JOURNAL ONKOLOGIE – STUDIE
XENOGBM
Andreas F Hottinger, MD-PhD
Study Chair
CHUV Lausanne University Hospital
Andreas F Hottinger, MD-PhD
Kontakt:
Phone: +41 21 314 0168
E-Mail: andreas.hottinger@chuv.ch» Kontaktdaten anzeigen
Laurence Benoit
Kontakt:
Phone: +41 21 314 0168
E-Mail: laurence.benoit@chuv.ch» Kontaktdaten anzeigen
Studienlocations
CHUV, University Hospital Lausanne
1066 Lausanne
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Andreas F Hottinger, MD, PhD
Phone: +41 21 314 0168
E-Mail: andreas.hottinger@chuv.ch
Laurence Benoit
Phone: +41 21 314 0168
E-Mail: laurence.benoit@chuv.ch» Ansprechpartner anzeigen
The presented project will focus on the evaluation of a multimodal approach comparing human
GBM to paired samples of orthotopic xenografts using high resolution MRI and MRS and
multidimensional molecular profiling.
20 patients with a high probability for newly diagnosed GBM based on MRI-scan ( 3 Tesla (3T)
MRI, T1, T2, T1 gadolinium, DWI & MRI Spectroscopy) will be identified in the CHUV prior to
undergoing neurosurgical resection. Patients will undergo extensive experimental radiological
examination using specific MRI sequences on the 7 Tesla (7T) MRI to identify specific
metabolic pathways (see below, section on imaging). Thereafter patients will undergo maximal
safe neurosurgical resection of their tumors. The portion of the tumor that is not used for
diagnostic purposes will be collected immediately for further use (see below, section on
molecular evaluations). Following resection, patients will undergo standard of care treatment
[usually combined radio-chemotherapy, or will be offered participation in a clinical trial.
The clinical parameters will be collected, including histopathological features and the
evolution and growth pattern of the residual tumor (if present), or the development of
recurrences will thereafter be compared to the parameters and evolution of the xenograft
models.
At high magnet field strength (7T), high signal-to-noise ratio and increased spectral
dispersion allow more reliable measurement of a large number of metabolites using Magnetic
Resonance Spectroscopy in comparison to clinical available field strengths (3T and below). In
addition, the authors have developed a full sensitivity short-echo-time single voxel
spectroscopy (SVS) sequence "semi-adiabatic SPECIAL"(2) which was implemented, validated at
7T and allows the quantification of 15 metabolites with high precision including
N-acetylaspartate(NAA), glutamine(Gln), glutamate(Glu), myo-inositol(Ins),
phosphorylethanolamine(PE), total choline(tCho), creatine, phosphocreatine,
N-acetylaspartylglutamate(NAAG), lactate(Lac), glutathione(GSH), aspartate (Asp),
taurine(Tau), scyllo-inositol and γ-aminobutyric acid(GABA). This localization technique was
further extended to a MR Spectroscopic Imaging (MRSI) technique at 7T, which allows mapping
of the spatial distributions of cerebral metabolites. Furthermore, glycine is a possible
marker for tumor malignancy and its detection in vivo has been established in our previous
study using TE=30ms with SPECIAL sequence at 7T. Therefore, in this study the aforementioned
techniques will be used to obtain the neurochemical information and its spatial distribution
in the glioblastoma of the patients. These data will be further compared with the
neurochemical information obtained in the orthotopic xenografts in the mouse brain derived
from the respective glioblastoma patient.
All MRS measurements of glioblastoma patients will be performed on a 7T MR scanner with a CP
Transmit / 32 channel receive array head coil. Based on the high resolution T1-weighted
images obtained using the MP2RAGE sequence, Volume of Interest (VOI) for spectroscopy will be
placed according to the location of the glioblastoma. Total acquisition time of MRS will be
within 30 min. In vivo MRS spectra will be post-processed and metabolite concentrations will
be quantified to create metabolite maps.
Molecular and functional investigations of paired samples of primary glioblastoma and
respective orthotopic xenografts in the mouse
The aim of the present study is to determine the molecular, histopathological, and functional
properties, including growth patterns such as invasiveness, of the original GBM and the
respective derived orthotopic xenografts in the mouse, and link them to imaging/ metabolism
parameters obtained by high resolution MRI.
GBM samples from patients collected at surgery will be divided into 2 parts, (i) snap frozen
for molecular analyses, and (ii) cultivated under stem cell conditions for subsequent
stereotactic transplantation into male immune-compromised mice and establishment of sphere
lines.
