Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon.
Hematology-Oncology Department, Hôtel-Dieu de France University Hospital, Saint Joseph University, Boulevard Alfred Naccache, Beirut, Lebanon; Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Clin Res Hepatol Gastroenterol. 2024 Oct;48(8):102417. doi: 10.1016/j.clinre.2024.102417. Epub 2024 Jul 14.
The absence of KRAS and NRAS gene mutations (RAS wild type) in metastatic colorectal cancer (mCRC), is associated with a good response to targeted therapy with anti-EGFR receptor antibodies. The current gold standard for RAS mutational status identification is genetic testing on tissue biopsy samples.
This study aimed to assess the relevance of liquid biopsy as a less invasive alternative to tissue biopsy for detecting KRAS/NRAS and BRAF mutations in patients with metastatic colorectal cancer (mCRC). The study also aimed to determine the concordance between liquid biopsy and tissue biopsy.
This is a phase IV, observational, uncontrolled, non-comparative, non-randomized, open label study. RAS/BRAF status will be tested at baseline using tissue and liquid biopsy using the Idylla/Biocartis PCR-based device. The primary endpoint is the comparison of the RAS status based on liquid biopsy with the RAS status based on tissue biopsy.
100 patients with mCRC were included in the study. 75 % of patients showed concordant results between liquid biopsy and tissue biopsy, while 25 % had discordant results. Liquid biopsy demonstrated a sensitivity of 62 % and a specificity of 93 %. The accuracy of liquid biopsy was 75 %, with a moderate agreement between the two tests. The most frequent mutations in concordant cases were in KRAS (41 %), followed by NRAS (4 %) and BRAF (3 %). Mutations were not detected in 42 % of tissue biopsy samples and 60 % of liquid biopsy samples. The presence of hepatic metastases did not significantly affect the concordance between the biopsy methods.
Liquid biopsy using the Idylla™ system showed a relatively low sensitivity but high specificity for detecting KRAS/NRAS and BRAF mutations in mCRC patients. Despite some discordant cases, liquid biopsy remains a promising alternative to tissue biopsy due to its non-invasiveness, ability to provide multiple samples, and better representation of tumor heterogeneity.
转移性结直肠癌（mCRC）中无 KRAS 和 NRAS 基因突变（RAS 野生型）与抗 EGFR 受体抗体的靶向治疗反应良好相关。目前，RAS 突变状态鉴定的金标准是组织活检样本的基因检测。
本研究旨在评估液体活检作为组织活检的替代方法，用于检测转移性结直肠癌（mCRC）患者 KRAS/NRAS 和 BRAF 突变的相关性。本研究还旨在确定液体活检与组织活检之间的一致性。
这是一项 IV 期、观察性、非对照、非随机、开放性标签研究。将使用基于 Idylla/Biocartis PCR 的设备，通过组织和液体活检在基线时检测 RAS/BRAF 状态。主要终点是基于液体活检的 RAS 状态与基于组织活检的 RAS 状态的比较。
共纳入 100 例 mCRC 患者。液体活检与组织活检结果的一致性为 75%，而不一致性为 25%。液体活检的敏感性为 62%，特异性为 93%。液体活检的准确性为 75%，两种检测方法具有中度一致性。在一致的病例中，最常见的突变是 KRAS（41%），其次是 NRAS（4%）和 BRAF（3%）。在 42%的组织活检样本和 60%的液体活检样本中未检测到突变。肝转移的存在并未显著影响两种活检方法之间的一致性。
使用 Idylla™ 系统的液体活检对 mCRC 患者的 KRAS/NRAS 和 BRAF 突变检测具有相对较低的敏感性，但特异性较高。尽管存在一些不一致的病例，但液体活检仍然是组织活检的一种有前途的替代方法，因为它具有非侵入性、能够提供多个样本以及更好地代表肿瘤异质性。
