Decision-Making Analysis of next generation sequencing in glioblastoma in Switzerland
| Kurzfassung |
Glioblastoma is the most frequent and most malignant primary brain
tumour with an annual incidence of 3.2/100’000 1,2. The
combination of histopathological features (nuclear atypia, mitosis,
neoangiogenesis and/or necrosis) and molecular aberrations (IDH 1/2
status, TERT-promotor mutations) leads to the integrated diagnosis
of the common IDH-wildtype glioblastoma. Additionally, the gain of
chromosome 7 and loss of chromosome 10 as well as
EGFR-overexpression and other mutations (EGFRvIII variant) are
genetic hallmarks of glioblastomas leading to the diagnosis of
diffuse gliomas with molecular features of glioblastoma, when
histological criteria are missing 3.Glioblastoma is common in the
elderly but quite rare in young adults with an annual incidence of
0.41 and 1.23/100000 in 20-34 and 35-44 year-old patients,
respectively. In the typically elderly glioblastoma patients (65-74
years) the incidence is 20 to 10-fold higher (13.09/100000) 2.
Younger glioblastoma patients sometimes harbour an unusual genotype
(i.e. IDH-aberrations) 2,4. IDH-mutant glioblastoma account for 10%
of all glioblastoma with a median age of manifestation of 45 years
5. These glioblastoma arise from lower grade gliomas through
malignant progression and have a far better prognosis as their
IDH-wildtype counterparts 6. However, overall survival of
glioblastoma patients is grim and most recent clinical phase III
studies failed to improve the prognosis using various therapeutic
strategies7. ”Actionable” mutations in the BRAF gene and
NTRK gene fusions are mostly found in younger glioblastoma patients
or in glioblastoma subtypes such as epitheloid glioblastoma 5,7.
However, at which age to search for actionable mutations remains
undefined. Furthermore, there is no consensus which genetic
aberrations should be screened for (i.e. glioblastoma panel) and
which technique is best suited to detect these aberrations
(mutations, fusions) remains to be defined. Of note, actionable gene
mutations in glioblastoma a rare. In a recent study of 48
glioblastomas, genetic aberrations were found in only 30 of 212
genes (14%) investigated 8. Beside mutations in the TP53, IDH1, EGFR
and PTEN genes, EGFR and CDK4 amplifications as well as CDKN2A
deletions were the most frequent copy number alterations. CDK4/6 and
PI3K inhibitors were used in this cohort to target the detected
aberrations in this small cohort of glioblastoma patients. When considering these criteria, individual decision makers may use a wide variety of decision making criteria 9 and these often differ among clinical experts or hospitals 10-15. We will perform a decision-making analysis of decision criteria regarding the application of next generation sequencing in glioblastoma among Swiss neuro-oncology centres on. This project will be performed among the members of the SWISS neuro-oncology society (SWISS-NOS). The group is motivated to collaborate, setting up new clinical |
| Projektpartner | SwissNOS; Swiss society of neuro-oncology |
| Art des Forschungsprojektes | Klinische Forschung |
| Status | Automatically closed |
| Projektstart | 2021 |
| Projektende | 2021 |
| Verantwortliche Person / Hauptprüfarzt am KSSG | PD Dr. Thomas Hundsberger |