Pathological prognosis classification of patients with neuroblastoma using computational pathology analysis

Neuroblastoma is the most common extracranial solid tumor in early childhood. International Neuroblastoma Pathology Classification (INPC) is a commonly used classification system that provides clinicians with a reference for treatment stratification. However, given the complex and subjective assessment of the INPC, there will be inconsistencies in the analysis of the same patient by multiple pathologists. An automated, comprehensive and objective classification method is needed to identify different prognostic groups in patients with neuroblastoma. In this study, we collected 563 hematoxylin and eosin-stained histopathology whole-slide images from 107 patients with neuroblastoma who underwent surgical resection. We proposed a novel processing pipeline for nuclear segmentation, cell-level image feature extraction, and patient-level feature aggregation. Logistic regression model was built to classify patients with favorable histology (FH) and patients with unfavorable histology (UH). On the training/test dataset, patient-level of nucleus morphological/intensity features and age could correctly classify patients with a mean area under the receiver operating characteristic curve (AUC) of 0.946, a mean accuracy of 0.856, and a mean Matthews Correlation Coefficient (MCC) of 0.703,respectively. On the independent validation dataset, the classification model achieved a mean AUC of 0.938, a mean accuracy of 0.865 and a mean MCC of 0.630, showing good generalizability. Our results suggested that automatically derived image features could identify the differences in nuclear morphological and intensity between different prognostic groups, which could provide a reference to pathologists and facilitate the evaluation of the pathological prognosis in patients with neuroblastoma.