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17.02.2022 | Clinical Study

The survival outcomes of molecular glioblastoma IDH-wildtype: a multicenter study

verfasst von: Andres Ramos-Fresnedo, Michael W. Pullen, Carlos Perez-Vega, Ricardo A. Domingo, Oluwaseun O. Akinduro, Joao P. Almeida, Paola Suarez-Meade, Lina Marenco-Hillembrand, Mark E. Jentoft, Bernard R. Bendok, Daniel M. Trifiletti, Kaisorn L. Chaichana, Alyx B. Porter, Alfredo Quiñones-Hinojosa, Terence C. Burns, Sani H. Kizilbash, Erik H. Middlebrooks, Wendy J. Sherman

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2022

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Abstract

Purpose

Histological diagnosis of glioblastoma (GBM) was determined by the presence of necrosis or microvascular proliferation (histGBM). The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/− 10 copy changes. The objective of this study was to explore and compare the survival outcomes between histGBM and molGBM.

Methods

Medical records for patients diagnosed with GBM at the three tertiary care academic centers of our institution from November 2017 to October 2021. Only patients who underwent adjuvant chemoradiation were included. Patients without molecular feature testing or with an IDH mutation were excluded. Univariable and multivariable analyses were performed to evaluate progression-free (PFS) and overall- survival (OS).

Results

708 consecutive patients were included; 643 with histGBM and 65 with molGBM. Median PFS was 8 months (histGBM) and 13 months (molGBM) (p = 0.0237) and median OS was 21 months (histGBM) versus 26 months (molGBM) (p = 0.435). Multivariable analysis on the molGBM sub-group showed a worse PFS if there was contrast enhancement on MRI (HR 6.224 [CI 95% 2.187–17.714], p < 0.001) and a superior PFS on patients with MGMT methylation (HR 0.026 [CI 95% 0.065–0.655], p = 0.007).

Conclusions

molGBM has a similar OS but significantly longer PFS when compared to histGBM. The presence of contrast enhancement and MGMT methylation seem to affect the clinical behavior of this subset of tumors.

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Aibaidula A, Chan AK, Shi Z, Li Y, Zhang R, Yang R, Li KK, Chung NY, Yao Y, Zhou L, Wu J, Chen H, Ng HK (2017) Adult IDH wild-type lower-grade gliomas should be further stratified. Neuro Oncol 19:1327–1337. https://doi.org/10.1093/neuonc/nox078CrossRefPubMedPubMedCentral

Aoki K, Nakamura H, Suzuki H, Matsuo K, Kataoka K, Shimamura T, Motomura K, Ohka F, Shiina S, Yamamoto T, Nagata Y, Yoshizato T, Mizoguchi M, Abe T, Momii Y, Muragaki Y, Watanabe R, Ito I, Sanada M, Yajima H, Morita N, Takeuchi I, Miyano S, Wakabayashi T, Ogawa S, Natsume A (2018) Prognostic relevance of genetic alterations in diffuse lower-grade gliomas. Neuro Oncol 20:66–77. https://doi.org/10.1093/neuonc/nox132CrossRefPubMed

Hirose Y, Sasaki H, Abe M, Hattori N, Adachi K, Nishiyama Y, Nagahisa S, Hayashi T, Hasegawa M, Yoshida K (2013) Subgrouping of gliomas on the basis of genetic profiles. Brain Tumor Pathol 30:203–208. https://doi.org/10.1007/s10014-013-0148-yCrossRefPubMed

Reuss DE, Kratz A, Sahm F, Capper D, Schrimpf D, Koelsche C, Hovestadt V, Bewerunge-Hudler M, Jones DTW, Schittenhelm J, Mittelbronn M, Rushing E, Simon M, Westphal M, Unterberg A, Platten M, Paulus W, Reifenberger G, Tonn J-C, Aldape K, Pfister SM, Korshunov A, Weller M, Herold-Mende C, Wick W, Brandner S, von Deimling A (2015) Adult IDH wild type astrocytomas biologically and clinically resolve into other tumor entities. Acta Neuropathol 130:407–417. https://doi.org/10.1007/s00401-015-1454-8CrossRefPubMed

Stichel D, Ebrahimi A, Reuss D, Schrimpf D, Ono T, Shirahata M, Reifenberger G, Weller M, Hänggi D, Wick W, Herold-Mende C, Westphal M, Brandner S, Pfister SM, Capper D, Sahm F, von Deimling A (2018) 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 IDHwt astrocytoma to glioblastoma. Acta Neuropathol 136:793–803. https://doi.org/10.1007/s00401-018-1905-0CrossRefPubMed

Brat DJ, Aldape K, Colman H, Holland EC, Louis DN, Jenkins RB, Kleinschmidt-DeMasters BK, Perry A, Reifenberger G, Stupp R, von Deimling A, Weller M (2018) cIMPACT-NOW update 3: recommended diagnostic criteria for “Diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV.” Acta Neuropathol 136:805–810. https://doi.org/10.1007/s00401-018-1913-0CrossRefPubMedPubMedCentral

Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW (2021) The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol 23:1231–1251. https://doi.org/10.1093/neuonc/noab106CrossRefPubMed

Cancer Genome Atlas Research Network (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372:2481–2498. https://doi.org/10.1056/NEJMoa1402121CrossRef

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/NEJMoa1407279CrossRefPubMedPubMedCentral

10.

