不可切除胰腺癌患者的循环肿瘤 DNA 是一线治疗疗效的有力预测指标：KRASCIPANC 前瞻性研究。
Circulating tumor DNA in unresectable pancreatic cancer is a strong predictor of first-line treatment efficacy: The KRASCIPANC prospective study.
机构信息
Medical Oncology Department, Poitiers University Hospital, Poitiers 86000, France; ProDicET, UR 24144, University of Poitiers, Poitiers 86000, France.
Department of Statistics, Faculty of Medicine, University of Poitiers, Poitiers 86000, France.
出版信息
Dig Liver Dis. 2023 Nov;55(11):1562-1572. doi: 10.1016/j.dld.2023.03.011. Epub 2023 Jun 10.
BACKGROUND
There is no robust predictor of response to chemotherapy (CT) in unresectable pancreatic adenocarcinomas (UPA). The objective of the KRASCIPANC study was to analyze the kinetics of cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) as a predictor of response to CT in UPA.
METHODS
Blood samples were collected just before first CT and at day 28. The primary endpoint was the kinetics of KRAS-mutated ctDNA by digital droplet PCR between D0 and D28 as a predictor of progression-free survival (PFS).
RESULTS
We analyzed 65 patients with a KRAS-mutated tumor. A high level of cfDNA and KRAS-mutated ctDNA at D0, as well as the presence of KRAS-mutated ctDNA at D28, were strongly associated with lower centralized disease control rate (cDCR), shorter cPFS and OS in multivariate analysis. A score combining cfDNA level at diagnosis ≥ or <30 ng/mL and presence or not of KRAS-mutated ctDNA at D28 was an optimal predictor of cDCR (OR=30.7, IC95% 4.31-218 P=.001), PFS (HR=6.79, IC95% 2.76-16.7, P<.001) and OS (HR=9.98, IC95% 4.14-24.1, P<.001).
CONCLUSION
A combined score using cfDNA level at diagnosis and KRAS-mutated ctDNA at D28 is strongly associated with patient survival/response to chemotherapy in UPA.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04560270.
背景
在不可切除的胰腺腺癌（UPA）中，没有针对化疗（CT）反应的可靠预测因子。KRASCIPANC 研究的目的是分析无细胞 DNA（cfDNA）/循环肿瘤 DNA（ctDNA）的动力学作为 UPA 中 CT 反应的预测因子。
方法
在首次 CT 前和第 28 天采集血液样本。主要终点是通过数字液滴 PCR 在 D0 和 D28 之间分析 KRAS 突变 ctDNA 的动力学，作为无进展生存期（PFS）的预测因子。
结果
我们分析了 65 例 KRAS 突变肿瘤患者。D0 时 cfDNA 和 KRAS 突变 ctDNA 水平高，以及 D28 时存在 KRAS 突变 ctDNA，与多变量分析中较低的中央疾病控制率（cDCR）、较短的 cPFS 和 OS 密切相关。一个将诊断时 cfDNA 水平≥或<30ng/mL 与 D28 时是否存在 KRAS 突变 ctDNA 相结合的评分是 cDCR（OR=30.7，95%CI 4.31-218，P=.001）、PFS（HR=6.79，95%CI 2.76-16.7，P<.001）和 OS（HR=9.98，95%CI 4.14-24.1，P<.001）的最佳预测因子。
结论
使用诊断时 cfDNA 水平和 D28 时 KRAS 突变 ctDNA 的联合评分与 UPA 患者的生存/化疗反应密切相关。
试验注册
ClinicalTrials.gov 标识符：NCT04560270。
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