Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma

Antonio Dono, Ping Zhu, Emma Holmes, Takeshi Takayasu, Jay jiguang Zhu, Angel I. Blanco, Sigmund Hsu, Meenakshi B. Bhattacharjee, Leomar Y. Ballester, Dong H. Kim, Yoshua Esquenazi, Nitin Tandon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)353-363
Number of pages11
JournalJournal of neuro-oncology
Volume156
Issue number2
DOIs
StatePublished - Jan 2022
Externally publishedYes

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

  • Glioblastoma
  • IDH
  • Molecular subgroups
  • Post-progression survival
  • Reoperation

PubMed: MeSH publication types

  • Journal Article

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