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Adjuvant radiotherapy and stereotactic radiosurgery in grade 3 meningiomas — a systematic review and meta-analysis

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Abstract

Malignant meningioma is a rare, aggressive form of meningioma. Radiation is commonly included in treatment guidelines either as adjuvant radiotherapy (RT) or stereotactic radiosurgery (SRS). Nevertheless, the treatment recommendations are not supported by prospective comparative trials and systematical, critical evaluation of supportive evidence is lacking. For this systematic review, studies analyzing the effectiveness of adjuvant RT and SRS in grade 3 (gr. 3) meningioma were reviewed. Thirty studies met the inclusion criteria for qualitative synthesis, and 6 studies were assessed in quantitative analysis. In quantitative analysis, the weighted average of hazard ratios for adjuvant RT in univariate analyses of overall survival (OS) was 0.55 (CI: 0.41; 0.69). The median 5-year OS after adjuvant RT in gr. 3 meningiomas was 56.3%, and the median OS ranged from 24 to 80 months for patients treated with adjuvant RT versus 13 to 41.2 months in patients not treated. For SRS, the 3-year progression free survival was 0% in one study and 57% in another. The 2-year OS ranged from 25 to 75% in 2 studies. The quality of evidence was rated as “very low” in 14 studies analyzed, and considerable allocation bias was detected. Treatment toxicity was reported in 47% of the studies. The severity, according to the CTCAE, ranged from grades I–V and 5.3 to 100% of patients experienced complications. Adjuvant RT is usually considered standard of care for WHO grade 3 meningiomas, although supporting evidence was of low quality. Better evidence from registries and prospective trials can improve the evidence base for adjuvant fractionated RT in malignant meningiomas.

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Data availability

The data that support the findings of this study are available upon reasonable request from the corresponding author.

Code availability

No custom code was used in this study.

Notes

  1. The study of Champeaux et al. [7] presents a single outcome for RT alone.

  2. Studies reporting “number of complications” instead of “number of patients with complications” were excluded [29, 34]. Adeberg et al. reporting “mild side effects […] could be observed in most patients” was excluded [28].

Abbreviations

RT:

Radiotherapy

SRS:

Stereotactic radiosurgery

OS:

Overall survival

PFS:

Progression free survival

TCR:

Tumor control rate

DFS:

Disease free survival

DSS:

Disease specific survival

RFS:

Recurrence free survival

TTR:

Time to recurrence

RSR:

Relative survival rate

LRC:

Locoregional control

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Authors and Affiliations

  1. Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Amon Bergner, Andrea Daniela Maier, Christian Mirian & Tiit Illimar Mathiesen

  2. Department of Pathology, Rigshospitalet, Copenhagen, Denmark

    Andrea Daniela Maier

  3. Department of Clinical Medicine, Copenhagen, Denmark

    Tiit Illimar Mathiesen

  4. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Tiit Illimar Mathiesen

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  1. Amon Bergner
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Contributions

Amon Bergner, Andrea Daniela Maier, and Tiit Illimar Mathiesen contributed to the study conception and design. Data collection was performed by Amon Bergner and Andrea Daniela Maier. Qualitative and quantitative analyses were performed by Amon Bergner, Andrea Daniela Maier, Tiit Illimar Mathiesen, and Christian Mirian. Quantitative analysis was performed by Amon Bergner, Andrea Daniela Maier, and Christian Mirian. The first draft of the manuscript was written by Amon Bergner, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Amon Bergner.

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Competing interests

Unrelated to this work, Christian Mirian is funded by The Novo Nordisk Foundation Grant No. 0052813. Second and last author received a grant from The Danish Cancer Society: R278-A16459. Second author received a grant from The Research Fund of Rigshospitalet, Copenhagen University Hospital. Last author received a grant from the Lundbeck Foundation (R266-2017–4029).

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Appendix

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Table 3 Search strategy
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Fig. 3
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Table 4 Findings of included studiesi
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Table 5 Complications
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Table 6 WHO classifications of Central Nervous System Tumors
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Bergner, A., Maier, A.D., Mirian, C. et al. Adjuvant radiotherapy and stereotactic radiosurgery in grade 3 meningiomas — a systematic review and meta-analysis. Neurosurg Rev 45, 2639–2658 (2022). https://doi.org/10.1007/s10143-022-01773-9

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