Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Thorac Cancer. 2022 Aug;13(15):2201-2209. doi: 10.1111/1759-7714.14545. Epub 2022 Jul 1.
OBJECTIVE: Circulating tumor DNA (ctDNA) monitoring proves to be a promising approach to assess response and predict survival in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKIs). However, whether the dynamic changes in ctDNA EGFR mutation status have the same predictive value as ctDNA remains unknown. This study aims to explore the predictive value of dynamic changes in both ctDNA and ctDNA EGFR status. METHODS: A retrospective analysis was performed using 91 ctDNA samples from a cohort of 28 patients who were diagnosed with EGFR-mutated NSCLC and treated with EGFR-TKIs, including 14 patients treated with first-/second-generation TKIs and 14 treated with osimertinib. Blood samples at baseline (BL), within 4 weeks after TKI initiation (Week4), within 12 weeks before progression (pre-PD), and at progression were collected. The relationship alternatives in ctDNA status, ctDNA EGFR status and response to EGFR-TKIs as well as progression-free survival (PFS) were analyzed. RESULTS: We categorized 20 BL-ctDNA positive patients with available Week4-ctDNA into two groups: ctDNA-clearance (N = 7, 35%) and ctDNA-non-clearance (N = 13, 65%). The ctDNA-clearance group had better PFS than the ctDNA-non-clearance group (ctDNA-clearance vs. ctDNA-non-clearance, p = 0.091, hazard ratio [HR] = 0.42, 95% confidence interval [CI] = 0.15-1.19). According to Week4-EGFR status, we observed that PFS was significantly longer in EGFR-clearance patients than EGFR-non-clearance groups, (p = 0.011, HR = 0.23, 95% CI = 0.08-0.72). We then categorized patients into three subgroups according to Week4-ctDNA and Week4-EGFR status: non-clearance (N = 9), only-EGFR-clearance (concomitant alterations non-clearance) (N = 4), and all-clearance (N = 7). The nonclearance group had a significantly worse PFS than the all-clearance group (median PFS = 5.07 vs. 11.40 months, p = 0.029, HR = 3.45, 95% CI = 1.05-11.49). The only-EGFR-clearance group had a similar PFS to the all-clearance group (p = 0.607), which was longer than that of the non-clearance group (median PFS = 9.20 vs. 5.07 months, p = 0.060, HR = 0.25, 95% CI = 0.05-1.18). We found that the all-clearance group had a similar objective response rate (ORR) to the only-EGFR-clearance group (p = 1.000) and a higher ORR than the non-clearance group (p = 0.012). CONCLUSION: Monitoring of EGFR clearance in ctDNA is promising and cost-effective in assessing response and predicting survival in EGFR-mutated NSCLC patients treated with EGFR-TKIs, with similar predictive value to ctDNA surveillance.
目的：循环肿瘤 DNA（ctDNA）监测已被证明是一种很有前途的方法，可用于评估表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）患者接受酪氨酸激酶抑制剂（TKI）治疗的反应和预测生存情况。然而，ctDNA EGFR 突变状态的动态变化是否与 ctDNA 具有相同的预测价值尚不清楚。本研究旨在探讨 ctDNA 和 ctDNA EGFR 状态的动态变化的预测价值。
方法：对 28 例 EGFR 突变型 NSCLC 患者接受 EGFR-TKI 治疗的队列中 91 例 ctDNA 样本进行回顾性分析，包括 14 例接受第一代/第二代 TKI 治疗和 14 例接受奥希替尼治疗的患者。在基线（BL）、TKI 起始后 4 周内（Week4）、进展前 12 周（pre-PD）和进展时采集血样。分析 ctDNA 状态、ctDNA EGFR 状态与 EGFR-TKI 反应及无进展生存期（PFS）的关系。
结果：我们将 20 例基线时 ctDNA 阳性且有可用 Week4-ctDNA 的患者分为两组：ctDNA 清除组（N=7，35%）和 ctDNA 未清除组（N=13，65%）。ctDNA 清除组的 PFS 明显长于 ctDNA 未清除组（ctDNA 清除组 vs. ctDNA 未清除组，p=0.091，HR=0.42，95%CI=0.15-1.19）。根据 Week4-EGFR 状态，我们发现 EGFR 清除组的 PFS 明显长于 EGFR 未清除组（p=0.011，HR=0.23，95%CI=0.08-0.72）。然后，我们根据 Week4-ctDNA 和 Week4-EGFR 状态将患者分为三组：未清除组（N=9）、仅 EGFR 清除组（同时存在未清除的改变）（N=4）和完全清除组（N=7）。未清除组的 PFS 明显短于完全清除组（中位 PFS=5.07 个月 vs. 11.40 个月，p=0.029，HR=3.45，95%CI=1.05-11.49）。仅 EGFR 清除组的 PFS 与完全清除组相似（p=0.607），但长于未清除组（中位 PFS=9.20 个月 vs. 5.07 个月，p=0.060，HR=0.25，95%CI=0.05-1.18）。我们发现完全清除组的客观缓解率（ORR）与仅 EGFR 清除组相似（p=1.000），且高于未清除组（p=0.012）。
结论：在接受 EGFR-TKI 治疗的 EGFR 突变型 NSCLC 患者中，监测 EGFR 清除的 ctDNA 具有很好的预测价值，在评估反应和预测生存方面具有成本效益，与 ctDNA 监测具有相似的预测价值。
Cancer Manag Res. 2024-10-11
Cancers (Basel). 2024-7-1
Nat Commun. 2021-1-4
Zotero 插件