Lee D, Riestenberg RA, Haskell-Mendoza A, Bloch O (2021) Diffuse astrocytic glioma, IDH-Wildtype, with molecular features of glioblastoma, WHO grade IV: a single-institution case series and review. J Neurooncol 152:89–98. https://doi.org/10.1007/s11060-020-03677-4CrossRefPubMed

11.

Wijnenga MMJ, Dubbink HJ, French PJ, Synhaeve NE, Dinjens WNM, Atmodimedjo PN, Kros JM, Dirven CMF, Vincent AJPE, van den Bent MJ (2017) Molecular and clinical heterogeneity of adult diffuse low-grade IDH wild-type gliomas: assessment of TERT promoter mutation and chromosome 7 and 10 copy number status allows superior prognostic stratification. Acta Neuropathol 134:957–959. https://doi.org/10.1007/s00401-017-1781-zCrossRefPubMed

12.

Tesileanu CMS, Dirven L, Wijnenga MMJ, Koekkoek JAF, Vincent AJPE, Dubbink HJ, Atmodimedjo PN, Kros JM, van Duinen SG, Smits M, Taphoorn MJB, French PJ, van den Bent MJ (2019) Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria. Neuro Oncol 22:515–523. https://doi.org/10.1093/neuonc/noz200CrossRefPubMedCentral

13.

Morshed RA, Han SJ, Hervey-Jumper SL, Pekmezci M, Troncon I, Chang SM, Butowski NA, Berger MS (2019) Molecular features and clinical outcomes in surgically treated low-grade diffuse gliomas in patients over the age of 60. J Neurooncol 141:383–391. https://doi.org/10.1007/s11060-018-03044-4CrossRefPubMed

14.

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330CrossRefPubMed

15.

Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu J-J, Stragliotto G, Tran DD, Brem S, Hottinger AF, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim C-Y, Paek S-H, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z (2017) Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 318:2306–2316. https://doi.org/10.1001/jama.2017.18718CrossRefPubMedPubMedCentral

16.

Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ (2017) Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med 377:1954–1963. https://doi.org/10.1056/NEJMoa1707358CrossRefPubMed

17.

Herrlinger U, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Sabel M, Hau P, Kortmann RD, Krex D, Grauer O, Goldbrunner R, Schnell O, Bähr O, Uhl M, Seidel C, Tabatabai G, Kowalski T, Ringel F, Schmidt-Graf F, Suchorska B, Brehmer S, Weyerbrock A, Renovanz M, Bullinger L, Galldiks N, Vajkoczy P, Misch M, Vatter H, Stuplich M, Schäfer N, Kebir S, Weller J, Schaub C, Stummer W, Tonn JC, Simon M, Keil VC, Nelles M, Urbach H, Coenen M, Wick W, Weller M, Fimmers R, Schmid M, Hattingen E, Pietsch T, Coch C, Glas M (2019) Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet 393:678–688. https://doi.org/10.1016/s0140-6736(18)31791-4CrossRefPubMed

18.

McGirt MJ, Than KD, Weingart JD, Chaichana KL, Attenello FJ, Olivi A, Laterra J, Kleinberg LR, Grossman SA, Brem H, Quiñones-Hinojosa A (2009) Gliadel (BCNU) wafer plus concomitant temozolomide therapy after primary resection of glioblastoma multiforme. J Neurosurg 110:583–588. https://doi.org/10.3171/2008.5.17557CrossRefPubMedPubMedCentral

19.

Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972. https://doi.org/10.1200/jco.2009.26.3541CrossRefPubMed

20.

Pope WB, Hessel C (2011) Response assessment in neuro-oncology criteria: implementation challenges in multicenter neuro-oncology trials. AJNR Am J Neuroradiol 32:794–797. https://doi.org/10.3174/ajnr.A2582CrossRefPubMedPubMedCentral

21.

Hegi ME, Diserens A-C, Gorlia T, Hamou M-F, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JEC, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003. https://doi.org/10.1056/NEJMoa043331CrossRefPubMed

22.

Ripari LB, Norton ES, Bodoque-Villar R, Jeanneret S, Lara-Velazquez M, Carrano A, Zarco N, Vazquez-Ramos CA, Quiñones-Hinojosa A, de la Rosa-Prieto C, Guerrero-Cázares H (2021) Glioblastoma proximity to the lateral ventricle alters neurogenic cell populations of the subventricular zone. Front Oncol. https://doi.org/10.3389/fonc.2021.650316CrossRefPubMedPubMedCentral

23.

