Skip to main content

Advertisement

SpringerLink
Log in

Histopathological correlates with survival in reoperated glioblastomas

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The addition of concomitant and adjuvant chemotherapy to radiation therapy after surgical resection has increased significantly the survival of patients with glioblastoma (GB). In conjunction, there has been an increasing fraction of patients who present with new enlarged areas of contrast enhancement and edema on post-treatment imaging that improve without further treatment. It remains to be established how this phenomenon, commonly termed pseudoprogression, can be distinguished from true tumor recurrence defined as the histological presence of active high-grade tumor, as well as its prognostic significance. Data for over 500 patients undergoing surgery for recurrent GB were reviewed. Pathological specimens were categorized as those that contained active high-grade glioma in any amount, and those that did not. Patient survival was compared between these two groups, and independent associations were assessed using Cox proportionate hazards regression analysis. 59 patients met the study criteria including complete pathological and follow-up data. Mean age was 53 ± 11 years. Median survival from suspected recurrence and initial diagnosis were 8 [5–14] and 20 [12–30] months. Seventeen patients (29 %) had no evidence of active high-grade tumor and 42 (71 %) had at least focal active high-grade glioma. Pathologic pseudoprogression at re-operation (p = 0.03) and gross total resection (p = 0.01) were independently associated with survival. The histopathological features defined here and used to assess the tumor at reoperation were independently associated with survival. These findings may be important in designing treatment strategies and clinical trial endpoints for patients with GB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996

    Article  PubMed  CAS  Google Scholar 

  2. de Wit MC, de Bruin HG, Eijkenboom W, Sillevis Smitt PA, van den Bent MJ (2004) Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression. Neurology 63(3):535–537

    Article  PubMed  Google Scholar 

  3. Chamberlain MC, Glantz MJ, Chalmers L, Van Horn A, Sloan AE (2007) Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. J Neurooncol 82(1):81–83

    Article  PubMed  Google Scholar 

  4. Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9(5):453–461

    Article  PubMed  Google Scholar 

  5. Chaskis C, Neyns B, Michotte A, De Ridder M, Everaert H (2009) Pseudoprogression after radiotherapy with concurrent temozolomide for high-grade glioma: clinical observations and working recommendations. Surg Neurol 72(4):423–428

    Article  PubMed  Google Scholar 

  6. Pouleau HB, Sadeghi N, Baleriaux D, Melot C, De Witte O, Lefranc F (2012) High levels of cellular proliferation predict pseudoprogression in glioblastoma patients. Int J Oncol 40(4):923–928

    PubMed  Google Scholar 

  7. Young RJ, Gupta A, Shah AD, Graber JJ, Zhang Z, Shi W et al (2011) Potential utility of conventional MRI signs in diagnosing pseudoprogression in glioblastoma. Neurology 76(22):1918–1924

    Article  PubMed  CAS  Google Scholar 

  8. Hu X, Wong KK, Young GS, Guo L, Wong ST (2011) Support vector machine multiparametric MRI identification of pseudoprogression from tumor recurrence in patients with resected glioblastoma. J Magn Reson Imaging 33(2):296–305

    Article  PubMed  Google Scholar 

  9. Gunjur A, Lau E, Taouk Y, Ryan G (2011) Early post-treatment pseudo-progression amongst glioblastoma multiforme patients treated with radiotherapy and temozolomide: a retrospective analysis. J Med Imaging Radiat Oncol 55(6):603–610

    Article  PubMed  Google Scholar 

  10. Gahramanov S, Raslan AM, Muldoon LL, Hamilton BE, Rooney WD, Varallyay CG et al (2011) Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: a pilot study. Int J Radiat Oncol Biol Phys 79(2):514–523

    Article  PubMed  Google Scholar 

  11. Forsyth PA, Kelly PJ, Cascino TL, Scheithauer BW, Shaw EG, Dinapoli RP et al (1995) Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful? J Neurosurg 82(3):436–444

    Article  PubMed  CAS  Google Scholar 

  12. Topkan E, Topuk S, Oymak E, Parlak C, Pehlivan B (2012) Pseudoprogression in patients with glioblastoma multiforme after concurrent radiotherapy and temozolomide. Am J Clin Oncol 35(3):284–289

    Google Scholar 

  13. Bland JM, Altman DG (1998) Survival probabilities (the Kaplan–Meier method). BMJ 317(7172):1572

    Article  PubMed  CAS  Google Scholar 

  14. Stel VS, Dekker FW, Tripepi G, Zoccali C, Jager KJ (2011) Survival analysis I: the Kaplan–Meier method. Nephron Clin Pract 119(1):c83–c88

    Article  PubMed  Google Scholar 

  15. Hart MG, Grant R, Garside R, Rogers G, Somerville M, Stein K (2008) Chemotherapeutic wafers for high grade glioma. Cochrane Database Syst Rev 16(3):CD007294

    Google Scholar 

  16. Perry J, Chambers A, Spithoff K, Laperriere N (2007) Gliadel wafers in the treatment of malignant glioma: a systematic review. Curr Oncol 14(5):189–194

    Article  PubMed  CAS  Google Scholar 

  17. Taal W, Brandsma D, de Bruin HG, Bromberg JE, Swaak-Kragten AT, Smitt PA et al (2008) Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 113(2):405–410

    Article  PubMed  CAS  Google Scholar 

  18. Chamberlain MC (2008) Pseudoprogression in glioblastoma. J Clin Oncol 26(26):4359 (author reply 4359–4360)

  19. Sanghera P, Perry J, Sahgal A, Symons S, Aviv R, Morrison M et al (2010) Pseudoprogression following chemoradiotherapy for glioblastoma multiforme. Can J Neurol Sci 37(1):36–42

