Center for Molecular Diagnosis, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.
Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.
Mol Oncol. 2023 Sep;17(9):1930-1942. doi: 10.1002/1878-0261.13481. Epub 2023 Jul 4.
A good response to neoadjuvant chemotherapy (NACT) is strongly associated with a higher curative resection rate and favorable outcomes for patients with gastric cancer (GC). We examined the utility of serial circulating tumor DNA (ctDNA) testing for monitoring NACT response and prognosis in stage II-III GC. Seventy-nine patients were enrolled to receive two cycles of NACT following gastrectomy with D2-lymphadenectomy. Plasma at baseline, post-NACT, and after surgery, and tissue at pretreatment and surgery were collected. We used a 425-gene panel to detect genomic alterations (GAs). Results show that the mean cell-free DNA concentration of patients with clinical stage III was significantly higher than patients with stage II (15.43 ng·mL vs 14.40 ng·mL ). After receiving NACT and surgery, the overall detection rate of ctDNA gradually reduced (59.5%, 50.8%, and 47.4% for baseline, post-NACT, and postsurgery). The maximum variant allele frequency (max-VAF) and the number of GAs decreased from 0.50% to 0.08% and from 2.9 to 1.7 after NACT. For patients with a partial response after NACT, the max-VAF and the number of GAs declined significantly, but they increased for patients with progressive disease. Patients with detectable ctDNA at baseline, after NACT, or after surgery have a worse overall survival (OS) than patients with undetectable ctDNA. The estimated 3-year OS was 73% for the post-NACT ctDNA-negative patients and 34% for ctDNA-positive. Patients with perpetual negative ctDNA before and after NACT have the best prognosis. In conclusion, ctDNA was proposed as a potential biomarker to predict prognosis and monitor the NACT response for stage II-III GC patients.
新辅助化疗（NACT）的良好反应与更高的根治性切除率和胃癌（GC）患者的良好预后密切相关。我们研究了连续循环肿瘤 DNA（ctDNA）检测在监测 II-III 期 GC 的 NACT 反应和预后中的效用。79 名患者接受了胃切除术后的两个周期 NACT，包括 D2 淋巴结清扫术。采集基线、NACT 后和手术后的血浆，以及治疗前和手术后的组织。我们使用 425 个基因panel 来检测基因组改变（GA）。结果表明，临床 III 期患者的无细胞 DNA 浓度平均值明显高于 II 期患者（15.43ng·mL-1 比 14.40ng·mL-1）。接受 NACT 和手术后，ctDNA 的总体检测率逐渐降低（基线、NACT 后和手术后分别为 59.5%、50.8%和 47.4%）。最大变异等位基因频率（max-VAF）和 GA 数量从 NACT 前的 0.50%降至 0.08%，从 2.9 降至 1.7。对于 NACT 后部分缓解的患者，max-VAF 和 GA 数量显著下降，但对于进展性疾病的患者则增加。基线、NACT 后或手术后可检测到 ctDNA 的患者的总生存（OS）比不可检测到 ctDNA 的患者差。NACT 后 ctDNA 阴性患者的估计 3 年 OS 为 73%，而 ctDNA 阳性患者为 34%。NACT 前后持续阴性 ctDNA 的患者预后最佳。总之，ctDNA 被提议作为预测 II-III 期 GC 患者预后和监测 NACT 反应的潜在生物标志物。
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