Cancer research has traditionally focused on identifying driver genes, those with mutations that initiate tumorigenesis. The Cancer Driver Gene (CDG) paradigm, further supported by the observation of oncogene addiction in tumors, has successfully guided the development of targeted therapies. However, the limitations of this driver-centric view, highlighted by the broad emergence of frequent therapeutic resistance, the presence of driver mutations in healthy tissues or individuals, and the lack of identifiable drivers in many tumors, call for a shift in perspective and clinical practice. The latest network controllability perspective on cancer cells introduced the concept of Cancer Keeper Genes (CKGs) and a CKG-based paradigm for cancer therapeutics. The new concept encompasses the concept of non-oncogene addiction, emphasizing reliance on non-mutated pathways crucial for maintaining oncogenic cellular states. Here, we explore the transition towards a system-level understanding of cancer based on the CKG paradigm, emphasizing the essential role of genes required for tumor maintenance, irrespective of their initiating function or mutational capacity. We discuss clinical implications
Cardiotoxicity induced by cancer treatment has become a major clinical concern, affecting the long-term survival and quality of life of cancer patients. Effective clinical decision-making, including the detection of cancer treatment-induced cardiotoxicity and the monitoring of associated symptoms, remains a challenging task for clinicians. This study investigates the current practices and needs of clinicians in the clinical decision making of cancer treatment-induced cardiotoxicity and explores the potential of digital health technologies to support this process. Through semi-structured interviews with seven clinical experts, we identify a three-step decision-making paradigm: 1) symptom identification, 2) diagnostic testing and specialist collaboration, and 3) clinical decision-making and intervention. Our findings highlight the difficulties of diagnosing cardiotoxicity (absence of unified protocols and high variability in symptoms) and monitoring patient symptoms (lacking accurate and timely patient self-reported symptoms). The clinicians also expressed their need for effective early detection tools that can integrate remote patient monitoring capabilities. Based on these insights
Clinical trials are pivotal in medical research, and NLP can enhance their success, with application in recruitment. This study aims to evaluate the generalizability of eligibility classification across a broad spectrum of clinical trials. Starting with phase 3 cancer trials, annotated with seven eligibility exclusions, then to determine how well models can generalize to non-cancer and non-phase 3 trials. To assess this, we have compiled eligibility criteria data for five types of trials: (1) additional phase 3 cancer trials, (2) phase 1 and 2 cancer trials, (3) heart disease trials, (4) type 2 diabetes trials, and (5) observational trials for any disease, comprising 2,490 annotated eligibility criteria across seven exclusion types. Our results show that models trained on the extensive cancer dataset can effectively handle criteria commonly found in non-cancer trials, such as autoimmune diseases. However, they struggle with criteria disproportionately prevalent in cancer trials, like prior malignancy. We also experiment with few-shot learning, demonstrating that a limited number of disease-specific examples can partially overcome this performance gap. We are releasing this new data
Objective: This review aims to analyze the application of natural language processing (NLP) techniques in cancer research using electronic health records (EHRs) and clinical notes. This review addresses gaps in the existing literature by providing a broader perspective than previous studies focused on specific cancer types or applications. Methods: A comprehensive literature search was conducted using the Scopus database, identifying 94 relevant studies published between 2019 and 2024. Data extraction included study characteristics, cancer types, NLP methodologies, dataset information, performance metrics, challenges, and future directions. Studies were categorized based on cancer types and NLP applications. Results: The results showed a growing trend in NLP applications for cancer research, with breast, lung, and colorectal cancers being the most studied. Information extraction and text classification emerged as predominant NLP tasks. A shift from rule-based to advanced machine learning techniques, particularly transformer-based models, was observed. The Dataset sizes used in existing studies varied widely. Key challenges included the limited generalizability of proposed solutions
