Clinical trial NCT05556382: Glioblastoma Evaluation for Heterogeneity In RadioseNsitivity
Official title: Glioblastoma Evaluation for Heterogeneity In RadioseNsitivity (GEHIRN): Preclinical Observational Study on Ex-vivo Surgical Specimens
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Glioblastoma
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2022-09-27
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Glioblastoma Patients eligible for surgical procedure.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Determination of distribution of number of γH2AX foci in each irradiated specimen (Nfoci) for each radiation dose level
timeFrame: 1 month
Secondary outcomes:
measure: correlation between n° of γH2AX foci and dose levels
timeFrame: 1 month
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Humanitas Clinical Institute
state: Milan
Study officials:
References: