Hikmat Khan

Hikmat Khan, Ziyu Su, Huina Zhang et al.

Triple-negative breast cancer (TNBC) remains a major clinical challenge due to its aggressive behavior and lack of targeted therapies. Accurate early prediction of response to neoadjuvant chemotherapy (NACT) is essential for guiding personalized treatment strategies and improving patient outcomes. In this study, we present an attention-based multiple instance learning (MIL) framework designed to predict pathologic complete response (pCR) directly from pre-treatment hematoxylin and eosin (H&E)-stained biopsy slides. The model was trained on a retrospective in-house cohort of 174 TNBC patients and externally validated on an independent cohort (n = 30). It achieved a mean area under the curve (AUC) of 0.85 during five-fold cross-validation and 0.78 on external testing, demonstrating robust predictive performance and generalizability. To enhance model interpretability, attention maps were spatially co-registered with multiplex immuno-histochemistry (mIHC) data stained for PD-L1, CD8+ T cells, and CD163+ macrophages. The attention regions exhibited moderate spatial overlap with immune-enriched areas, with mean Intersection over Union (IoU) scores of 0.47 for PD-L1, 0.45 for CD8+ T cells, and 0.46 for CD163+ macrophages. The presence of these biomarkers in high-attention regions supports their biological relevance to NACT response in TNBC. This not only improves model interpretability but may also inform future efforts to identify clinically actionable histological biomarkers directly from H&E-stained biopsy slides, further supporting the utility of this approach for accurate NACT response prediction and advancing precision oncology in TNBC.

Hikmat Khan, Nidhal Carla Bouaynaya, Ghulam Rasool

Artificial intelligence (AI) and neuroscience share a rich history, with advancements in neuroscience shaping the development of AI systems capable of human-like knowledge retention. Leveraging insights from neuroscience and existing research in adversarial and continual learning, we introduce a novel framework comprising two core concepts: feature distillation and re-consolidation. Our framework, named Robust Rehearsal, addresses the challenge of catastrophic forgetting inherent in continual learning (CL) systems by distilling and rehearsing robust features. Inspired by the mammalian brain's memory consolidation process, Robust Rehearsal aims to emulate the rehearsal of distilled experiences during learning tasks. Additionally, it mimics memory re-consolidation, where new experiences influence the integration of past experiences to mitigate forgetting. Extensive experiments conducted on CIFAR10, CIFAR100, and real-world helicopter attitude datasets showcase the superior performance of CL models trained with Robust Rehearsal compared to baseline methods. Furthermore, examining different optimization training objectives-joint, continual, and adversarial learning-we highlight the crucial role of feature learning in model performance. This underscores the significance of rehearsing CL-robust samples in mitigating catastrophic forgetting. In conclusion, aligning CL approaches with neuroscience insights offers promising solutions to the challenge of catastrophic forgetting, paving the way for more robust and human-like AI systems.