Background: Existing clinical prediction models often represent patient data using features that ignore the semantic relationships between clinical concepts. This study integrates domain-specific semantic information by mapping the SNOMED medical term hierarchy into a low-dimensional hyperbolic space using Poincaré embeddings, with the aim of improving lung cancer onset prediction. Methods: Using a retrospective cohort from the Optum EHR dataset, we derived a clinical knowledge graph from the SNOMED taxonomy and generated Poincaré embeddings via Riemannian stochastic gradient descent. These embeddings were then incorporated into two deep learning architectures, a ResNet and a Transformer model. Models were evaluated for discrimination (area under the receiver operating characteristic curve) and calibration (average absolute difference between observed and predicted probabilities) performance. Results: Incorporating pre-trained Poincaré embeddings resulted in modest and consistent improvements in discrimination performance compared to baseline models using randomly initialized Euclidean embeddings. ResNet models, particularly those using a 10-dimensional Poincaré embedding, showed e
The competency of any intelligent agent is bounded by its formal account of the world in which it operates. Clinical AI lacks such an account. Existing frameworks address evaluation, regulation, or system design in isolation, without a shared model of the clinical world to connect them. We introduce the Clinical World Model, a framework that formalizes care as a tripartite interaction among Patient, Provider, and Ecosystem. To formalize how any agent, whether human or artificial, transforms information into clinical action, we develop parallel decision-making architectures for providers, patients, and AI agents, grounded in validated principles of clinical cognition. The Clinical AI Skill-Mix operationalizes competency through eight dimensions. Five define the clinical competency space (condition, phase, care setting, provider role, and task) and three specify how AI engages human reasoning (assigned authority, agent facing, and anchoring layer). The combinatorial product of these dimensions yields a space of billions of distinct competency coordinates. A central structural implication is that validation within one coordinate provides minimal evidence for performance in another, re
Skin cancer is one of the most common types of cancer around the world. For this reason, over the past years, different approaches have been proposed to assist detect it. Nonetheless, most of them are based only on dermoscopy images and do not take into account the patient clinical information. In this work, first, we present a new dataset that contains clinical images, acquired from smartphones, and patient clinical information of the skin lesions. Next, we introduce a straightforward approach to combine the clinical data and the images using different well-known deep learning models. These models are applied to the presented dataset using only the images and combining them with the patient clinical information. We present a comprehensive study to show the impact of the clinical data on the final predictions. The results obtained by combining both sets of information show a general improvement of around 7% in the balanced accuracy for all models. In addition, the statistical test indicates significant differences between the models with and without considering both data. The improvement achieved shows the potential of using patient clinical information in skin cancer detection and
We introduce SoftTiger, a clinical large language model (CLaM) designed as a foundation model for healthcare workflows. The narrative and unstructured nature of clinical notes is a major obstacle for healthcare intelligentization. We address a critical problem of structuring clinical notes into clinical data, according to international interoperability standards. We collect and annotate data for three subtasks, namely, international patient summary, clinical impression and medical encounter. We then supervised fine-tuned a state-of-the-art LLM using public and credentialed clinical data. The training is orchestrated in a way that the target model can first support basic clinical tasks such as abbreviation expansion and temporal information extraction, and then learn to perform more complex downstream clinical tasks. Moreover, we address several modeling challenges in the healthcare context, e.g., extra long context window. Our blind pairwise evaluation shows that SoftTiger outperforms other popular open-source models and GPT-3.5, comparable to Gemini-pro, with a mild gap from GPT-4. We believe that LLMs may become a step-stone towards healthcare digitalization and democratization.
We discuss a cancer hallmark network framework for modelling genome-sequencing data to predict cancer clonal evolution and associated clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for a cancer patient, as well as cancer risks for a healthy individual are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial impact on timely diagnosis, personalized management and prevention of cancer.
