Xu AM, White FM. Oncogenic EGFR signaling networks in glioma. Sci Signal. 2009;2:re6.
12.
Mellinghoff IK, Wang MY, Vivanco I, et al. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005;353:2012–24.PubMedCrossRef
13.
Lal A, Glazer CA, Martinson HM, et al. Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion. Cancer Res. 2002;62:3335–9.PubMed
14.
Gan HK, Kaye AH, Luwor RB. The EGFRvIII variant in glioblastoma multiforme. J Clin Neurosci. 2009;16:748–54.PubMedCrossRef
15.
Liu L, Backlund LM, Nilsson BR, et al. Clinical significance of EGFR amplification and the aberrant EGFRvIII transcript in conventionally treated astrocytic gliomas. J Mol Med (Berl). 2005;83:917–26.
16.
Pelloski CE, Ballman KV, Furth AF, et al. Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol. 2007;25:2288–94.PubMedCrossRef
17.
Uhm JH, Ballman KV, Wu W, et al. Phase II evaluation of gefitinib in patients with newly diagnosed grade 4 astrocytoma: Mayo/North central cancer treatment group study N0074. Int J Radiat Oncol Biol Phys. 2011;80:347–53.PubMedCrossRef
18.
Peereboom DM, Shepard DR, Ahluwalia MS, et al. Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme. J Neurooncol. 2010;98:93–9.PubMedCrossRef
19.
Sampson JH, Heimberger AB, Archer GE, et al. Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010;28:4722–9.PubMedCentralPubMedCrossRef
20.
Diehn M, Nardini C, Wang DS, et al. Identification of noninvasive imaging surrogates for brain tumor gene-expression modules. Proc Natl Acad Sci U S A. 2008;105:5213–8.PubMedCentralPubMedCrossRef
21.
Aghi M, Gaviani P, Henson JW, et al. Magnetic resonance imaging characteristics predict epidermal growth factor receptor amplification status in glioblastoma. Clin Cancer Res. 2005;11:8600–5.PubMedCrossRef
22.
Young RJ, Gupta A, Shah AD, et al. Potential role of preoperative conventional MRI including diffusion measurements in assessing EGFR gene amplification status in glioblastoma patients. AJNR Am J Neuroradiol. 2013. Accepted, in press.
23.
Tykocinski ES, Grant RA, Kapoor GS, et al. Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma. Neuro Oncol. 2012;14:613–23.PubMedCentralPubMedCrossRef
24.
Goldman CK, Kim J, Wong WL, et al. Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: A model of glioblastoma multiforme pathophysiology. Mol Biol Cell. 1993;4:121–33.PubMedCentralPubMedCrossRef
25.
Cha S, Knopp EA, Johnson G, et al. Intracranial mass lesions: dynamic contrast-enhanced susceptibility-weighted echo-planar perfusion MR imaging. Radiology. 2002;223:11–29.PubMedCrossRef
26.
27.
Kong DS, Kim ST, Kim EH, et al. Diagnostic dilemma of pseudoprogression in the treatment of newly diagnosed glioblastomas: the role of assessing relative cerebral blood flow volume and oxygen-6-methylguanine-DNA methyltransferase promoter methylation status. AJNR Am J Neuroradiol. 2011;32:382–7.PubMedCrossRef
28.
Mangla R, Kolar B, Zhu T, et al. Percentage signal recovery derived from MR dynamic susceptibility contrast imaging is useful to differentiate common enhancing malignant lesions of the brain. AJNR Am J Neuroradiol. 2011;32:1004–10.PubMedCrossRef
29.
Barajas RF, Chang JS, Sneed PK, et al. Distinguishing recurrent intra-axial metastatic tumor from radiation necrosis following gamma knife radiosurgery using dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. AJNR Am J Neuroradiol. 2009;30:367–72.PubMedCrossRef
30.
Hatanpaa KJ, Burma S, Zhao D, et al. Epidermal growth factor receptor in glioma: signal transduction, neuropathology, imaging, and radioresistance. Neoplasia. 2010;12:675–84.PubMedCentralPubMedCrossRef
31.
Cha S, Johnson G, Wadghiri YZ, et al. Dynamic, contrast-enhanced perfusion MRI in mouse gliomas: correlation with histopathology. Magn Reson Med. 2003;49:848–55.PubMedCrossRef
32.
Price SJ, Green HA, Dean AF, et al. Correlation of MR relative cerebral blood volume measurements with cellular density and proliferation in high-grade gliomas: an image-guided biopsy study. AJNR Am J Neuroradiol. 2011;32:501–6.PubMedCrossRef
33.
Cha S, Lu S, Johnson G, et al. Dynamic susceptibility contrast MR imaging: correlation of signal intensity changes with cerebral blood volume measurements. J Magn Reson Imaging. 2000;11:114–9.PubMedCrossRef
34.
Hobbs J, Nikiforova MN, Fardo DW, et al. Paradoxical relationship between the degree of EGFR amplification and outcome in glioblastomas. Am J Surg Pathol. 2012;36:1186–93.PubMedCentralPubMedCrossRef
35.
Del Vecchio CA, Li G, Wong AJ. Targeting EGF receptor variant III: tumor-specific peptide vaccination for malignant gliomas. Expert Rev Vaccines. 2012;11:133–44.PubMedCrossRef
36.
Finocchiaro G, Pellegatta S. Immunotherapy for glioma: getting closer to the clinical arena? Curr Opin Neurol. 2011;24:641–7.PubMedCrossRef
37.
Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98–110.PubMedCentralPubMedCrossRef
38.
Toh CH, Wei KC, Chang CN, et al. Differentiation of primary central nervous system lymphomas and glioblastomas: comparisons of diagnostic performance of dynamic susceptibility contrast-enhanced perfusion MR imaging without and with contrast-leakage correction. AJNR Am J Neuroradiol. 2013 Jun–Jul;34(6):1145–9. doi: 10.3174/ajnr.A3383. Epub 2013 Jan 24.
Metadata
Title
Pretreatment Dynamic Susceptibility Contrast MRI Perfusion in Glioblastoma: Prediction of EGFR Gene Amplification
Authors
A. Gupta, MD
R. J. Young, MD
A. D. Shah, MD
A. D. Schweitzer, MD
J. J. Graber, MD
W. Shi, MS
Z. Zhang, PhD
J. Huse, MD
A. M. P. Omuro, MD
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
Clinical Neuroradiology / Issue 2/2015
Print ISSN: 1869-1439
Electronic ISSN: 1869-1447
DOI
https://doi.org/10.1007/s00062-014-0289-3

Other articles of this Issue 2/2015

Clinical Neuroradiology 2/2015 Go to the issue

Clinical Case

Freiburg Neuropathology Case Conference: An Infant with a Supratentorial Mass Lesion

Original Article

Posterior Reversible Encephalopathy Syndrome: The Spectrum of MR Imaging Patterns

Editorial

Editorial

Review Article

Cavernous Sinus: A Comprehensive Review of its Anatomy, Pathologic Conditions, and Imaging Features

Correspondence

A Case of Giant Thrombosed Persistent Primitive Trigeminal Artery Aneurysm Presenting with Trigeminal Neuralgia and Successfully Treated by a Covered Stent: Case Report and Review of Literature

Correspondence

Extreme Anemia Causing Unusual “Black-out” of the Cerebral Vessels on Noncontrast Brain CT