Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

Neoadjuvant Radio-chemotherapy Safety Pilot Study in Patients With Glioblastoma

The goal of this clinical trial is to evaluate the safety and efficacy of neoadjuvant radiochemotherapy in the surgical resection of glioblastoma (GBM). The main questions it aims to answer are:

• What is the safety profile of neoadjuvant radiochemotherapy in terms of neurological deficit, radionecrosis, edema, headache, wound dehiscence, infection, and cerebrospinal fluid fistula?
• What is the efficacy of neoadjuvant radiochemotherapy in terms of progression-free survival, overall survival, cognitive function, and quality of life?

Participants will undergo the following tasks and treatments:

• Stereotactic biopsy and diagnosis confirmation.
• Conformal hypofractionated stereotactic radiotherapy with concurrent temozolomide.
• Supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring.
• Maintenance temozolomide administration for 6 months.

Researchers will compare the group receiving neoadjuvant radiochemotherapy to the control group following the standard Stupp protocol to assess safety and efficacy outcomes.

Objectives: To study the safety (primary) and efficacy (secondary) of neoadjuvant radiochemotherapy in the surgical resection of glioblastoma (GBM). Safety measures include: neurological deficit, radionecrosis (radiological and clinical), edema, headache, wound dehiscence, infection, and cerebrospinal fluid fistula. Efficacy measures include progression-free survival (PFS), overall survival (OS), cognitive function (MoCA Scale), and quality of life (EuroQol scales, EORTC QLQ-HN35, FACT-Br, and TWiST). Methods: Pilot safety and efficacy study in 6 patients compared to 6 controls. 2-year follow-up. A data safety monitoring committee will review the data one month after surgery for each of the first three patients to decide whether to stop or continue the study. Stereotactic biopsy will be performed, and if GBM is diagnosed, patients will undergo conformal hypofractionated stereotactic radiotherapy to the FLAIR hyperintense signal including the contrast-enhancing tumor on T1, with a total dose of 3990 cGy at the margin in 15 fractions of 266 cGy and concurrent temozolomide (TMZ). 5 weeks later, patients will undergo supramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring. 7 days after surgery, maintenance TMZ will be administered for 6 months. The control group will follow standard treatment (Stupp protocol). Data analysis will be performed using non-parametric tests. Samples from successive surgeries will be studied with histology, molecular biology, and cell cultures.

Inclusion Criteria:

• Age between 18 and 75 years.
• Unifocal disease.
• Unilobar tumor.
• Clinical-radiological diagnosis of supratentorial unicentric high-grade glioma, eligible for macroscopically complete resection.

Exclusion Criteria:

• Multilobar tumor, interhemispheric or infratentorial extension, or multifocal disease.
• Midline shift greater than 1 cm.
• Intracranial hypertension symptoms requiring corticosteroid treatment.
• Synchronous neoplasia.
• Any contraindication for surgery, radiotherapy, or TMZ treatment.
• Cognitive impairment.
• Rejection of informed consent.
• Inability to follow up for 2 years.
• Women of childbearing potential according to the Clinical Trial Facilitation Group (CTFG) criteria. (https://www.hma.eu/fileadmin/dateien/Human\_Medicines/01-About\_HMA/Working\_Groups/CTFG/2020\_09\_HMA\_CTFG\_Contraception\_guidance\_Version\_1.1.pdf)
• Hypersensitivity to the active ingredient or any excipients of the investigational drug.