Janssen R&D, LLC, a Johnson & Johnson Company. Data Science and Digital Health, San Diego, CA, USA.
Janssen R&D, LLC, a Johnson & Johnson Company. Data Science and Digital Health, Cambridge, MA, USA.
Nat Commun. 2024 Jun 1;15(1):4690. doi: 10.1038/s41467-024-49153-9.
Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular testing can delay patient care due to the time and tissue required. Successful development, validation, and deployment of an AI-based, biomarker-detection algorithm could reduce screening cost and accelerate patient recruitment. Here, we develop a deep-learning algorithm using >3000 H&E-stained whole slide images from patients with advanced urothelial cancers, optimized for high sensitivity to avoid ruling out trial-eligible patients. The algorithm is validated on a dataset of 350 patients, achieving an area under the curve of 0.75, specificity of 31.8% at 88.7% sensitivity, and projected 28.7% reduction in molecular testing. We successfully deploy the system in a non-interventional study comprising 89 global study clinical sites and demonstrate its potential to prioritize/deprioritize molecular testing resources and provide substantial cost savings in the drug development and clinical settings.
准确识别肿瘤中的遗传改变,如成纤维细胞生长因子受体,对于靶向治疗至关重要;然而,由于所需的时间和组织,分子检测可能会延迟患者的治疗。成功开发、验证和部署基于人工智能的生物标志物检测算法可以降低筛选成本并加速患者招募。在这里,我们使用来自晚期尿路上皮癌患者的超过 3000 张 H&E 染色全切片图像开发了一种深度学习算法,该算法针对高灵敏度进行了优化,以避免排除符合试验条件的患者。该算法在包含 350 名患者的数据集上进行了验证,曲线下面积为 0.75,特异性为 31.8%,灵敏度为 88.7%,预计分子检测减少 28.7%。我们成功地将该系统部署在一项包括 89 个全球研究临床站点的非干预性研究中,并证明了其在优先/降级分子检测资源方面的潜力,并在药物开发和临床环境中节省了大量成本。