Fengtao Zhou

Fengtao Zhou, Yingxue Xu, Zhengyu Zhang et al.

Comprehensive molecular profiling is essential for modern precision oncology but remains hindered by prohibitive costs, specimen exhaustion, and protracted turnaround times. While pathology foundation models (PFMs) have demonstrated potential for inferring molecular phenotypes from routine hematoxylin and eosin (H&E) whole-slide images (WSIs), current architectures primarily rely on vision-centric self-supervised learning or vision-language alignment, lacking the spatially resolved molecular supervision required to connect subtle morphological features with underlying genomic alterations. Spatial transcriptomics (ST) emerges as a transformative technology that enables transcriptomic quantification within intact tissue sections, thereby preserving the precise spatial link between histology and molecular profiles. In this study, we present a Spatial Transcriptomics-guided Alignment framework for Molecular Profiling (STAMP), which endows PFMs with intrinsic molecular awareness. To support this paradigm, we curated HumanST-1k, a human ST dataset spanning diverse anatomical organs and sequencing platforms. This atlas yields 1.8 million pairs of H&E patches and corresponding transcriptomic profiles, providing a corpus that links histological structures with their molecular states. To mitigate the technical noise inherent to raw transcriptomics, STAMP applies a pathway-informed alignment strategy that aggregates transcriptomic data into biologically functional pathways, which are subsequently integrated into PFMs via parameter-efficient fine-tuning. This alignment enriches the representation space of PFMs and unlocks their capacity to resolve sub-visual molecular signatures. The clinical utility of these augmented representations was validated through a multi-tier evaluation framework.

Ling Liang, Jiabo Ma, Zhengyu Zhang et al.

Gastric cancer remains a major cause of cancer mortality, yet its histological and molecular heterogeneity complicates diagnosis and risk stratification. General-purpose pathology foundation models (PFMs) often plateau on fine-grained endpoints central to gastric cancer care, and few have undergone rigorous prospective validation or clinical reader studies. We present GRACE, a Gastric-specific foundation model for Real-world Assessment and Clinical dEcision support. GRACE was developed from multicenter gastric pathology datasets totaling 48,364 primarily HE-stained whole-slide images from 37,493 patients. When evaluated on 28 clinically relevant tasks, GRACE consistently outperformed representative pancancer PFMs, achieving a macro-AUC of 0.9188, with strong performance for precancerous lesion diagnosis (macro-AUC 0.9322), tumor histopathological assessment (macro-AUC 0.9119), molecular profiling (macro-AUC 0.8682), and prognostic prediction. Beyond benchmarking, GRACE's translational value was substantiated through a rigorous evidence chain. Under safety-gated criteria requiring 100% NPV for rule-out and 100% PPV for rule-in, GRACE streamlined review for up to 69.6% of malignancy-diagnosis cases and triaged 46.8% of MMR-IHC follow-up requests. This translational feasibility was further strengthened by a randomized crossover reader study of pathologist-AI collaboration. With GRACE assistance, diagnostic accuracy improved from 82.0% to 89.9%, yielding nearly twofold higher adjusted odds of a correct diagnosis (OR 1.987) alongside concurrent gains in sensitivity and specificity. AI assistance also reduced diagnostic time by 14.9%, elevated diagnostic confidence by 9.0%, and markedly improved inter-rater agreement. When calibrated to maintain non-inferior performance to senior pathologists, the AI-assisted workflow could triage 60.7% of atrophy and 82.7% of intestinal metaplasia cases.

Wenhao Tang, Sheng Huang, Xiaoxian Zhang et al.

The whole slide image (WSI) classification is often formulated as a multiple instance learning (MIL) problem. Since the positive tissue is only a small fraction of the gigapixel WSI, existing MIL methods intuitively focus on identifying salient instances via attention mechanisms. However, this leads to a bias towards easy-to-classify instances while neglecting hard-to-classify instances. Some literature has revealed that hard examples are beneficial for modeling a discriminative boundary accurately. By applying such an idea at the instance level, we elaborate a novel MIL framework with masked hard instance mining (MHIM-MIL), which uses a Siamese structure (Teacher-Student) with a consistency constraint to explore the potential hard instances. With several instance masking strategies based on attention scores, MHIM-MIL employs a momentum teacher to implicitly mine hard instances for training the student model, which can be any attention-based MIL model. This counter-intuitive strategy essentially enables the student to learn a better discriminating boundary. Moreover, the student is used to update the teacher with an exponential moving average (EMA), which in turn identifies new hard instances for subsequent training iterations and stabilizes the optimization. Experimental results on the CAMELYON-16 and TCGA Lung Cancer datasets demonstrate that MHIM-MIL outperforms other latest methods in terms of performance and training cost. The code is available at: https://github.com/DearCaat/MHIM-MIL.

Fengtao Zhou, Hao Chen

With the rapid advances in high-throughput sequencing technologies, the focus of survival analysis has shifted from examining clinical indicators to incorporating genomic profiles with pathological images. However, existing methods either directly adopt a straightforward fusion of pathological features and genomic profiles for survival prediction, or take genomic profiles as guidance to integrate the features of pathological images. The former would overlook intrinsic cross-modal correlations. The latter would discard pathological information irrelevant to gene expression. To address these issues, we present a Cross-Modal Translation and Alignment (CMTA) framework to explore the intrinsic cross-modal correlations and transfer potential complementary information. Specifically, we construct two parallel encoder-decoder structures for multi-modal data to integrate intra-modal information and generate cross-modal representation. Taking the generated cross-modal representation to enhance and recalibrate intra-modal representation can significantly improve its discrimination for comprehensive survival analysis. To explore the intrinsic crossmodal correlations, we further design a cross-modal attention module as the information bridge between different modalities to perform cross-modal interactions and transfer complementary information. Our extensive experiments on five public TCGA datasets demonstrate that our proposed framework outperforms the state-of-the-art methods.

Jiazhi Xu, Sheng Huang, Fengtao Zhou et al.

Multi-Label Image Classification (MLIC) approaches usually exploit label correlations to achieve good performance. However, emphasizing correlation like co-occurrence may overlook discriminative features of the target itself and lead to model overfitting, thus undermining the performance. In this study, we propose a generic framework named Parallel Self-Distillation (PSD) for boosting MLIC models. PSD decomposes the original MLIC task into several simpler MLIC sub-tasks via two elaborated complementary task decomposition strategies named Co-occurrence Graph Partition (CGP) and Dis-occurrence Graph Partition (DGP). Then, the MLIC models of fewer categories are trained with these sub-tasks in parallel for respectively learning the joint patterns and the category-specific patterns of labels. Finally, knowledge distillation is leveraged to learn a compact global ensemble of full categories with these learned patterns for reconciling the label correlation exploitation and model overfitting. Extensive results on MS-COCO and NUS-WIDE datasets demonstrate that our framework can be easily plugged into many MLIC approaches and improve performances of recent state-of-the-art approaches. The explainable visual study also further validates that our method is able to learn both the category-specific and co-occurring features. The source code is released at https://github.com/Robbie-Xu/CPSD.

Yingxue Xu, Yihui Wang, Fengtao Zhou et al.

Remarkable strides in computational pathology have been made in the task-agnostic foundation model that advances the performance of a wide array of downstream clinical tasks. Despite the promising performance, there are still several challenges. First, prior works have resorted to either vision-only or image-caption data, disregarding pathology reports with more clinically authentic information from pathologists and gene expression profiles which respectively offer distinct knowledge for versatile clinical applications. Second, the current progress in pathology FMs predominantly concentrates on the patch level, where the restricted context of patch-level pretraining fails to capture whole-slide patterns. Even recent slide-level FMs still struggle to provide whole-slide context for patch representation. In this study, for the first time, we develop a pathology foundation model incorporating three levels of modalities: pathology slides, pathology reports, and gene expression data, which resulted in 26,169 slide-level modality pairs from 10,275 patients across 32 cancer types, amounting to over 116 million pathological patch images. To leverage these data for CPath, we propose a novel whole-slide pretraining paradigm that injects the multimodal whole-slide context into the patch representation, called Multimodal Self-TAught PRetraining (mSTAR). The proposed paradigm revolutionizes the pretraining workflow for CPath, enabling the pathology FM to acquire the whole-slide context. To the best of our knowledge, this is the first attempt to incorporate three modalities at the whole-slide context for enhancing pathology FMs. To systematically evaluate the capabilities of mSTAR, we built the largest spectrum of oncological benchmark, spanning 7 categories of oncological applications in 15 types of 97 practical oncological tasks.

Zhengrui Guo, Zhengyu Zhang, Jiabo Ma et al.

Pathological assessment guides lung cancer diagnosis, treatment selection, and prognostic evaluation, yet current CPath approaches rely on task-specific models for isolated objectives. Although pan-cancer foundation models offer versatility, they lack subspecialty-level depth and have not been evaluated across clinical workflows or prospectively validated in real-world settings. We introduce PulmoFoundation, a multi-center, prospectively validated, randomized controlled trial (RCT)-evaluated foundation model for comprehensive lung pathology assessment across pre-operative, intra-operative, and post-operative care. Built upon Virchow2 via subspecialty-specific pretraining using ~40,000 diagnostic H&E-stained whole-slide images (WSIs), PulmoFoundation was systematically evaluated on ~26,000 WSIs across 32 clinically relevant tasks. In addition to accurately predicting molecular markers and patient survival, our model achieves clinical-grade performance in core diagnostic tasks across biopsy, frozen section, and surgical resection slides. In a registered prospective study of 1,357 patients across 11 diagnostic tasks, our model achieved an average AUC of 92.3%. Using pre-specified triage thresholds, PulmoFoundation could reduce additional second-review burden for 68.8% of biopsies and 83.0% of frozen sections, and defer 44.5% of IHC stain orders, with PPVs of 1.0, 0.991, and 0.966. Beyond prospective validation, we conducted a crossover RCT with eight pathologists, in which AI assistance improved diagnostic accuracy across 4,928 case-reader pairs (91.7% w/ AI vs. 83.8% w/o AI). AI assistance also reduced median diagnostic time by 19.6%, increased diagnostic confidence by 8.7%, and improved inter-rater agreement from moderate (kappa = 0.56) to substantial (kappa = 0.76). Together, these evaluations support PulmoFoundation as a clinically validated decision-support system for lung pathology.

Jiabo Ma, Zhengrui Guo, Fengtao Zhou et al.

Foundation models pretrained on large-scale datasets are revolutionizing the field of computational pathology (CPath). The generalization ability of foundation models is crucial for the success in various downstream clinical tasks. However, current foundation models have only been evaluated on a limited type and number of tasks, leaving their generalization ability and overall performance unclear. To address this gap, we established a most comprehensive benchmark to evaluate the performance of off-the-shelf foundation models across six distinct clinical task types, encompassing a total of 72 specific tasks, including slide-level classification, survival prediction, ROI-tissue classification, ROI retrieval, visual question answering, and report generation. Our findings reveal that existing foundation models excel at certain task types but struggle to effectively handle the full breadth of clinical tasks. To improve the generalization of pathology foundation models, we propose a unified knowledge distillation framework consisting of both expert and self-knowledge distillation, where the former allows the model to learn from the knowledge of multiple expert models, while the latter leverages self-distillation to enable image representation learning via local-global alignment. Based on this framework, we curated a dataset of 96,000 whole slide images (WSIs) and developed a Generalizable Pathology Foundation Model (GPFM). This advanced model was trained on a substantial dataset comprising 190 million images extracted from approximately 72,000 publicly available slides, encompassing 34 major tissue types. Evaluated on the established benchmark, GPFM achieves an impressive average rank of 1.6, with 42 tasks ranked 1st, while the second-best model, UNI, attains an average rank of 3.7, with only 6 tasks ranked 1st.

Wenhao Tang, Fengtao Zhou, Sheng Huang et al.

Multiple instance learning (MIL) is the most widely used framework in computational pathology, encompassing sub-typing, diagnosis, prognosis, and more. However, the existing MIL paradigm typically requires an offline instance feature extractor, such as a pre-trained ResNet or a foundation model. This approach lacks the capability for feature fine-tuning within the specific downstream tasks, limiting its adaptability and performance. To address this issue, we propose a Re-embedded Regional Transformer (R$^2$T) for re-embedding the instance features online, which captures fine-grained local features and establishes connections across different regions. Unlike existing works that focus on pre-training powerful feature extractor or designing sophisticated instance aggregator, R$^2$T is tailored to re-embed instance features online. It serves as a portable module that can seamlessly integrate into mainstream MIL models. Extensive experimental results on common computational pathology tasks validate that: 1) feature re-embedding improves the performance of MIL models based on ResNet-50 features to the level of foundation model features, and further enhances the performance of foundation model features; 2) the R$^2$T can introduce more significant performance improvements to various MIL models; 3) R$^2$T-MIL, as an R$^2$T-enhanced AB-MIL, outperforms other latest methods by a large margin.The code is available at: https://github.com/DearCaat/RRT-MIL.

Andong Tan, Fengtao Zhou, Hao Chen

The concept bottleneck model (CBM) is an interpretable-by-design framework that makes decisions by first predicting a set of interpretable concepts, and then predicting the class label based on the given concepts. Existing CBMs are trained with a fixed set of concepts (concepts are either annotated by the dataset or queried from language models). However, this closed-world assumption is unrealistic in practice, as users may wonder about the role of any desired concept in decision-making after the model is deployed. Inspired by the large success of recent vision-language pre-trained models such as CLIP in zero-shot classification, we propose "OpenCBM" to equip the CBM with open vocabulary concepts via: (1) Aligning the feature space of a trainable image feature extractor with that of a CLIP's image encoder via a prototype based feature alignment; (2) Simultaneously training an image classifier on the downstream dataset; (3) Reconstructing the trained classification head via any set of user-desired textual concepts encoded by CLIP's text encoder. To reveal potentially missing concepts from users, we further propose to iteratively find the closest concept embedding to the residual parameters during the reconstruction until the residual is small enough. To the best of our knowledge, our "OpenCBM" is the first CBM with concepts of open vocabularies, providing users the unique benefit such as removing, adding, or replacing any desired concept to explain the model's prediction even after a model is trained. Moreover, our model significantly outperforms the previous state-of-the-art CBM by 9% in the classification accuracy on the benchmark dataset CUB-200-2011.

Andong Tan, Shuyu Dai, Jinglu Wang et al.

Clinical practice guidelines (CPGs) play a pivotal role in ensuring evidence-based decision-making and improving patient outcomes. While Large Language Models (LLMs) are increasingly deployed in healthcare scenarios, it is unclear to which extend LLMs could identify and adhere to CPGs during conversations. To address this gap, we introduce CPGBench, an automated framework benchmarking the clinical guideline detection and adherence capabilities of LLMs in multi-turn conversations. We collect 3,418 CPG documents from 9 countries/regions and 2 international organizations published in the last decade spanning across 24 specialties. From these documents, we extract 32,155 clinical recommendations with corresponding publication institute, date, country, specialty, recommendation strength, evidence level, etc. One multi-turn conversation is generated for each recommendation accordingly to evaluate the detection and adherence capabilities of 8 leading LLMs. We find that the 71.1%-89.6% recommendations can be correctly detected, while only 3.6%-29.7% corresponding titles can be correctly referenced, revealing the gap between knowing the guideline contents and where they come from. The adherence rates range from 21.8% to 63.2% in different models, indicating a large gap between knowing the guidelines and being able to apply them. To confirm the validity of our automatic analysis, we further conduct a comprehensive human evaluation involving 56 clinicians from different specialties. To our knowledge, CPGBench is the first benchmark systematically revealing which clinical recommendations LLMs fail to detect or adhere to during conversations. Given that each clinical recommendation may affect a large population and that clinical applications are inherently safety critical, addressing these gaps is crucial for the safe and responsible deployment of LLMs in real world clinical practice.

Wenhao Tang, Rong Qin, Heng Fang et al.

Pre-trained encoders for offline feature extraction followed by multiple instance learning (MIL) aggregators have become the dominant paradigm in computational pathology (CPath), benefiting cancer diagnosis and prognosis. However, performance limitations arise from the absence of encoder fine-tuning for downstream tasks and disjoint optimization with MIL. While slide-level supervised end-to-end (E2E) learning is an intuitive solution to this issue, it faces challenges such as high computational demands and suboptimal results. These limitations motivate us to revisit E2E learning. We argue that prior work neglects inherent E2E optimization challenges, leading to performance disparities compared to traditional two-stage methods. In this paper, we pioneer the elucidation of optimization challenge caused by sparse-attention MIL and propose a novel MIL called ABMILX. It mitigates this problem through global correlation-based attention refinement and multi-head mechanisms. With the efficient multi-scale random patch sampling strategy, an E2E trained ResNet with ABMILX surpasses SOTA foundation models under the two-stage paradigm across multiple challenging benchmarks, while remaining computationally efficient (<10 RTX3090 hours). We show the potential of E2E learning in CPath and calls for greater research focus in this area. The code is https://github.com/DearCaat/E2E-WSI-ABMILX.

Yingxue Xu, Fengtao Zhou, Chenyu Zhao et al.

The integration of multimodal data including pathology images and gene profiles is widely applied in precise survival prediction. Despite recent advances in multimodal survival models, collecting complete modalities for multimodal fusion still poses a significant challenge, hindering their application in clinical settings. Current approaches tackling incomplete modalities often fall short, as they typically compensate for only a limited part of the knowledge of missing modalities. To address this issue, we propose a Distilled Prompt Learning framework (DisPro) to utilize the strong robustness of Large Language Models (LLMs) to missing modalities, which employs two-stage prompting for compensation of comprehensive information for missing modalities. In the first stage, Unimodal Prompting (UniPro) distills the knowledge distribution of each modality, preparing for supplementing modality-specific knowledge of the missing modality in the subsequent stage. In the second stage, Multimodal Prompting (MultiPro) leverages available modalities as prompts for LLMs to infer the missing modality, which provides modality-common information. Simultaneously, the unimodal knowledge acquired in the first stage is injected into multimodal inference to compensate for the modality-specific knowledge of the missing modality. Extensive experiments covering various missing scenarios demonstrated the superiority of the proposed method. The code is available at https://github.com/Innse/DisPro.

Qian Zeng, Yihui Wang, Shu Yang et al.

Whole-slide images (WSIs) are an important data modality in computational pathology, yet their gigapixel resolution and lack of fine-grained annotations challenge conventional deep learning models. Multiple instance learning (MIL) offers a solution by treating each WSI as a bag of patch-level instances, but effectively modeling ultra-long sequences with rich spatial context remains difficult. Recently, Mamba has emerged as a promising alternative for long sequence learning, scaling linearly to thousands of tokens. However, despite its efficiency, it still suffers from limited spatial context modeling and memory decay, constraining its effectiveness to WSI analysis. To address these limitations, we propose MambaMIL+, a new MIL framework that explicitly integrates spatial context while maintaining long-range dependency modeling without memory forgetting. Specifically, MambaMIL+ introduces 1) overlapping scanning, which restructures the patch sequence to embed spatial continuity and instance correlations; 2) a selective stripe position encoder (S2PE) that encodes positional information while mitigating the biases of fixed scanning orders; and 3) a contextual token selection (CTS) mechanism, which leverages supervisory knowledge to dynamically enlarge the contextual memory for stable long-range modeling. Extensive experiments on 20 benchmarks across diagnostic classification, molecular prediction, and survival analysis demonstrate that MambaMIL+ consistently achieves state-of-the-art performance under three feature extractors (ResNet-50, PLIP, and CONCH), highlighting its effectiveness and robustness for large-scale computational pathology

Chenyu Zhao, Yingxue Xu, Fengtao Zhou et al.

Current multimodal survival prediction methods typically rely on pathology images (WSIs) and genomic data, both of which are high-dimensional and redundant, making it difficult to extract discriminative features from them and align different modalities. Moreover, using a simple survival follow-up label is insufficient to supervise such a complex task. To address these challenges, we propose KEMM, an LLM-driven Knowledge-Enhanced Multimodal Model for cancer survival prediction, which integrates expert reports and prognostic background knowledge. 1) Expert reports, provided by pathologists on a case-by-case basis and refined by large language model (LLM), offer succinct and clinically focused diagnostic statements. This information may typically suggest different survival outcomes. 2) Prognostic background knowledge (PBK), generated concisely by LLM, provides valuable prognostic background knowledge on different cancer types, which also enhances survival prediction. To leverage these knowledge, we introduce the knowledge-enhanced cross-modal (KECM) attention module. KECM can effectively guide the network to focus on discriminative and survival-relevant features from highly redundant modalities. Extensive experiments on five datasets demonstrate that KEMM achieves state-of-the-art performance. The code will be released upon acceptance.

Wenhao Tang, Sheng Huang, Heng Fang et al.

Digitizing pathological images into gigapixel Whole Slide Images (WSIs) has opened new avenues for Computational Pathology (CPath). As positive tissue comprises only a small fraction of gigapixel WSIs, existing Multiple Instance Learning (MIL) methods typically focus on identifying salient instances via attention mechanisms. However, this leads to a bias towards easy-to-classify instances while neglecting challenging ones. Recent studies have shown that hard examples are crucial for accurately modeling discriminative boundaries. Applying such an idea at the instance level, we elaborate a novel MIL framework with masked hard instance mining (MHIM-MIL), which utilizes a Siamese structure with a consistency constraint to explore the hard instances. Using a class-aware instance probability, MHIM-MIL employs a momentum teacher to mask salient instances and implicitly mine hard instances for training the student model. To obtain diverse, non-redundant hard instances, we adopt large-scale random masking while utilizing a global recycle network to mitigate the risk of losing key features. Furthermore, the student updates the teacher using an exponential moving average, which identifies new hard instances for subsequent training iterations and stabilizes optimization. Experimental results on cancer diagnosis, subtyping, survival analysis tasks, and 12 benchmarks demonstrate that MHIM-MIL outperforms the latest methods in both performance and efficiency. The code is available at: https://github.com/DearCaat/MHIM-MIL.

Fengtao Zhou, Sheng Huang, Yun Xing

Compared with single-label image classification, multi-label image classification is more practical and challenging. Some recent studies attempted to leverage the semantic information of categories for improving multi-label image classification performance. However, these semantic-based methods only take semantic information as type of complements for visual representation without further exploitation. In this paper, we present an innovative path towards the solution of the multi-label image classification which considers it as a dictionary learning task. A novel end-to-end model named Deep Semantic Dictionary Learning (DSDL) is designed. In DSDL, an auto-encoder is applied to generate the semantic dictionary from class-level semantics and then such dictionary is utilized for representing the visual features extracted by Convolutional Neural Network (CNN) with label embeddings. The DSDL provides a simple but elegant way to exploit and reconcile the label, semantic and visual spaces simultaneously via conducting the dictionary learning among them. Moreover, inspired by iterative optimization of traditional dictionary learning, we further devise a novel training strategy named Alternately Parameters Update Strategy (APUS) for optimizing DSDL, which alternately optimizes the representation coefficients and the semantic dictionary in forward and backward propagation. Extensive experimental results on three popular benchmarks demonstrate that our method achieves promising performances in comparison with the state-of-the-arts. Our codes and models have been released at {https://github.com/ZFT-CQU/DSDL}.

Yingxue Xu, Zhengyu Zhang, Xiuming Zhang et al.

Pathology foundation models have shown strong retrospective performance, but whether such systems can support clinically relevant use remains unclear. This challenge is particularly important in breast cancer, where pathological assessment serves as the gold standard for diagnosis and guides treatment planning, surgical decision-making and risk stratification across pre-, intra- and post-operative stages. Here we present \textbf{BRAVE}, a breast-adaptive pathology foundation model developed and evaluated using a total resource of 101,638 breast whole-slide images from 32 sources across Asia, Europe and North America. We assessed BRAVE across 34 tasks in 82 cohorts spanning pre-operative biopsy, intra-operative frozen section and post-operative resection, using an evidence chain comprising retrospective benchmarking, clinically challenging scenarios, workflow-oriented clinical impact simulations, prospective observational validation with the thresholds locked in the retrospective cohorts and crossover pathologist-AI interaction studies. Across these settings, BRAVE supported practical roles in the clinical workflow, including safe exclusion of low-risk cases from routine review, AI-assisted second-review rescue of initially missed positives and prioritization of cases for further assessment. In prospective validation across three centres, BRAVE excluded 76.9% of negative biopsy cases (NPV 0.953) and 70.1% of negative frozen-section cases (NPV 0.973), and triaged 78.8% of post-operative subtyping cases as high-confidence clear-cut cases (NPV 1.000). In reader studies, AI assistance improved balanced accuracy from 88.5% to 95.1% (OR 3.14, P<0.001), with better efficiency, confidence and inter-rater agreement. BRAVE-derived scores also independently predicted disease-free survival (adjusted HR 4.79, P<0.001) and overall survival (adjusted HR 8.14, P<0.001).

Huajun Zhou, Fengtao Zhou, Hao Chen

Recently, we have witnessed impressive achievements in cancer survival analysis by integrating multimodal data, e.g., pathology images and genomic profiles. However, the heterogeneity and high dimensionality of these modalities pose significant challenges for extracting discriminative representations while maintaining good generalization. In this paper, we propose a Cohort-individual Cooperative Learning (CCL) framework to advance cancer survival analysis by collaborating knowledge decomposition and cohort guidance. Specifically, first, we propose a Multimodal Knowledge Decomposition (MKD) module to explicitly decompose multimodal knowledge into four distinct components: redundancy, synergy and uniqueness of the two modalities. Such a comprehensive decomposition can enlighten the models to perceive easily overlooked yet important information, facilitating an effective multimodal fusion. Second, we propose a Cohort Guidance Modeling (CGM) to mitigate the risk of overfitting task-irrelevant information. It can promote a more comprehensive and robust understanding of the underlying multimodal data, while avoiding the pitfalls of overfitting and enhancing the generalization ability of the model. By cooperating the knowledge decomposition and cohort guidance methods, we develop a robust multimodal survival analysis model with enhanced discrimination and generalization abilities. Extensive experimental results on five cancer datasets demonstrate the effectiveness of our model in integrating multimodal data for survival analysis.

Shu Yang, Fengtao Zhou, Leon Mayer et al.

Computer-Assisted Intervention (CAI) has the potential to revolutionize modern surgery, with surgical scene understanding serving as a critical component in supporting decision-making, improving procedural efficacy, and ensuring intraoperative safety. While existing AI-driven approaches alleviate annotation burdens via self-supervised spatial representation learning, their lack of explicit temporal modeling during pre-training fundamentally restricts the capture of dynamic surgical contexts, resulting in incomplete spatiotemporal understanding. In this work, we introduce the first video-level surgical pre-training framework that enables joint spatiotemporal representation learning from large-scale surgical video data. To achieve this, we constructed a large-scale surgical video dataset comprising 3,650 videos and approximately 3.55 million frames, spanning more than 20 surgical procedures and over 10 anatomical structures. Building upon this dataset, we propose SurgVISTA (Surgical Video-level Spatial-Temporal Architecture), a reconstruction-based pre-training method that captures intricate spatial structures and temporal dynamics through joint spatiotemporal modeling. Additionally, SurgVISTA incorporates image-level knowledge distillation guided by a surgery-specific expert to enhance the learning of fine-grained anatomical and semantic features. To validate its effectiveness, we established a comprehensive benchmark comprising 13 video-level datasets spanning six surgical procedures across four tasks. Extensive experiments demonstrate that SurgVISTA consistently outperforms both natural- and surgical-domain pre-trained models, demonstrating strong potential to advance intelligent surgical systems in clinically meaningful scenarios.

Fengtao Zhou, Yingxue Xu, Yanfen Cui et al.

Gastric cancer (GC) is a prevalent malignancy worldwide, ranking as the fifth most common cancer with over 1 million new cases and 700 thousand deaths in 2020. Locally advanced gastric cancer (LAGC) accounts for approximately two-thirds of GC diagnoses, and neoadjuvant chemotherapy (NACT) has emerged as the standard treatment for LAGC. However, the effectiveness of NACT varies significantly among patients, with a considerable subset displaying treatment resistance. Ineffective NACT not only leads to adverse effects but also misses the optimal therapeutic window, resulting in lower survival rate. However, existing multimodal learning methods assume the availability of all modalities for each patient, which does not align with the reality of clinical practice. The limited availability of modalities for each patient would cause information loss, adversely affecting predictive accuracy. In this study, we propose an incomplete multimodal data integration framework for GC (iMD4GC) to address the challenges posed by incomplete multimodal data, enabling precise response prediction and survival analysis. Specifically, iMD4GC incorporates unimodal attention layers for each modality to capture intra-modal information. Subsequently, the cross-modal interaction layers explore potential inter-modal interactions and capture complementary information across modalities, thereby enabling information compensation for missing modalities. To evaluate iMD4GC, we collected three multimodal datasets for GC study: GastricRes (698 cases) for response prediction, GastricSur (801 cases) for survival analysis, and TCGA-STAD (400 cases) for survival analysis. The scale of our datasets is significantly larger than previous studies. The iMD4GC achieved impressive performance with an 80.2% AUC on GastricRes, 71.4% C-index on GastricSur, and 66.1% C-index on TCGA-STAD, significantly surpassing other compared methods.

Jiabo MA, Wenqiang Li, Jinbang Li et al.

