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Transformation of low grade glioma and correlation with outcome: an NCCTG database analysis

  • Clinical Study - Patient Study
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Abstract

Glioblastomas (GBM) may originate de novo (primary), or following transformation from a lower grade glioma (secondary), and it has been postulated that these tumors may have different biological behaviors. We performed a correlative analysis involving 204 patients with glioma treated prospectively on NCCTG clinical trials. Central pathology review of tumor tissues taken at the time of initial diagnosis and at recurrence were performed in all patients. Tumors progressed from low (WHO grade 2) to high (grade 3–4) at recurrence in 45% low grade oligodendroglioma patients, in 70% with low grade oligoastrocytoma, and 74% with low grade astrocytoma (P = 0.031). Median overall survival (OS) from initial diagnosis varied by histology: oligodendroglioma, 8.8 years; (95% CI 5.7–10.2); oligoastrocytoma, 4.4 years (95% CI 3.5–5.6); astrocytoma grade 2 3.1 years (astrocytoma grade 2–4, 2.1 years) (95% CI 1.7–2.5, P < 0.001). Mean time to recurrence (TTR) also varied between patients with de novo GBM, those secondary GBM, and those that remained non-GBM at recurrence (1.1 ± 1.1 vs. 2.9 ± 1.8 vs. 4.0 ± 2.9 years, respectively, P < 0.001). Median OS from time of recurrence also varied between these three categories (0.7 years, 95% CI: 0.5–1.1 vs. 0.6 years, CI: 0.5–1.0 vs. 1.4 years, 95% CI: 1.1–2.0, respectively) (P < 0.001). At time of relapse, transformation to higher grade is frequent in low grade pure and mixed astrocytomas, but is observed in less than half of those with low grade oligodendroglioma. From time of recurrence, OS was not significantly different for those with primary versus secondary GBM, and it may thus be reasonable include patients with secondary GBM in clinical therapeutic trials for recurrent disease.

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References

  1. Wu W, Lamborn KR, Buckner JC, Novotny P, Chang SM, O’Fallon JR, Galanis E, Jaeckle KA, Prados MD (2010) Joint NCCTG and NABTC prognostic factors analysis for high grade recurrent glioma. Neuro Oncol 12(2):164–172

    PubMed  CAS  Google Scholar 

  2. Ohgaki H (2007) Kleihues: genetic pathways to primary and secondary glioblastoma. Am J Path 170:1445–1453

    Article  PubMed  CAS  Google Scholar 

  3. Dropcho EJ, Soong SJ (1996) The prognositic impact of prior low grade histology in patients with anaplastic gliomas: a case-control study. Neurology 47:684–690

    PubMed  CAS  Google Scholar 

  4. Ohgaki H, Dessen P, Jourde B et al (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899

    Article  PubMed  CAS  Google Scholar 

  5. Ohgaki H (2005) Kleihues: population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 64:479–489

    PubMed  CAS  Google Scholar 

  6. Pignatti F, van den Bent M, Curran D, European Organization for Research and Treatment of Cancer Radiotherapy Cooperative Group et al (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084

    Article  PubMed  Google Scholar 

  7. Chang EF, Smith JS, Chang SM et al (2008) Preoperative prognosic classification system for hemispheric low-grade gliomas in adults. J Neurosurg 109:817–824

    Article  PubMed  Google Scholar 

  8. Law M, Oh S, Johnson G et al (2006) Perfusion magnetic resonance imaging predicts patient outcome as an adjunct to histopathology: a second reference standard in the surgical and nonsurgical treatment of low-grade gliomas. Neurosurgery 58:1099–1107

    Article  PubMed  Google Scholar 

  9. Caseiras B, Ciccarelli O, Altmann DR et al (2009) Low-grade gliomas: six-month tumor growth predicts patient outcome better than admission tumor volume, relative cerebral blood volume, and apparent diffusion coefficient. Radiology 253:505–512

    Article  Google Scholar 

  10. Kruer MC, Kaplan AM, Etzl MM Jr et al (2009) The value of positron emission tomography and proliferation index in predicting progression in low-grade astrocytomas of childhood. J Neurooncol 95:239–245

    Article  PubMed  Google Scholar 

  11. Smith JS, Perry A, Borell TJ et al (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas and mixed oligoastrocytomas. J Clin Oncol 18:636–645

