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

  • Stephen J. BagleyEmail author
  • Robert D. Schwab
  • Ernest Nelson
  • Angela N. Viaene
  • Zev A. Binder
  • Robert A. Lustig
  • Donald M. O’Rourke
  • Steven Brem
  • Arati S. Desai
  • MacLean P. Nasrallah
Clinical Study

Abstract

Purpose

The prognostic impact of the histopathologic features of recurrent glioblastoma surgical specimens is unknown. We sought to determine whether key histopathologic characteristics in glioblastoma tumors resected after chemoradiotherapy are associated with overall survival (OS).

Methods

The following characteristics were quantified in recurrent glioblastoma specimens at our institution: extent of viable tumor (accounting for % of specimen comprised of tumor and tumor cellularity), mitoses per 10 high-power fields (0, 1–10, > 10), Ki-67 proliferative index (0–100%), hyalinization (0–6; none to extensive), rarefaction (0–6), hemosiderin (0–6), and % of specimen comprised of geographic necrosis (0–100%; converted to 0–6 scale). Variables associated with OS in univariate analysis, as well as age, eastern cooperative oncology group performance status (ECOG PS), extent of repeat resection, time from initial diagnosis to repeat surgery, and O6-methylguanine-DNA methyltransferase promoter methylation, were included in a multivariable Cox proportional hazards model.

Results

37 specimens were assessed. In a multivariate model, high Ki-67 proliferative index was the only histopathologic characteristic associated with worse OS following repeat surgery for glioblastoma (hazard ratio (HR) 1.3, 95% CI 1.1–1.5, p = 0.003). Shorter time interval from initial diagnosis to repeat surgery (HR 1.11, 95% CI 1.02–1.21, p = 0.016) and ECOG PS ≥ 2 (HR 4.19, 95% CI 1.72–10.21, p = 0.002) were also independently associated with inferior OS.

Conclusion

In patients with glioblastoma undergoing repeat resection following chemoradiotherapy, high Ki-67 index in the recurrent specimen, short time to recurrence, and poor PS are independently associated with worse OS. Histopathologic quantification of viable tumor versus therapy-related changes has limited prognostic influence.

Keywords

Glioblastoma Radiation therapy Ki-67 Survival Radiation effects Neuropathology 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human and animal participants

