Abstract:Non-small cell lung cancer (NSCLC) remains a major global health challenge, with high post-surgical recurrence rates underscoring the need for accurate pathological response predictions to guide personalized treatments. Although artificial intelligence models show promise in this domain, their clinical adoption is limited by the lack of medically grounded guidance during training, often resulting in non-explainable intrinsic predictions. To address this, we propose Doctor-in-the-Loop, a novel framework that integrates expert-driven domain knowledge with explainable artificial intelligence techniques, directing the model toward clinically relevant anatomical regions and improving both interpretability and trustworthiness. Our approach employs a gradual multi-view strategy, progressively refining the model's focus from broad contextual features to finer, lesion-specific details. By incorporating domain insights at every stage, we enhance predictive accuracy while ensuring that the model's decision-making process aligns more closely with clinical reasoning. Evaluated on a dataset of NSCLC patients, Doctor-in-the-Loop delivers promising predictive performance and provides transparent, justifiable outputs, representing a significant step toward clinically explainable artificial intelligence in oncology.