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Rundle-Thiele D, Day B, Stringer B, et al. Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method. J Med Radiat Sci. 2015;62(2):92-8doi: 10.1002/jmrs.103.
Rundle-Thiele, D., Day, B., Stringer, B., Fay, M., Martin, J., Jeffree, R. L., Thomas, P., Bell, C., Salvado, O., Gal, Y., Coulthard, A., Crozier, S., & Rose, S. (2015). Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method. Journal of medical radiation sciences, 62(2), 92-8. https://doi.org/10.1002/jmrs.103
Rundle-Thiele, Dayle, et al. "Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method." Journal of medical radiation sciences vol. 62,2 (2015): 92-8. doi: https://doi.org/10.1002/jmrs.103
Rundle-Thiele D, Day B, Stringer B, Fay M, Martin J, Jeffree RL, Thomas P, Bell C, Salvado O, Gal Y, Coulthard A, Crozier S, Rose S. Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method. J Med Radiat Sci. 2015 Jun;62(2):92-8. doi: 10.1002/jmrs.103. Epub 2015 Apr 16. PMID: 26229673; PMCID: PMC4462980.
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J Med Radiat Sci. 2015 Jun;62(2):92-8. doi: 10.1002/jmrs.103. Epub 2015 Apr 16.

Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method.

Journal of medical radiation sciences

Dayle Rundle-Thiele, Bryan Day, Brett Stringer, Michael Fay, Jennifer Martin, Rosalind L Jeffree, Paul Thomas, Christopher Bell, Olivier Salvado, Yaniv Gal, Alan Coulthard, Stuart Crozier, Stephen Rose

Affiliations

  1. Centre for Clinical Research, University of Queensland Brisbane, Queensland, Australia.
  2. Brain Cancer Research Unit, Queensland Institute of Medical Research Brisbane, Queensland, Australia.
  3. Department of Radiation Oncology, Royal Brisbane and Women's Hospital Brisbane, Queensland, Australia.
  4. Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle Newcastle, New South Wales, Australia.
  5. Department of Neurosurgery, Royal Brisbane and Women's Hospital Brisbane, Queensland, Australia.
  6. Queensland PET Service, Royal Brisbane and Women's Hospital Brisbane, Queensland, Australia.
  7. CSIRO Digital Productivity Flagship, CSIRO Herston, Queensland, Australia.
  8. Centre for Medical Diagnostic Technologies in Queensland, University of Queensland Brisbane, Queensland, Australia.
  9. Discipline of Medical Imaging, University of Queensland St Lucia, Queensland, Australia ; Department of Medical Imaging, Royal Brisbane and Women's Hospital Brisbane, Queensland, Australia.

PMID: 26229673 PMCID: PMC4462980 DOI: 10.1002/jmrs.103

Abstract

INTRODUCTION: Accurate knowledge of O(6)-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC.

METHODS: We undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods.

RESULTS: A strong trend between a measure of 'minimum ADC' and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the 'low ADC' component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246).

CONCLUSION: This study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.

Keywords: ADC; MGMT; diffusion MRI; glioblastoma

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