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.
Age between 18 and 75 years.
Unifocal disease.
Unilobar tumor.
Clinical-radiological diagnosis of supratentorial unicentric high-grade glioma, eligible for macroscopically complete resection.
Multilobar tumor, interhemispheric or infratentorial extension, or multifocal disease.
Midline shift greater than 1 cm.
Intracranial hypertension symptoms requiring corticosteroid treatment.
Synchronous neoplasia.
Parallel
hypofractionated stereotactic radiotherapy
Radiationconformal 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, one session per day, five days a week, and concurrent temozolomide (TMZ) at 75 mg/m2/day for 7 days/week during the irradiation period
Stereotactic biopsy
Procedure/SurgeryStereotactic biopsy
resection
Procedure/Surgerysupramarginal resection guided by 5-ALA under intraoperative neurophysiological monitoring
Chemotherapy
Drug4 weeks post-surgery, temozolomide (TMZ) will be administered for 6 months
radiotherapy Stupp protocol
Radiationradiotherapy + TMZ concurrently after 4 weeks of resection surgery, as per usual protocol: Three-dimensional radiotherapy planning to deliver a total dose of 60 Gy, with a fractionation of 2 Gy/day, 5 days/week, encompassing a 1-2 cm margin around the contrast-enhancing region defined on T1 imaging or the entire abnormal volume defined on T2 or FLAIR imaging (Li et al., 2016) + TMZ at 75 mg/m2/day for 7 days/week, for 6 weeks during radiotherapy.
Chemotherapy Stupp Protocol
Drugtemozolomide (TMZ) will be administered for 6 months according to the Stupp protocol.
Emergent Adverse Events assessed by physical and neurological examination
Information on adverse events will be reviewed through direct questioning of the patient.
Emergent Adverse Events assessed by evaluation of the results of the analysis with hematology and biochemistry.
Information on adverse events will be reviewed through the results of examinations, complementary tests and analytical parameters.
Emergent Adverse Events assessed by brain RM image
brain RM image, for neuroradiological follow-up
Emergent Adverse Events assessed by AC_PET with 18-FdG
AC\_PET image, for neuroradiological follow-up
Efficacy assessed by progression-free survival (PFS)
Progression-free survival (PFS), a measure of how long a patient receives treatment before the cancer begins to grow.
Efficacy assessed by overall survival (OS)
Overall survival (OS), how long patients live after starting treatment.
Quality of life assessed by The Functional Assessment of Cancer Therapy-Brain (FACT-Br)
A commonly used instrument measuring general quality of life (QOL) that reflects symptoms or problems associated with brain malignancies across 5 scales. Patients rate all 5 items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher QOL
Cognitive functionality assessed by MONTREAL COGNITIVE ASSESSMENT (MOCA)
It has been shown to be useful at detecting cognitive dysfunction in brain metastases. The test is a one-page, 30-point test that can be administered in 10 minutes. It assesses short-term memory recall (5 points), visuospatial abilities through clock-drawing (3 points) and cube copy (1 point), and orientation (6 points). Executive function is assessed through modified Trail Making Part B (1 point), phonemic fluency (1 point), and verbal abstraction (2 points). A sustained-attention task (1 point), digit span (2 points), and serial calculation (3 points) test attention, concentration, and working memory. And lastly, language is assessed through naming low-familiarity animals (3 points), sentence repetition (2 points), and the fluency task
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Hospital San Carlos, Madrid
Lead sponsor
Asociación de Afectados Por Tumores Cerebrales en España (ASATE)
Collaborator
