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Baby, Manuel V.; Narendranath, Rithvik M.; Kaur-Paneser, Symriti; Ramsay, Daniele S. C.; Ponniah, Hariharan Subbiah; Namireddy, Srikar R.; Salih, Ahmed; Thavarajasingam, Ahkash; Scurtu, Daniel; Kramer, Andreas; Stöcklein, Veit; Kalasauskas, Darius; Jankovic, Dragan; Ringel, Florian; Thavarajasingam, Santhosh G. (2026): Determinants of survival after re-resection for recurrent glioblastoma: a meta-analysis. Acta Neurochirurgica, 168: 11. ISSN 0942-0940

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Abstract

Purpose

Glioblastoma (GBM) inevitably recurs despite maximal safe resection and standard chemoradiotherapy. The factors influencing survival after first recurrence and re-resection remain controversial.

Research question

What are the prognostic factors influencing survival following re-resection of glioblastoma?

Methods

A systematic search of major databases was conducted for original studies reporting on survival outcomes. Data on hazard ratios (HR) for overall survival and key prognostic factors were extracted, followed by meta-analyses of univariate and multivariate Cox models. Study quality and risk of bias were assessed.

Results

A total of 30 studies were included. Gross total resection and methylated MGMT promoter status were significantly associated with improved survival, with pooled HRs of 0.52 (95% CI: 0.36–0.76, p < 0.001) and 0.58 (95% CI: 0.45–0.75, p < 0.001), respectively. In contrast, age was modestly associated with worse survival (HR: 1.02, 95% CI: 1.01–1.03, p < 0.001). Preoperative Karnofsky Performance Status (KPS) < 70 was associated with worse survival (HR: 2.25, 95% CI: 1.59–3.19, p < 0.001). Adjuvant chemotherapy (HR: 0.69, 95% CI: 0.33–1.45, p = 0.33) and time to re-resection (HR: 0.69, 95% CI: 0.41–1.16, p = 0.16) failed to show consistent survival benefits.

Conclusion

Our findings suggest gross total resection of contrast-enhancing tumour and MGMT promoter methylation are strongly associated with improved survival following first recurrence of glioblastoma. Conversely, age, preoperative KPS, adjuvant chemotherapy, and timing of re-resection showed inconsistent or non-significant associations, emphasizing the need for prospective studies to refine prognostic assessments and guide individualized treatment strategies in recurrent glioblastoma.

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