The Combined Use of 5-ALA and Chlorin e6 Photosensitizers for Fluorescence-Guided Resection and Photodynamic Therapy under Neurophysiological Control for Recurrent Glioblastoma in the Functional Motor Area after Ineffective Use of 5-ALA: Preliminary Results.

Elizaveta I Kozlikina,Victor B Loschenov,Mikhail V Sinkin,Igor S Trifonov,Vladimir V Krylov

doi:10.3390/bioengineering9030104

Abstract

The treatment of glial brain tumors is an unresolved problem in neurooncology, and all existing methods (tumor resection, chemotherapy, radiotherapy, radiosurgery, fluorescence diagnostics, photodynamic therapy, etc.) are directed toward increasing progression-free survival for patients. Fluorescence diagnostics and photodynamic therapy are promising methods for achieving gross total resection and additional treatment of residual parts of the tumor. However, sometimes the use of one photosensitizer for photodynamic therapy does not help, and the time until tumor relapse barely increases. This translational case report describes the preliminary results of the first combined use of 5-ALA and chlorin e6 photosensitizers for fluorescence-guided resection and photodynamic therapy of glioblastoma, which allowed us to perform total resection of tumor tissue according to magnetic resonance and computed tomography images, remove additional tissue with increased fluorescence intensity without neurophysiological consequences, and perform additional therapy. Two months after surgery, no recurrent tumor and no contrast uptake in the tumor bed were detected. Additionally, the patient had ischemic changes in the access zone and along the periphery and cystic-glial changes in the left parietal lobe.

Highlights

Glial brain tumors have diffuse and infiltrative growth patterns, so achieving their complete resection is often complicated [1,2]
Since gross total resection is accompanied by better outcomes fluorescence diagsevere neurological complications nostics (FD) is of particular interest
Since the use of only 5-ALA for photodynamic therapy (PDT) had not shown a good result for this patient during the second intervention, we proposed that use of two PSs with different mechanisms of accumulation and action during PDT would show a better result

Summary

Introduction

Glial brain tumors have diffuse and infiltrative growth patterns, so achieving their complete resection is often complicated [1,2]. Combined methods of treatment are a priority because monotherapy does not lead to significant improvements in immediate and long-term results. Combined treatments can include surgical removal of the tumor, radiation, and chemotherapy [3,4], and new methods of treatment, such as specific antitumor immunotherapy [5], fluorescence-guided resection (FGR) [6,7], and photodynamic therapy (PDT) using modern photosensitizers (PSs) [8–10]. The prerequisites for the latter’s use as an alternative method of therapy for malignant brain neoplasms were the results of clinical studies that showed significant increases in the median overall. Bioengineering 2022, 9, x FOR PEER REVIEW survival of patients and the relapse-free period, while reducing the risk of developing were the results of clinical studies that[11]. Showed significant increases in the median overall severe neurological complications survival of patients and the relapse-free period, while reducing the risk[2], of developing.

Results

Discussion

Conclusion