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Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial

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Abstract

Purpose

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection.

Methods

Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death.

Results

There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months).

Conclusions

This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable for that section.

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Funding

The authors of this publication received research support from INSERM, University of Lille, University Hospital of Lille, American Society for Laser Medicine and Surgery, Ligue contre le Cancer and Agence Nationale pour la Recherche.

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Correspondence to Nicolas Reyns.

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Conflicts of interest

M. Vermandel, C. Dupont, S. Mordon and N. Reyns are co-founders of Hemerion Therapeutics SAS, Lille, France. Constantinos Hadjipanayis is a consultant for NX Development Corporation (NXDC) and Synaptive Medical Inc. He receives royalties from the sale of Gleolan® (5-ALA) which is marketed by NXDC. Gleolan® is an optical imaging agent approved in the United States for the visualization of malignant tissue during glioma surgery.

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All procedures performed in studies were in accordance with the ethical standards of the National Research Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The French National Agency for Medicine and Health Product Safety (ANSM) as well as the French National Ethics Committee approved this study.

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Vermandel, M., Dupont, C., Lecomte, F. et al. Standardized intraoperative 5-ALA photodynamic therapy for newly diagnosed glioblastoma patients: a preliminary analysis of the INDYGO clinical trial. J Neurooncol 152, 501–514 (2021). https://doi.org/10.1007/s11060-021-03718-6

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