We introduce Clinical ModernBERT, a transformer based encoder pretrained on large scale biomedical literature, clinical notes, and medical ontologies, incorporating PubMed abstracts, MIMIC IV clinical data, and medical codes with their textual descriptions. Building on ModernBERT the current state of the art natural language text encoder featuring architectural upgrades such as rotary positional embeddings (RoPE), Flash Attention, and extended context length up to 8,192 tokens our model adapts these innovations specifically for biomedical and clinical domains. Clinical ModernBERT excels at producing semantically rich representations tailored for long context tasks. We validate this both by analyzing its pretrained weights and through empirical evaluation on a comprehensive suite of clinical NLP benchmarks.
Embryology has long played a foundational role in shaping our scientific understanding of animal evolution. In recent decades, growing evidence has also highlighted its role in cancer. Despite the indisputable similarities between embryonic development and cancer, there has been limited discussion on the profound embryological implications for the disease. This article explores the understanding of cancer as an embryological and evolutionary phenomenon, offering a fresh perspective on the disease and discussing immediate consequences in the search for therapeutic approaches
Developing AI models that are useful in clinical practice, requires efficient collaboration between clinicians and AI developers. This poses a practical challenge: clinicians must repeatedly communicate and refine their requirements with AI developers before those requirements can be translated into executable model development. This iterative process is time-consuming, and even after repeated discussion, misalignment may still exist because the two sides do not fully share each other's expertise. Coding agents may help close this gap. They can write and refine code on their own, and they carry working knowledge of both medicine and AI to understand commands formulated by both medical experts and developers. We present a prototype that lets clinicians drive AI development directly. A clinician describes the task in plain language, and the system turns the description into a working pipeline, refines it through repeated experiments together with the clinician, and returns a model that meets the stated clinical objective. Across five clinical tasks, the system reliably produces models that matched the clinician's request and reached competitive performance. Most notably, on chest rad
This paper is dedicated to the design and evaluation of the first AMR parser tailored for clinical notes. Our objective was to facilitate the precise transformation of the clinical notes into structured AMR expressions, thereby enhancing the interpretability and usability of clinical text data at scale. Leveraging the colon cancer dataset from the Temporal Histories of Your Medical Events (THYME) corpus, we adapted a state-of-the-art AMR parser utilizing continuous training. Our approach incorporates data augmentation techniques to enhance the accuracy of AMR structure predictions. Notably, through this learning strategy, our parser achieved an impressive F1 score of 88% on the THYME corpus's colon cancer dataset. Moreover, our research delved into the efficacy of data required for domain adaptation within the realm of clinical notes, presenting domain adaptation data requirements for AMR parsing. This exploration not only underscores the parser's robust performance but also highlights its potential in facilitating a deeper understanding of clinical narratives through structured semantic representations.
Accurately identifying distant recurrences in breast cancer from the Electronic Health Records (EHR) is important for both clinical care and secondary analysis. Although multiple applications have been developed for computational phenotyping in breast cancer, distant recurrence identification still relies heavily on manual chart review. In this study, we aim to develop a model that identifies distant recurrences in breast cancer using clinical narratives and structured data from EHR. We apply MetaMap to extract features from clinical narratives and also retrieve structured clinical data from EHR. Using these features, we train a support vector machine model to identify distant recurrences in breast cancer patients. We train the model using 1,396 double-annotated subjects and validate the model using 599 double-annotated subjects. In addition, we validate the model on a set of 4,904 single-annotated subjects as a generalization test. We obtained a high area under curve (AUC) score of 0.92 (SD=0.01) in the cross-validation using the training dataset, then obtained AUC scores of 0.95 and 0.93 in the held-out test and generalization test using 599 and 4,904 samples respectively. Our mo
