Utilizing Combined Circulating Tumor DNA and Tumor Markers to Evaluate Neoadjuvant Therapy Response and Predict Recurrence in Patients with Locally Advanced Gastric Cancer.

[BACKGROUND] Accurately assessing treatment response and predicting recurrence in patients with locally advanced gastric cancer undergoing neoadjuvant chemotherapy is challenging. This study explores the use of circulating tumor DNA (ctDNA) and its combination with tumor markers (TM) for this purpose.

[PATIENTS AND METHODS] We retrospectively analyzed 44 patients, collecting plasma samples at pretreatment (T0), after neoadjuvant chemotherapy (T1), and 3-10 days after surgery (T2), along with tissue samples. Tumor markers (TMs), including carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9, CA72-4, CA125, and CA242, were also measured.

[RESULTS] ctDNA was detected in 64.1% of patients at T0, gradually decreasing to 41.0% at T1 and further to 33.3% at T2. Among those with ctDNA-positive at T0, 64.3% of the responders achieved ctDNA clearance, whereas only 8.3% of the non-responders exhibited this outcome (P = 0.005). When being positive at either T0 or T1 was defined as positive, 66.7% of patients were ctDNA positive, and 51.3% were TM positive. Combining both markers increased the overall positive rate to 94.9%. In assessing treatment effectiveness, the agreement with pathological response is 83.8%, higher than using ctDNA alone (76.9%) or TM (80.0%). After surgery, patients with ctDNA positive or TM positive (ctDNA+/TM+) showed worse overall survival (OS, HR 14.667; P < 0.001) compared with those negative for both (ctDNA-/TM-). ctDNA+/TM+ was an independent prognostic factor in a multivariate Cox analysis (adjusted HR 9.771, P = 0.045).

[CONCLUSIONS] ctDNA demonstrates promise as a predictive marker for NACT response and recurrence risk. TMs can be cross complemented with ctDNA to better evaluate patient outcomes and enable more patients to be accurately evaluated.