A study used non-interventional, prospectively collected plasma from the ARIC cohort to assess a multi-cancer early detection (MCED) strategy using circulating tumor DNA (ctDNA). This unique design allowed for the observation of cancer’s natural progression.
In Phase I, analyzing “Early plasma samples” (collected ≤6 months before diagnosis) from 26 cancer cases and 26 controls, ctDNA was detected in 8 out of 26 cases (31% sensitivity), all of whom were diagnosed within four months. None of the controls tested positive. This detection was achieved using a targeted gene panel combined with aneuploidy analysis.
In Phase II, researchers designed highly sensitive, personalized mutation panels using whole-genome sequencing (WGS) of the Early plasma, which proved 10- to 46-fold more effective than the targeted panel. Re-analyzing “Very Early plasma samples” (collected ∼3 years prior to diagnosis) from six cases, ctDNA was detected in four of them (67%). Critically, the ctDNA mutant allele frequencies (MAFs) in the Very Early samples were a median of 45-fold lower than those in the Early samples.
The study establishes that ctDNA is detectable years before clinical diagnosis and sets a key benchmark: successful MCED detection three years out will require a sensitivity ∼50-fold greater than that needed for detection six months out. Future work must increase plasma volume and integrate other biomarkers to meet this goal.