Abstract
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 (n = 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 (CR+PR+SD) 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 (P = 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 (P = 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 (P = 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.
Highlights
Gastric cancer (GC), the third leading cause of cancer-related mortality worldwide with more than 800,000 deaths annually, has its greatest incidence in East Asia [1]
The 63 patients included in this study were allocated into four groups: Dendritic cells (DC)-Cytokine-induced killer (CIK) combined with S-1 plus cisplatin (n 1⁄4 13), S-1 plus cisplatin (n 1⁄4 15), DC-CIK combined with S-1 (n 1⁄4 17) and S-1 alone (n 1⁄4 18)
S-1 alone, S-1 plus cisplatin, DC-CIK combined with S-1 and DC-CIK combined with S-1 plus cisplatin groups, respectively
Summary
Gastric cancer (GC), the third leading cause of cancer-related mortality worldwide with more than 800,000 deaths annually, has its greatest incidence in East Asia [1]. The majority of newly diagnosed cases are identified in the advanced stage [2] for which outcomes are extremely poor marked by a median survival ranging from 3 to 5 months with best supportive care [3, 4]. Several multiagent chemotherapy regimens have demonstrated modest survival benefits in the first line treatment. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).
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