Detection of epidermal growth factor receptor (EGFR) mutations from preoperative circulating tumor DNA (ctDNA) as a prognostic predictor for stage I-III non-small cell lung cancer (NSCLC) patients with baseline tissue EGFR mutations.
Detection of epidermal growth factor receptor (EGFR) mutations from preoperative circulating tumor DNA (ctDNA) as a prognostic predictor for stage I-III non-small cell lung cancer (NSCLC) patients with baseline tissue EGFR mutations.
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检测术前循环肿瘤 DNA (ctDNA) 中的表皮生长因子受体 (EGFR) 突变，作为具有基线组织 EGFR 突变的 I-III 期非小细胞肺癌 (NSCLC) 患者的预后预测因子
DOI：
10.21037/tlcr-21-530
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发表时间：
2021-07
影响因子：
4
通讯作者：
Yan X
中科院分区：
文献类型：
--
作者：
Guo K;Shao C;Han L;Liu H;Ma Z;Yang Y;Feng Y;Pan M;Santarpia M;Carmo-Fonseca M;Silveira C;Lee KY;Han J;Li X;Yan X
血浆循环肿瘤DNA（ctDNA）可能是非小细胞肺癌（NSCLC）患者中基于组织的表皮生长因子受体（EGFR）突变检测的替代微创方法。然而，术前ctDNA EGFR突变检测对术后长期生存和肿瘤转移发展的预测能力尚未得到广泛研究。本研究入组了具有组织EGFR突变的I-III期NSCLC患者（n=174）。在配对的术前血浆样本中鉴定ctDNA EGFR突变。使用Scorpion扩增难治性突变系统（ARMS）技术进行EGFR突变检测。分析ctDNA EGFR突变状态与临床病理参数的相关性。通过结合至少5年的随访数据，我们评估了ctDNA EGFR突变状态与无病生存期（DFS）和总生存期（OS）之间的关系。在27例患者中检测到基于血浆的ctDNA EGFR突变。突变类型与配对组织样本中的突变类型完全匹配。血检敏感性与N分期、TNM分期及肿瘤分化程度密切相关（P<0.001）。ctDNA EGFR突变阳性和ctDNA EGFR突变阴性患者的总体5年生存率分别为18.5%和76.9%。ctDNA EGFR突变阳性患者的中位OS和DFS分别为29.00±2.55和19.00±2.50个月，均明显优于ctDNA EGFR突变阴性亚组（P<0.001）。ctDNA EGFR突变是OS和DFS的独立危险因素[危险比（HR）3.289，95% CI，1.816-5.956，P<0.001; HR 4.860，95% CI，2.660-8.880，P<0.001]。对于组织和血浆样本中存在19号外显子缺失或L 858 R突变的III期患者，酪氨酸激酶抑制剂（TKI）治疗显示OS（P=0.025）和可能的DFS获益（P=0.060）显著优于化疗。采用Scorpion-ARMS方法检测术前血浆中EGFR突变可能是NSCLC患者术后生存和转移的强有力预测因素。因此，这一人群的子集可能受益于有针对性的策略和管理。
Plasma circulating tumor DNA (ctDNA) may be a surrogate, minimally invasive approach to tissue-based epidermal growth factor receptor (EGFR) mutation detection in non-small cell lung cancer (NSCLC) patients. However, the predictive ability of preoperative ctDNA EGFR mutation test on long-term postoperative survival and tumor metastasis development has not been extensively investigated. Stage I–III NSCLC patients with tissue EGFR mutations were enrolled in this study (n=174). The ctDNA EGFR mutations were identified in paired preoperative plasma samples. EGFR mutation testing was performed using Scorpion amplified refractory mutation system (ARMS) technology. The correlation between ctDNA EGFR mutation status and clinicopathologic parameters was analyzed. By combining at least 5 years of follow-up data, we assessed the relationship between ctDNA EGFR mutation status and disease-free survival (DFS) and overall survival (OS). Plasma-based ctDNA EGFR mutations were detected in 27 patients. The mutation types were exactly matched with those in paired tissue samples. Blood test sensitivity was closely associated with N stages, tumor-node-metastasis (TNM) stages and tumor differentiation (P<0.001). The overall 5-year survival rate was 18.5% versus 76.9% for ctDNA EGFR mutation-positive and ctDNA EGFR mutation-negative patients, respectively. For patients with ctDNA EGFR mutation positive, the median OS and DFS were 29.00±2.55 and 19.00±2.50 months, respectively, which were both significantly better than those in the ctDNA EGFR mutation-negative subgroup (P<0.001). ctDNA EGFR mutation was an independent risk factor of OS and DFS [hazard ratio (HR) 3.289, 95% confidence interval (CI), 1.816–5.956, P<0.001; HR, 4.860, 95% CI, 2.660–8.880, P<0.001]. For stage III patients with exon 19 deletion or L858R mutations in both tissue and plasma samples, tyrosine kinase inhibitor (TKI) therapy showed significantly better OS (P=0.025) and possible DFS benefit (P=0.060) than did chemotherapy. EGFR mutation testing using the Scorpion-ARMS method in preoperative plasma could be a strong predictor for postoperative survival and metastasis of NSCLC patients. Thus, the subset of this population may be benefit from targeted strategies and management.
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影响因子：
16.6
作者：
Sausen M;Phallen J;Adleff V;Jones S;Leary RJ;Barrett MT;Anagnostou V;Parpart-Li S;Murphy D;Kay Li Q;Hruban CA;Scharpf R;White JR;O'Dwyer PJ;Allen PJ;Eshleman JR;Thompson CB;Klimstra DS;Linehan DC;Maitra A;Hruban RH;Diaz LA Jr;Von Hoff DD;Johansen JS;Drebin JA;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
51.1
作者：
Mitsudomi, Tetsuya;Morita, Satoshi;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro
影响因子：
11.5
作者：
Mok, Tony;Wu, Yi-Long;Wu, Lin
通讯作者：
Wu, Lin
影响因子：
4
作者：
Guo K;Zhang Z;Han L;Han J;Wang J;Zhou Y;Liu H;Tong L;Li X;Yan X
通讯作者：
Yan X
影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C