PDF(Pubmed)
Abstract：
Programmed Death Receptor 1 (PD-1) inhibitors, when combined with chemotherapy, have exhibited notable effectiveness in enhancing the survival outcomes of patients afflicted with advanced gastric cancer. However, it is important to acknowledge that not all patients derive substantial benefits from this therapeutic approach, highlighting the crucial necessity of identifying efficacious biomarkers to inform immunotherapy interventions. In this study, we sought to investigate the predictive utility of circulating tumor DNA (ctDNA) as a biomarker in a cohort of 30 patients diagnosed with advanced gastric cancer, all of whom underwent first-line treatment involving PD-1 inhibitor administration alongside chemotherapy. We procured peripheral blood samples both at baseline and following the completion of two treatment cycles. Additionally, baseline tissue specimens were collected for the purpose of genomic alteration assessment, employing both 47-gene and 737-gene next-generation sequencing panels for plasma and tumor tissue, respectively. We delineated a ctDNA response as the eradication of maximum variant allele frequencies relative to baseline levels. Notably, the objective response rate among individuals exhibiting a ctDNA response proved significantly superior in comparison to non-responders (P = 0.0073). Furthermore, patients who manifested a ctDNA response experienced markedly prolonged progression-free survival (PFS) and overall survival (OS) when juxtaposed with those devoid of a ctDNA response (median PFS: 15.6 vs. 6.0 months, P = 0.003; median OS: not reached [NR] vs. 9.0 months, P = 0.011). In summation, patients with advanced gastric cancer receiving first-line treatment with PD-1 inhibitors and chemotherapy, dynamic changes in ctDNA can serve as a potential biomarker for predicting treatment efficacy and long-term outcomes.
摘要：
程序性死亡受体1（PD-1）抑制剂，当联合化疗时，在提高晚期胃癌患者的生存结局方面表现出显著的有效性。然而,重要的是要承认，并不是所有的患者都能从这种治疗方法中获得实质性的好处，强调确定有效的生物标志物以告知免疫治疗干预措施的关键必要性。在这项研究中,我们试图研究循环肿瘤DNA（ctDNA）作为生物标志物在30名诊断为晚期胃癌的患者队列中的预测效用。所有患者均接受了包括PD-1抑制剂给药和化疗的一线治疗.我们在基线和两个治疗周期完成后都获得了外周血样本。此外,收集基线组织标本用于基因组改变评估，采用47基因和737基因的下一代测序小组用于血浆和肿瘤组织，分别。我们将ctDNA应答描述为相对于基线水平的最大变异等位基因频率的根除。值得注意的是,与无反应者相比，显示ctDNA反应的个体的客观反应率显着优于无反应者（P=0.0073）。此外，与无ctDNA反应的患者并列时，表现出ctDNA反应的患者的无进展生存期（PFS）和总生存期（OS）显着延长（中位PFS：15.6vs.6.0个月,P=0.003；中位OS：未达到[NR]与9.0个月，P=0.011)。总之，接受PD-1抑制剂和化疗一线治疗的晚期胃癌患者，ctDNA的动态变化可作为预测治疗疗效和长期结局的潜在生物标志物.
