Glioblastoma Evaluation for Heterogeneity In RadioseNsitivity

Study Overview
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Brief Summary
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This is an observational study on GBM surgical samples to investigate if increasing doses of radiation therapy could improve the radiation response; and in particular the investigators will assess if there is a correlation between the number of the phosphorylated H2AX nuclear foci and the different dose level of radiation therapy.

Detailed Description
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Standard of care for newly diagnosed glioblastoma (GBM) patients consists of surgical resection followed by radiotherapy with concurrent and adjuvant Temozolomide chemotherapy. Despite these treatments, the prognosis remains poor. Nevertheless, preliminary data on GBM patients show variable outcomes related to a different treatment response, that could be related to the GBM intrinsic heterogeneity, but also to a different patient sensitivity to radiation therapy. The assessment of this individual radio-sensitivity may provide valuable data to define more tailored treatment schedules, that could potentially be more effective. Published studies on small cohort of patients show that a possible system to investigate the tumor radiation sensitivity, is to monitor the cellular DNA damage after tissue irradiation, that correlates with the survival fraction of in vitro tumor cells; the DNA damage could be identified through the quantification of Phosphorylated histone H2AX nuclear foci that correlate with the unrepaired DNA double strand breaks (DSBs). Based on this background, The investigators designed an observational study on GBM surgical samples to investigate if increasing doses of radiation therapy could improve the radiation response; and in particular they will assess if there is a correlation between the number of the phosphorylated H2AX nuclear foci and the different dose level of radiation therapy.

Official Title
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Glioblastoma Evaluation for Heterogeneity In RadioseNsitivity (GEHIRN): Preclinical Observational Study on Ex-vivo Surgical Specimens

Conditions
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Glioblastoma

Intervention / Treatment
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* Radiation: radiation of brain tissue specimen and dna damage analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged >18 years Patients eligible for diagnostic or therapeutic surgical procedure Written informed consent Histopathologically confirmed newly diagnosed glioblastoma according to WHO 2021 Availability of fresh tissue samples Exclusion Criteria: Other extra-cranial cancer Non GBM glioma Previous brain radiation therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Radiation: radiation of brain tissue specimen and dna damage analysis|increasing doses of radiation on brain tissue specimen and analysis of related dna damage.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of distribution of number of γH2AX foci in each irradiated specimen (Nfoci) for each radiation dose level | Number of foci per irradiated sample (Nfoci) for each dose level expressed as [(number of observed γH2AX foci per selected dose level)-(number of observed γH2AX foci in control unirradiated sample)]. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| correlation between n° of γH2AX foci and dose levels | this correlation will be described by the slope for each sample Nfoci at increasing dose levels | 1 month |