Decline in Circulating Tumor Cell Count and Treatment Outcome in Advanced Prostate Cancer.
Decline in Circulating Tumor Cell Count and Treatment Outcome in Advanced Prostate Cancer.
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晚期前列腺癌中循环细胞计数和治疗结果的下降。
DOI：
10.1016/j.eururo.2016.05.023
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发表时间：
2016-12
期刊：
影响因子：
23.4
通讯作者：
de Bono JS
中科院分区：
文献类型：
--
作者：
Lorente D;Olmos D;Mateo J;Bianchini D;Seed G;Fleisher M;Danila DC;Flohr P;Crespo M;Figueiredo I;Miranda S;Baeten K;Molina A;Kheoh T;McCormack R;Terstappen LW;Scher HI;de Bono JS
去势抵抗性前列腺癌（CRPC）迫切需要治疗反应生物标志物。基线和治疗后循环肿瘤细胞（CTC）计数≥5个细胞/7.5 ml与CRPC结局较差相关。确定CTC下降≥30%的值作为治疗反应指标。我们在两项前瞻性试验中确定了基线CTC计数≥5个细胞/7.5 ml且治疗后CTC计数可评价的患者。患者在COU-AA-301（化疗后阿比特龙）和IMMC-38（化疗）试验中接受治疗。在3个标志性时间点（4、8和12周），使用单变量和多变量考克斯回归模型评价治疗后CTC下降≥30%与生存期之间的相关性。通过计算受试者工作特征曲线下面积（AUC）和c指数评价模型性能。总体上，486例患者（IMMC-38中122例，COU-AA-301中364例）在基线时CTC计数≥5个细胞/7.5 ml，分别有440、380和351例患者在第4、8和12周可评价。CTC下降30%与4周生存率增加相关（风险比[HR] 0.45，95%置信区间[CI] 0.36-0.56; p < 0.001），8周在单变量和多变量分析中，HR 0.41，95% CI 0.33-0.53; p < 0.001）和12周（HR 0.39，95% CI 0.3-0.5; p < 0.001）。与CTC计数增加相比，稳定的CTC计数（下降<30%或增加<30%）与生存益处无关。治疗后CTC下降30%与生存期之间的相关性与基线CTC计数无关。CTC下降显著改善了所有时间点的AUC。最后，在COU-AA-301试验中，CTC ≥5个细胞/7.5 ml且CTC下降30%的患者在两组中的总生存期相似。治疗后CTC从初始计数≥5个细胞/7.5 ml下降30%与阿比特龙和化疗后的CRPC总生存期独立相关，早在治疗后4周就改善了多变量模型的性能。这个潜在的替代品现在必须进行前瞻性评估。循环肿瘤细胞（CTC）是可以在前列腺癌患者的血液中检测到的癌细胞。我们在两项大型临床试验中分析了阿比特龙和化疗治疗后CTC的变化，发现CTC计数下降的患者具有更好的生存结局。
Treatment response biomarkers are urgently needed for castration-resistant prostate cancer (CRPC). Baseline and post-treatment circulating tumor cell (CTC) counts of ≥5 cells/7.5 ml are associated with poor CRPC outcome. To determine the value of a ≥30% CTC decline as a treatment response indicator. We identified patients with a baseline CTC count ≥5 cells/7.5 ml and evaluable post-treatment CTC counts in two prospective trials. Patients were treated in the COU-AA-301 (abiraterone after chemotherapy) and IMMC-38 (chemotherapy) trials. The association between a ≥30% CTC decline after treatment and survival was evaluated using univariable and multivariable Cox regression models at three landmark time points (4, 8, and 12 wk). Model performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC) and c-indices. Overall 486 patients (122 in IMMC-38 and 364 in COU-AA-301) had a CTC count ≥5 cells/7.5 ml at baseline, with 440, 380, and 351 patients evaluable at 4, 8, and 12 wk, respectively. A 30% CTC decline was associated with increased survival at 4 wk (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.36–0.56; p < 0.001), 8 wk (HR 0.41, 95% CI 0.33–0.53; p < 0.001), and 12 wk (HR 0.39, 95% CI 0.3–0.5; p < 0.001) in univariable and multivariable analyses. Stable CTC count (<30% fall or <30% increase) was not associated with a survival benefit when compared with increased CTC count. The association between a 30% CTC decline after treatment and survival was independent of baseline CTC count. CTC declines significantly improved the AUC at all time-points. Finally, in the COU-AA-301 trial, patients with CTC ≥5 cells/7.5 ml and a 30% CTC decline had similar overall survival in both arms. A 30% CTC decline after treatment from an initial count ≥5 cells/7.5 ml is independently associated with CRPC overall survival following abiraterone and chemotherapy, improving the performance of a multivariable model as early as 4 wk after treatment. This potential surrogate must now be prospectively evaluated. Circulating tumor cells (CTCs) are cancer cells that can be detected in the blood of prostate cancer patients. We analyzed changes in CTCs after treatment with abiraterone and chemotherapy in two large clinical trials, and found that patients who have a decline in CTC count have a better survival outcome.
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影响因子：
158.5
作者：
Parker, C.;Nilsson, S.;Sartor, O.
通讯作者：
Sartor, O.
影响因子：
158.5
作者：
Scher, Howard I.;Fizazi, Karim;de Bono, Johann S.
通讯作者：
de Bono, Johann S.
影响因子：
11.5
作者：
Danila, Daniel C.;Heller, Glenn;Scher, Howard I.
通讯作者：
Scher, Howard I.
影响因子：
50.5
作者：
Olmos, D.;Arkenau, H. -T.;de Bono, J. S.
通讯作者：
de Bono, J. S.
DOI：
10.1093/jnci/djj129
发表时间：
2006-04-19
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Petrylak, DP;Ankerst, DP;Crawford, ED
通讯作者：
Crawford, ED