Department of Medical Oncology, Beijing Key Laboratory for Therapeutic Cancer Vaccines, Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Clin Cancer Res. 2019 Mar 1;25(5):1494-1504. doi: 10.1158/1078-0432.CCR-18-2360. Epub 2018 Dec 4.
We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer (AGC) and the role of mutational analysis of circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire in predicting clinical outcomes.
Consecutive patients ( = 63) with AGC were allocated to treatment with S-1 alone, S-1 plus cisplatin, DC-CIK combined with S-1 or DC-CIK combined with S-1 plus cisplatin. The primary endpoints were progression-free survival (PFS) and overall survival (OS) at 1 year; the secondary endpoints were disease control rate and analysis of ctDNA and TCR repertoire.
The DC-CIK infusions were well tolerated with no serious adverse events. The disease control rates (CRPRSD) were 5.6%, 33.3%, 47.1%, and 76.9% in the S-1 alone, the S-1 plus cisplatin, DC-CIK combined with S-1 and DC-CIK combined with the S-1 plus cisplatin groups, respectively ( = 0.001). After adjusting for competing risk factors, treatment with DC-CIK combined with S-1 plus cisplatin was confirmed to be an independent predictor of PFS and OS ( = 0.001). A decrease in the frequency and number of mutations in ctDNA was observed in 19 patients (63.3%) following the DC-CIK infusions. Decreased ctDNA mutational frequency and restored TCR repertoire were associated with improved PFS and OS ( = 0.001).
DC-CIK combined with S-1 plus cisplatin provided a favorable PFS and OS in patients with AGC and the combination therapy was safe with tolerable toxicities. Clinical efficacy correlated with decreases in ctDNA mutational profiles and restored TCR repertoire.
我们评估了树突状细胞-细胞因子诱导的杀伤细胞（DC-CIK）联合 S-1 加顺铂化疗治疗晚期胃癌（AGC）的疗效，并分析循环肿瘤 DNA（ctDNA）和 T 细胞受体（TCR）谱突变分析在预测临床结局中的作用。
连续入组的 AGC 患者（n=63）被分配接受 S-1 单药、S-1 加顺铂、DC-CIK 联合 S-1 或 DC-CIK 联合 S-1 加顺铂治疗。主要终点为 1 年时的无进展生存期（PFS）和总生存期（OS）；次要终点为疾病控制率和 ctDNA 及 TCR 谱分析。
DC-CIK 输注耐受性良好，无严重不良事件。S-1 单药、S-1 加顺铂、DC-CIK 联合 S-1 和 DC-CIK 联合 S-1 加顺铂组的疾病控制率（CRPRSD）分别为 5.6%、33.3%、47.1%和 76.9%（ = 0.001）。校正竞争风险因素后，DC-CIK 联合 S-1 加顺铂治疗被证实是 PFS 和 OS 的独立预测因素（ = 0.001）。19 例（63.3%）患者在 DC-CIK 输注后观察到 ctDNA 突变频率和数量减少。ctDNA 突变频率降低和 TCR 谱恢复与 PFS 和 OS 改善相关（ = 0.001）。
DC-CIK 联合 S-1 加顺铂为 AGC 患者提供了有利的 PFS 和 OS，且联合治疗安全，毒性可耐受。临床疗效与 ctDNA 突变谱降低和 TCR 谱恢复相关。
