Top

Published in:

01-01-2019 | Clinical Study

Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups

Authors: Tareq A. Juratli, Shilpa S. Tummala, Angelika Riedl, Dirk Daubner, Silke Hennig, Tristan Penson, Amir Zolal, Christian Thiede, Gabriele Schackert, Dietmar Krex, Julie J. Miller, Daniel P. Cahill

Published in: Journal of Neuro-Oncology | Issue 2/2019

Abstract

Purpose

With the updated World Health Organization (WHO) 2016 neuropathological diagnostic criteria, radiographic prognostic associations in lower-grade gliomas (LGG, WHO grade II and III) are undergoing re-evaluation.

Methods

We identified 316 LGG patients (151 grade II and 165 grade III) for a combined cohort from three independent databases. We analyzed the preoperative axial FLAIR, axial T2-weighted and post-gadolinium volumetric T1-weighted MR images. The molecular data collected included the status of IDH1/2, TP53, TERT promoter and ATRX mutations, in addition to 1p/19q co-deletions. In a subset of cases (n = 133), we assessed the “T2-FLAIR mismatch” sign.

Results

Gliomas were assigned to one of the three molecular groups: Group O (IDH-mutant, 1p/19q co-deleted oligodendrogliomas, n = 95), Group A (IDH-mutant, ATRX inactivated astrocytomas, n = 175) and Group G (IDH wild-type, GBM-like, n = 46). A contrast-enhancing tumor was seen in 98 patients (31%), most frequently in Group G (n = 28/45, 57%), when compared to Group A (n = 49/175, 28%) and Group O (n = 24/95, 25.3%) tumors (p = 0.008 and p = 0.0011, respectively). Consistent with previous reports, T2-FLAIR mismatch was preferentially found in Group A tumors (73.1%, 60 of 82), although its presence was not associated with survival, after controlling for molecular group. False positive mismatch sign was noted in 28.5% (12/42) Group O tumors, but none of the tumors in Group G. A combination of all three factors: age under 40 years at first diagnosis, a tumor size larger than 6 cm and T2-FLAIR mismatch was highly specific for IDH mutant astrocytoma (Group A).

Conclusion

We identify radiographic correlates of molecular groups in lower-grade gliomas, which join clinical demographic features in defining the characteristic presentation of these tumors. Radiographic correlates of prognosis in LGG require re-evaluation within molecular group.

Available only for authorised users

Dhermain FG, Hau P, Lanfermann H, Jacobs AH, van den Bent MJ (2010) Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol 9:906–920. https://doi.org/10.1016/S1474-4422(10)70181-2 CrossRefPubMed

Andronesi OC, Loebel F, Bogner W, Marjanska M, Vander Heiden MG, Iafrate AJ, Dietrich J, Batchelor T, Gerstner ER, Kaelin W, Chi AS, Rosen B, Cahill DP (2015) Treatment response assessment in IDH-mutant glioma patients by non-invasive 3D functional spectroscopic mapping of 2-hydroxyglutarate. Clin Cancer Res. https://doi.org/10.1158/1078-0432.CCR-15-0656 CrossRefPubMedPubMedCentral

Pope WB, Prins RM, Albert Thomas M, Nagarajan R, Yen KE, Bittinger MA, Salamon N, Chou AP, Yong WH, Soto H, Wilson N, Driggers E, Jang HG, Su SM, Schenkein DP, Lai A, Cloughesy TF, Kornblum HI, Wu H, Fantin VR, Liau LM (2012) Non-invasive detection of 2-hydroxyglutarate and other metabolites in IDH1 mutant glioma patients using magnetic resonance spectroscopy. J Neurooncol 107:197–205. https://doi.org/10.1007/s11060-011-0737-8 CrossRefPubMed

Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M (2013) Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31:337–343. https://doi.org/10.1200/JCO.2012.43.2674 CrossRefPubMed

Cairncross JG, Wang M, Jenkins RB, Shaw EG, Giannini C, Brachman DG, Buckner JC, Fink KL, Souhami L, Laperriere NJ, Huse JT, Mehta MP, Curran WJ (2014) Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol 32:783–790. https://doi.org/10.1200/JCO.2013.49.3726 CrossRefPubMedPubMedCentral

Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, Coons S, Ricci P, Bullard D, Brown PD, Stelzer K, Brachman D, Suh JH, Schultz CJ, Bahary JP, Fisher BJ, Kim H, Murtha AD, Bell EH, Won M, Mehta MP, Curran WJ (2016) Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 374:1344–1355. https://doi.org/10.1056/NEJMoa1500925 CrossRefPubMedPubMedCentral

