Barrios Wayner, Abdollahi Behnaz, Goyal Manu, Song Qingyuan, Suriawinata Matthew, Richards Ryland, Ren Bing, Schned Alan, Seigne John, Karagas Margaret, Hassanpour Saeed
Department of Computer Science, Dartmouth College, Hanover, NH, USA.
Department of Biomedical Data Science, Dartmouth College, Hanover, NH, USA.
J Pathol Inform. 2022 Aug 28;13:100135. doi: 10.1016/j.jpi.2022.100135. eCollection 2022.
Recent studies indicate that bladder cancer is among the top 10 most common cancers in the world (Saginala et al. 2022). Bladder cancer frequently reoccurs, and prognostic judgments may vary among clinicians. As a favorable prognosis may help to inform less aggressive treatment plans, classification of histopathology slides is essential for the accurate prognosis and effective treatment of bladder cancer patients. Developing automated and accurate histopathology image analysis methods can help pathologists determine the prognosis of patients with bladder cancer.
In this study, we introduced Bladder4Net, a deep learning pipeline, to classify whole-slide histopathology images of bladder cancer into two classes: low-risk (combination of PUNLMP and low-grade tumors) and high-risk (combination of high-grade and invasive tumors). This pipeline consists of four convolutional neural network (CNN)-based classifiers to address the difficulties of identifying PUNLMP and invasive classes. We evaluated our pipeline on 182 independent whole-slide images from the New Hampshire Bladder Cancer Study (NHBCS) (Karagas et al., 1998; Sverrisson et al., 2014; Sverrisson et al., 2014) collected from 1994 to 2004 and 378 external digitized slides from The Cancer Genome Atlas (TCGA) database (https://www.cancer.gov/tcga).
The weighted average F1-score of our approach was 0.91 (95% confidence interval (CI): 0.86-0.94) on the NHBCS dataset and 0.99 (95% CI: 0.97-1.00) on the TCGA dataset. Additionally, we computed Kaplan-Meier survival curves for patients who were predicted as high risk versus those predicted as low risk. For the NHBCS test set, patients predicted as high risk had worse overall survival than those predicted as low risk, with a log-rank p-value of 0.004.
If validated through prospective trials, our model could be used in clinical settings to improve patient care.
近期研究表明,膀胱癌是全球十大最常见癌症之一(萨吉纳拉等人,2022年)。膀胱癌经常复发,临床医生之间的预后判断可能存在差异。由于良好的预后有助于制定不太激进的治疗方案,组织病理学切片的分类对于膀胱癌患者的准确预后和有效治疗至关重要。开发自动化且准确的组织病理学图像分析方法有助于病理学家确定膀胱癌患者的预后。
在本研究中,我们引入了深度学习管道Bladder4Net,将膀胱癌的全切片组织病理学图像分为两类:低风险(乳头状瘤样病变和低级别肿瘤的组合)和高风险(高级别和浸润性肿瘤的组合)。该管道由四个基于卷积神经网络(CNN)的分类器组成,以解决识别乳头状瘤样病变和浸润性类别的困难。我们在1994年至2004年收集的来自新罕布什尔州膀胱癌研究(NHBCS)(卡拉加斯等人,1998年;斯韦里松等人,2014年;斯韦里松等人,2014年)的182张独立全切片图像以及来自癌症基因组图谱(TCGA)数据库(https://www.cancer.gov/tcga)的378张外部数字化切片上评估了我们的管道。
我们的方法在NHBCS数据集上的加权平均F1分数为0.91(95%置信区间(CI):0.86 - 0.94),在TCGA数据集上为0.99(95%CI:0.97 - 1.00)。此外,我们计算了预测为高风险患者与预测为低风险患者的Kaplan-Meier生存曲线。对于NHBCS测试集,预测为高风险的患者总体生存率低于预测为低风险的患者,对数秩p值为0.004。
如果通过前瞻性试验验证,我们的模型可用于临床环境以改善患者护理。