Journal: European journal of human genetics : EJHG
This publication describes the design and aims of the CHARM2 trial, a Canadian, prospective randomized controlled study evaluating cell-free DNA (cfDNA)–based multi-cancer early detection in individuals with hereditary cancer syndromes.
Key points:
- Population: 1000 adults with high-risk germline syndromes: Hereditary Breast and Ovarian Cancer, Lynch syndrome, Li-Fraumeni syndrome, Neurofibromatosis type 1, and Hereditary Diffuse Gastric Cancer.
- Study design:
- Standard surveillance: All participants continue standard, syndrome-specific surveillance (imaging, endoscopy, etc.).
- Randomization (1:1):
- Control arm: standard surveillance only.
- Experimental arm: standard surveillance plus cfDNA testing at least three times per year.
- Follow-up after abnormal cfDNA: Abnormal cfDNA results prompt targeted clinical imaging, diagnostic work-up, and intensified surveillance.
- Rationale:
- High-risk individuals face substantial cancer burden and mortality, but current surveillance is time-consuming, logistically difficult, and anxiety-provoking.
- cfDNA-based multi-cancer tests may detect cancers earlier and potentially more sensitively than current single-organ screenings, while being more convenient.
- Outcomes:
- Clinical: feasibility and performance of adding cfDNA to standard surveillance, and the downstream diagnostic evaluation triggered by positive findings.
- Patient-centered: psychosocial impact, engagement with surveillance, and preferences, assessed using validated patient-reported outcome and experience measures in both arms.
- Equity: the trial specifically aims to inform how cfDNA testing could be integrated into routine care to improve equitable access to early detection for high-risk Canadians.
Overall: The study is positioned as a platform to determine whether cfDNA-based multi-cancer early detection can augment existing hereditary cancer surveillance in a clinically acceptable, patient-centered, and scalable way.