ideasIdea
Read the spinal fluid to track brain tumours without opening the skull
Fluid taken from the lower back contains DNA from brain tumours. Testing it can diagnose, monitor and detect resistance without brain surgery.
Cerebrospinal fluid ctDNA outperforms plasma for central nervous system tumours and detects leptomeningeal disease earlier than cytology or MRI in several studies, including paediatric brain tumours and lymphoma. Standardisation, assay validation and demonstrating that acting on the result improves outcomes are the missing pieces.
Hypothesis
Serial cerebrospinal fluid ctDNA detects central nervous system progression a median of two months before MRI and identifies resistance mutations that change treatment in at least a quarter of patients.
Rationale
Cerebrospinal fluid is a low-background compartment adjacent to the tumour, giving far higher tumour fraction than plasma. Lumbar puncture is routine, repeatable and cheap compared with any brain imaging or biopsy.
What would test it
A prospective monitoring cohort in glioma and in HER2-positive or ALK-positive brain metastasis with paired MRI, reporting lead time and the proportion of patients whose management changes.
Maturity
early clinical
Who has to act
clinic
Cost to try
Small (under $1M)
Years to first evidence
4
Bottlenecks it attacks
- The brain: barrier and sanctuary · Most drugs cannot cross into the brain, so brain tumours and brain metastases lag every other site.
- Dormant cells and minimal residual disease · After a 'successful' treatment, cells can sleep for years then relapse. We can barely detect them and cannot target them.
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.