Objectives: To assess evaluative methodologies for comparative measurements of test sensitivity in clinical mammographic screening trials of computer-aided detection (CAD) technologies. Materials and Methods: This meta-analysis was performed by analytically reviewing the relevant literature on the clinical application of computer-aided detection (CAD) technologies as part of a breast cancer screening program based on x-ray mammography. Each clinical study's method for measuring the CAD system's improvement in test sensitivity is examined in this meta-analysis. The impact of the chosen sensitivity measurement on the study's conclusions are analyzed. Results: This meta-analysis demonstrates that some studies have inappropriately compared sensitivity measurements between control groups and CAD enabled groups. The inappropriate comparison of control groups and CAD enabled groups can lead to an underestimation of the benefits of the clinical application of computer-aided detection technologies. Conclusions: The potential for the sensitivity measurement issues raised in this meta-analysis to alter the conclusions of multiple existing large clinical studies is discussed. Two large scale s
We evaluate the impact of large language model-based clinical decision support in live care. In partnership with Penda Health, a network of primary care clinics in Nairobi, Kenya, we studied AI Consult, a tool that serves as a safety net for clinicians by identifying potential documentation and clinical decision-making errors. AI Consult integrates into clinician workflows, activating only when needed and preserving clinician autonomy. We conducted a quality improvement study, comparing outcomes for 39,849 patient visits performed by clinicians with or without access to AI Consult across 15 clinics. Visits were rated by independent physicians to identify clinical errors. Clinicians with access to AI Consult made relatively fewer errors: 16% fewer diagnostic errors and 13% fewer treatment errors. In absolute terms, the introduction of AI Consult would avert diagnostic errors in 22,000 visits and treatment errors in 29,000 visits annually at Penda alone. In a survey of clinicians with AI Consult, all clinicians said that AI Consult improved the quality of care they delivered, with 75% saying the effect was "substantial". These results required a clinical workflow-aligned AI Consult i
Processing information locked within clinical health records is a challenging task that remains an active area of research in biomedical NLP. In this work, we evaluate a broad set of machine learning techniques ranging from simple RNNs to specialised transformers such as BioBERT on a dataset containing clinical notes along with a set of annotations indicating whether a sample is cancer-related or not. Furthermore, we specifically employ efficient fine-tuning methods from NLP, namely, bottleneck adapters and prompt tuning, to adapt the models to our specialised task. Our evaluations suggest that fine-tuning a frozen BERT model pre-trained on natural language and with bottleneck adapters outperforms all other strategies, including full fine-tuning of the specialised BioBERT model. Based on our findings, we suggest that using bottleneck adapters in low-resource situations with limited access to labelled data or processing capacity could be a viable strategy in biomedical text mining. The code used in the experiments are going to be made available at https://github.com/omidrohanian/bottleneck-adapters.
Purpose: Tumor-associated vasculature differs from healthy blood vessels by its chaotic architecture and twistedness, which promotes treatment resistance. Measurable differences in these attributes may help stratify patients by likely benefit of systemic therapy (e.g. chemotherapy). In this work, we present a new category of radiomic biomarkers called quantitative tumor-associated vasculature (QuanTAV) features, and demonstrate their ability to predict response and survival across multiple cancers, imaging modalities, and treatment regimens. Experimental Design: We segmented tumor vessels and computed mathematical measurements of twistedness and organization on routine pre-treatment radiology (CT or contrast-enhanced MRI) from 558 patients, who received one of four first-line chemotherapy-based therapeutic intervention strategies for breast (n=371) or non-small cell lung cancer (NSCLC, n=187). Results: Across 4 chemotherapy-based treatment strategies, classifiers of QuanTAV measurements significantly (p<.05) predicted response in held out testing cohorts alone (AUC=0.63-0.71) and increased AUC by 0.06-0.12 when added to models of significant clinical variables alone. QuanTAV ris
We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers and natural {\em in vivo} cancers. The theory lays the foundation for a new research paradigm for understanding and investigating cancer. The theory of cancer networks implies that new diagnostic methods
Digital Twins hold great potential to personalize clinical patient care, provided the concept is translated to meet specific requirements emerging from established clinical workflows. We present a general and unspecialized Digital Twin design combining knowledge graphs and ensemble learning to reflect the entire patient's clinical journey and assist clinicians in their decision-making. Such a design is predictive, modular, evolving, informed, interpretable and explainable, thus opening broad clinical applications.