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Association of 5-aminolevulinic acid fluorescence guided resection with photodynamic therapy in recurrent glioblastoma: a matched cohort study

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Abstract

Purpose

Glioblastoma is a malignant and aggressive brain tumour that, although there have been improvements in the first line treatment, there is still no consensus regarding the best standard of care (SOC) upon its inevitable recurrence. There are novel adjuvant therapies that aim to improve local disease control. Nowadays, the association of intraoperative photodynamic therapy (PDT) immediately after a 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) in malignant gliomas surgery has emerged as a potential and feasible strategy to increase the extent of safe resection and destroy residual tumour in the surgical cavity borders, respectively.

Objectives

To assess the survival rates and safety of the association of intraoperative PDT with 5-ALA FGR, in comparison with a 5-ALA FGR alone, in patients with recurrent glioblastoma.

Methods

This article describes a matched-pair cohort study with two groups of patients submitted to 5-ALA FGR for recurrent glioblastoma. Group 1 was a prospective series of 11 consecutive cases submitted to 5-ALA FGR plus intraoperative PDT; group 2 was a historical series of 11 consecutive cases submitted to 5-ALA FGR alone. Age, sex, Karnofsky performance scale (KPS), 5-ALA post-resection status, T1-contrast-enhanced extent of resection (EOR), previous and post pathology, IDH (Isocitrate dehydrogenase), Ki67, previous and post treatment, brain magnetic resonance imaging (MRI) controls and surgical complications were documented.

Results

The Mantel-Cox test showed a significant difference between the survival rates (p = 0.008) of both groups. 4 postoperative complications occurred (36.6%) in each group. As of the last follow-up (January 2024), 7/11 patients in group 1, and 0/11 patients in group 2 were still alive. 6- and 12-months post-treatment, a survival proportion of 71,59% and 57,27% is expected in group 1, versus 45,45% and 9,09% in group 2, respectively. 6 months post-treatment, a progression free survival (PFS) of 61,36% and 18,18% is expected in group 1 and group 2, respectively.

Conclusion

The association of PDT immediately after 5-ALA FGR for recurrent malignant glioma seems to be associated with better survival without additional or severe morbidity. Despite the need for larger, randomized series, the proposed treatment is a feasible and safe addition to the reoperation.

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Acknowledgements

We would like to thank professors Fábio Alberto Silva and Rodrigo Napoli for their assistance with the grammar revision and statistical analysis, respectively.

Funding

No funding was received for this research.

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Authors and Affiliations

  1. Division of Neurooncology, Department of Neurosurgery, Instituto de Neurologia de Curitiba, Rua Jeremias Maciel Perretto, 300 - Campo Comprido, Curitiba, PR, 81210-310, Brazil

    Erasmo Barros da Silva Jr, Maurício Coelho Neto, Jorge Luis Novak Filho & Ricardo Ramina

  2. Instituto de Oncologia Do Paraná, Curitiba, PR, Brazil

    Erasmo Barros da Silva Jr

  3. DMC Equipamentos LTDA, São Carlos, SP, Brazil

    Marília Wellichan Mancini Vasquez & Luciana Almeida-Lopes

  4. Nupen Institute, São Carlos, SP, Brazil

    Marília Wellichan Mancini Vasquez & Luciana Almeida-Lopes

  5. Department of Neuroradiology, Instituto de Neurologia de Curitiba, Curitiba, PR, Brazil

    Bernardo Correa de Almeida Teixeira & Flávia Sprenger

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  1. Erasmo Barros da Silva Jr
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Contributions

The authors confirm contribution to the paper as follows: study conception and design: da Silva Jr, EB; data collection: Novak Filho, JL, Sprenger, F; analysis and interpretation of results: Vasquez, MWM, Teixeira, BCA, Almeida-Lopes, L, Coelho Neto, M, Ramina, R; draft manuscript preparation: da Silva Jr, EB. All authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Erasmo Barros da Silva Jr.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Human Research Ethics Committee and the National Research Ethics Committee, certificate of presentation of ethical review number 48191121.9.0000.5227 and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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The Author confirms: that the work described has not been published before (except in the form of an abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; that its publication has been approved by all co-authors, if any; that its publication has been approved (tacitly or explicitly) by the responsible authorities at the institution where the work is carried out.

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Comments

Albeit this paper has low evidence for demonstrating the efficacy of 5-ALA PDT on outcome in glioblastoma, being retrospective and on a small population of patients, the authors' experience does suggest that beneficial effects may be present, and that the procedure is safe. As always it remains to be stated that at this stage the community would like to see prospective randomized studies to further corroborate these promising preliminary observations.

Walter Stummer

Muenster, Germany

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da Silva, E.B., Vasquez, M.W.M., de Almeida Teixeira, B.C. et al. Association of 5-aminolevulinic acid fluorescence guided resection with photodynamic therapy in recurrent glioblastoma: a matched cohort study. Acta Neurochir 166, 212 (2024). https://doi.org/10.1007/s00701-024-06108-9

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