Mas Leo, Bachet Jean-Baptiste, Taly Valerie, Bouché Olivier, Taieb Julien, Cohen Romain, Meurisse Aurelia, Normand Corinne, Gornet Jean-Marc, Artru Pascal, Louafi Samy, Thirot-Bidault Anne, Baumgaertner Isabelle, Coriat Romain, Tougeron David, Lecomte Thierry, Mary Florence, Aparicio Thomas, Marthey Lysiane, Blons Helene, Vernerey Dewi, Laurent-Puig Pierre
Department of Hepato-Gastroenterology, Groupe Hospitalier Pitié Salpêtrière, 75013 Paris, France.
AGEO (Association des Gastroentérologues Oncologues), 75013 Paris, France.
Cancers (Basel). 2019 Jul 17;11(7):998. doi: 10.3390/cancers11070998.
In patients with metastatic colorectal cancer (mCRC), and mutations are currently determined by tumor sample analysis. Here, we report mutation status analysis in paired tumor tissue and plasma samples of mCRC patients included in the AGEO RASANC prospective cohort study. Four hundred and twenty-five patients were enrolled. Plasma samples were analyzed by next-generation sequencing (NGS). When no mutation was identified, we used two methylated specific biomarkers (digital droplet PCR) to determine the presence or absence of circulating tumor DNA (ctDNA). Patients with conclusive ctDNA results were defined as those with at least one mutation or one methylated biomarker. The kappa coefficient and accuracy were 0.79 (95% CI: 0.67-0.91) and 97.3% (95% CI: 95.2-98.6%) between the status in plasma and tissue for patients with available paired samples ( = 405), and 0.89 (95% CI: 0.80-0.99) and 98.5% (95% CI: 96.4-99.5%) for those with conclusive ctDNA ( = 323). The absence of liver metastasis was the main factor associated to inconclusive ctDNA results. In patients with liver metastasis, the kappa coefficient was 0.91 (95% CI, 0.81-1.00) and accuracy was 98.6% (95% CI, 96.5-99.6%). We demonstrate satisfying concordance between tissue and plasma mutation detection, especially in patients with liver metastasis, arguing for plasma ctDNA testing for routine mutation analysis in these patients.
在转移性结直肠癌（mCRC）患者中，目前通过肿瘤样本分析来确定 和 突变。在此，我们报告了AGEO RASANC前瞻性队列研究中mCRC患者配对肿瘤组织和血浆样本的 突变状态分析。共纳入425例患者。血浆样本通过二代测序（NGS）进行分析。当未检测到突变时，我们使用两种甲基化特异性生物标志物（数字液滴PCR）来确定循环肿瘤DNA（ctDNA）的存在与否。ctDNA结果明确的患者定义为至少有一个突变或一个甲基化生物标志物的患者。对于有配对样本的患者（n = 405），血浆和组织中 状态之间的kappa系数和准确性分别为0.79（95%CI：0.67 - 0.91）和97.3%（95%CI：95.2 - 98.6%），对于ctDNA结果明确的患者（n = 323），kappa系数和准确性分别为0.89（95%CI：0.80 - 0.99）和98.5%（95%CI：96.4 - 99.5%）。无肝转移是与ctDNA结果不明确相关的主要因素。在有肝转移的患者中，kappa系数为0.91（95%CI，0.81 - 1.00），准确性为98.6%（95%CI，96.5 - 99.6%）。我们证明了组织和血浆 突变检测之间具有令人满意的一致性，尤其是在有肝转移的患者中，这表明对于这些患者，血浆ctDNA检测可用于常规 突变分析。
