下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Analysis of computational tumor-infiltrating lymphocytes in breast cancer from the results of the TIGER challenge.
在此,我们展示了一项多中心分析,针对来自临床实践和3期试验的3,708例人表皮生长因子受体2阳性(HER2+)或三阴性乳腺癌(TNBC)的切除标本和活检标本的cTILs方法。
TIL(肿瘤浸润淋巴细胞)(TILs)是乳腺癌中公认的预后生物标志物。然而,观察者间一致性差和可重复性有限凸显了对计算方法的需求。尽管取得了进展,但由于缺乏标准化方法和稳健的基准,计算模型的采用一直受到阻碍。为解决这一问题,我们发起了 TIGER,一项旨在构建开源计算 TILs(cTILs)模型的国际竞赛。在此,我们展示了对来自临床实践和 3 期试验的 3,708 例人表皮生长因子受体 2 阳性(HER2+)或三阴性乳腺癌(TNBC)切除标本和活检标本的 cTILs 方法的多中心分析。我们报告了图像分析性能的基准,显示 cTILs 与病理学家高度一致,并证明 cTILs 与 HER2+ 中新辅助治疗反应呈正相关,优于视觉评分的 TILs。我们还表明,在 TNBC 切除标本中,cTILs 为临床变量增加了独立的预后信息。数据、方法和基准已公开:https://tiger.grand-challenge.org/。
Tumor-infiltrating lymphocytes (TILs) is a recognized prognostic biomarker in breast cancer. However, poor interobserver agreement and limited reproducibility highlight the need for computational approaches. Despite advances, adoption of computational models has been hindered by lack of standardized methods and robust benchmarks. To address this, we launched TIGER, an international competition to build open-source computational TILs (cTILs) models. Here, we present a multi-centric analysis of cTILs methods on resections and biopsies from 3,708 human epidermal growth factor receptor 2-positive (HER2+) or triple-negative breast cancers (TNBC) from clinical practice and phase 3 trials. We report benchmarks on image analysis performance, show strong agreement of cTILs with pathologists, and demonstrate positive association of cTILs with neoadjuvant therapy response in HER2+, superior to visually scored TILs. We also show that cTILs add independent prognostic information to clinical variables in TNBC resections. Data, methods and benchmarks are publicly available: https://tiger.grand-challenge.org/ .
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