- High level of suspicion of glioblastoma
- Planned neurosurgical resection
- Adequate bone marrow function
- Adequate liver and kidney function
Exclusion Criteria:
- inability to undergo MRI
- inability to undergo neurosurgical resection
1. GBM metabolites using high resolution spectroscopy (Time Frame - 2 years):
High resolution spectroscopy metabolite analysis of GBM
2. Next generation sequencing of GBM tumor tissue (Time Frame - 2 years):
Molecular comparison of primary GBM tumor and paired orthotropic xenograft
Glioblastoma: Validation and Comparison Between Primary Tumor and Its Murine Model
Rekrutierend
NCT-Nummer:
NCT02904525
Studienbeginn:
Juni 2015
Letztes Update:
27.01.2021
Wirkstoff:
-
Indikation (Clinical Trials):
Glioblastoma
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
-
Sponsor:
Andreas Hottinger
Collaborator:
Ecole Polytechnique Fédérale de Lausanne
Studienleiter
Study Chair
CHUV Lausanne University Hospital
Kontakt
Kontakt:
Phone: +41 21 314 0168
E-Mail: andreas.hottinger@chuv.ch» Kontaktdaten anzeigen
Kontakt:
Phone: +41 21 314 0168
E-Mail: laurence.benoit@chuv.ch» Kontaktdaten anzeigen
Studienlocations
(1 von 1)
1066 Lausanne
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Andreas F Hottinger, MD, PhD
Phone: +41 21 314 0168
E-Mail: andreas.hottinger@chuv.ch
Laurence Benoit
Phone: +41 21 314 0168
E-Mail: laurence.benoit@chuv.ch» Ansprechpartner anzeigen
Studien-Informationen
Detailed Description:The presented project will focus on the evaluation of a multimodal approach comparing human
GBM to paired samples of orthotopic xenografts using high resolution MRI and MRS and
multidimensional molecular profiling.
20 patients with a high probability for newly diagnosed GBM based on MRI-scan ( 3 Tesla (3T)
MRI, T1, T2, T1 gadolinium, DWI & MRI Spectroscopy) will be identified in the CHUV prior to
undergoing neurosurgical resection. Patients will undergo extensive experimental radiological
examination using specific MRI sequences on the 7 Tesla (7T) MRI to identify specific
metabolic pathways (see below, section on imaging). Thereafter patients will undergo maximal
safe neurosurgical resection of their tumors. The portion of the tumor that is not used for
diagnostic purposes will be collected immediately for further use (see below, section on
molecular evaluations). Following resection, patients will undergo standard of care treatment
[usually combined radio-chemotherapy, or will be offered participation in a clinical trial.
The clinical parameters will be collected, including histopathological features and the
evolution and growth pattern of the residual tumor (if present), or the development of
recurrences will thereafter be compared to the parameters and evolution of the xenograft
models.
At high magnet field strength (7T), high signal-to-noise ratio and increased spectral
dispersion allow more reliable measurement of a large number of metabolites using Magnetic
Resonance Spectroscopy in comparison to clinical available field strengths (3T and below). In
addition, the authors have developed a full sensitivity short-echo-time single voxel
spectroscopy (SVS) sequence "semi-adiabatic SPECIAL"(2) which was implemented, validated at
7T and allows the quantification of 15 metabolites with high precision including
N-acetylaspartate(NAA), glutamine(Gln), glutamate(Glu), myo-inositol(Ins),
phosphorylethanolamine(PE), total choline(tCho), creatine, phosphocreatine,
N-acetylaspartylglutamate(NAAG), lactate(Lac), glutathione(GSH), aspartate (Asp),
taurine(Tau), scyllo-inositol and γ-aminobutyric acid(GABA). This localization technique was
further extended to a MR Spectroscopic Imaging (MRSI) technique at 7T, which allows mapping
of the spatial distributions of cerebral metabolites. Furthermore, glycine is a possible
marker for tumor malignancy and its detection in vivo has been established in our previous
study using TE=30ms with SPECIAL sequence at 7T. Therefore, in this study the aforementioned
techniques will be used to obtain the neurochemical information and its spatial distribution
in the glioblastoma of the patients. These data will be further compared with the
neurochemical information obtained in the orthotopic xenografts in the mouse brain derived
from the respective glioblastoma patient.
All MRS measurements of glioblastoma patients will be performed on a 7T MR scanner with a CP
Transmit / 32 channel receive array head coil. Based on the high resolution T1-weighted
images obtained using the MP2RAGE sequence, Volume of Interest (VOI) for spectroscopy will be
placed according to the location of the glioblastoma. Total acquisition time of MRS will be
within 30 min. In vivo MRS spectra will be post-processed and metabolite concentrations will
be quantified to create metabolite maps.
Molecular and functional investigations of paired samples of primary glioblastoma and
respective orthotopic xenografts in the mouse
The aim of the present study is to determine the molecular, histopathological, and functional
properties, including growth patterns such as invasiveness, of the original GBM and the
respective derived orthotopic xenografts in the mouse, and link them to imaging/ metabolism
parameters obtained by high resolution MRI.
GBM samples from patients collected at surgery will be divided into 2 parts, (i) snap frozen
for molecular analyses, and (ii) cultivated under stem cell conditions for subsequent
stereotactic transplantation into male immune-compromised mice and establishment of sphere
lines.
Ein-/Ausschlusskriterien
Inclusion Criteria:- High level of suspicion of glioblastoma
- Planned neurosurgical resection
- Adequate bone marrow function
- Adequate liver and kidney function
Exclusion Criteria:
- inability to undergo MRI
- inability to undergo neurosurgical resection
Studien-Rationale
Primary outcome:1. GBM metabolites using high resolution spectroscopy (Time Frame - 2 years):
High resolution spectroscopy metabolite analysis of GBM
2. Next generation sequencing of GBM tumor tissue (Time Frame - 2 years):
Molecular comparison of primary GBM tumor and paired orthotropic xenograft
Geprüfte Regime
- 7 Tesla MRI, no contrast agent:
Patients with newly diagnosed glioblastoma undergo a 7Tesla MRI
Quelle: ClinicalTrials.gov
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