Miller JJ, Shih HA, Andronesi OC, Cahill DP (2017) Isocitrate dehydrogenase-mutant glioma: evolving clinical and therapeutic implications. Cancer 123:4535–4546. https://doi.org/10.1002/cncr.31039 CrossRefPubMed

Juratli TA, Lautenschläger T, Geiger KD, Pinzer T, Krause M, Schackert G, Krex D (2015) Radio-chemotherapy improves survival in IDH-mutant, 1p/19q non-codeleted secondary high-grade astrocytoma patients. J Neurooncol. https://doi.org/10.1007/s11060-015-1822-1 CrossRefPubMed

Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV, Sarkar G, Caron AA, Kollmeyer TM, Praska CE, Chada AR, Halder C, Hansen HM, McCoy LS, Bracci PM, Marshall R, Zheng S, Reis GF, Pico AR, O’Neill BP, Buckner JC, Giannini C, Huse JT, Perry A, Tihan T, Berger MS, Chang SM, Prados MD, Wiemels J, Wiencke JK, Wrensch MR, Jenkins RB (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372:2499–2508. https://doi.org/10.1056/NEJMoa1407279 CrossRefPubMedPubMedCentral

10.

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–820. https://doi.org/10.1007/s00401-016-1545-1 CrossRefPubMed

11.

Lai A, Kharbanda S, Pope WB, Tran A, Solis OE, Peale F, Forrest WF, Pujara K, Carrillo JA, Pandita A, Ellingson BM, Bowers CW, Soriano RH, Schmidt NO, Mohan S, Yong WH, Seshagiri S, Modrusan Z, Jiang Z, Aldape KD, Mischel PS, Liau LM, Escovedo CJ, Chen W, Nghiemphu PL, James CD, Prados MD, Westphal M, Lamszus K, Cloughesy T, Phillips HS (2011) Evidence for sequenced molecular evolution of IDH1 mutant glioblastoma from a distinct cell of origin. J Clin Oncol 29:4482–4490. https://doi.org/10.1200/JCO.2010.33.8715 CrossRefPubMedPubMedCentral

12.

van den Bent MJ, Wefel JS, Schiff D, Taphoorn MJ, Jaeckle K, Junck L, Armstrong T, Choucair A, Waldman AD, Gorlia T, Chamberlain M, Baumert BG, Vogelbaum MA, Macdonald DR, Reardon DA, Wen PY, Chang SM, Jacobs AH (2011) Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol 12:583–593. https://doi.org/10.1016/S1470-2045(11)70057-2 CrossRefPubMed

13.

Barker FG, Chang SM, Huhn SL, Davis RL, Gutin PH, McDermott MW, Wilson CB, Prados MD (1997) Age and the risk of anaplasia in magnetic resonance-nonenhancing supratentorial cerebral tumors. Cancer 80:936–941CrossRefPubMed

14.

Ginsberg LE, Fuller GN, Hashmi M, Leeds NE, Schomer DF (1998) The significance of lack of MR contrast enhancement of supratentorial brain tumors in adults: histopathological evaluation of a series. Surg Neurol 49:436–440CrossRefPubMed

15.

Pallud J, Capelle L, Taillandier L, Fontaine D, Mandonnet E, Guillevin R, Bauchet L, Peruzzi P, Laigle-Donadey F, Kujas M, Guyotat J, Baron MH, Mokhtari K, Duffau H (2009) Prognostic significance of imaging contrast enhancement for WHO grade II gliomas. Neuro Oncol 11:176–182. https://doi.org/10.1215/15228517-2008-066 CrossRefPubMedPubMedCentral

16.

Pallud J, Mandonnet E, Duffau H, Kujas M, Guillevin R, Galanaud D, Taillandier L, Capelle L (2006) Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas. Ann Neurol 60:380–383. https://doi.org/10.1002/ana.20946 CrossRefPubMed

17.

Pignatti F, van den Bent M, Curran D, Debruyne C, Sylvester R, Therasse P, Afra D, Cornu P, Bolla M, Vecht C, Karim AB, Group EOfRaToCBTC, Group EOfRaToCRC (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084CrossRefPubMed

18.

