Early cancer detection remains one of the most critical challenges in modern healthcare, where delayed diagnosis significantly reduces survival outcomes. Recent advancements in artificial intelligence, particularly deep learning, have enabled transformative progress in medical imaging analysis. Deep learning-based computer vision models, such as convolutional neural networks (CNNs), transformers, and hybrid attention architectures, can automatically extract complex spatial, morphological, and temporal patterns from multimodal imaging data including MRI, CT, PET, mammography, histopathology, and ultrasound. These models surpass traditional radiological assessment by identifying subtle tissue abnormalities and tumor microenvironment variations invisible to the human eye. At a broader scale, the integration of multimodal imaging with radiogenomics linking quantitative imaging features with genomics, transcriptomics, and epigenetic biomarkers has introduced a new paradigm for personalized oncology. This radiogenomic fusion allows the prediction of tumor genotype, immune response, molecular subtypes, and treatment resistance without invasive biopsies.

Emerging from NASA's spacecraft simulations in the 1960s, digital twin technology has advanced through industrial adoption to spark a healthcare transformation. A digital twin is a dynamic, data-driven virtual counterpart of a physical system, continuously updated through real-time data streams and capable of bidirectional interaction. In medicine, digital twin integrates imaging, biosensors, and computational models to generate patient-specific simulations that support diagnosis, treatment planning, and drug development. Representative applications include cardiac digital twin for predicting arrhythmia treatment outcomes, oncology digital twin for tracking tumor progression and optimizing radiotherapy, and pharmacological digital twin for accelerating drug discovery. Despite rapid progress, major challenges, including interoperability, data privacy, and model fidelity, continue to limit widespread clinical integration. Emerging solutions such as explainable AI, federated learning, and harmonized regulatory frameworks offer promising pathways forward. Looking ahead, advances in multi-organ digital twin, genomics integration, and ethical governance will be essential to ensure that digital twin shifts healthcare from reactive treatment to predictive, preventive, and truly personalized medicine.

The application of AI in oncology has been limited by its reliance on large, annotated datasets and the need for retraining models for domain-specific diagnostic tasks. Taking heed of these limitations, we investigated in-context learning as a pragmatic alternative to model retraining by allowing models to adapt to new diagnostic tasks using only a few labeled examples at inference, without the need for retraining. Using four vision-language models (VLMs)-Paligemma, CLIP, ALIGN and GPT-4o, we evaluated the performance across three oncology datasets: MHIST, PatchCamelyon and HAM10000. To the best of our knowledge, this is the first study to compare the performance of multiple VLMs on different oncology classification tasks. Without any parameter updates, all models showed significant gains with few-shot prompting, with GPT-4o reaching an F1 score of 0.81 in binary classification and 0.60 in multi-class classification settings. While these results remain below the ceiling of fully fine-tuned systems, they highlight the potential of ICL to approximate task-specific behavior using only a handful of examples, reflecting how clinicians often reason from prior cases. Notably, open-source models like Paligemma and CLIP demonstrated competitive gains despite their smaller size, suggesting feasibility for deployment in computing constrained clinical environments. Overall, these findings highlight the potential of ICL as a practical solution in oncology, particularly for rare cancers and resource-limited contexts where fine-tuning is infeasible and annotated data is difficult to obtain.

Causal machine learning (CML) enables individualized estimation of treatment effects, offering critical advantages over traditional correlation-based methods. However, existing approaches for medical survival data with censoring such as causal survival forests estimate effects at fixed time points, limiting their ability to capture dynamic changes over time. We introduce Causal Analysis for Survival Trajectories (CAST), a novel framework that models treatment effects as continuous functions of time following treatment. By combining parametric and non-parametric methods, CAST overcomes the limitations of discrete time-point analysis to estimate continuous effect trajectories. Using the RADCURE dataset [1] of 2,651 patients with head and neck squamous cell carcinoma (HNSCC) as a clinically relevant example, CAST models how chemotherapy and radiotherapy effects evolve over time at the population and individual levels. By capturing the temporal dynamics of treatment response, CAST reveals how treatment effects rise, peak, and decline over the follow-up period, helping clinicians determine when and for whom treatment benefits are maximized. This framework advances the application of CML to personalized care in HNSCC and other life-threatening medical conditions. Source code/data available at: https://github.com/CAST-FW/HNSCC

Cancer evolves continuously over time through a complex interplay of genetic, epigenetic, microenvironmental, and phenotypic changes. This dynamic behavior drives uncontrolled cell growth, metastasis, immune evasion, and therapy resistance, posing challenges for effective monitoring and treatment. However, today's data-driven research in oncology has primarily focused on cross-sectional analysis using data from a single modality, limiting the ability to fully characterize and interpret the disease's dynamic heterogeneity. Advances in multiscale data collection and computational methods now enable the discovery of longitudinal multimodal biomarkers for precision oncology. Longitudinal data reveal patterns of disease progression and treatment response that are not evident from single-timepoint data, enabling timely abnormality detection and dynamic treatment adaptation. Multimodal data integration offers complementary information from diverse sources for more precise risk assessment and targeting of cancer therapy. In this review, we survey methods of longitudinal and multimodal modeling, highlighting their synergy in providing multifaceted insights for personalized care tailored to the unique characteristics of a patient's cancer. We summarize the current challenges and future directions of longitudinal multimodal analysis in advancing precision oncology.

