Glioblastoma Evaluation for Heterogeneity In RadioseNsitivity

Recruiting

• Conditions: Glioblastoma

• Registration Number: NCT05556382
• Lead Sponsor: Istituto Clinico Humanitas

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.

Study Timeline

• Study Start: 2022-06-28
• Study First Submitted: 2022-09-22
• Study First Submitted QC: 2022-09-22
• Study First Posted: 2022-09-27
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-04
• Last Update Posted: 2022-10-06
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
correlation between n° of γH2AX foci and dose levels	1 month	this correlation will be described by the slope for each sample Nfoci at increasing dose levels

Trial Locations

Locations (1)

Humanitas Clinical Institute; 🇮🇹 Rozzano, Milan, Italy