Patel SH, Poisson LM, Brat DJ, Zhou Y, Cooper L, Snuderl M, Thomas C, Franceschi AM, Griffith B, Flanders AE, Golfinos JG, Chi AS, Jain R (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. https://doi.org/10.1158/1078-0432.CCR-17-0560 CrossRefPubMed

19.

Broen MPG, Smits M, Wijnenga MMJ, Dubbink HJ, Anten MHME, Schijns OEMG, Beckervordersandforth J, Postma AA, van den Bent MJ (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. https://doi.org/10.1093/neuonc/noy048 CrossRefPubMedPubMedCentral

20.

Zheng Z, Liebers M, Zhelyazkova B, Cao Y, Panditi D, Lynch KD, Chen J, Robinson HE, Shim HS, Chmielecki J, Pao W, Engelman JA, Iafrate AJ, Le LP (2014) Anchored multiplex PCR for targeted next-generation sequencing. Nat Med 20:1479–1484. https://doi.org/10.1038/nm.3729 CrossRefPubMed

21.

Juratli TA, Kirsch M, Robel K, Soucek S, Geiger K, von Kummer R, Schackert G, Krex D (2012) IDH mutations as an early and consistent marker in low-grade astrocytomas WHO grade II and their consecutive secondary high-grade gliomas. J Neurooncol 108:403–410. https://doi.org/10.1007/s11060-012-0844-1 CrossRefPubMed

22.

Capper D, Sahm F, Hartmann C, Meyermann R, von Deimling A, Schittenhelm J (2010) Application of mutant IDH1 antibody to differentiate diffuse glioma from nonneoplastic central nervous system lesions and therapy-induced changes. Am J Surg Pathol 34:1199–1204. https://doi.org/10.1097/PAS.0b013e3181e7740d CrossRefPubMed

23.

Heckman LD, Chahrour MH, Zoghbi HY (2014) Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice. Elife. https://doi.org/10.7554/eLife.02676 CrossRefPubMedPubMedCentral

24.

Shankar GM, Francis JM, Rinne ML, Ramkissoon SH, Huang FW, Venteicher AS, Akama-Garren EH, Kang YJ, Lelic N, Kim JC, Brown LE, Charbonneau SK, Golby AJ, Sekhar Pedamallu C, Hoang MP, Sullivan RJ, Cherniack AD, Garraway LA, Stemmer-Rachamimov A, Reardon DA, Wen PY, Brastianos PK, Curry WT, Barker FG, Hahn WC, Nahed BV, Ligon KL, Louis DN, Cahill DP, Meyerson M (2015) Rapid intraoperative molecular characterization of glioma. JAMA Oncol 1:662–667. https://doi.org/10.1001/jamaoncol.2015.0917 CrossRefPubMedPubMedCentral

25.

Juratli TA, Thiede C, Koerner MVA, Tummala SS, Daubner D, Shankar GM, Williams EA, Martinez-Lage M, Soucek S, Robel K, Penson T, Krause M, Appold S, Meinhardt M, Pinzer T, Miller JJ, Krex D, Ely HA, Silverman IM, Christiansen J, Schackert G, Wakimoto H, Kirsch M, Brastianos PK, Cahill DP (2017) Intratumoral heterogeneity and TERT promoter mutations in progressive/higher-grade meningiomas. Oncotarget 8:109228–109237. https://doi.org/10.18632/oncotarget.22650 CrossRefPubMedPubMedCentral

26.

Woehrer A, Sander P, Haberler C, Kern S, Maier H, Preusser M, Hartmann C, Kros JM, Hainfellner JA, Societies RCotECoN (2011) FISH-based detection of 1p 19q codeletion in oligodendroglial tumors: procedures and protocols for neuropathological practice—a publication under the auspices of the Research Committee of the European Confederation of Neuropathological Societies (Euro-CNS). Clin Neuropathol 30:47–55CrossRefPubMed

27.

Smith JS, Alderete B, Minn Y, Borell TJ, Perry A, Mohapatra G, Hosek SM, Kimmel D, O’Fallon J, Yates A, Feuerstein BG, Burger PC, Scheithauer BW, Jenkins RB (1999) Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene 18:4144–4152. https://doi.org/10.1038/sj.onc.1202759 CrossRefPubMed

28.

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, Von Deimling A (2016) WHO classification of tumours of the central nervous system. Acta Neuropathol. https://doi.org/10.1007/s00401-016-1545-1 CrossRefPubMedPubMedCentral

29.

Wefel JS, Noll KR, Rao G, Cahill DP (2016) Neurocognitive function varies by IDH1 genetic mutation status in patients with malignant glioma prior to surgical resection. Neuro Oncol. https://doi.org/10.1093/neuonc/now165 CrossRefPubMedPubMedCentral

30.

Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, Weinberg J, Lang FF, Aldape KD, Sulman EP, Rao G, McCutcheon IE, Cahill DP (2014) IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol 16:81–91. https://doi.org/10.1093/neuonc/not159 CrossRefPubMed

31.

Wijnenga MMJ, French PJ, Dubbink HJ, Dinjens WNM, Atmodimedjo PN, Kros JM, Smits M, Gahrmann R, Rutten GJ, Verheul JB, Fleischeuer R, Dirven CMF, Vincent AJPE, van den Bent MJ (2018) The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis. Neuro Oncol 20:103–112. https://doi.org/10.1093/neuonc/nox176 CrossRefPubMed

32.

Gutman DA, Cooper LA, Hwang SN, Holder CA, Gao J, Aurora TD, Dunn WD, Scarpace L, Mikkelsen T, Jain R, Wintermark M, Jilwan M, Raghavan P, Huang E, Clifford RJ, Mongkolwat P, Kleper V, Freymann J, Kirby J, Zinn PO, Moreno CS, Jaffe C, Colen R, Rubin DL, Saltz J, Flanders A, Brat DJ (2013) MR imaging predictors of molecular profile and survival: multi-institutional study of the TCGA glioblastoma data set. Radiology 267:560–569. https://doi.org/10.1148/radiol.13120118 CrossRefPubMedPubMedCentral

33.

Hempel JM, Brendle C, Bender B, Bier G, Skardelly M, Gepfner-Tuma I, Eckert F, Ernemann U, Schittenhelm J (2018) Contrast enhancement predicting survival in integrated molecular subtypes of diffuse glioma: an observational cohort study. J Neurooncol. https://doi.org/10.1007/s11060-018-2872-y CrossRefPubMed

34.

Reuss DE, Mamatjan Y, Schrimpf D, Capper D, Hovestadt V, Kratz A, Sahm F, Koelsche C, Korshunov A, Olar A, Hartmann C, Reijneveld JC, Wesseling P, Unterberg A, Platten M, Wick W, Herold-Mende C, Aldape K, von Deimling A (2015) IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. Acta Neuropathol 129:867–873. https://doi.org/10.1007/s00401-015-1438-8 CrossRefPubMedPubMedCentral

35.

Olar A, Wani KM, Alfaro-Munoz KD, Heathcock LE, van Thuijl HF, Gilbert MR, Armstrong TS, Sulman EP, Cahill DP, Vera-Bolanos E, Yuan Y, Reijneveld JC, Ylstra B, Wesseling P, Aldape KD (2015) IDH mutation status and role of WHO grade and mitotic index in overall survival in grade II-III diffuse gliomas. Acta Neuropathol 129:585–596. https://doi.org/10.1007/s00401-015-1398-z CrossRefPubMedPubMedCentral

36.

Wu CC, Jain R, Radmanesh A, Poisson LM, Guo WY, Zagzag D, Snuderl M, Placantonakis DG, Golfinos J, Chi AS (2018) Predicting genotype and survival in glioma using standard clinical MR imaging apparent diffusion coefficient images: a pilot study from the cancer genome atlas. AJNR Am J Neuroradiol. https://doi.org/10.3174/ajnr.A5794 CrossRefPubMedPubMedCentral

Title: Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups
Authors: Tareq A. Juratli
Shilpa S. Tummala
Angelika Riedl
Dirk Daubner
Silke Hennig
Tristan Penson
Amir Zolal
Christian Thiede
Gabriele Schackert
Dietmar Krex
Julie J. Miller
Daniel P. Cahill
Publication date: 01-01-2019
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-03034-6

At a glance: The STEP trials

Springer Medicine

Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2019

Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma

Correction to: Volumetric response of progressing post-SRS lesions treated with laser interstitial thermal therapy

Incidentally found brain tumors in the pediatric population: a case series and proposed treatment algorithm

The consistency of neuropathological diagnoses in patients undergoing surgery for suspected recurrence of glioblastoma

Histopathologic quantification of viable tumor versus treatment effect in surgically resected recurrent glioblastoma

Paraneoplastic neurological syndromes: a single institution 10-year case series