ideasIdea
Whole-body MRI plus blood DNA surveillance for people with Li-Fraumeni syndrome
People with an inherited TP53 mutation face a near-certain lifetime cancer risk. Yearly whole-body MRI catches cancers early; adding blood DNA tests may catch them earlier still.
The Toronto Protocol (whole-body MRI, brain MRI, ultrasound) improved survival in Li-Fraumeni syndrome. Propose a global registry with standardised imaging and prospective cell-free DNA and fragmentomics testing, to determine whether blood adds lead time over imaging.
Hypothesis
Adding cell-free DNA surveillance to imaging detects at least 30% of incident cancers before imaging, with lead time of six months or more.
Rationale
Very high prior probability makes positive predictive value acceptable, and the multiplicity of tumour types favours a tumour-agnostic blood test.
What would test it
Follow a 1,000-carrier prospective cohort over five years.
Maturity
early clinical
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
5
Bottlenecks it attacks
- Inherited risk is mostly unidentified · Most people who carry a high-risk cancer gene do not know it until they or a relative gets cancer.
- Most lethal cancers are found late · Screening exists for only a few cancers. Pancreatic, ovarian, liver, oesophageal and most lung cancers are found when cure is unlikely.