<b>Experts' </b><b>C</b><b>ognition-Driven Ensemble Deep Learning </b><b>f</b><b>or External Validation of Predicting Pathological Complete Response to Neoadjuvant Chemotherapy </b><b>

In breast cancer, neoadjuvant chemotherapy (NAC) provides a standard treatment option for patients who have locally advanced cancer and some large operable tumors. A patient will have better prognosis when he has achieved a pathological complete response (pCR) with the treatment of NAC. There has been a trend to directly predict pCR to NAC from histological images based on deep learning (DL). However, the DL-based predictive models numerically have better performances in internal validation than in external validation. In this paper, we aim to alleviate this situation with an intrinsic approach. We propose an experts’ cognition-driven ensemble deep learning (ECDEDL) approach. Taking the cognition of both pathology and artificial intelligence experts into consideration to improve the generalization of the predictive model to the external validation, ECDEDL can intrinsically approximate the working paradigm of a human being which will refer to his various working experiences to make decisions. ECDEDL was validated with 695 WSIs collected from the same center as the primary dataset to develop the predictive model and perform the internal validation, and was also validated with 340 WSIs collected from other three centers as the external dataset to perform the external validation. In external validation, ECDEDL improves the AUCs of pCR prediction from 61.52(59.80-63.26) to 67.75(66.74-68.80) and the Accuracies of pCR prediction from 56.09(49.39-62.79) to 71.01(69.44-72.58). ECDEDL was quite effective for external validation of predicting pCR to NAC from histological images in breast cancer, numerically approximating the internal validation. Received: 16 August 2024 | Revised: 14 October 2024 | Accepted: 4 November 2024 Conflicts of Interest The authors declare that they have no conflicts of interest to this work. Data Availability Statement The data that support this work are available upon reasonable request to the corresponding author. Author Contribution Statement Yongquan Yang: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Resources, Data curation, Writing - original draft, Visualization, Supervision, Project administration. Fengling Li: Conceptualization, Validation, Resources, Data curation, Writing - review & editing. Yani Wei: Resources, Writing - review & editing. Yuanyuan Zhao: Resources, Writing - review & editing. Jing Fu: Resources, Writing - review & editing. Xiuli Xiao: Resources, Writing - review & editing. Hong Bu: Resources, Writing - review & editing, Supervision, Funding acquisition.