Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847, Amanuma-cho, Omiya-ku, Saitama, 330-8503, Japan.
Sci Rep. 2023 Mar 23;13(1):4809. doi: 10.1038/s41598-023-31051-7.
Molecular assessment using circulating tumor DNA (ctDNA) has not been well-defined. We recruited 61 pancreatic cancer (PC) patients who underwent initial computed tomography (CT) imaging study during first-line chemotherapy. Initial molecular assessment was performed using droplet digital PCR and defined as the change in KRAS-mutated ctDNA before and after treatments, which was classified into five categories: mNT, molecular negative; mCR, complete response; mPR, partial response; mSD, stable disease; mPD, progressive disease. Of 61 patients, 14 diagnosed with PD after initial CT imaging showed significantly worse therapeutic outcomes than 47 patients with disease control. In these 47 patients, initial molecular assessment exhibited significant differences in therapeutic outcomes between patients with and without ctDNA (mPD + mSD vs. mCR + mNT; 13.2 M vs. 21.7 M, P = 0.0029) but no difference between those with mPD and mSD + mCR + mNT, suggesting that the presence of ctDNA had more impact on the therapeutic outcomes than change in its number. Multivariate analysis revealed that it was the only independent prognostic factor (P = 0.0405). The presence of ctDNA in initial molecular assessment predicted early tumor progression and identified PC patients more likely to benefit from chemotherapy.
利用循环肿瘤 DNA（ctDNA）进行分子评估尚未得到充分定义。我们招募了 61 名接受一线化疗期间首次计算机断层扫描（CT）成像研究的胰腺癌（PC）患者。最初的分子评估使用液滴数字 PCR 进行，并定义为治疗前后 KRAS 突变 ctDNA 的变化，分为五类：mNT，分子阴性；mCR，完全缓解；mPR，部分缓解；mSD，稳定疾病；mPD，进展性疾病。在 61 名患者中，14 名在初始 CT 成像后被诊断为 PD 的患者的治疗结果明显差于 47 名疾病得到控制的患者。在这 47 名患者中，初始分子评估显示 ctDNA 存在与否的患者之间的治疗结果存在显著差异（mPD+mSD 与 mCR+mNT；13.2M 与 21.7M，P=0.0029），但 mPD 与 mSD+mCR+mNT 之间无差异，这表明 ctDNA 的存在对治疗结果的影响大于其数量的变化。多变量分析显示，它是唯一的独立预后因素（P=0.0405）。初始分子评估中 ctDNA 的存在预测了肿瘤的早期进展，并确定了更有可能从化疗中获益的 PC 患者。