Accurate histopathological diagnosis often requires multiple differently stained tissue sections, a process that is time-consuming, labor-intensive, and environmentally taxing due to the use of multiple chemical stains. Recently, virtual staining has emerged as a promising alternative that is faster, tissue-conserving, and environmentally friendly. However, existing virtual staining methods face significant challenges in clinical applications, primarily due to their reliance on well-aligned paired data. Obtaining such data is inherently difficult because chemical staining processes can distort tissue structures, and a single tissue section cannot undergo multiple staining procedures without damage or loss of information. As a result, most available virtual staining datasets are either unpaired or roughly paired, making it difficult for existing methods to achieve accurate pixel-level supervision. To address this challenge, we propose a robust virtual staining framework featuring cascaded registration mechanisms to resolve spatial mismatches between generated outputs and their corresponding ground truth. Experimental results demonstrate that our method significantly outperforms state-of-the-art models across five datasets, achieving an average improvement of 3.2% on internal datasets and 10.1% on external datasets. Moreover, in datasets with substantial misalignment, our approach achieves a remarkable 23.8% improvement in peak signal-to-noise ratio compared to baseline models. The exceptional robustness of the proposed method across diverse datasets simplifies the data acquisition process for virtual staining and offers new insights for advancing its development.

Yu Cai, Cheng Jin, Jiabo Ma et al.

Pathology foundation models (PFMs) have enabled robust generalization in computational pathology through large-scale datasets and expansive architectures, but their substantial computational cost, particularly for gigapixel whole slide images, limits clinical accessibility and scalability. Here, we present LitePath, a deployment-friendly foundational framework designed to mitigate model over-parameterization and patch level redundancy. LitePath integrates LiteFM, a compact model distilled from three large PFMs (Virchow2, H-Optimus-1 and UNI2) using 190 million patches, and the Adaptive Patch Selector (APS), a lightweight component for task-specific patch selection. The framework reduces model parameters by 28x and lowers FLOPs by 403.5x relative to Virchow2, enabling deployment on low-power edge hardware such as the NVIDIA Jetson Orin Nano Super. On this device, LitePath processes 208 slides per hour, 104.5x faster than Virchow2, and consumes 0.36 kWh per 3,000 slides, 171x lower than Virchow2 on an RTX3090 GPU. We validated accuracy using 37 cohorts across four organs and 26 tasks (26 internal, 9 external, and 2 prospective), comprising 15,672 slides from 9,808 patients disjoint from the pretraining data. LitePath ranks second among 19 evaluated models and outperforms larger models including H-Optimus-1, mSTAR, UNI2 and GPFM, while retaining 99.71% of the AUC of Virchow2 on average. To quantify the balance between accuracy and efficiency, we propose the Deployability Score (D-Score), defined as the weighted geometric mean of normalized AUC and normalized FLOP, where LitePath achieves the highest value, surpassing Virchow2 by 10.64%. These results demonstrate that LitePath enables rapid, cost-effective and energy-efficient pathology image analysis on accessible hardware while maintaining accuracy comparable to state-of-the-art PFMs and reducing the carbon footprint of AI deployment.

Zihan Zhao, Fengtao Zhou, Ronggang Li et al.

Intraoperative pathology is pivotal to precision surgery, yet its clinical impact is constrained by diagnostic complexity and the limited availability of high-quality frozen-section data. While computational pathology has made significant strides, the lack of large-scale, prospective validation has impeded its routine adoption in surgical workflows. Here, we introduce CRISP, a clinical-grade foundation model developed on over 100,000 frozen sections from eight medical centers, specifically designed to provide Clinical-grade Robust Intraoperative Support for Pathology (CRISP). CRISP was comprehensively evaluated on more than 15,000 intraoperative slides across nearly 100 retrospective diagnostic tasks, including benign-malignant discrimination, key intraoperative decision-making, and pan-cancer detection, etc. The model demonstrated robust generalization across diverse institutions, tumor types, and anatomical sites-including previously unseen sites and rare cancers. In a prospective cohort of over 2,000 patients, CRISP sustained high diagnostic accuracy under real-world conditions, directly informing surgical decisions in 92.6% of cases. Human-AI collaboration further reduced diagnostic workload by 35%, avoided 105 ancillary tests and enhanced detection of micrometastases with 87.5% accuracy. Together, these findings position CRISP as a clinical-grade paradigm for AI-driven intraoperative pathology, bridging computational advances with surgical precision and accelerating the translation of artificial intelligence into routine clinical practice.

Huajun Zhou, Fengtao Zhou, Jiabo Ma et al.

Multimodal data provides heterogeneous information for a holistic understanding of the tumor microenvironment. However, existing AI models often struggle to harness the rich information within multimodal data and extract poorly generalizable representations. Here we present MICE (Multimodal data Integration via Collaborative Experts), a multimodal foundation model that effectively integrates pathology images, clinical reports, and genomics data for precise pan-cancer prognosis prediction. Instead of conventional multi-expert modules, MICE employs multiple functionally diverse experts to comprehensively capture both cross-cancer and cancer-specific insights. Leveraging data from 11,799 patients across 30 cancer types, we enhanced MICE's generalizability by coupling contrastive and supervised learning. MICE outperformed both unimodal and state-of-the-art multi-expert-based multimodal models, demonstrating substantial improvements in C-index ranging from 3.8% to 11.2% on internal cohorts and 5.8% to 8.8% on independent cohorts, respectively. Moreover, it exhibited remarkable data efficiency across diverse clinical scenarios. With its enhanced generalizability and data efficiency, MICE establishes an effective and scalable foundation for pan-cancer prognosis prediction, holding strong potential to personalize tailored therapies and improve treatment outcomes.

