Ignite Creation Date:
2024-05-06 @ 5:37 PM
Last Modification Date:
2024-10-26 @ 2:32 PM
Study NCT ID:
NCT05375318
Status:
UNKNOWN
Last Update Posted:
2022-05-16
First Post:
2022-02-01
Brief Title:
BIOhabitats Biological Validation of Vascular Habitats Within Astrocytoma Grade 4 at Molecular Cellular and Histopathological Levels
Sponsor:
Juan M Garcia-Gomez
Organization:
Universitat Politècnica de València
Study Overview
Official Title:
BIOhabitats Biological Validation of Vascular Habitats Within Astrocytoma Grade 4 at Molecular Cellular and Histopathological Levels
Status:
UNKNOWN
Status Verified Date:
2022-02
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BIOhabitats
Brief Summary:
The main purposes of this study are
I To assess that the four habitats within the tumor HAT and LAT and edema IPE and VPE in high-grade glioma are different at vascular tissular cellular and molecular levels
II To analyze the associations between the perfusion imaging markers and relevant molecular markers at the HTS habitats for high-grade glioma diagnosis prognosisaggressiveness progression andor prediction
III To analyze the associations between the perfusion imaging markers and immune markers at the HTS habitats useful in immunotherapy evaluation andor patient selection
IV To prospectively validate the prognostic capacity association with OS and PFS and stratification capacity of the perfusion imaging markers calculated at the HTS habitats
I To assess that the four habitats within the tumor HAT and LAT and edema IPE and VPE in high-grade glioma are different at vascular tissular cellular and molecular levels
II To analyze the associations between the perfusion imaging markers and relevant molecular markers at the HTS habitats for high-grade glioma diagnosis prognosisaggressiveness progression andor prediction
III To analyze the associations between the perfusion imaging markers and immune markers at the HTS habitats useful in immunotherapy evaluation andor patient selection
IV To prospectively validate the prognostic capacity association with OS and PFS and stratification capacity of the perfusion imaging markers calculated at the HTS habitats
Detailed Description:
High-grade glioma HGG are the most aggressive malignant primary brain tumor in adults with a median survival rate of 12-15 months It still carries a poor prognosis despite aggressive treatment which includes tumor resection followed by chemo-radiotherapy cycles The inter-patient and intra-patient tumor heterogeneity is one of the responsible factors for the high aggressiveness of solid malignant tumors and their resistance against effective therapies
Due to the extremely complex and heterogeneous biology of this tumor the same treatment for all approach does not work well in this disease and standard of care is not always the best option calling for precision medicine to select the best therapeutic option in the right moment to each patient This requires quantitative medical imaging patient profiling prognosis estimation and expected response to treatment for objective decision making along with the patient management
The Hemodynamic Tissue Signature HTS methodology included in the ONCOhabitats site wwwoncohabitatsupves provides an automated unsupervised method to describe the heterogeneity of the enhancing tumor and edema areas in terms of the angiogenic process located at these regions HTS considers 4 habitats within the tumour 1 the HAT habitat which refers to the high angiogenic enhancing tumor part of the tumour 2 the LAT habitat which refers to the less angiogenic enhancing tumor area of the tumour 2 the IPE habitat which refers to the potentially infiltrated peripheral edema and 4 the VPE habitat which refers to the vasogenic peripheral edema of the tumour Juan-Albarracin et al 2016 Perfusion imaging markers such as relative cerebral blood volume can be calculated from these different vascular habitats and they have been proven as clinically relevant for prognosis The HTS methodology as well as the prognostic capacity of these perfusion imaging markers have been validated with a retrospective multicenter study that included 184 high-grade glioma patients from 7 European centers
Furthermore relevant associations have been found between the perfusion markers and clinical-routine biomarkers such as IDH mutation MGMT methylation Fuster-Garcia et al 2020 molecular subtype or microvessel area
Considering these promising results and in order to develop a decision support system based on pixel level Artificial Intelligent models for deciding treatment in high-grade glioma it is necessary to develop a prospective study and to validate at biological level the vascular habitats defined by the HTS methodology
The proposed objectives are based on the following hypothesis
I Since the tumor and edema HTS habitats HAT LAT IPE and VPE have been proven as different in relation to their hemodynamic and vascular behavior the main hypothesis are that these are habitats are also significantly different at the vascular tissular cellular and molecular level
