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



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).


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.


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.


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.


Glioblastoma Radiation therapy Ki-67 Survival Radiation effects Neuropathology 


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.


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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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