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Radiogenomic association between the T2-FLAIR mismatch sign and IDH mutation status in adult patients with lower-grade gliomas: an updated systematic review and meta-analysis

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Abstract

Objectives

To reveal a radiogenomic correlation between the presence of the T2-fluid-attenuated inversion recovery resection (T2-FLAIR) mismatch sign on MR images and isocitrate dehydrogenase (IDH) mutation status in adult patients with lower-grade gliomas (LGGs).

Methods

A web-based systemic search for eligible literature up to April 13, 2021, was conducted on PubMed, Embase, and the Cochrane Library databases by two independent reviewers. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We included studies evaluating the accuracy of the T2-FLAIR mismatch sign in diagnosing the IDH mutation in adult patients with LGGs. The T2-FLAIR mismatch sign was defined as a T2-hyperintense lesion that is hypointense on FLAIR except for a hyperintense rim.

Results

Fourteen studies (n = 1986) were finally identified. The mean age of patients in the included studies ranged from 38.5 to 56 years. The pooled area under the curve (AUC), sensitivity, and specificity were obtained for each molecular profile: IDHmut-Codel: 0.46 (95% confidence interval [CI]: 0.42–0.50), 1% (95%CI: 0–7%), and 69% (95%CI: 62–75%), respectively; IDHmut-Noncodel: 0.75 (95%CI: 0.71–0.79), 42% (95%CI: 34–50%), and 99% (95%CI: 96–100%), respectively; IDH-Mutation regardless of 1p/19q codeletion status: 0.77 (95%CI: 0.73–0.80), 29% (95%CI: 21–40%), and 99% (95%CI: 92–100%), respectively.

Conclusions

The T2-FLAIR mismatch sign was an insensitive but highly specific marker for IDHmut-Noncodel and IDH-Mutation LGGs, whereas it was not a useful marker for IDHmut-Codel LGGs. The findings might identify the T2-FLAIR mismatch sign as a non-invasive imaging biomarker for the selection of patients with IDH-mutant LGGs.

Key Points

• The T2-FLAIR mismatch sign was not a sensitive sign for IDH mutation in LGGs.

• The T2-FLAIR mismatch sign was related to IDHmut-Noncodel with a specificity of 99%.

• The pooled specificity (69%) of the T2-FLAIR mismatch sign for IDHmut-Codel was low.

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Abbreviations

AUC:

Area under the curve

CI:

Confidence interval

IDH:

Isocitrate dehydrogenase

IDHmut-Codel:

IDH-mutant, 1p/19q-codeleted

IDHmut-Noncodel:

IDH-mutant, 1p/19q-noncodeleted

IDHwt:

IDH wild-type

LGGs:

Lower-grade gliomas

MRI:

Magnetic resonance imaging

T2-FLAIR:

T2-fluid-attenuated inversion recovery

T2WI:

T2-weighted imaging

References

  1. Louis DN, Perry A, Reifenberger G et al (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820

    Article  Google Scholar 

  2. van den Bent MJ, Smits M, Kros JM, Chang SM (2017) Diffuse infiltrating oligodendroglioma and astrocytoma. J Clin Oncol 35:2394–2401

    Article  Google Scholar 

  3. Kawaguchi T, Sonoda Y, Shibahara I et al (2016) Impact of gross total resection in patients with WHO grade III glioma harboring the IDH 1/2 mutation without the 1p/19q co-deletion. J Neurooncol 129:505–514

    Article  CAS  Google Scholar 

  4. Cairncross G, Wang M, Shaw E et al (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31:337–343

    Article  CAS  Google Scholar 

  5. Intergroup Radiation Therapy Oncology Group Trial 9402, Cairncross G, Berkey B et al (2006) Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol 24:2707–2714

  6. Foltyn M, Nieto Taborda KN, Neuberger U et al (2020) T2/FLAIR-mismatch sign for noninvasive detection of IDH-mutant 1p/19q non-codeleted gliomas: validity and pathophysiology. Neurooncol Adv 2:vdaa004

  7. Jain R, Johnson DR, Patel SH et al (2020) “Real world” use of a highly reliable imaging sign: “T2-FLAIR mismatch” for identification of IDH mutant astrocytomas. Neuro Oncol 22:936–943

    Article  CAS  Google Scholar 

  8. Aliotta E, Dutta SW, Feng X et al (2020) Automated apparent diffusion coefficient analysis for genotype prediction in lower grade glioma: association with the T2-FLAIR mismatch sign. J Neurooncol 149:325–335

    Article  CAS  Google Scholar 

  9. Batchala PP, Muttikkal TJE, Donahue JH et al (2019) Neuroimaging-based classification algorithm for predicting 1p/19q-codeletion status in IDH-mutant lower grade gliomas. AJNR Am J Neuroradiol 40:426–432

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Broen MPG, Smits M, Wijnenga MMJ et al (2018) The T2-FLAIR mismatch sign as an imaging marker for non-enhancing IDH-mutant, 1p/19q-intact lower-grade glioma: a validation study. Neuro Oncol 20:1393–1399

    Article  CAS  Google Scholar 

  11. Kinoshita M, Arita H, Takahashi M et al (2020) Impact of inversion time for FLAIR acquisition on the T2-FLAIR mismatch detectability for IDH-mutant, non-CODEL astrocytomas. Front Oncol 10:596448

