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

  • Clinical Study
  • Published:
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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.

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Author notes

  1. Stephen J. Bagley and Robert D. Schwab contributed equally to this work.

Authors and Affiliations

  1. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Stephen J. Bagley, Robert A. Lustig, Donald M. O’Rourke, Steven Brem & Arati S. Desai

  2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Robert D. Schwab

  3. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Ernest Nelson, Angela N. Viaene & MacLean P. Nasrallah

  4. Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Zev A. Binder, Donald M. O’Rourke & Steven Brem

  5. Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Robert A. Lustig

Authors
  1. Stephen J. Bagley
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  2. Robert D. Schwab
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  3. Ernest Nelson
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  4. Angela N. Viaene
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Correspondence to Stephen J. Bagley.

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Bagley, S.J., Schwab, R.D., Nelson, E. et al. Histopathologic quantification of viable tumor versus treatment effect in surgically resected recurrent glioblastoma. J Neurooncol 141, 421–429 (2019). https://doi.org/10.1007/s11060-018-03050-6

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  • DOI: https://doi.org/10.1007/s11060-018-03050-6

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