Leal A, van Grieken NCT, Palsgrove DN, et al. 

Despite major breakthroughs in precision medicine, the survival of patients with gastric cancer (GC) is still poor. Gastric cancer remains a clinically challenging disease, characterized by lacking of effective treatment options and the need of accurate molecular tools for the prediction of patient outcome and response to therapy. Novel non-invasive biomarkers are required to detect residual disease after curative treatment and identify patients with a high risk of recurrence.

Patients with resectable GC were recruited for a phase III randomized controlled study of perioperative treatment. The current study demonstrates how ultrasensitive targeted sequencing analyses of matched cell-free DNA (cfDNA) and white blood cells (WBC) are able to distinguish ctDNA alterations from genomic aberrations associated with clonal hematopoiesis. The present article highlights that sequencing matched cfDNA and WBC detects accurately tumor-specific mutations in cfDNA, without requiring tumor tissue, after neoadjuvant chemotherapy and curative surgery in patients with operable GC. The detection of ctDNA at the preoperative and postoperative timepoints was also associated with higher risk of recurrence and shorter median OS.