Photodynamic therapy in glioblastoma: Detection of intraoperative inadvertent 5-ALA mediated photodynamic therapeutical effect after gross total resection

Abel Ferrés; Alberto Di Somma; Alejandra Mosteiro; Thomaz Eduardo Topczewski; Pedro Roldán; Leire Pedrosa; Diouldé Diao; Estela Pineda; Àngels Sierra; Joaquim Enseñat; José Juan González-Sánchez

doi:10.3389/fonc.2022.1080685

Photodynamic therapy in glioblastoma: Detection of intraoperative inadvertent 5-ALA mediated photodynamic therapeutical effect after gross total resection

Front Oncol. 2022 Dec 2:12:1080685. doi: 10.3389/fonc.2022.1080685. eCollection 2022.

Authors

Abel Ferrés¹, Alberto Di Somma^{1

2}, Alejandra Mosteiro¹, Thomaz Eduardo Topczewski¹, Pedro Roldán^{1

2}, Leire Pedrosa³, Diouldé Diao³, Estela Pineda^{2

4}, Àngels Sierra⁵, Joaquim Enseñat^{1

2}, José Juan González-Sánchez^{1

2}

Affiliations

¹ Department of Neurosurgery, Clínic Institute of Neurosciences, Hospital Clínic of Barcelona, Barcelona, Spain.
² Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
³ Department of Biomedicine, Faculty of Medicine, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
⁴ Servicio de Oncología Médica, Clinical Institute of Hematological and Oncological Diseases, Hospital Clinic of Barcelona, Barcelona, Spain.
⁵ Department of Medicine and Life Sciences, Facultad de Ciencias de la Salud y de la Vida, Universidad Pompeu Fabra, Barcelona, Spain.

Abstract

Introduction: Glioblastoma (GBM) remains the most frequent and lethal primary brain tumor in adults, despite advancements in surgical resection techniques and adjuvant chemo- and radiotherapy. The most frequent recurrence pattern (75-90%) occurs in the form of continuous growth from the border of the surgical cavity, thus emphasizing the need for locoregional tumor control. Fluorescence-guided surgical resection using 5-ALA has been widely implemented in surgical protocols for such tumors. Recent literature also highlights the applicability of 5-ALA-mediated photodynamic therapy to obtain locoregional tumor control further. This study aims to identify if 5-ALA mediated photodynamic therapeutic effect after gross total glioblastoma resection has inadvertently occurred due to the exposition of protoporphyrin IX charged peripheral tumoral cells to operative room light sources.

Methods: Of 146 patients who were intervened from glioblastoma between 2015 and 2020, 33 were included in the present study. Strict gross total resection (without supralocal resection) had been accomplished, and adjuvant chemoradiotherapy protocol was administered. Two comparison groups were created regarding the location of the recurrence (group A: up to 1 centimeter from the surgical cavity, and group B: beyond 1 centimeter from the surgical cavity). The cutoff point was determined to be 1 centimeter because of the visible light penetrance to the normal brain tissue.

Results: In univariate analysis, both groups only differed regarding 5-ALA administration, which was significantly related to a minor relative risk of presenting the recurrence within the first centimeter from the surgical cavity (Relative Risk = 0,655 (95% CI 0,442-0,970), p-value=0,046). Results obtained in univariate analysis were corroborated posteriorly in multivariate analysis (RR=0,730 (95% CI 0,340-0,980), p=0,017).

Discussion: In the present study, a probable inadvertent 5-ALA photodynamic therapeutical effect has been detected in vivo. This finding widely opens the door for further research on this promising theragnostic tool.

Keywords: 5-aminolevulinic acid; glioblastoma; locorregional adjuvant therapy; neurosurgical oncology; photodynamic therapy.