Regional and Volumetric Parameters for Diffusion-Weighted WHO Grade II and III Glioma Genotyping: A Method Comparison

doi:10.3174/ajnr.A6965

Comparative Study

. 2021 Mar;42(3):441-447.

doi: 10.3174/ajnr.A6965. Epub 2021 Jan 7.

Regional and Volumetric Parameters for Diffusion-Weighted WHO Grade II and III Glioma Genotyping: A Method Comparison

S C Thust^{1

2

3}, J A Maynard^{4

2}, M Benenati^{2

5}, S J Wastling^{4

2}, L Mancini^{4

2}, Z Jaunmuktane⁶, S Brandner⁷, H R Jäger^{4

2

3}

Affiliations

¹ From the Neuroradiological Academic Unit (S.C.T., J.A.M, S.J.W., L.M., H.R.J.), Department of Brain, Repair and Rehabilitation, UCL Institute of Neurology, London, UK s.thust@ucl.ac.uk.
² Lysholm Department of Neuroradiology (S.C.T., J.A.M., M.B., S.J.W., L.M., H.R.J.), National Hospital for Neurology and Neurosurgery, London, UK.
³ Imaging Department (S.C.T., H.R.J.), University College London Foundation Hospital, London, UK.
⁴ From the Neuroradiological Academic Unit (S.C.T., J.A.M, S.J.W., L.M., H.R.J.), Department of Brain, Repair and Rehabilitation, UCL Institute of Neurology, London, UK.
⁵ Dipartimento di Diagnostica per Immagini (M.B.), Radioterapia, Oncologia ed Ematologia, Fondazione Policlinico Universitario A. Gemelli Institute for Research, Hospitalization and Health Care, Rome, Italy.
⁶ Department of Clinical and Movement Neurosciences (Z.J.).
⁷ Neurodegenerative Disease (S.B.), UCL Queen Square Institute of Neurology, and Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.

PMID: 33414227
PMCID: PMC7959449
DOI: 10.3174/ajnr.A6965

Comparative Study

Regional and Volumetric Parameters for Diffusion-Weighted WHO Grade II and III Glioma Genotyping: A Method Comparison

S C Thust et al. AJNR Am J Neuroradiol. 2021 Mar.

. 2021 Mar;42(3):441-447.

doi: 10.3174/ajnr.A6965. Epub 2021 Jan 7.

Authors

S C Thust^{1

2

3}, J A Maynard^{4

2}, M Benenati^{2

5}, S J Wastling^{4

2}, L Mancini^{4

2}, Z Jaunmuktane⁶, S Brandner⁷, H R Jäger^{4

2

3}

Affiliations

¹ From the Neuroradiological Academic Unit (S.C.T., J.A.M, S.J.W., L.M., H.R.J.), Department of Brain, Repair and Rehabilitation, UCL Institute of Neurology, London, UK s.thust@ucl.ac.uk.
² Lysholm Department of Neuroradiology (S.C.T., J.A.M., M.B., S.J.W., L.M., H.R.J.), National Hospital for Neurology and Neurosurgery, London, UK.
³ Imaging Department (S.C.T., H.R.J.), University College London Foundation Hospital, London, UK.
⁴ From the Neuroradiological Academic Unit (S.C.T., J.A.M, S.J.W., L.M., H.R.J.), Department of Brain, Repair and Rehabilitation, UCL Institute of Neurology, London, UK.
⁵ Dipartimento di Diagnostica per Immagini (M.B.), Radioterapia, Oncologia ed Ematologia, Fondazione Policlinico Universitario A. Gemelli Institute for Research, Hospitalization and Health Care, Rome, Italy.
⁶ Department of Clinical and Movement Neurosciences (Z.J.).
⁷ Neurodegenerative Disease (S.B.), UCL Queen Square Institute of Neurology, and Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.

PMID: 33414227
PMCID: PMC7959449
DOI: 10.3174/ajnr.A6965

Abstract

Background and purpose: Studies consistently report lower ADC values in isocitrate dehydrogenase (IDH) wild-type gliomas than in IDH mutant tumors, but their methods and thresholds vary. This research aimed to compare volumetric and regional ADC measurement techniques for glioma genotyping, with a focus on IDH status prediction.

Materials and methods: Treatment-naïve World Health Organization grade II and III gliomas were analyzed by 3 neuroradiologist readers blinded to tissue results. ADC minimum and mean ROIs were defined in tumor and in normal-appearing white matter to calculate normalized values. T2-weighted tumor VOIs were registered to ADC maps with histogram parameters (mean, 2nd and 5th percentiles) extracted. Nonparametric testing (eta² and ANOVA) was performed to identify associations between ADC metrics and glioma genotypes. Logistic regression was used to probe the ability of VOI and ROI metrics to predict IDH status.