Chaichana KL, McGirt MJ, Frazier J, Attenello F, Guerrero-Cazares H, Quinones-Hinojosa A (2008) Relationship of glioblastoma multiforme to the lateral ventricles predicts survival following tumor resection. J Neurooncol 89:219–224. https://doi.org/10.1007/s11060-008-9609-2CrossRefPubMed

24.

Lim DA, Cha S, Mayo MC, Chen M-H, Keles E, VandenBerg S, Berger MS (2007) Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol 9:424–429. https://doi.org/10.1215/15228517-2007-023CrossRefPubMedPubMedCentral

25.

Mistry AM, Hale AT, Chambless LB, Weaver KD, Thompson RC, Ihrie RA (2017) Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis. J Neurooncol 131:125–133CrossRef

26.

Kim KH, Yoo J, Kim N, Moon JH, Byun HK, Kang SG, Chang JH, Yoon HI, Suh CO (2021) Efficacy of whole-ventricular radiotherapy in patients undergoing maximal tumor resection for glioblastomas involving the ventricle. Front Oncol 11:736482. https://doi.org/10.3389/fonc.2021.736482CrossRefPubMedPubMedCentral

27.

Chen L, Guerrero-Cazares H, Ye X, Ford E, McNutt T, Kleinberg L, Lim M, Chaichana K, Quinones-Hinojosa A, Redmond K (2013) Increased subventricular zone radiation dose correlates with survival in glioblastoma patients after gross total resection. Int J Radiat Oncol Biol Phys 86:616–622CrossRef

28.

Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, Raza SM, Pascual-Gallego M, Ibrahim A, Hernandez-Hermann M, Gomez L, Ye X, Weingart JD, Olivi A, Blakeley J, Gallia GL, Lim M, Brem H, Quinones-Hinojosa A (2014) Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol 16:113–122. https://doi.org/10.1093/neuonc/not137CrossRefPubMed

29.

Chaichana KL, Cabrera-Aldana EE, Jusue-Torres I, Wijesekera O, Olivi A, Rahman M, Quinones-Hinojosa A (2014) When gross total resection of a glioblastoma is possible, how much resection should be achieved? World Neurosurg 82:e257-265. https://doi.org/10.1016/j.wneu.2014.01.019CrossRefPubMed

30.

Vivas-Buitrago T, Domingo RA, Tripathi S, De Biase G, Brown D, Akinduro OO, Ramos-Fresnedo A, Sabsevitz DS, Bendok BR, Sherman W, Parney IF, Jentoft ME, Middlebrooks EH, Meyer FB, Chaichana KL, Quinones-Hinojosa A (2021) Influence of supramarginal resection on survival outcomes after gross-total resection of IDH-wild-type glioblastoma. J Neurosurg. https://doi.org/10.3171/2020.10.Jns203366CrossRefPubMed

31.

Tripathi S, Vivas-Buitrago T, Domingo RA, Biase G, Brown D, Akinduro OO, Ramos-Fresnedo A, Sherman W, Gupta V, Middlebrooks EH, Sabsevitz DS, Porter AB, Uhm JH, Bendok BR, Parney I, Meyer FB, Chaichana KL, Swanson KR, Quiñones-Hinojosa A (2021) IDH-wild-type glioblastoma cell density and infiltration distribution influence on supramarginal resection and its impact on overall survival: a mathematical model. J Neurosurg. https://doi.org/10.3171/2021.6.Jns21925CrossRefPubMed

32.

Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198. https://doi.org/10.3171/jns.2001.95.2.0190CrossRefPubMed

33.

Chaichana KL, Garzon-Muvdi T, Parker S, Weingart JD, Olivi A, Bennett R, Brem H, Quiñones-Hinojosa A (2011) Supratentorial glioblastoma multiforme: the role of surgical resection versus biopsy among older patients. Ann Surg Oncol 18:239–245. https://doi.org/10.1245/s10434-010-1242-6CrossRefPubMed

34.

Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS (2011) An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 115:3–8. https://doi.org/10.3171/2011.2.jns10998CrossRefPubMed

35.

Parker NR, Khong P, Parkinson JF, Howell VM, Wheeler HR (2015) Molecular heterogeneity in glioblastoma: potential clinical implications. Front Oncol. https://doi.org/10.3389/fonc.2015.00055CrossRefPubMedPubMedCentral

Titel: The survival outcomes of molecular glioblastoma IDH-wildtype: a multicenter study
verfasst von: Andres Ramos-Fresnedo
Michael W. Pullen
Carlos Perez-Vega
Ricardo A. Domingo
Oluwaseun O. Akinduro
Joao P. Almeida
Paola Suarez-Meade
Lina Marenco-Hillembrand
Mark E. Jentoft
Bernard R. Bendok
Daniel M. Trifiletti
Kaisorn L. Chaichana
Alyx B. Porter
Alfredo Quiñones-Hinojosa
Terence C. Burns
Sani H. Kizilbash
Erik H. Middlebrooks
Wendy J. Sherman
Publikationsdatum: 17.02.2022
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 1/2022
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-022-03960-6

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