Sitthideatphaiboon Piyada, Simseekeaw Pronwasun, Teerapakpinyo Chinachote, Zungsontiporn Nicha, Chintanapakdee Wariya, Itthisawatpan Itthi, Shuangshoti Shanop, Sriuranpong Virote, Tongbai Thanisa, Vinayanuwattikun Chanida
Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
Chula GenePRO Center, Research Affairs, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
Sci Rep. 2025 Jan 2;15(1):165. doi: 10.1038/s41598-024-83930-2.
EGFR-TKIs are effective therapies for non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. However, responses vary within individuals and resistant disease inevitably emerges. A prospective cohort of 130 patients with advanced EGFR mutation NSCLC were enrolled. Pre-and post-treatment plasma from subjects treated with EGFR-TKIs were obtained. The correlation between EGFR mutation abundance using the Idylla™ ctEGFR mutation assay, radiographic assessment, and clinical outcomes were analyzed. Eighty-nine patients with retrieved blood collection were analyzed. Undetectable ctEGFR (49.5%), detectable ctEGFR CqMut-high (23.5%), and detectable ctEGFR CqMut low (27%) using CqMut cutoff at 28.1, represented consecutive incremental tumor burden by radiographic assessment and outcome of treatment. Median PFS was 13.4 months [95% CI 12.0-14.8] in undetectable ctEGFR, 10.4 months [95% CI 9.9-10.9] in ctEGFR CqMut-high, and 5.9 months [95% CI 3.8-7.4] in ctEGFR CqMut-low. Number of metastasis sites > 3 was found in 22.7%, 23.8%, and 58.3% of the 3-tier ctEGFR tumor burden levels, respectively (p-value 0.01). Presence of liver metastasis was significantly correlated with number of metastasis sites > 3 and ctEGFR CqMut-low (45.8%). Liver metastasis was an independent factor of reduced PFS and OS by multivariate analysis with an HR = 2.41 [95% CI 1.27-4.60, p-value 0.007]) and HR = 2.96 [95% CI 1.35-6.51, p-value 0.007], respectively. The pretreatment ctEGFR detection using the Idylla™ ctEGFR mutation assay served as a surrogate marker for tumor abundance and tumor burden. Presence of liver metastasis was found to be a clinical predictor associated with high tumor abundance and worsening treatment outcomes.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）是治疗具有EGFR激活突变的非小细胞肺癌（NSCLC）患者的有效疗法。然而，个体反应存在差异，耐药性疾病不可避免地会出现。招募了一个由130例晚期EGFR突变NSCLC患者组成的前瞻性队列。获取了接受EGFR-TKIs治疗的受试者治疗前和治疗后的血浆。分析了使用Idylla™ ctEGFR突变检测法检测的EGFR突变丰度、影像学评估与临床结果之间的相关性。对89例有血样采集的患者进行了分析。使用28.1的CqMut临界值时，检测不到的ctEGFR（49.5%）、可检测到的ctEGFR CqMut高（23.5%）和可检测到的ctEGFR CqMut低（27%），通过影像学评估和治疗结果显示肿瘤负荷呈连续增加。检测不到ctEGFR的患者中位无进展生存期（PFS）为13.4个月[95%置信区间12.0 - 14.8]，ctEGFR CqMut高的患者为10.4个月[95%置信区间9.9 - 10.9]，ctEGFR CqMut低的患者为5.9个月[95%置信区间3.8 - 7.4]。在3层ctEGFR肿瘤负荷水平中，转移部位数量>3的患者分别占22.7%、23.8%和58.3%（p值0.01）。肝转移的存在与转移部位数量>3和ctEGFR CqMut低显著相关（45.8%）。通过多因素分析，肝转移是PFS和总生存期（OS）降低的独立因素，HR分别为2.41[95%置信区间1.27 - 4.60，p值0.007]和HR为2.96[95%置信区间1.35 - 6.51，p值0.007]。使用Idylla™ ctEGFR突变检测法进行的治疗前ctEGFR检测可作为肿瘤丰度和肿瘤负荷的替代标志物。肝转移的存在被发现是与高肿瘤丰度和恶化治疗结果相关的临床预测指标。
