Taus Álvaro, Camacho Laura, Rocha Pedro, Hernández Ainhoa, Longarón Raquel, Clavé Sergi, Fernández-Ibarrondo Lierni, Salido Marta, Hardy-Werbin Max, Fernández-Rodríguez Concepción, Albanell Joan, Bellosillo Beatriz, Arriola Edurne
Medical Oncology Department, Hospital del Mar-CIBERONC, Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Barcelona (UAB), Barcelona, Spain; Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; Pathology Department, Hospital del Mar, Barcelona, Spain.
Arch Bronconeumol (Engl Ed). 2021 May;57(5):323-329. doi: 10.1016/j.arbres.2020.01.023. Epub 2020 Apr 3.
KRAS is the most common driver mutation in lung cancer. ctDNA-based assessment offers advantages over tumor as a minimally invasive method able to capture tumor heterogeneity. Monitoring KRAS mutational load in ctDNA may be useful in the management of the patients.
Consecutive patients diagnosed with KRAS mutant lung adenocarcinoma in the tumor biopsy were included in this study. Plasma samples were obtained at different time points during the course of the disease. KRAS mutations in plasma were quantified using digital PCR and correlated with mutations in tumor and with radiological response and progression.
Two hundred and forty-five plasma samples from 56 patients were analyzed. The rate of detection of KRAS mutations in plasma in our previously characterized KRAS-mutant cases was 82% overall, reaching 96% in cases with more than 1 metastatic location. The dynamics of KRAS mutational load predicted response in 93% and progression in 63% of cases, 33 and 50 days respectively in advance of radiological evaluation. Progression-free survival for patients in whom ctDNA was not detectable in plasma after treatment initiation was significantly longer than for those in whom ctDNA remained detectable (7.7 versus 3.2 months; HR: 0.44, p=0.004).
The detection of KRAS mutations in ctDNA showed a good correlation with that in tumor biopsy and, in most cases, predicted tumor response and progression to chemotherapy in advance of radiographic evaluation. The liquid biopsies for ctDNA-based molecular analyses are a reliable tool for KRAS testing in clinical practice.
KRAS是肺癌中最常见的驱动基因突变。基于循环肿瘤DNA（ctDNA）的评估作为一种能够捕捉肿瘤异质性的微创方法，相较于肿瘤组织具有优势。监测ctDNA中的KRAS突变负荷可能对患者的管理有用。
本研究纳入了在肿瘤活检中被诊断为KRAS突变型肺腺癌的连续患者。在疾病过程中的不同时间点采集血浆样本。使用数字PCR对血浆中的KRAS突变进行定量，并与肿瘤中的突变以及放射学反应和进展相关联。
分析了来自56例患者的245份血浆样本。在我们之前已表征的KRAS突变病例中，血浆中KRAS突变的总体检测率为82%，在有多个转移部位的病例中达到96%。KRAS突变负荷的动态变化在93%的病例中预测了反应，在63%的病例中预测了进展，分别比放射学评估提前33天和50天。治疗开始后血浆中无法检测到ctDNA的患者的无进展生存期明显长于ctDNA仍可检测到的患者（7.7个月对3.2个月；风险比：0.44，p = 0.004）。
ctDNA中KRAS突变的检测与肿瘤活检中的检测显示出良好的相关性，并且在大多数情况下，在放射学评估之前预测了肿瘤对化疗的反应和进展。基于ctDNA的分子分析的液体活检是临床实践中KRAS检测的可靠工具。
