Glioblastoma
Glioblastoma is now defined as an IDH-wildtype tumour, with IDH-mutant tumours reclassified as astrocytoma. That reclassification matters: it means older literature on "glioblastoma" describes a partly different disease from the one the term now names.
Disease categories
Major disease categories
- Glioblastoma, IDH-wildtype
- Glioblastoma with specific molecular features
- Gliosarcoma
- Giant cell glioblastoma
Molecular
Molecular considerations
IDH-wildtype status is definitional. TERT promoter alteration, EGFR amplification and combined chromosome 7 gain with 10 loss support the diagnosis. MGMT promoter methylation status is central to treatment discussion.
Markers commonly discussed in glioblastoma
- IDH1 / IDH2 (wildtype)
- MGMT promoter methylation
- TERT promoter
- EGFR amplification
- +7/−10
- Methylation class
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Integrated histological and molecular diagnosis is standard. Methylation profiling is discussed for difficult cases.
Germline
Germline considerations
Considered where a syndromic pattern such as Li-Fraumeni is suggested.
Molecular monitoring
ctDNA and liquid biopsy considerations
Plasma ctDNA is limited by the blood–brain barrier; cerebrospinal fluid analysis is an active research area.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in neuro-oncology is used to characterise the cellular hierarchy within a tumour, including the stem-like populations implicated in recurrence, and to describe the immune compartment that bulk profiling represents poorly. Single-cell DNA analysis addresses regional heterogeneity, which is pronounced in glioma. Algorithm work is dominated by DNA methylation classification, which has become one of the more reliable diagnostic tools in difficult central nervous system cases, alongside cerebrospinal fluid analysis methods.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has MGMT promoter methylation status been assessed?
- Is the diagnosis integrated, confirming IDH-wildtype status?
- Has the extent of resection been documented?
Resistance
Resistance and recurrence questions
- Has pseudoprogression been distinguished from true progression?
- Has re-biopsy been considered where the imaging is ambiguous?
Trials
Clinical trial considerations
Molecular status and prior therapy are frequently determinative; trial participation is common in this disease.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.