Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.
Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.
复制标题
DOI：
10.1093/annonc/mdx266
复制
发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Caldas C
中科院分区：
文献类型：
--
作者：
Ali HR;Dariush A;Thomas J;Provenzano E;Dunn J;Hiller L;Vallier AL;Abraham J;Piper T;Bartlett JMS;Cameron DA;Hayward L;Brenton JD;Pharoah PDP;Irwin MJ;Walton NA;Earl HM;Caldas C
我们以前已经表明淋巴细胞密度，使用计算病理学测量，与乳腺癌的病理完全反应（pCR）。在接受不同化疗的患者中进行的独立研究中，这一发现的临床有效性尚不清楚。ARTemis试验将2009年5月至2013年1月期间患有早期乳腺癌的800名女性随机分配到三个周期的多西他赛，随后是三个周期的氟尿嘧啶，表阿霉素和环磷酰胺，每21天一次，有或没有四个周期的贝伐单抗。主要终点是pCR（乳腺和淋巴结中无浸润性癌）。我们使用我们先前描述的计算病理学方法定量苏木精和伊红（H&E）全载玻片图像内的淋巴细胞密度：对于每个检测到的淋巴细胞，计算与最近50个淋巴细胞的平均距离，并从该统计量中获得密度。我们分析了治疗前活检和治疗后肿瘤床的手术样本。在最初纳入试验主要终点分析的781例患者中，609例（78%）被纳入基线淋巴细胞密度分析，383例（781例中的49%）被纳入淋巴细胞密度变化分析。患者流失的主要原因是数字化全切片图像的可用性。在单变量分析（比值比[OR]，2.92; 95%CI，1.78-4.85; P < 0.001）和临床协变量校正后（OR，2.13; 95%CI，1.24-3.67; P = 0.006），将治疗前淋巴细胞密度建模为连续变量与pCR相关。治疗前后淋巴细胞密度的增加与pCR呈独立的负相关（校正OR，0.1; 95%CI，0.033-0.31; P < 0.001）。治疗前活检组织中的淋巴细胞密度被验证为乳腺癌pCR的独立预测因子。计算病理学正在成为识别癌症患者的预测性生物标志物的可行且客观的手段。NCT01093235。
We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78–4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24–3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033–0.31; P < 0.001). Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients. NCT01093235.
登录
查看更多内容
DOI：
10.1093/annonc/mdx173
发表时间：
2017-08-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Earl HM;Hiller L;Dunn JA;Blenkinsop C;Grybowicz L;Vallier AL;Gounaris I;Abraham JE;Hughes-Davies L;McAdam K;Chan S;Ahmad R;Hickish T;Rea D;Caldas C;Bartlett JMS;Cameron DA;Provenzano E;Thomas J;Hayward RL;ARTemis Investigators Group
通讯作者：
ARTemis Investigators Group
乳腺癌中免疫浸润及其临床意义的模式：一项基于基因表达的回顾性研究。
影响因子：
15.8
作者：
Ali HR;Chlon L;Pharoah PD;Markowetz F;Caldas C
通讯作者：
Caldas C
影响因子：
51.1
作者：
Earl, Helena M.;Hiller, Louise;Hayward, Larry
通讯作者：
Hayward, Larry
影响因子：
51.1
作者：
Earl, Helena M.;Vallier, Anne-Laure;Caldas, Carlos
通讯作者：
Caldas, Carlos
影响因子：
50.5
作者：
Loi, S.;Michiels, S.;Sotiriou, C.
通讯作者：
Sotiriou, C.