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Genomic alterations predictive of response to radiosurgery in recurrent IDH-WT glioblastoma

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Abstract

Introduction

Despite aggressive treatment, glioblastoma invariably recurs. The optimal treatment for recurrent glioblastoma (rGBM) is not well defined. Stereotactic radiosurgery (SRS) for rGBM has demonstrated favorable outcomes for selected patients; however, its efficacy in molecular GBM subtypes is unknown. We sought to identify genetic alterations that predict response/outcomes from SRS in rGBM-IDH-wild-type (IDH-WT).

Methods

rGBM-IDH-WT patients undergoing SRS at first recurrence and tested by next-generation sequencing (NGS) were reviewed (2009–2018). Demographic, clinical, and molecular characteristics were evaluated. NGS interrogating 205-genes was performed. Primary outcome was survival from GK-SRS assessed by Kaplan-Meier method and multivariable Cox proportional-hazards.

Results

Sixty-three lesions (43-patients) were treated at 1st recurrence. Median age was 61-years. All patients were treated with resection and chemoradiotherapy. Median time from diagnosis to 1st recurrence was 8.7-months. Median cumulative volume was 2.895 cm3 and SRS median marginal dose was 18 Gy (median isodose-54%). Bevacizumab was administered in 81.4% patients. PFS from SRS was 12.9-months. Survival from SRS was 18.2-months. PTEN-mutant patients had a longer PFS (p = 0.049) and survival from SRS (p = 0.013) in multivariable analysis. Although no statistically significant PTEN-mutants patients had higher frequency of radiation necrosis (21.4% vs. 3.4%) and lower in-field recurrence (28.6% vs. 37.9%) compared to PTEN-WT patients.

Conclusions

SRS is a safe and effective treatment option for selected rGBM-IDH-WT patients following first recurrence. rGBM-IDH-WT harboring PTEN-mutation have improved survival with salvage SRS compared to PTEN-WT patients. PTEN may be used as a molecular biomarker to identify a subset of rGBM patients who may benefit the most from SRS.

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Availability of data and materials

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

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Acknowledgements

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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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Authors and Affiliations

  1. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Antonio Dono, Mark Amsbaugh, Magda Martir, Richard H. Smilie, Jay-Jiguang Zhu, Sigmund Hsu, Dong H. Kim, Nitin Tandon, Leomar Y. Ballester, Angel I. Blanco & Yoshua Esquenazi

  2. Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Antonio Dono & Leomar Y. Ballester

  3. Memorial Hermann Hospital-TMC, Houston, TX, USA

    Mark Amsbaugh, Magda Martir, Roy F. Riascos, Jay-Jiguang Zhu, Sigmund Hsu, Dong H. Kim, Nitin Tandon, Leomar Y. Ballester, Angel I. Blanco & Yoshua Esquenazi

  4. Department of Diagnostic and Interventional Imaging, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Roy F. Riascos

  5. Center for Precision Health, School of Biomedical Informatics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Yoshua Esquenazi

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  1. Antonio Dono
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Contributions

Study design: AD, YE. Data Recollection: AD, MA, MM, RHS, YE Data analysis: AD. Manuscript writing: AD, MA, RHS, YE. Manuscript revision and editing: AD, MA, RFR, JJZ, SH, DHK, NT, LYB, AIB, YE. Study Supervision: YE. Approved final manuscript: all authors.

Corresponding authors

Correspondence to Leomar Y. Ballester or Yoshua Esquenazi.

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The authors declared 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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Dono, A., Amsbaugh, M., Martir, M. et al. Genomic alterations predictive of response to radiosurgery in recurrent IDH-WT glioblastoma. J Neurooncol 152, 153–162 (2021). https://doi.org/10.1007/s11060-020-03689-0

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