II Significant associations between the perfusion imaging markers calculated with the HTS methodology and both molecular and histopathological markers useful in prognosis monitoring and evaluation of therapies have been found in previous studies Therefore the hypothesis are that relevant associations between the imaging markers and clinical-routine biomarkers such as molecular and histopathological markers exist
III Preliminary studies have shown associations between the perfusion imaging markers and molecular markers related with the immune actionsuppression In addition previous works have demonstrated that immune and genomic correlates of response to immunotherapy treatments such as anti-PD-1 in glioblastoma Therefore to find correlations between these immune and genomic signatures with perfusion imaging markers can be useful for decision making and evaluation of immunotherapies
IV Preliminary retrospective studies have demonstrated robust association between the perfusion imaging markers calculated at high and low angiogenic habitats and patient overall survival These robust associations between the perfusion imaging markers and survival times will be demonstrated with a prospective study
Due to the extremely complex and heterogeneous biology of this tumor the same treatment for all approach does not work well in this disease and standard of care is not always the best option calling for precision medicine to select the best therapeutic option in the right moment to each patient This requires quantitative medical imaging patient profiling prognosis estimation and expected response to treatment for objective decision making along with the patient management
The Hemodynamic Tissue Signature HTS methodology included in the ONCOhabitats site wwwoncohabitatsupves provides an automated unsupervised method to describe the heterogeneity of the enhancing tumor and edema areas in terms of the angiogenic process located at these regions HTS considers 4 habitats within the tumour 1 the HAT habitat which refers to the high angiogenic enhancing tumor part of the tumour 2 the LAT habitat which refers to the less angiogenic enhancing tumor area of the tumour 2 the IPE habitat which refers to the potentially infiltrated peripheral edema and 4 the VPE habitat which refers to the vasogenic peripheral edema of the tumour Juan-Albarracin et al 2016 Perfusion imaging markers such as relative cerebral blood volume can be calculated from these different vascular habitats and they have been proven as clinically relevant for prognosis The HTS methodology as well as the prognostic capacity of these perfusion imaging markers have been validated with a retrospective multicenter study that included 184 high-grade glioma patients from 7 European centers
Furthermore relevant associations have been found between the perfusion markers and clinical-routine biomarkers such as IDH mutation MGMT methylation Fuster-Garcia et al 2020 molecular subtype or microvessel area
Considering these promising results and in order to develop a decision support system based on pixel level Artificial Intelligent models for deciding treatment in high-grade glioma it is necessary to develop a prospective study and to validate at biological level the vascular habitats defined by the HTS methodology
The proposed objectives are based on the following hypothesis
I Since the tumor and edema HTS habitats HAT LAT IPE and VPE have been proven as different in relation to their hemodynamic and vascular behavior the main hypothesis are that these are habitats are also significantly different at the vascular tissular cellular and molecular level
II Significant associations between the perfusion imaging markers calculated with the HTS methodology and both molecular and histopathological markers useful in prognosis monitoring and evaluation of therapies have been found in previous studies Therefore the hypothesis are that relevant associations between the imaging markers and clinical-routine biomarkers such as molecular and histopathological markers exist
III Preliminary studies have shown associations between the perfusion imaging markers and molecular markers related with the immune actionsuppression In addition previous works have demonstrated that immune and genomic correlates of response to immunotherapy treatments such as anti-PD-1 in glioblastoma Therefore to find correlations between these immune and genomic signatures with perfusion imaging markers can be useful for decision making and evaluation of immunotherapies
IV Preliminary retrospective studies have demonstrated robust association between the perfusion imaging markers calculated at high and low angiogenic habitats and patient overall survival These robust associations between the perfusion imaging markers and survival times will be demonstrated with a prospective study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None