Zhe Xu, Ziyi Liu, Junlin Hou et al.

Multimodal large language models (MLLMs) have emerged as powerful tools for computational pathology, offering unprecedented opportunities to integrate pathological images with language context for comprehensive diagnostic analysis. These models hold particular promise for automating complex tasks that traditionally require expert interpretation of pathologists. However, current MLLM approaches in pathology demonstrate significantly constrained reasoning capabilities, primarily due to their reliance on expensive chain-of-thought annotations. Additionally, existing methods remain limited to simplex application of visual question answering (VQA) at the region-of-interest (ROI) level, failing to address the full spectrum of diagnostic needs such as ROI classification, detection, segmentation, whole-slide-image (WSI) classification and VQA in clinical practice. In this study, we present SmartPath-R1, a versatile MLLM capable of simultaneously addressing both ROI-level and WSI-level tasks while demonstrating robust pathological reasoning capability. Our framework combines scale-dependent supervised fine-tuning and task-aware reinforcement fine-tuning, which circumvents the requirement for chain-of-thought supervision by leveraging the intrinsic knowledge within MLLM. Furthermore, SmartPath-R1 integrates multiscale and multitask analysis through a mixture-of-experts mechanism, enabling dynamic processing for diverse tasks. We curate a large-scale dataset comprising 2.3M ROI samples and 188K WSI samples for training and evaluation. Extensive experiments across 72 tasks validate the effectiveness and superiority of the proposed approach. This work represents a significant step toward developing versatile, reasoning-enhanced AI systems for precision pathology.

Cheng Jin, Fengtao Zhou, Yunfang Yu et al.

Precision oncology requires accurate molecular insights, yet obtaining these directly from genomics is costly and time-consuming for broad clinical use. Predicting complex molecular features and patient prognosis directly from routine whole-slide images (WSI) remains a major challenge for current deep learning methods. Here we introduce PathLUPI, which uses transcriptomic privileged information during training to extract genome-anchored histological embeddings, enabling effective molecular prediction using only WSIs at inference. Through extensive evaluation across 49 molecular oncology tasks using 11,257 cases among 20 cohorts, PathLUPI demonstrated superior performance compared to conventional methods trained solely on WSIs. Crucially, it achieves AUC $\geq$ 0.80 in 14 of the biomarker prediction and molecular subtyping tasks and C-index $\geq$ 0.70 in survival cohorts of 5 major cancer types. Moreover, PathLUPI embeddings reveal distinct cellular morphological signatures associated with specific genotypes and related biological pathways within WSIs. By effectively encoding molecular context to refine WSI representations, PathLUPI overcomes a key limitation of existing models and offers a novel strategy to bridge molecular insights with routine pathology workflows for wider clinical application.

Huajun Zhou, Fengtao Zhou, Chenyu Zhao et al.

The essence of precision oncology lies in its commitment to tailor targeted treatments and care measures to each patient based on the individual characteristics of the tumor. The inherent heterogeneity of tumors necessitates gathering information from diverse data sources to provide valuable insights from various perspectives, fostering a holistic comprehension of the tumor. Over the past decade, multimodal data integration technology for precision oncology has made significant strides, showcasing remarkable progress in understanding the intricate details within heterogeneous data modalities. These strides have exhibited tremendous potential for improving clinical decision-making and model interpretation, contributing to the advancement of cancer care and treatment. Given the rapid progress that has been achieved, we provide a comprehensive overview of about 300 papers detailing cutting-edge multimodal data integration techniques in precision oncology. In addition, we conclude the primary clinical applications that have reaped significant benefits, including early assessment, diagnosis, prognosis, and biomarker discovery. Finally, derived from the findings of this survey, we present an in-depth analysis that explores the pivotal challenges and reveals essential pathways for future research in the field of multimodal data integration for precision oncology.

Andong Tan, Fengtao Zhou, Hao Chen

Post-hoc explainability methods such as Grad-CAM are popular because they do not influence the performance of a trained model. However, they mainly reveal "where" a model looks at for a given input, fail to explain "what" the model looks for (e.g., what is important to classify a bird image to a Scott Oriole?). Existing part-prototype networks leverage part-prototypes (e.g., characteristic Scott Oriole's wing and head) to answer both "where" and "what", but often under-perform their black box counterparts in the accuracy. Therefore, a natural question is: can one construct a network that answers both "where" and "what" in a post-hoc manner to guarantee the model's performance? To this end, we propose the first post-hoc part-prototype network via decomposing the classification head of a trained model into a set of interpretable part-prototypes. Concretely, we propose an unsupervised prototype discovery and refining strategy to obtain prototypes that can precisely reconstruct the classification head, yet being interpretable. Besides guaranteeing the performance, we show that our network offers more faithful explanations qualitatively and yields even better part-prototypes quantitatively than prior part-prototype networks.