数字病理学和人工智能是精准肿瘤学中有前景的新兴工具，因为它们能够对肿瘤细胞及其周围微环境的组织学、形态学和拓扑学特征进行更强大和可重复的分析。本研究旨在开发数字图像分析工作流，用于在体外预临床模型中进行治疗评估。为此，我们生成了能够自动检测和量化异位高危神经母细胞瘤异种移植瘤中的血浆纤维粘连蛋白（vitronectin）和αvβ3的流程，证明了数字分析工作流可用于强大地检测恶性神经母细胞的血浆纤维粘连蛋白分泌和αvβ3表达，并评估传统化疗（依托泊苷）与细胞外基质靶向治疗（西来替）的结合可能性。数字图像分析进一步证明了领土性血浆纤维粘连蛋白作为神经母细胞瘤治疗靶点的相关性，因为其表达在治疗后发生改变，组合治疗瘤中的平均百分比为60.44%，对照组中为45.08%。此外，本研究揭示了西来替降低αvβ3表达的疗效，与对照组相比，西来替处理的材料中平均αvβ3阳性率为34.17%，控制组为66.14%，且与依托泊苷联合使用时肿瘤生长得到减少，组合治疗的最终平均体积为0.04 cm3，对照组为1.45 cm3。本研究结果凸显了细胞外基质为焦点的治疗在高危神经母细胞瘤患者的临床前研究中的重要性。版权所有©2023作者。由Elsevier Ltd.出版。保留所有权利。

Digital pathology and artificial intelligence are promising emerging tools in precision oncology as they provide more robust and reproducible analysis of histologic, morphologic and topologic characteristics of tumor cells and the surrounding microenvironment. This study aims to develop digital image analysis workflows for therapeutic assessment in preclinical in vivo models. For this purpose, we generated pipelines that enable automatic detection and quantification of vitronectin and αvβ3 in heterotopic high-risk neuroblastoma xenografts, demonstrating that digital analysis workflows can be used to provide robust detection of vitronectin secretion and αvβ3 expression by malignant neuroblasts and to evaluate the possibility of combining traditional chemotherapy (etoposide) with extracellular matrix-targeted therapies (cilengitide). Digital image analysis added evidence for the relevance of territorial vitronectin as a therapeutic target in neuroblastoma, since its expression is modified after treatment, with a mean percentage of 60.44% in combined therapy tumors vs 45.08% in control ones. In addition, the present study revealed the efficacy of cilengitide for reducing αvβ3 expression, with a mean αvβ3 positivity of 34.17% in cilengitide treated material vs 66.14% in control and with less tumor growth when combined with etoposide, with a final mean volume of 0.04 cm3 in combined therapy vs 1.45 cm3 in control. The results of this work highlight the importance of extracellular matrix-focused therapies in preclinical studies to improve therapeutic assessment for high-risk neuroblastoma patients.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.