    Article  Google Scholar 

  12. Kinoshita M, Uchikoshi M, Sakai M, Kanemura Y, Kishima H, Nakanishi K (2021) T2-FLAIR mismatch sign is caused by long T1 and T2 of IDH-mutant, 1p19q non-codeleted astrocytoma. Magn Reson Med Sci 20:119–123

    Article  CAS  Google Scholar 

  13. Lasocki A, Gaillard F, Gorelik A, Gonzales M (2018) MRI features can predict 1p/19q status in intracranial gliomas. AJNR Am J Neuroradiol 39:687–692

    Article  CAS  Google Scholar 

  14. Patel SH, Poisson LM, Brat DJ et al (2017) T2-FLAIR mismatch, an imaging biomarker for IDH and 1p/19q status in lower-grade gliomas: a TCGA/TCIA Project. Clin Cancer Res 23:6078–6085

    Article  CAS  Google Scholar 

  15. Throckmorton P, Graber JJ (2020) T2-FLAIR mismatch in isocitrate dehydrogenase mutant astrocytomas: variability and evolution. Neurology 95:e1582–e1589

    Article  CAS  Google Scholar 

  16. Yang X, Lin Y, Xing Z, She D, Su Y, Cao D (2020) Predicting 1p/19q codeletion status using diffusion-, susceptibility-, perfusion-weighted, and conventional MRI in IDH-mutant lower-grade gliomas. Acta Radiol:284185120973624

  17. Maynard J, Okuchi S, Wastling S et al (2020) World Health Organization Grade II/III glioma molecular status: prediction by MRI morphologic features and apparent diffusion coefficient. Radiology 296:111–121

    Article  Google Scholar 

  18. Deguchi S, Oishi T, Mitsuya K et al (2020) Clinicopathological analysis of T2-FLAIR mismatch sign in lower-grade gliomas. Sci Rep 10:10113

    Article  CAS  Google Scholar 

  19. Juratli TA, Tummala SS, Riedl A et al (2019) Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups. J Neurooncol 141:327–335

    Article  CAS  Google Scholar 

  20. Lee MK, Park JE, Jo Y, Park SY, Kim SJ, Kim HS (2020) Advanced imaging parameters improve the prediction of diffuse lower-grade gliomas subtype, IDH mutant with no 1p19q codeletion: added value to the T2/FLAIR mismatch sign. Eur Radiol 30:844–854

    Article  CAS  Google Scholar 

  21. Johnson DR, Kaufmann TJ, Patel SH, Chi AS, Snuderl M, Jain R (2019) There is an exception to every rule-T2-FLAIR mismatch sign in gliomas. Neuroradiology 61:225–227

    Article  Google Scholar 

  22. Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

    Article  Google Scholar 

  23. Whiting PF, Rutjes AW, Westwood ME et al (2011) QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 155:529–536

  24. Deeks JJ, Macaskill P, Irwig L (2005) The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J Clin Epidemiol 58:882–893

    Article  Google Scholar 

  25. Hoaglin DC (2016) Misunderstandings about Q and ‘Cochran’s Q test’ in meta-analysis. Stat Med 35:485–495

    Article  Google Scholar 

  26. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  Google Scholar 

  27. Devillé WL, Buntinx F, Bouter LM et al (2002) Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol 2:9

  28. Hellmich M, Lehmacher W (2005) A ruler for interpreting diagnostic test results. Methods Inf Med 44:124–126

  29. Corell A, Ferreyra Vega S, Hoefling N et al (2020) The clinical significance of the T2-FLAIR mismatch sign in grade II and III gliomas: a population-based study. BMC Cancer 20:450

    Article  CAS  Google Scholar 

  30. Fujita Y, Nagashima H, Tanaka K et al (2021) The Histopathologic and Radiologic Features of T2-FLAIR Mismatch Sign in IDH-Mutant 1p/19q Non-codeleted Astrocytomas. World Neurosurg 149:e253–e260

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Funding

This work received funding from the National Natural Science Foundation of China (81871323 and 81801665); National Natural Science Foundation of Guangdong Province (2018B030311024); Scientific Research Cultivation and Innovation Foundation of Jinan University (21620447). The funders had no role in study design, data collection, and analysis, preparation of the manuscript, or decision to publish.

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Author notes

  1. Ziqin Han and Qiuying Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, the First Affiliated Hospital, Jinan University, No.613, Huangpu West Road, Tianhe District, Guangzhou, Guangdong, People’s Republic of China

    Ziqin Han, Qiuying Chen, Lu Zhang, Xiaokai Mo, Jingjing You, Luyan Chen, Jin Fang, Fei Wang, Zhe Jin, Shuixing Zhang & Bin Zhang

  2. Graduate College, Jinan University, Guangzhou, Guangdong, People’s Republic of China

    Ziqin Han, Qiuying Chen, Lu Zhang, Jingjing You, Luyan Chen & Zhe Jin

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  1. Ziqin Han
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Corresponding authors

Correspondence to Shuixing Zhang or Bin Zhang.

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Ethical approval

Institutional Review Board of the First Affiliated Hospital of Jinan University approved this meta-analysis.

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Written informed consent was waived by the Institutional Review Board.

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The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

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The scientific guarantor of this publication is Shuixing Zhang.

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Han, Z., Chen, Q., Zhang, L. et al. Radiogenomic association between the T2-FLAIR mismatch sign and IDH mutation status in adult patients with lower-grade gliomas: an updated systematic review and meta-analysis. Eur Radiol 32, 5339–5352 (2022). https://doi.org/10.1007/s00330-022-08607-8

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  • DOI: https://doi.org/10.1007/s00330-022-08607-8

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