Prospective study of ctDNA analysis during treatment of locally advanced resesctable gastric or gastroesophageal junction adenocarcinoma

Patients with locally advanced resectable (LAR) gastric/gastroesophageal junction (G/GEJ) adenocarcinomas have a high recurrence risk despite pre- and post-operative treatment. The PLAGAST prospective study, at the European Hospital Georges Pompidou (Paris, France) investigated the ability of circulating tumor DNA (ctDNA) to predict treatment response and improve risk stratification. Plasma samples were prospectively collecte befor neoadjuvant therapy (NAT), during NAT, post-NAT, and post-surgery. ctDNA-positivity decreased of these four therapeutic timelines. ctDNA-positivity was associated with significantly worse outcomes during NAT, post-NAT, and after surgery. Patients with early ctDNA clearance during NAT had better outcomes compared to those who cleared ctDNA post-NAT, while patients who remained ctDNA-positive pre-, during, and post-NAT had worse outcomes. The authors conclude that longitudinal ctDNA monitoring is prognostic of patient outcomes and may guide therapeutic decision-making in patients with LAR G/GEJ adenocarcinoma.