Results: The study included 283 patients with 79 IDH wild-type and 204 IDH mutant gliomas. Across the study population, IDH status was most accurately predicted by ROI mean normalized ADC and VOI mean normalized ADC, with areas under the curve of 0.83 and 0.82, respectively_. The results for ROI-based genotyping of nonenhancing and solid-patchy enhancing gliomas were comparable with volumetric parameters (area under the curve = 0.81-0.84). In rim-enhancing, centrally necrotic tumors (n = 23), only volumetric measurements were predictive (0.90).

Conclusions: Regional normalized mean ADC measurements are noninferior to volumetric segmentation for defining solid glioma IDH status. Partially necrotic, rim-enhancing tumors are unsuitable for ROI assessment and may benefit from volumetric ADC quantification.

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Figures

**FIG 1.**
An example of regional and volumetric ADC measurements in a patient with *IDH* mutant 1p19q intact glioma. T2-weighted image (A) and ADC maps (*B–D*) show ADC_min (3 × 30–40 mm² (black, B and C), ADC_mean (white, C), and ADC_NAWM (white, D) ROI measurements. T2-weighted image (E) and ADC map (F) in the same patient demonstrate the volumetric segmentation and image registration, respectively.

**FIG 2.**
ROC curves for the prediction of *IDH* genotype in the study population (n = 283).

See this image and copyright information in PMC

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References

1. Brat DJ, Verhaak RG, Aldape KD, et al. ; Cancer Genome Atlas Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372:2481–98 10.1056/NEJMoa1402121 - DOI - PMC - PubMed
1. Louis DN, Perry A, Reifenberger G, et al. . The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131:803–20 10.1007/s00401-016-1545-1 - DOI - PubMed
1. Stichel D, Ebrahimi A, Reuss D, et al. . Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDH wild type astrocytoma to glioblastoma. Acta Neuropathol 2018;136:793–803 10.1007/s00401-018-1905-0 - DOI - PubMed
1. Tesileanu CM, Dirven L, Wijnenga MM, et al. . Survival of diffuse astrocytic glioma, IDH1/2-wild type, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria. Neuro Oncol 2020;22:515–23 10.1093/neuonc/noz200] - DOI - PMC - PubMed
1. van den Bent MJ, Brandes AA, Taphoorn MJ, et al. . Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 2013;31:344–50 10.1200/JCO.2012.43.2229 - DOI - PubMed

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[1] Brat DJ, Verhaak RG, Aldape KD, et al. ; Cancer Genome Atlas Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372:2481–98 10.1056/NEJMoa1402121 - DOI - PMC - PubMed

[2] Brat DJ, Verhaak RG, Aldape KD, et al. ; Cancer Genome Atlas Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 2015;372:2481–98 10.1056/NEJMoa1402121 - DOI - PMC - PubMed

[3] Louis DN, Perry A, Reifenberger G, et al. . The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131:803–20 10.1007/s00401-016-1545-1 - DOI - PubMed

[4] Louis DN, Perry A, Reifenberger G, et al. . The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 2016;131:803–20 10.1007/s00401-016-1545-1 - DOI - PubMed

[5] Stichel D, Ebrahimi A, Reuss D, et al. . Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDH wild type astrocytoma to glioblastoma. Acta Neuropathol 2018;136:793–803 10.1007/s00401-018-1905-0 - DOI - PubMed

[6] Stichel D, Ebrahimi A, Reuss D, et al. . Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDH wild type astrocytoma to glioblastoma. Acta Neuropathol 2018;136:793–803 10.1007/s00401-018-1905-0 - DOI - PubMed

[7] Tesileanu CM, Dirven L, Wijnenga MM, et al. . Survival of diffuse astrocytic glioma, IDH1/2-wild type, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria. Neuro Oncol 2020;22:515–23 10.1093/neuonc/noz200] - DOI - PMC - PubMed

[8] Tesileanu CM, Dirven L, Wijnenga MM, et al. . Survival of diffuse astrocytic glioma, IDH1/2-wild type, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria. Neuro Oncol 2020;22:515–23 10.1093/neuonc/noz200] - DOI - PMC - PubMed

[9] van den Bent MJ, Brandes AA, Taphoorn MJ, et al. . Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 2013;31:344–50 10.1200/JCO.2012.43.2229 - DOI - PubMed

[10] van den Bent MJ, Brandes AA, Taphoorn MJ, et al. . Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 2013;31:344–50 10.1200/JCO.2012.43.2229 - DOI - PubMed

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Regional and Volumetric Parameters for Diffusion-Weighted WHO Grade II and III Glioma Genotyping: A Method Comparison

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Regional and Volumetric Parameters for Diffusion-Weighted WHO Grade II and III Glioma Genotyping: A Method Comparison

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