Longitudinal Monitoring of EGFR and PIK3CA Mutations by Saliva-Based EFIRM in Advanced NSCLC Patients With Local Ablative Therapy and Osimertinib Treatment: Two Case Reports
Longitudinal Monitoring of EGFR and PIK3CA Mutations by Saliva-Based EFIRM in Advanced NSCLC Patients With Local Ablative Therapy and Osimertinib Treatment: Two Case Reports
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基于唾液的 EFIRM 对局部消融治疗和奥希替尼治疗的晚期 NSCLC 患者中 EGFR 和 PIK3CA 突变的纵向监测：两个病例报告
DOI：
10.3389/fonc.2020.01240
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发表时间：
2020-07-24
影响因子：
4.7
通讯作者：
Wong, David T. W.
中科院分区：
文献类型：
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作者：
Li, Ning;Guha, Udayan;Wong, David T. W.
背景：非小细胞肺癌（NSCLC）循环肿瘤DNA（ctDNA）中可作用癌基因的纵向监测对于临床医生评估当前治疗反应和调整治疗策略至关重要。基于唾液的电场诱导释放和测量（EFIRM）是液体活检平台，可以用少量样本直接检测突变基因。在此，我们比较了两名晚期 NSCLC 患者在局部消融治疗 (LAT) 前后接受奥希替尼治疗时，基于唾液的 EFIRM 和基于血浆的平台（ddPCR 和 NGS）对表皮生长因子受体 (EGFR) 和磷脂酰肌醇 4,5-二磷酸 3-激酶、催化亚基 α (PIK3CA) 突变组合的纵向监测的有效性。患者和方法：两名不可切除的晚期 NSCLC 患者被纳入美国国立卫生研究院临床中心 (NIHCC) 研究（ClinicalTrials.gov：16-C-0092；奥希替尼治疗后用于治疗少进展型、EGFR 突变非小细胞肺癌的局部消融疗法）。连续收集唾液、血浆，并通过计算机断层扫描（CT）测量转移性肿瘤体积。使用 EFIRM（唾液）、ddPCR 和 NGS（血浆）分析纵向配对的唾液和血浆样本中的 p.L858R EGFR、exon19 del EGFR 和 p.E545K PIK3CA ctDNA。结果：在病例1中，EFIRM检测的exon19 del EGFR唾液ctDNA曲线与ddPCR检测的肿瘤体积（R = 0.78，P = 0.00）和exon19 del EGFR的唾液ctDNA曲线（R = 0.53，P = 0.01）具有很强的相似性。此外，EFIRM 中 p.E545K PIK3CA 的曲线与肿瘤体积曲线（R = 0.70，P = 0.00）和 NGS 中 p.E545K PIK3CA 的曲线相似（R = 0.72，P = 0.00）。在病例2中，EFIRM中p.E545K PIK3CA的曲线显示与肿瘤体积的曲线呈反向关系（R = -0.65，P = 0.01）。结论：在这两个病例报告中，基于唾液的 EFIRM 平台与基于血浆的平台（ddPCR 和 NGS）在纵向监测 EGFR 和 PIK3CA ctDNA 组合方面表现出高度一致性，并且可以成为监测 NSCLC 患者肿瘤进展和靶向治疗反应的有用平台。
Background: The longitudinal monitoring of actionable oncogenes in circulating tumor DNA (ctDNA) of non-small cell lung cancer (NSCLC) is crucial for clinicians to evaluate current therapeutic response and adjust therapeutic strategies. Saliva-based electric field–induced release and measurement (EFIRM) is liquid biopsy platform to that can directly detect mutation genes with a small volume of samples. Herein, we compared the effectiveness of longitudinal monitoring for the combination of epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations between saliva-based EFIRM and plasma-based platforms (ddPCR and NGS) in two advanced NSCLC patients undergoing the treatment with osimertinib before and after local ablative therapy (LAT). Patients and Methods: Two patients with unresectable advanced NSCLC were enrolled into the National Institutes of Health Clinical Center (NIHCC) Study (ClinicalTrials.gov: 16-C-0092; local ablative therapy for the treatment of oligoprogressive, EGFR-mutated, non-small cell lung cancer after treatment with osimertinib). Serial collections of saliva, plasma, and metastatic tumor volume measurement by computed tomography (CT) were performed. Longitudinal paired saliva and plasma samples were analyzed for p.L858R EGFR, exon19 del EGFR, and p.E545K PIK3CA ctDNA using EFIRM (saliva) and ddPCR and NGS (plasma). Results: In Case 1, the saliva ctDNA curve of exon19 del EGFR by EFIRM demonstrated a strong similarity to those of tumor volume (R = 0.78, P = 0.00) and exon19 del EGFR in ddPCR (R = 0.53, P = 0.01). Moreover, the curve of p.E545K PIK3CA in EFIRM showed similarity to those of tumor volume (R = 0.70, P = 0.00) and p.E545K PIK3CA in NGS (R = 0.72, P = 0.00). In Case 2, the curve of p.E545K PIK3CA in EFIRM revealed a reverse relationship to that of tumor volume (R = −0.65, P = 0.01). Conclusion: In these two case reports, saliva-based EFIRM platform demonstrates a high level of concordance to plasma-based platforms (ddPCR and NGS) for longitudinally monitoring the combination of EGFR and PIK3CA ctDNA and can be a useful platform to monitor tumor progression and response to targeted therapy in NSCLC patients.