Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer.
Concordance of blood- and tumor-based detection of RAS mutations to guide anti-EGFR therapy in metastatic colorectal cancer.
复制标题
DOI：
10.1093/annonc/mdx112
复制
发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Vivancos A
中科院分区：
文献类型：
--
作者：
Grasselli J;Elez E;Caratù G;Matito J;Santos C;Macarulla T;Vidal J;Garcia M;Viéitez JM;Paéz D;Falcó E;Lopez Lopez C;Aranda E;Jones F;Sikri V;Nuciforo P;Fasani R;Tabernero J;Montagut C;Azuara D;Dienstmann R;Salazar R;Vivancos A
循环肿瘤DNA（ctDNA）是肿瘤基因组分析的潜在来源。我们探讨了转移性结直肠癌（mCRC）患者肿瘤组织中RAS突变状态与ctDNA之间的一致性，以确定抗表皮生长因子受体（EGFR）治疗的资格。进行了一项前瞻性-回顾性队列研究。采用标准护理（SoC）PCR技术检测146例mCRC患者的肿瘤组织的RAS状态，并在血浆和肿瘤组织中使用数字PCR（BEAMing）。ctDNA BEAMing RAS检测显示与SoC的一致率为89.7%（Kappa指数0.80; 95% CI 0.71 − 0.90），组织中的BEAMing与SoC的一致率为90.9%（Kappa指数0.83; 95% CI 0.74 − 0.92）。15例（10.3%）显示组织-血浆结果不一致。ctDNA分析确定了9例组织中未检测到的低频率RAS突变，可能是由于技术敏感性或异质性。在6例病例中，血浆中未检测到RAS突变，可能由低肿瘤负荷或ctDNA脱落解释。如果使用SoC PCR和ctDNA进行检测，则二线或三线接受抗EGFR+伊立替康治疗的患者的治疗获益预测是等效的。48%的患者血浆中突变等位基因分数低于1%。血浆RAS测定显示出较高的总体一致性，并捕获了对抗EGFR治疗有反应的mCRC人群，其预测水平与SoC组织检测相同。ctDNA分析的可行性和实用性可以转化为抗EGFR治疗选择的替代工具。
Circulating tumor DNA (ctDNA) is a potential source for tumor genome analysis. We explored the concordance between the mutational status of RAS in tumor tissue and ctDNA in metastatic colorectal cancer (mCRC) patients to establish eligibility for anti-epidermal growth factor receptor (EGFR) therapy. A prospective-retrospective cohort study was carried out. Tumor tissue from 146 mCRC patients was tested for RAS status with standard of care (SoC) PCR techniques, and Digital PCR (BEAMing) was used both in plasma and tumor tissue. ctDNA BEAMing RAS testing showed 89.7% agreement with SoC (Kappa index 0.80; 95% CI 0.71 − 0.90) and BEAMing in tissue showed 90.9% agreement with SoC (Kappa index 0.83; 95% CI 0.74 − 0.92). Fifteen cases (10.3%) showed discordant tissue-plasma results. ctDNA analysis identified nine cases of low frequency RAS mutations that were not detected in tissue, possibly due to technical sensitivity or heterogeneity. In six cases, RAS mutations were not detected in plasma, potentially explained by low tumor burden or ctDNA shedding. Prediction of treatment benefit in patients receiving anti-EGFR plus irinotecan in second- or third-line was equivalent if tested with SoC PCR and ctDNA. Forty-eight percent of the patients showed mutant allele fractions in plasma below 1%. Plasma RAS determination showed high overall agreement and captured a mCRC population responsive to anti-EGFR therapy with the same predictive level as SoC tissue testing. The feasibility and practicality of ctDNA analysis may translate into an alternative tool for anti-EGFR treatment selection.
登录
查看更多内容
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
50.5
作者：
Douillard, J. Y.;Siena, S.;Sidhu, R.
通讯作者：
Sidhu, R.
影响因子：
6.6
作者：
Schmiegel W;Scott RJ;Dooley S;Lewis W;Meldrum CJ;Pockney P;Draganic B;Smith S;Hewitt C;Philimore H;Lucas A;Shi E;Namdarian K;Chan T;Acosta D;Ping-Chang S;Tannapfel A;Reinacher-Schick A;Uhl W;Teschendorf C;Wolters H;Stern J;Viebahn R;Friess H;Janssen KP;Nitsche U;Slotta-Huspenina J;Pohl M;Vangala D;Baraniskin A;Dockhorn-Dworniczak B;Hegewisch-Becker S;Ronga P;Edelstein DL;Jones FS;Hahn S;Fox SB
通讯作者：
Fox SB
根据KRAS突变状态和大肠癌患者KRAS状态的特定地点不一致的不同转移模式。
影响因子：
3.8
作者：
Kim MJ;Lee HS;Kim JH;Kim YJ;Kwon JH;Lee JO;Bang SM;Park KU;Kim DW;Kang SB;Kim JS;Lee JS;Lee KW
通讯作者：
Lee KW
影响因子：
50.5
作者：
Tie, J.;Kinde, I.;Gibbs, P.
通讯作者：
Gibbs, P.