    PubMed  CAS  Google Scholar 

  12. Huang Q, Zhang QB, Dong J et al (2008) Glioma stem cells are more aggressive in recurrent tumors with malignant progression than in the de novo tumor, and both can be maintained long-term in vitro. BMC Cancer 8:304

    Article  PubMed  Google Scholar 

  13. Sanai N, Berger MS (2009) Operative techniques for gliomas and the value of extent of resection. Neurotherapeutics 6:478–486

    Article  PubMed  Google Scholar 

  14. Shaw EG, Berkey B, Coons SW et al (2008) Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg 109:835–841

    Article  PubMed  Google Scholar 

  15. Chang EF, Clark A, Jensen RL et al (2009) Multiinstitutional validation of the University of California at San Francisco Low-Grade Glioma Prognostic Scoring System. Clinical article. J Neurosurg 111:203–210

    Article  PubMed  Google Scholar 

  16. Martinez R, Rohde V, Schackert G: Different molecular patterns in glioblastoma multiforme subtypes upon recurrence. J Neurooncol 2009; Jul 31 (epub ahead of print)

  17. Martinez R, Setien F, Voelter C et al (2007) CpG island promoter hypermethylation of the pro-apoptotic gene caspase-8 is a common hallmark of relapsed glioblastoma multiforme. Carcinogenesis 28:1264–1268

    Article  PubMed  CAS  Google Scholar 

  18. Maher EA, Brennan C, Wen PY et al (2006) Marked genomic differences characterize de novo and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. Cancer Res 66:11502–11513

    Article  PubMed  CAS  Google Scholar 

  19. Zheng H, Ying H, Yan H, Kimmelman AC et al (2008) p53 and PTEN control neural and glioma stem/progenitor cell renewal and differentiation. Nature 455:1129–1133

    Article  PubMed  CAS  Google Scholar 

  20. Ruano Y, Ribalta T, de Lope AR et al (2009) Worse outcome in de novo glioblastoma multiforme with concurrent epidermal growth factor receptor and p53 alteration. Am J Clin Pathol 131:257–263

    Article  PubMed  CAS  Google Scholar 

  21. Xie D, Zeng YX, Wang HJ et al (2006) Expression of cytoplasmic and nuclear survivin in de novo and secondary human glioblastoma. Br J Cancer 94:108–114

    Article  PubMed  CAS  Google Scholar 

  22. Somasundaram K, Reddy SP, Vinnakota K et al (2005) Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma. Oncogene 24:7073–7083

    Article  PubMed  CAS  Google Scholar 

  23. Mineo JF, Bordron A, Baroncini M et al (2007) Low HER2-expressing glioblastomas are more often secondary to anaplastic transformation of low-grade glioma. J Neurooncol 85:281–287

    Article  PubMed  Google Scholar 

  24. Nobusawa S, Watanabe T, Kleihues P et al (2009) IDH1 mutations as a molecular signature and predictive factor of secondary glioblastomas. Clin Cancer Res 15:6002–6007

    Article  PubMed  CAS  Google Scholar 

  25. Smith JS, Chang EF, Lamborn KR et al (2008) Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 26:1338–1345

    Article  PubMed  Google Scholar 

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The authors have no relevant conflicts of interest to disclose.

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Authors and Affiliations

  1. Mayo Clinic, Cannaday 2-E, Jacksonville, FL, 32224, USA

    K. A. Jaeckle

  2. Mayo Clinic, Rochester, MN, USA

    P. A. Decker, K. V. Ballman, C. Giannini, B. W. Scheithauer, R. B. Jenkins & J. C. Buckner

  3. Metro MN, St. Louis Park, MN, USA

    P. J. Flynn

Authors
  1. K. A. Jaeckle
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  2. P. A. Decker
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  3. K. V. Ballman
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  4. P. J. Flynn
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  5. C. Giannini
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  6. B. W. Scheithauer
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  7. R. B. Jenkins
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  8. J. C. Buckner
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Correspondence to K. A. Jaeckle.

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Jaeckle, K.A., Decker, P.A., Ballman, K.V. et al. Transformation of low grade glioma and correlation with outcome: an NCCTG database analysis. J Neurooncol 104, 253–259 (2011). https://doi.org/10.1007/s11060-010-0476-2

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  • DOI: https://doi.org/10.1007/s11060-010-0476-2

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