Tumor recurrence or treatment-related changes following chemoradiation in patients with glioblastoma: does pathology predict outcomes?

Abstract

Background

Despite surgical resection and chemoradiation, all patients with GBM invariably recur. Radiological imaging is limited in differentiating tumor recurrence (TR) from treatment-related changes (TRC); therefore, re-resection is often needed. Few studies have assessed the relationship between re-resection histopathology and overall survival (OS). We performed a large retrospective study to analyze the clinical significance of histopathology following re-resection and its influence on genomic sequencing results.

Methods

Clinical, radiographic, and histological information was compiled from 675 patients with GBM (2005–2017). 137-patients met the inclusion criteria. IDH1 p.R132H immunohistochemistry was performed in all patients. Next-generation sequencing interrogating 205 tumor-related genes was performed in 68-patients. Molecular alterations from initial and subsequent resections were compared in a subset of cases.

Results

There were no differences in OS (17.3-months TRC vs. 21-months TR, p = 0.881) and survival from progression (9.0 vs. 11.7-months, p = 0.778) between patients with TR and TRC on re-resection. TR patients were more likely to receive salvage radiotherapy (26% vs. 0%) and tumor-treating fields (25% vs. 5%,) after the 2nd surgery than the TRC group (p = < 0.045). There was no correlation between mutations and TRC. IDH status was not predictive of TRC. Fifteen-patients had sequencing results from multiple surgeries without evident differences in genomic alterations.

Conclusions

Histopathologic findings following chemoradiation do not correlate with clinical outcomes. Such findings should be considered during patient management and clinical trial enrollment. Standardization of tissue sampling and interpretation following reoperation is urgently needed. Future work is required to understand the relationship between the mutation profile following TRC and outcomes.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

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Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number K08CA241651 (LYB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Contributions

Study design: AP, LYB, and YE. Data Recollection: AP and AD. Data analysis: AD and PZ. Manuscript writing: AP, AD, and YE. Manuscript revision and editing: AP, AD, NT, LYB, and YE. Study Supervision: LYB and YE. Approved final manuscript: all authors.

Corresponding authors

Correspondence to Leomar Y. Ballester or Yoshua Esquenazi.

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The authors declare that they have no conflict of interest.

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This retrospective study was approved by the institutional review board of The University of Texas Health Science Center at Houston and Memorial Hermann Hospital, Houston, TX following the 1964 Helsinki Declaration and its later amendments.

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Patrizz, A., Dono, A., Zhu, P. et al. Tumor recurrence or treatment-related changes following chemoradiation in patients with glioblastoma: does pathology predict outcomes?. J Neurooncol 152, 163–172 (2021). https://doi.org/10.1007/s11060-020-03690-7

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Keywords

  • Glioblastoma
  • Tumor recurrence
  • Radiation necrosis
  • Radiotherapy
  • Treatment-related changes
  • Reoperation