Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma.
Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma.
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DOI：
10.1186/s13046-018-0723-5
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发表时间：
2018-03-12
期刊：
影响因子：
--
通讯作者：
Jakobsen A
中科院分区：
文献类型：
--
作者：
Thomsen CB;Hansen TF;Andersen RF;Lindebjerg J;Jensen LH;Jakobsen A
精准医疗需要一个治疗效率的早期指标。在这种情况下，循环肿瘤DNA （ctDNA）是一个很有前途的标志物。我们的前瞻性研究探讨了RAS/RAF突变的转移性结直肠癌（mCRC）患者在一线化疗期间疾病发展与ctDNA变化之间的关系。该研究包括138例接受标准一线治疗的mCRC患者。在RAS/RAF突变的肿瘤DNA患者中，使用液滴数字PCR定量血浆中相同的突变。在治疗开始前和每个治疗周期评估血浆中ctDNA的分数丰度，直到放射学定义的进展性疾病。77例患者血浆中检测到RAS/RAF突变。20例患者治疗进展，57例无进展停止治疗。血浆中DNA突变的存在与较差的总生存率相关。第一周期化疗后低水平的ctDNA与低进展风险相关。另一方面，在治疗过程中的任何时候，ctDNA的显著增加与持续治疗进展的高风险相关。ctDNA水平首次升高发生在放射学证实进展前的中位51天。结果表明，ctDNA水平有潜力作为mCRC一线治疗的临床有价值的标志物。快速下降与延长无进展间隔有关，而显著增加则提示有相关提前时间的早期进展。本文的在线版本（10.1186/s13046-018-0723-5）包含补充资料，仅供授权用户使用。
Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). The study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR. The fractional abundance of ctDNA was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease. RAS/RAF mutations were detected in the plasma from 77 patients. Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of mutated DNA in plasma was correlated with poor overall survival. A low level of ctDNA after the first cycle of chemotherapy was associated with a low risk of progression. On the other hand, a significant increase of ctDNA at any time during the treatment course was associated with a high risk of progression on continuous treatment. The first increase in ctDNA level occurred at a median of 51 days before radiologically confirmed progression. The results indicate that the ctDNA level holds potential as a clinically valuable marker in first line treatment of mCRC. A rapid decrease was associated with a prolonged progression free interval, whereas a significant increase gave notice of early progression with a relevant lead time. The online version of this article (10.1186/s13046-018-0723-5) contains supplementary material, which is available to authorized users.
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DOI：
10.1093/annonc/mdx112
发表时间：
2017-06-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
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
通讯作者：
Vivancos A
影响因子：
11.5
作者：
Garlan, Fanny;Laurent-Puig, Pierre;Zaanan, Aziz
通讯作者：
Zaanan, Aziz
影响因子：
3.8
作者：
Ocana, Alberto;Diez-Gonzalez, Laura;Amir, Eitan
通讯作者：
Amir, Eitan
通过不同的检测，肿瘤组织和血浆中的 KRAS 突变可预测转移性结直肠癌患者的生存。
DOI：
10.1186/s13046-014-0104-7
发表时间：
2014-12-10
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Xu JM;Liu XJ;Ge FJ;Lin L;Wang Y;Sharma MR;Liu ZY;Tommasi S;Paradiso A
通讯作者：
Paradiso A
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