The early detection of relapse following primary surgery for non-small-cell lung cancer
and the characterization of emerging subclones, which seed metastatic sites, might
offer new therapeutic approaches for limiting tumour recurrence. The ability to track
the evolutionary dynamics of early-stage lung cancer non-invasively in circulating
tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic
approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung
Cancer Evolution Through Therapy (Rx)) study participants, including one patient who
was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment)
post-mortem study. We identify independent predictors of ctDNA release and analyse
the tumour-volume detection limit. Through blinded profiling of postoperative plasma,
we observe evidence of adjuvant chemotherapy resistance and identify patients who
are very likely to experience recurrence of their lung cancer. Finally, we show that
phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and
metastasis, providing a new approach for ctDNA-driven therapeutic studies.
