Zhu Honglin, Jia Yongning, Pang Fei, Xing Xiaofang, Li Shuangxi, Shan Fei, Li Ziyu
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Ann Surg Oncol. 2025 Jun 3. doi: 10.1245/s10434-025-17397-4.
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.
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.
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).
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.
准确评估接受新辅助化疗的局部晚期胃癌患者的治疗反应并预测复发具有挑战性。本研究探讨了循环肿瘤DNA（ctDNA）及其与肿瘤标志物（TM）联合用于此目的的情况。
我们回顾性分析了44例患者，在治疗前（T0）、新辅助化疗后（T1）以及术后3 - 10天（T2）采集血浆样本，并采集组织样本。还检测了肿瘤标志物（TMs），包括癌胚抗原（CEA）、糖类抗原（CA）19 - 9、CA72 - 4、CA125和CA242。
在T0时，64.1%的患者检测到ctDNA，在T1时逐渐降至41.0%，在T2时进一步降至33.3%。在T0时ctDNA阳性的患者中，64.3%的反应者实现了ctDNA清除，而无反应者中只有8.3%出现此结果（P = 0.005）。当将T0或T1时阳性定义为阳性时，66.7%的患者ctDNA阳性，51.3%的患者TM阳性。两种标志物联合使用使总体阳性率提高到94.9%。在评估治疗效果时，与病理反应的一致性为83.8%，高于单独使用ctDNA（76.9%）或TM（80.0%）。术后，ctDNA阳性或TM阳性（ctDNA+/TM+）的患者与两者均为阴性（ctDNA-/TM-）的患者相比，总生存期（OS，HR 14.667；P < 0.001）更差。在多因素Cox分析中，ctDNA+/TM+是一个独立的预后因素（校正HR 9.771，P = 0.045）。
ctDNA有望作为新辅助化疗反应和复发风险的预测标志物。TMs可与ctDNA相互补充，以更好地评估患者预后，并使更多患者得到准确评估。
