Search

Background: Despite improvements in surgical as well as adjuvant therapies over the last decades, the prognosis for patients with glioblastoma remains poor. Five-Aminolevulinic acid (5-ALA) induced porphyrins are already used for fluorescence-guided resection and as photosensitizer for photodynamic therapy. New findings reveal their potential use as sensitizing agents in combination with ionizing radiation., Methods: We initiated a phase I/II dose escalation study, treating patients with recurrence of glioblastoma with oral 5-ALA concurrent to radiotherapy (RT). This prospective single-center study based in the University Hospital Münster aims to recruit 30 patients over 18 years of age with histologically verified recurrence of supratentorial glioblastoma in good performance status (KPS ≥ 60). Following a 3 + 3 dose-escalation design, patients having undergone re-resection will receive a 36 Gy RT including radiodynamic therapy fractions (RDT). RDT constitutes of oral administration of 5-ALA before the irradiation session. Two cohorts will additionally receive two fractions of neoadjuvant treatment three and two days before surgery. To determine the maximum tolerated dose of repeated 5-ALA-administration, the number of RDT-fractions will increase, starting with one to a maximum of eight fractions, while closely monitoring for safety and toxicity. Follow-up will be performed at two and five months after treatment. Primary endpoint will be the maximum tolerated dose (MTD) of repeated ALA-administration, secondary endpoints are event-free-, progression-free-, and overall-survival. Additionally, 5-ALA metabolites and radiobiological markers will be analysed throughout the course of therapy and tissue effects after neoadjuvant treatment will be determined in resected tissue. This protocol is in accordance with the SPIRIT guidelines for clinical trial protocols., Discussion: This is the protocol of the ALA-RDT in GBM-study, the first-in-man evaluation of repeated administration of 5-ALA as a radiosensitizer for treatment of recurrent glioblastoma., Trial Registration: This study was approved by the local ethics committee of the Medical Association of Westphalia-Lippe and the University of Münster on 12.10.2022, the German federal institute for Drugs and medical devices on 13.10.2022 and the federal office for radiation protection on 29.08.2022. This trial was registered on the public European EudraCT database (EudraCT-No.: 2021-004631-92) and is registered under www.cliniclatrials.gov (Identifier: NCT05590689)., (© 2024. The Author(s).)

Background: The value of early postoperative 18F-FET-PET in patients with glioblastoma (GBM) is unclear. Five-aminolevulinic acid (5-ALA) is used for fluorescence-guided resections in these patients and previous data suggest that fluorescence and 18F-FET-PET both demarcate larger tumor volumes than gadolinium enhanced magnet resonance imaging (MRI)., Objective: To correlate fluorescence with enhancing volumes on postoperative MRI and 18F-FET-PET tumor volumes, and determine the value of postoperative 18F-FET-PET for predicting survival through observational study., Methods: GBM patients underwent fluorescence-guided resection after administration of 5-ALA followed by early postoperative MRI and 18F-FET-PET for determination of residual tissue volumes. All patients were treated with standard temozolomide radiochemotherapy and monitored for progression-free and overall survival (PFS, OS)., Results: A total of 31 patients were included. For functional reasons, residual 5-ALA derived fluorescent tissue was left unresected in 18 patients with a median 18F-FET-PET volume of 17.82 cm3 (interquartile range 6.50-29.19). In patients without residual fluorescence, median 18F-FET-PET volume was 1.20 cm3 (interquartile range 0.87-5.50) and complete resection of gadolinium enhancing tumor was observed in 100% of patients. A 18F-FET-PET volume of above 4.3 cm3 was associated with worse OS (logrank P-value ≤ .05), also in patients with no residual contrast enhancing tumor on MRI. More patients in whom fluorescencing tissue had been removed completely had postoperative 18F-FET-PET tumor volumes below 4.3 cm3., Conclusion: Postoperative 18F-FET-PET volumes predict OS and PFS. Resection of 5-ALA derived fluorescence beyond gadolinium enhancing tumor tissue leads to lower postoperative 18F-FET-PET tumor volumes and improved OS and PFS without additional deficits., (© Congress of Neurological Surgeons 2019.)