Aguilar Héctor, López-Roldán Belén, Vilalta-Lacarra Anna, Alkorta-Aranburu Gorka, Claramunt R, López-Guerrero José Antonio, Sandiego S, Gil-Bazo I
Department of Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
Department of Medical Oncology, Hospital Santa Bárbara, Soria, Spain.
J Liq Biopsy. 2024 Feb 10;4:100145. doi: 10.1016/j.jlb.2024.100145. eCollection 2024 Jun.
Blood-based biomarkers investigation does not require invasive tissue biopsies and may explore diverse tumoral components such as proteins, microRNAs, circulating tumor cells, ctDNA, and exosomes and may better reflect tumor molecular heterogeneity, either temporal or spatial. ctDNA is related to tumor burden and represents a more objective measure of the total body disease burden than imaging findings. ctDNA profiling can be therefore useful to determine minimal residual disease (MRD), which is defined as the remaining tumor cells or tumor-derived material after definitive treatment in patients with no clinical evidence of disease. The detection of MRD is highly predictive of future disease recurrence. Although detectable MRD is associated with a poor prognosis, it is not clear whether MRD detection can guide therapy escalation to improve patient outcomes. In this review, we present four cases of epidermal growth factor receptor () mutant NSCLC patients who received standard of care curative treatment and periodic radiological assessment and liquid biopsy analyses were carried out as follow-up. A tumor-informed 52 genes Oncomine Pan-Cancer Cell-Free assay (Thermo Fisher Scientific, Waltham, MA, USA), was used to identify single-nucleotide variants (SNVs), indels, copy number variations (CNVs), and RNA fusions in blood based liquid biopsy ctDNA in three of four patients. In one patient the approach used was through Commercial Kit Cobas Mutation Test v2 CE-IVD (Roche Diagnostics SL) that identifies 42 mutations in the gene. In one patient, an actionable oncogene driver alteration was identified in the ctDNA analysis, four months after radical intent concurrent chemoradiotherapy and six weeks before radiological distant relapse was clearly confirmed. There is no evidence of ctDNA or radiological disease relapse in the other three patients. Finally, a review of the literature addressing the potential value of MRD detection in this clinical setting is presented and discussed as well.
基于血液的生物标志物研究不需要进行侵入性组织活检，并且可以探索多种肿瘤成分，如蛋白质、微小RNA、循环肿瘤细胞、ctDNA和外泌体，还可以更好地反映肿瘤的分子异质性，包括时间或空间上的异质性。ctDNA与肿瘤负荷相关，与影像学检查结果相比，它是衡量全身疾病负担的更客观指标。因此，ctDNA分析有助于确定微小残留病（MRD），微小残留病定义为接受确定性治疗后，无疾病临床证据的患者体内残留的肿瘤细胞或肿瘤衍生物质。MRD的检测对未来疾病复发具有高度预测性。虽然可检测到的MRD与不良预后相关，但尚不清楚MRD检测是否能指导强化治疗以改善患者预后。在本综述中，我们介绍了4例表皮生长因子受体（EGFR）突变的非小细胞肺癌患者，他们接受了标准的根治性治疗，并进行了定期的影像学评估和液体活检分析作为随访。在4例患者中的3例中，使用了肿瘤知情的52基因Oncomine泛癌游离细胞分析（美国马萨诸塞州沃尔瑟姆市赛默飞世尔科技公司）来识别血液液体活检ctDNA中的单核苷酸变异（SNV）、插入缺失、拷贝数变异（CNV）和RNA融合。在1例患者中，使用的方法是通过商业试剂盒Cobas EGFR Mutation Test v2 CE-IVD（罗氏诊断公司）来识别EGFR基因中的42个突变。在1例患者中，在根治性同步放化疗4个月后且在影像学明确证实远处复发前6周，ctDNA分析中发现了一个可操作的致癌基因驱动改变。其他3例患者没有ctDNA或影像学疾病复发的证据。最后，还介绍并讨论了一篇关于在这种临床环境中MRD检测潜在价值的文献综述。
