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Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma

  • Clinical Study
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Abstract

Introduction

Recurrent glioblastoma (rGBM) prognosis is dismal. In the absence of effective adjuvant treatments for rGBM, re-resections remain prominent in our arsenal. This study evaluates the impact of reoperation on post-progression survival (PPS) considering rGBM genetic makeup.

Methods

To assess the genetic heterogeneity and treatment-related changes (TRC) roles in re-operated or medically managed rGBMs, we compiled demographic, clinical, histopathological, and next-generation genetic sequencing (NGS) characteristics of these tumors from 01/2005 to 10/2019. Survival data and reoperation were analyzed using conventional and random survival forest analysis (RSF).

Results

Patients harboring CDKN2A/B loss (p = 0.017) and KDR mutations (p = 0.031) had notably shorter survival. Reoperation or bevacizumab were associated with longer PPS (11.2 vs. 7.4-months, p = 0.006; 13.1 vs 6.2, p < 0.001). Reoperated patients were younger, had better performance status and greater initial resection. In 136/273 (49%) rGBMs undergoing re-operation, CDKN2A/B loss (p = 0.03) and KDR mutations (p = 0.02) were associated with shorter survival. In IDH-WT rGBMs with NGS data (n = 166), reoperation resulted in 7.0-month longer survival (p = 0.004) than those managed medically. This reoperation benefit was independently identified by RSF analysis. Stratification analysis revealed that EGFR-mutant, CDKN2A/B-mutant, NF1-WT, and TP53-WT rGBM IDH-WT subgroups benefit most from reoperation (p = 0.03). Lastly, whether or not TRC was prominent at re-operation does not have any significant impact on PPS (10.5 vs. 11.5-months, p = 0.77).

Conclusions

Maximal safe re-resection significantly lengthens PPS regardless of genetic makeup, but reoperations are especially beneficial for IDH-WT rGBMs with EGFR and CDKN2A/B mutations with TP53-WT, and NF1-WT. Histopathology at recurrence may be an imperfect gauge of disease severity at progression and the imaging progression may be more reflective of the prognosis.

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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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Acknowledgements

None.

Funding

Research by NT is gunned by NINDS, NIDCD, UT STARS, and Medtronic. None of this funding is relevant to this work nor influenced its content. 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 at UT Health, Houston, TX, USA

    Antonio Dono, Ping Zhu, Emma Holmes, Jay-jiguang Zhu, Angel I. Blanco, Sigmund Hsu, Dong H. Kim, Yoshua Esquenazi & Nitin Tandon

  2. Department of Pathology and Laboratory Medicine, McGovern Medical School at UT Health, Houston, TX, USA

    Antonio Dono, Takeshi Takayasu, Meenakshi B. Bhattacharjee & Leomar Y. Ballester

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

    Jay-jiguang Zhu, Angel I. Blanco, Sigmund Hsu, Meenakshi B. Bhattacharjee, Leomar Y. Ballester, Dong H. Kim, Yoshua Esquenazi & Nitin Tandon

  4. Texas Institute for Restorative Neurotechnologies, UT Health, Houston, TX, USA

    Nitin Tandon

  5. Department of Neurosurgery, Texas Institute of Restorative Neurotechnology, McGovern Medical School at UT Health, 6400 Fannin Street, Suite 2800, Houston, TX, 77030, USA

    Nitin Tandon

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  1. Antonio Dono
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Contributions

Study design: AD, NT; data collection AD, EH, TT; data analysis and visualization: PZ; data interpretation: AD, PZ, NT; manuscript preparation: AD, PZ, NT; manuscript critical review: AD, PZ, AIB, SH, JJZ, MBB, LYB, DHK, YE, NT; final manuscript approval: all authors.

Corresponding author

Correspondence to Nitin Tandon.

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The authors declared no conflict of interest.

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This 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., Zhu, P., Holmes, E. et al. Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma. J Neurooncol 156, 353–363 (2022). https://doi.org/10.1007/s11060-021-03917-1

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