Multicenter retrospective analysis of circulating tumor DNA to inform clinical practice in patients with recurrent or metastatic gastroesophageal cancers

In advanced esophageal and gastric cancer (aEGC), circulating tumor DNA (ctDNA) dynamics are poorly understood. A multicenter retrospective analysis of 200 aECG patients (cohort A, n=36; stage I-III with recurrence, and cohort B, n=164, metastatic at diagnosis) evaluated the clinical utility of ctDNA assessment. In cohort A, 31 of 36 patients (86%) had ctDNA collected ≤ 90 days before recurrence; of these, 25 of 31 (81%) were ctDNA-positive before recurrence. In cohort B, baseline ctDNA was available for 29 or 164 patients (18%) and all 29 were ctDNA-positive. Among 52 patients who had on-treatment ctDNA assessments, 62 treatment lines were analyzed. All patients who remained ctDNA-negative throughout treatment (Neg-Neg) showed treatment benefit, whereas those who converted to ctDNA-positive (Neg-Pos) progressed. Patients who cleared ctDNA (Pos-Neg) had favorable outcomes. A decrease > 90% in ctDNA levels among Pos-Pos patients was linked to superior progression-free survival. Grouping treatment lines into favorable (Neg-Neg, Pos-Neg, and Pos-Pos with > 90% decrease) versus unfavorable (Neg-Pos and Pos-Pos with a < 90% decrease or an increase) had significantly improved progression-free survival in the favorable group (p<0.0001). The authors conclude that ctDNA dynamics predicted progression and may guide treatment or imaging. ctDNA offers a minimally invasive, cost-effective adjunct to radiographic surveillance.