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996CrossRefPubMedGoogle Scholar
  2. 2.
    Cloughesy T, Perry JR, Wick W (2013) Standards of care for treatment of recurrent glioblastoma—are we there yet? Neuro Oncol 15(1):4–27CrossRefPubMedGoogle Scholar
  3. 3.
    Weller M, van den Bent M, Tonn JC et al (2017) European association for neuro-oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 18(6):e315–e329CrossRefPubMedGoogle Scholar
  4. 4.
    Montemurro N, Perrini P, Blanco MO, Vannozzi R (2016) Second surgery for recurrent glioblastoma: a concise overview of the current literature. Clin Neurol Neurosurg 142:60–64CrossRefPubMedGoogle Scholar
  5. 5.
    Verma N, Cowperthwaite MC, Burnett MG, Markey MK (2013) Differentiating tumor recurrence from treatment necrosis: a review of neuro-oncologic imaging strategies. Neuro-Oncology 15(5):515–534CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Burger PC, Mahley MS Jr, Dudka L, Vogel FS (1979) The morphologic effects of radiation administered therapeutically for intracranial gliomas: a postmortem study of 25 cases. Cancer 44(4):1256–1272CrossRefPubMedGoogle Scholar
  7. 7.
    Woodworth GF, Garzon-Muvdi T, Ye X, Blakeley JO, Weingart JD, Burger PC (2013) Histopathological correlates with survival in reoperated glioblastomas. J Neurooncol 113(3):485–493CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    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):272–282CrossRefPubMedGoogle Scholar
  9. 9.
    Clarke JL, Chang S (2009) Pseudoprogression and pseudoresponse: challenges in brain tumor imaging. Curr Neurol Neurosci Rep 9(3):241–246CrossRefPubMedGoogle Scholar
  10. 10.
    Forsyth PA, Kelly PJ, Cascino TL et al (1995) Radiation necrosis or glioma recurrence: is computer-assisted stereotactic biopsy useful? J Neurosurg 82(3):436–444CrossRefPubMedGoogle Scholar
  11. 11.
    McGirt MJ, Bulsara KR, Cummings TJ et al (2003) Prognostic value of magnetic resonance imaging-guided stereotactic biopsy in the evalution of recurrent malignant astrocytoma compared with a lesion due to radiation effect. J Neurosurg 98(1):14–20CrossRefPubMedGoogle Scholar
  12. 12.
    van Nifterik KA, van den Berg J, Stalpers LJ et al (2007) Differential radiosensitizing potential of temozolomide in MGMT promoter methylated glioblastoma multiforme cell lines. Int J Radiat Oncol Biol Phys 69(4):1246–1253CrossRefPubMedGoogle Scholar
  13. 13.
    Pala A, Schmitz AL, Knoll A et al (2018) Is MGMT promoter methylation to be considered in the decision making for recurrent surgery in glioblastoma patients? Clin Neurol Neurosurg 167:6–10CrossRefPubMedGoogle Scholar
  14. 14.
    Audureau E, Chivet A, Ursu R et al (2018) Prognostic factors for survival in adult patients with recurrent glioblastoma: a decision-tree-based model. J Neuro-Oncol 136(3):565–576CrossRefGoogle Scholar
  15. 15.
    Brandes AA, Bartolotti M, Tosoni A et al (2016) Patient outcomes following second surgery for recurrent glioblastoma. Future Oncol (Lond Engl) 12(8):1039–1044CrossRefGoogle Scholar
  16. 16.
    Melguizo-Gavilanes I, Bruner JM, Guha-Thakurta N, Hess KR, Puduvalli VK (2015) Characterization of pseudoprogression in patients with glioblastoma: is histology the gold standard? J Neuro-Oncol 123(1):141–150CrossRefGoogle Scholar
  17. 17.
    Ralte AM, Sharma MC, Karak AK, Mehta VS, Sarkar C (2001) Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors. Pathol Oncol Res 7(4):267–278CrossRefPubMedGoogle Scholar
  18. 18.
    Schroder R, Feisel KD, Ernestus RI (2002) Ki-67 labeling is correlated with the time to recurrence in primary glioblastomas. J Neuro-Oncol 56(2):127–132CrossRefGoogle Scholar
  19. 19.
    Kuriyama H, Lamborn KR, O’Fallon JR et al (2002) Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas. Neuro-Oncology 4(3):179–186CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tortosa A, Vinolas N, Villa S et al (2003) Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas. Cancer 97(4):1063–1071CrossRefPubMedGoogle Scholar
  21. 21.
    Kato H, Fujimura M, Kumabe T, Ishioka C, Kanamaru R, Yoshimoto T (2004) PTEN gene mutation and high MIB-1 labeling index may contribute to dissemination in patients with glioblastoma. J Clin Neurosci 11(1):37–41CrossRefPubMedGoogle Scholar
  22. 22.
    Torp SH (1997) Proliferative activity in human glioblastomas: evaluation of different Ki-67 equivalent antibodies. Mol Pathol 50(4):198–200CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Chen WJ, He DS, Tang RX, Ren FH, Chen G (2015) Ki-67 is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis. Asian Pac J cancer Prev 16(2):411–420CrossRefPubMedGoogle Scholar
  24. 24.
    Vaquero J, Zurita M, Morales C, Oya S, Coca S (2000) Prognostic significance of endothelial surface score and MIB-1 labeling index in glioblastoma. J Neuro-Oncol 46(1):11–16CrossRefGoogle Scholar
  25. 25.
    Persson A, Englund E (2008) Different assessments of immunohistochemically stained Ki-67 and hTERT in glioblastoma multiforme yield variable results: a study with reference to survival prognosis. Clin Neuropathol 27(4):224–233CrossRefPubMedGoogle Scholar
  26. 26.
    Dirks P, Bernstein M, Muller PJ, Tucker WS (1993) The value of reoperation for recurrent glioblastoma. Can J Surg J Can de chirurgie 36(3):271–275Google Scholar
  27. 27.
    Young B, Oldfield EH, Markesbery WR et al (1981) Reoperation for glioblastoma. J Neurosurg 55(6):917–921CrossRefPubMedGoogle Scholar
  28. 28.
    Sughrue ME, Sheean T, Bonney PA, Maurer AJ, Teo C (2015) Aggressive repeat surgery for focally recurrent primary glioblastoma: outcomes and theoretical framework. Neurosurg Focus 38(3):E11CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Stephen J. Bagley
    • 1
    Email author return OK on get
  • Robert D. Schwab
    • 2
  • Ernest Nelson
    • 3
  • Angela N. Viaene
    • 3
  • Zev A. Binder
    • 4
  • Robert A. Lustig
    • 1
    • 5
  • Donald M. O’Rourke
    • 1
    • 4
  • Steven Brem
    • 1
    • 4
  • Arati S. Desai
    • 1
  • MacLean P. Nasrallah
    • 3
  1. 1.Abramson Cancer Center, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Pathology and Laboratory Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Neurosurgery, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of Radiation Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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