Personalized cancer treatment is revolutionizing oncology by leveraging precision medicine and advanced computational techniques to tailor therapies to individual patients. Despite its transformative potential, challenges such as limited generalizability, interpretability, and reproducibility of predictive models hinder its integration into clinical practice. Current methodologies often rely on black-box machine learning models, which, while accurate, lack the transparency needed for clinician trust and real-world application. This paper proposes the development of an innovative framework that bridges Kolmogorov-Arnold Networks (KANs) and Evolutionary Game Theory (EGT) to address these limitations. Inspired by the Kolmogorov-Arnold representation theorem, KANs offer interpretable, edge-based neural architectures capable of modeling complex biological systems with unprecedented adaptability. Their integration into the EGT framework enables dynamic modeling of cancer progression and treatment responses. By combining KAN's computational precision with EGT's mechanistic insights, this hybrid approach promises to enhance predictive accuracy, scalability, and clinical usability.

Thanks to the rapidly evolving integration of LLMs into decision-support tools, a significant transformation is happening across large-scale systems. Like other medical fields, the use of LLMs such as GPT-4 is gaining increasing interest in radiation oncology as well. An attempt to assess GPT-4's performance in radiation oncology was made via a dedicated 100-question examination on the highly specialized topic of radiation oncology physics, revealing GPT-4's superiority over other LLMs. GPT-4's performance on a broader field of clinical radiation oncology is further benchmarked by the ACR Radiation Oncology In-Training (TXIT) exam where GPT-4 achieved a high accuracy of 74.57%. Its performance on re-labelling structure names in accordance with the AAPM TG-263 report has also been benchmarked, achieving above 96% accuracies. Such studies shed light on the potential of LLMs in radiation oncology. As interest in the potential and constraints of LLMs in general healthcare applications continues to rise5, the capabilities and limitations of LLMs in radiation oncology decision support have not yet been fully explored.

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

The interactions between tumor cells and the tumor microenvironment (TME) dictate therapeutic efficacy of radiation and many systemic therapies in breast cancer. However, to date, there is not a widely available method to reproducibly measure tumor and immune phenotypes for each patient's tumor. Given this unmet clinical need, we applied multiple instance learning (MIL) algorithms to assess activity of ten biologically relevant pathways from the hematoxylin and eosin (H&E) slide of primary breast tumors. We employed different feature extraction approaches and state-of-the-art model architectures. Using binary classification, our models attained area under the receiver operating characteristic (AUROC) scores above 0.70 for nearly all gene expression pathways and on some cases, exceeded 0.80. Attention maps suggest that our trained models recognize biologically relevant spatial patterns of cell sub-populations from H&E. These efforts represent a first step towards developing computational H&E biomarkers that reflect facets of the TME and hold promise for augmenting precision oncology.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can result in severe immune-related adverse events (IrAEs). Monitoring IrAEs on a large scale is essential for personalized risk profiling and assisting in treatment decisions. Methods: In this study, we conducted an analysis of clinical notes from patients who received ICIs at the Tel Aviv Sourasky Medical Center. By employing a Natural Language Processing algorithmic pipeline, we systematically identified seven common or severe IrAEs. We examined the utilization of corticosteroids, treatment discontinuation rates following IrAEs, and constructed survival curves to visualize the occurrence of adverse events during treatment. Results: Our analysis encompassed 108,280 clinical notes associated with 1,635 patients who had undergone ICI therapy. The detected incidence of IrAEs was consistent with previous reports, exhibiting substantial variation across different ICIs. Treatment with corticosteroids varied depending on the specific IrAE, ranging from 17.3% for thyroiditis to 57.4% for myocarditis. Our algorithm demonstrated high accuracy in identifying IrAEs, as indicated by an area under the curve (AUC) of 0.89 for each suspected note and F1 scores of 0.87 or higher for five out of the seven IrAEs examined at the patient level. Conclusions: This study presents a novel, large-scale monitoring approach utilizing deep neural networks for IrAEs. Our method provides accurate results, enhancing understanding of detrimental consequences experienced by ICI-treated patients. Moreover, it holds potential for monitoring other medications, enabling comprehensive post-marketing surveillance to identify susceptible populations and establish personalized drug safety profiles.