Prognostic association of plasma cell-free DNA-based androgen receptor amplification and circulating tumor cells in pre-chemotherapy metastatic castration-resistant prostate cancer patients.
Prognostic association of plasma cell-free DNA-based androgen receptor amplification and circulating tumor cells in pre-chemotherapy metastatic castration-resistant prostate cancer patients.
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化疗前转移性去势抵抗性前列腺癌患者血浆游离 DNA 雄激素受体扩增与循环肿瘤细胞的预后相关性。
DOI：
10.1038/s41391-018-0043-z
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发表时间：
2018-09
影响因子：
4.8
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Kohli M;Li J;Du M;Hillman DW;Dehm SM;Tan W;Carlson R;Campion MB;Wang L;Wang L;Zhang H;Zhang P;Kilari D;Huang CC;Wang L
与循环肿瘤细胞（CTC）计数相比，转移性去势抵抗性前列腺癌（mCRPC）中血浆游离DNA（cfDNA）雄激素受体扩增（ARamp）的预后意义尚不清楚。作为mCRPC前瞻性研究相关目的的一部分，同时和连续采集血浆和CTC。在雄激素剥夺治疗进展后的基线和12周后进行标本采集。使用QuantStudio 3D数字PCR系统（dPCR）测定血浆cfDNA AR拷贝数变异，并使用Cell search试验计数CTC计数。使用Kaplan-Meier方法和对数秩检验（显著性为p ≤ 0.05）以及ARamp状态和CTC ≥ 5的受试者工作曲线（ROC）评价基线cfDNA ARamp状态/CTC计数与总生存期（OS）（主要目标）的相关性。使用包括ARamp、CTC计数和其他临床因素的考克斯回归模型进行多变量分析。基线时，在19/70例患者中检测到ARamp。在分析时，70例患者中有28例死亡（中位随访时间为806天（IQR：535-966））。ARamp与较差的OS相关（ARamp的2年OS为35%，非ARamp为71%;对数秩p值= <0.0001）。基线CTC计数≥ 5（vs < 5）也与生存率差相关（2年OS为44% vs 74%;对数秩p=0.001）。ROC分析表明，基于ARamp的预后的曲线下面积（AUC）为0.66，基于CTC计数的预后的曲线下面积（AUC）为0.68（差异p=0.84）。纳入多变量分析的最佳两个变量是ARamp和CTC ≥ 5，然而，双因素模型在预测生存期方面并不显著优于单独使用ARamp（HR=5.25; p=0.0002）。观察到CTC和血浆cfDNA ARamp在mCRPC中具有相等的预后价值。需要纳入分子和临床因素的更大队列来进一步改善CRPC的预后。
The prognostic significance of plasma cell-free DNA (cfDNA) androgen receptor amplification (ARamp) in metastatic castration resistant prostate cancer (mCRPC) compared with circulating tumor cell (CTC) counts is not known. As part of correlative aims of a prospective study in mCRPC, concurrent and serial collections of plasma and CTCs were performed. Specimen collections were performed at baseline after progression on androgen deprivation therapy and then 12 weeks later. QuantStudio3D digital PCR system (dPCR) was used to determine plasma cfDNA AR copy number variations and Cell search assay for enumerating CTC counts. Association of baseline cfDNA ARamp status/CTC counts with overall survival (OS) (primary goal) was evaluated using Kaplan–Meier method and log-rank test (p ≤ 0.05 for significance) and Receiver Operator Curves (ROC) for ARamp status and CTCs ≥ 5. A multivariate analysis was performed using Cox regression models that included ARamp, CTC counts and other clinical factors. ARamp was detected in 19/70 patients at baseline. At the time of analysis, 28/70 patients had died (median follow-up 806 days (IQR: 535–966)). ARamp was associated with poor OS (2 year OS of 35% in ARamp vs. 71% in non-ARamp; log-rank p-value= <0.0001). Baseline CTC count ≥ 5 (vs < 5) was also associated with poor survival (2 year OS of 44% vs 74%; log-rank p=0.001). ROC analysis demonstrated area under the curve (AUC) of 0.66 for ARamp- and 0.68 for CTC counts-based prognosis (p=0.84 for difference). The best two variables included for multivariable analysis were ARamp and CTC ≥ 5, however the two factor model was not significantly better than using ARamp alone for predicting survival (HR=5.25; p=0.0002). CTCs and plasma cfDNA ARamp were observed to have equal prognostic value in mCRPC. Larger cohorts that incorporate molecular and clinical factors are needed to further refine prognosis in CRPC.
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影响因子：
--
作者：
van der Toom EE;Verdone JE;Gorin MA;Pienta KJ
通讯作者：
Pienta KJ
影响因子：
11.5
作者：
Danila, Daniel C.;Heller, Glenn;Scher, Howard I.
通讯作者：
Scher, Howard I.
DOI：
10.1056/nejmoa1315815
发表时间：
2014-09-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Antonarakis ES;Lu C;Wang H;Luber B;Nakazawa M;Roeser JC;Chen Y;Mohammad TA;Chen Y;Fedor HL;Lotan TL;Zheng Q;De Marzo AM;Isaacs JT;Isaacs WB;Nadal R;Paller CJ;Denmeade SR;Carducci MA;Eisenberger MA;Luo J
通讯作者：
Luo J
影响因子：
45.3
作者：
Scher, Howard I.;Morris, Michael J.;Armstrong, Andrew J.
通讯作者：
Armstrong, Andrew J.
DOI：
10.1056/nejmoa1209096
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ryan CJ;Smith MR;de Bono JS;Molina A;Logothetis CJ;de Souza P;Fizazi K;Mainwaring P;Piulats JM;Ng S;Carles J;Mulders PF;Basch E;Small EJ;Saad F;Schrijvers D;Van Poppel H;Mukherjee SD;Suttmann H;Gerritsen WR;Flaig TW;George DJ;Yu EY;Efstathiou E;Pantuck A;Winquist E;Higano CS;Taplin ME;Park Y;Kheoh T;Griffin T;Scher HI;Rathkopf DE;COU-AA-302 Investigators
通讯作者：
COU-AA-302 Investigators