    PubMed  Google Scholar 

  20. Yaman E, Buyukberber S, Benekli M, Oner Y, Coskun U, Akmansu M et al (2010) Radiation induced early necrosis in patients with malignant gliomas receiving temozolomide. Clin Neurol Neurosurg 112(8):662–667

    Article  PubMed  Google Scholar 

  21. Yang I, Huh NG, Smith ZA, Han SJ, Parsa AT (2010) Distinguishing glioma recurrence from treatment effect after radiochemotherapy and immunotherapy. Neurosurg Clin N Am 21(1):181–186

    Article  PubMed  CAS  Google Scholar 

  22. Brandes AA, Tosoni A, Spagnolli F, Frezza G, Leonardi M, Calbucci F et al (2008) Disease progression or pseudoprogression after concomitant radiochemotherapy treatment: pitfalls in neurooncology. Neuro Oncol 10(3):361–367

    Article  PubMed  Google Scholar 

  23. Zhou J, Blakeley JO, Hua J, Kim M, Laterra J, Pomper MG et al (2008) Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging. Magn Reson Med 60(4):842–849

    Article  PubMed  Google Scholar 

  24. Sanghera P, Perry J, Sahgal A, Symons S, Aviv R, Morrison M et al (2010) Pseudoprogression following chemoradiotherapy for glioblastoma multiforme. Can J Neurol Sci 37(1):36–42

    Google Scholar 

  25. Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G et al (2008) MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 26(13):2192–2197

    Article  PubMed  Google Scholar 

  26. Ozdemir N, Celkan T (2010) Pseudoprogression after radiotherapy with concurrent temozolomide in a child with anaplastic astrocytoma. Pediatr Hematol Oncol 27(4):317–319

    Article  PubMed  CAS  Google Scholar 

  27. Pytel P, Lukas RV (2009) Update on diagnostic practice: tumors of the nervous system. Arch Pathol Lab Med 133(7):1062–1077

    PubMed  CAS  Google Scholar 

  28. Roldan GB, Scott JN, McIntyre JB, Dharmawardene M, de Robles PA, Magliocco AM et al (2009) Population-based study of pseudoprogression after chemoradiotherapy in GBM. Can J Neurol Sci 36(5):617–622

    PubMed  Google Scholar 

  29. Yang I, Aghi MK (2009) New advances that enable identification of glioblastoma recurrence. Nat Rev Clin Oncol 6(11):648–657

    Article  PubMed  Google Scholar 

  30. Gahramanov S, Raslan AM, Muldoon LL, Hamilton BE, Rooney WD, Varallyay CG et al (2011) Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: a pilot study. Int J Radiat Oncol Biol Phys 79(2):514–523

    Google Scholar 

  31. Brandsma D, van den Bent MJ (2009) Pseudoprogression and pseudoresponse in the treatment of gliomas. Curr Opin Neurol 22(6):633–638

    Google Scholar 

  32. Salhotra A, Lal B, Laterra J, Sun PZ, van Zijl PC, Zhou J (2008) Amide proton transfer imaging of 9L gliosarcoma and human glioblastoma xenografts. NMR Biomed 21(5):489–497

    Article  PubMed  Google Scholar 

  33. Zhao X, Wen Z, Huang F, Lu S, Wang X, Hu S et al (2011) Saturation power dependence of amide proton transfer image contrasts in human brain tumors and strokes at 3 T. Magn Reson Med 66(4):1033–1041

    Google Scholar 

  34. Zhou J, Lal B, Wilson DA, Laterra J, van Zijl PC (2003) Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med 50(6):1120–1126

    Article  PubMed  Google Scholar 

  35. Barajas RF Jr, Chang JS, Segal MR, Parsa AT, McDermott MW, Berger MS et al (2009) Differentiation of recurrent glioblastoma multiforme from radiation necrosis after external beam radiation therapy with dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging. Radiology 253(2):486–496

    Article  PubMed  Google Scholar 

  36. Tsien C, Galban CJ, Chenevert TL, Johnson TD, Hamstra DA, Sundgren PC et al (2010) Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma. J Clin Oncol 28(13):2293–2299

    Article  PubMed  CAS  Google Scholar 

  37. Tihan T, Barletta J, Parney I, Lamborn K, Sneed PK, Chang S (2006) Prognostic value of detecting recurrent glioblastoma multiforme in surgical specimens from patients after radiotherapy: should pathology evaluation alter treatment decisions? Hum Pathol 37(3):272–282

    Article  PubMed  Google Scholar 

  38. Kim JH, Bae Kim Y, Han JH, Cho KG, Kim SH, Sheen SS et al (2012) Pathologic diagnosis of recurrent glioblastoma: morphologic, immunohistochemical, and molecular analysis of 20 paired cases. Am J Surg Pathol 36(4):620–628

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Departments of Neurosurgery, Oncology, and Pathology for their support of this project. The authors did not have any funding related to this study or manuscript.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA

    Graeme F. Woodworth

  2. Division of Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Xiaobu Ye

  3. Division of Neuro-Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jaishri O. Blakeley

  4. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Tomas Garzon-Muvdi & Jon D. Weingart

  5. Division of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Sheikh Zayed Tower, Room M2101, 1800 Orleans Street, Baltimore, MD, 21231, USA

    Peter C. Burger

Authors
  1. Graeme F. Woodworth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomas Garzon-Muvdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaobu Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jaishri O. Blakeley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jon D. Weingart
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter C. Burger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Graeme F. Woodworth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woodworth, G.F., Garzon-Muvdi, T., Ye, X. et al. Histopathological correlates with survival in reoperated glioblastomas. J Neurooncol 113, 485–493 (2013). https://doi.org/10.1007/s11060-013-1141-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-013-1141-3

Keywords

Search

Navigation