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Relationship between tumor cell infiltration and 5-aminolevulinic acid fluorescence signals after resection of MR-enhancing lesions and its prognostic significance in glioblastoma

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Abstract

Purpose

This study investigated the degree of tumor cell infiltration in the tumor cavity and ventricle wall based on fluorescent signals of 5-aminolevulinic acid (5-ALA) after removal of the magnetic resonance (MR)-enhancing area and analyzed its prognostic significance in glioblastoma.

Methods

Twenty-five newly developed isocitrate dehydrogenase (IDH)-wildtype glioblastomas with complete resection both of MR-enhancing lesions and strong purple fluorescence on resection cavity were retrospectively analyzed. The fluorescent signals of 5-ALA were divided into strong purple, vague pink, and blue colors. The pathologic findings were classified into massively infiltrating tumor cells, infiltrating tumor cells, suspicious single-cell infiltration, and normal-appearing cells. The pathological findings were analyzed according to the fluorescent signals in the resection cavity and ventricle wall.

Results

There was no correlation between fluorescent signals and infiltrating tumor cells in the resection cavity (p = 0.199) and ventricle wall (p = 0.704) after resection of the MR-enhancing lesion. The median progression-free survival (PFS) and median overall survival (OS) were 12.5 (± 2.1) and 21.1 (± 3.5) months, respectively. In univariate analysis, the presence of definitive infiltrating tumor cells in the resection cavity and ventricle wall was significantly related to the PFS (p = 0.002) and OS (p = 0.027). In multivariate analysis, the absence of definitive infiltrating tumor cells improved PFS (hazard ratio: 0.184; 95% CI: 0.049–0.690, p = 0.012) and OS (hazard ratio: 0.124; 95% CI: 0.015–0.998, p = 0.050).

Conclusions

After resection both of the MR-enhancing lesions and strong purple fluorescence on resection cavity, there was no correlation between remnant fluorescent signals and infiltrating tumor cells. The remnant definitive infiltrating tumor cells in the resection cavity and ventricle wall significantly influenced the prognosis of patients with glioblastoma. Aggressive surgical removal of infiltrating tumor cells may improve their prognosis.

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Acknowledgments

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, and Future Planning (2017R1A1A1A05001020).

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Correspondence to T. -Y. Jung.

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The authors report no conflicts of interest. The authors alone were responsible for the content and writing of the paper.

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This retrospective study was approved by our Institutional Review Board.

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This manuscript doesn’t contain any individual person’s data in any form (including individual details, images or videos). The need for written informed consent was waived.

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Kim, J.K., Jung, T.Y., Jung, S. et al. Relationship between tumor cell infiltration and 5-aminolevulinic acid fluorescence signals after resection of MR-enhancing lesions and its prognostic significance in glioblastoma. Clin Transl Oncol 23, 459–467 (2021). https://doi.org/10.1007/s12094-020-02438-z

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