The long-touted, far-reaching predictive potential of circulating tumor DNA (ctDNA) has been realized in this huge international prospective observational study of 1127 patients with non-small cell lung cancer receiving ctDNA-guided treatment. Independent of all other clinical and imaging data, the two-thirds of patients (n=722) with detectable levels of ctDNA had double the risk of death (HR 2.05). Fortunately this did not hold true for the quarter of those (n=255) with actionable mutations matched to targeted therapies. Perhaps most intriguing was the detection in one quarter of patients of “subclonal drivers of resistance,” meaning tumor alterations were present in ctDNA but not present in tissue samples and were heavily weighted towards non-targetable mutations such as RICTOR and PIK3CA.
- Jee, Nat Med 2022