High Grade Glioma, Low-grade Glioma
Conditions
Keywords
Prospective study, Patient-derived organoids
Brief summary
There is a high medical need to improve treatment outcome for high-grade and low-grade glioma since no curative treatment is available. To achieve this goal, a broader understanding is needed of the causes of inter-and intratumoral heterogeneity; glioma dedifferentiation and invasion; the major determinants of malignancy and treatment failure in glioma patients. Patient-derived organoid (PDOs) of high-grade gliomas and low-grade gliomas will be used to identify the mechanisms that underlie this malignant behaviour and treatment resistance. This insight may be used to develop patient avatars to simultaneously test multiple new treatment modalities that are predictive for survival and quality of life of glioma patients.
Detailed description
To establish primary patient-derived three-dimensional organoid cultures from low grade and high-grade gliomas to study the mechanisms that contribute to i.e. resistance to radiotherapy and/or chemotherapy and immunotherapy, dedifferentiation, tumor invasion among others, in primary and recurrent tumors. Primary Objectives: 1. Establishment of primary patient-derived organoids (PDO) of 'de novo' and recurrent high-grade glioma (HGG) and low-grade glioma (LGG) 2. Phenotypic, genetic, epigenetic and transcriptomic characterization of HGG and LGG organoids and resemblance to the parental tumor (i.e. characterization of specific cell populations and genomic and transcriptomic profiles of PDOs) 3. Investigation of combinations of new or standard glioma systemic treatments (i.e immunotherapy, chemotherapy) with or without radiation (i.e. protons, photons). Secondary objectives 1. Establishment of co-cultures of HGG and LGG organoids with immune cells. 2. Investigation of radiation-triggered cell death mechanisms on PDOs after irradiation with photons and protons. 3. Investigation of dedifferentiation mechanisms of LGG to HGG in the context of radiation w/wo immunotherapy.
Interventions
None listed
Sponsors
Maastricht Radiation Oncology
Maastricht University Medical Center
Zuyderland Medisch Centrum
Ziekenhuis Oost-Limburg
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* MRI diagnosis of low grade glioma (LGG) or high grade glioma (HGG) * Age 18 years or older * Patient is eligible for a resection of the tumor
Exclusion criteria
* Contra-inidication for neurosurgical resection of the tumor. * Incapacitated patient, unable to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phenotypic, genetic, epigenetic proteomic and transcriptomic profile of the LGG/HGG PDOs | Baseline tumor resection and blood sampling | Phenotypic, genetic, epigenetic proteomic and transcriptomic profile of the LGG/HGG PDOs will be performed after establishing PDO and the data will be compared with the phenotypic, genetic, epigenetic, proteomic and transcriptomic profile of the parental tumor. DNA isolated from peripheral blood will be used as normal reference DNA for (epi)genetic profiling. |
Countries
Netherlands
Contacts
CONTACTAnnika Noordink, Msc
CONTACTChantal Overhof
PRINCIPAL_INVESTIGATORMarc Vooijs, Prof. Dr.
Maastro Radiaton Oncology clinic
Outcome results
None listed