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.
Mechanistic learning, the synergistic combination of knowledge-driven and data-driven modeling, is an emerging field. In particular, in mathematical oncology, the application of mathematical modeling to cancer biology and oncology, the use of mechanistic learning is growing. This review aims to capture the current state of the field and provide a perspective on how mechanistic learning may further progress in mathematical oncology. We highlight the synergistic potential of knowledge-driven mechanistic mathematical modeling and data-driven modeling, such as machine and deep learning. We point out similarities and differences regarding model complexity, data requirements, outputs generated, and interpretability of the algorithms and their results. Then, organizing combinations of knowledge- and data-driven modeling into four categories (sequential, parallel, intrinsic, and extrinsic mechanistic learning), we summarize a variety of approaches at the interface between purely data- and knowledge-driven models. Using examples predominantly from oncology, we discuss a range of techniques including physics-informed neural networks, surrogate model learning, and digital twins. We see that m
Multimodal Large Language Models (LLMs) hold promise for biomedical reasoning, but current benchmarks fail to capture the complexity of real-world clinical workflows. Existing evaluations primarily assess unimodal, decontextualized question-answering, overlooking multi-agent decision-making environments such as Molecular Tumor Boards (MTBs). MTBs bring together diverse experts in oncology, where diagnostic and prognostic tasks require integrating heterogeneous data and evolving insights over time. Current benchmarks lack this longitudinal and multimodal complexity. We introduce MTBBench, an agentic benchmark simulating MTB-style decision-making through clinically challenging, multimodal, and longitudinal oncology questions. Ground truth annotations are validated by clinicians via a co-developed app, ensuring clinical relevance. We benchmark multiple open and closed-source LLMs and show that, even at scale, they lack reliability -- frequently hallucinating, struggling with reasoning from time-resolved data, and failing to reconcile conflicting evidence or different modalities. To address these limitations, MTBBench goes beyond benchmarking by providing an agentic framework with foun
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
Clinical oncology generates vast, unstructured data that often contain inconsistencies, missing information, and ambiguities, making it difficult to extract reliable insights for data-driven decision-making. General-purpose large language models (LLMs) struggle with these challenges due to their lack of domain-specific reasoning, including specialized clinical terminology, context-dependent interpretations, and multi-modal data integration. We address these issues with an oncology-specialized, efficient, and adaptable NLP framework that combines instruction tuning, retrieval-augmented generation (RAG), and graph-based knowledge integration. Our lightweight models prove effective at oncology-specific tasks, such as named entity recognition (e.g., identifying cancer diagnoses), entity linking (e.g., linking entities to standardized ontologies), TNM staging, document classification (e.g., cancer subtype classification from pathology reports), and treatment response prediction. Our framework emphasizes adaptability and resource efficiency. We include minimal German instructions, collected at the University Hospital Zurich (USZ), to test whether small amounts of non-English language dat
Land use expansion is linked to major sustainability concerns including climate change, food security and biodiversity loss. This expansion is largely concentrated in so-called frontiers, defined here as places experiencing marked transformations due to rapid resource exploitation. Understanding the mechanisms shaping these frontiers is crucial for sustainability. Previous work focused mainly on explaining how active frontiers advance, in particular into tropical forests. Comparatively, our understanding of how frontiers emerge in territories considered marginal in terms of agricultural productivity and global market integration remains weak. We synthesize conceptual tools explaining resource and land-use frontiers, including theories of land rent and agglomeration economies, of frontiers as successive waves, spaces of territorialization, friction, and opportunities, anticipation and expectation. We then propose a new theory of frontier emergence, which identifies exogenous pushes, legacies of past waves, and actors anticipations as key mechanisms by which frontiers emerge. Processes of abnormal rent creation and capture and the built-up of agglomeration economies then constitute k
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 presen
Accurate trend forecasting in healthcare time series is essential for planning and resource allocation. This paper proposes a Bayesian framework for predicting oncology demand trends, modeling weekly appointments as a Poisson process with a Gamma prior to the demand rate. To enhance adaptability and capture persistent directional patterns, we incorporate a residual-based boosting mechanism grounded in a Gamma-Log-Normal conjugate structure. This boosting approach allows the model to track both short- and long-term trend shifts while maintaining the analytical tractability of conjugate Bayesian updating. The methodology was evaluated on real oncology service data from Cariri, Ceara, Brazil, and compared against established baselines, including linear regression, ARIMA, naive forecasting, LSTM neural networks, and XGBoost. Results showed that the proposed model outperforms competing methods in trend detection accuracy, with gains in terms of percentage of correct direction of 38.25% in relation to the second best approach in some cases.
Cancer remains a leading cause of death worldwide, necessitating personalized treatment approaches to improve outcomes. Theranostics, combining molecular-level imaging with targeted therapy, offers potential for precision oncology but requires optimized, patient-specific care plans. This paper investigates state-of-the-art data-driven decision support applications with a reinforcement learning focus in precision oncology. We review current applications, training environments, state-space representation, performance evaluation criteria, and measurement of risk and reward, highlighting key challenges. We propose a framework integrating data-driven modeling with reinforcement learning-based decision support to optimize radiopharmaceutical therapy dosing, addressing identified challenges and setting directions for future research. The framework leverages Neural Ordinary Differential Equations and Physics-Informed Neural Networks to enhance Physiologically Based Pharmacokinetic models while applying reinforcement learning algorithms to iteratively refine treatment policies based on patient-specific data.
Personalized oncology aims to tailor treatment strategies to the unique molecular and clinical profiles of individual patients, moving beyond the traditional paradigm of treating the disease not the patient. Achieving this vision requires the integration and interpretation of vast, heterogeneous biomedical data within a meaningful scientific framework. Knowledge graphs, structured according to biomedical ontologies, offer a powerful approach to contextualize and interconnect diverse datasets, enabling more precise and informed clinical decision-making. We present ECKO (Explainable Clinical Knowledge for Oncology), a comprehensive knowledge graph that integrates 33 biomedical ontologies and aggregates data from multiple studies to create a unified resource optimized for data-driven clinical applications in oncology. Designed to support personalized drug recommendations, ECKO facilitates the identification of optimal therapeutic options by linking patient-specific molecular data to relevant pharmacological knowledge. It provides transparent, interpretable explanations for drug recommendations, fostering greater trust and understanding among clinicians and researchers. This resource r
In the past year, there has been a growing trend in applying Large Language Models (LLMs) to the field of medicine, particularly with the advent of advanced language models such as ChatGPT developed by OpenAI. However, there is limited research on LLMs specifically addressing oncology-related queries. The primary aim of this research was to develop a specialized language model that demonstrates improved accuracy in providing advice related to oncology. We performed an extensive data collection of online question-answer interactions centered around oncology, sourced from reputable doctor-patient platforms. Following data cleaning and anonymization, a dataset comprising over 180K+ oncology-related conversations was established. The conversations were categorized and meticulously reviewed by field specialists and clinicians to ensure precision. Employing the LLaMA model and other selected open-source datasets, we conducted iterative fine-tuning to enhance the model's proficiency in basic medical conversation and specialized oncology knowledge. We observed a substantial enhancement in the model's understanding of genuine patient inquiries and its reliability in offering oncology-relate
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
Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious conditions with an unmet medical need. This is accomplished typically by granting accelerated approval based on a surrogate endpoint that can be measured earlier than a traditional approval endpoint. Minimal residual disease (MRD) is a sensitive measure of residual cancer cells in hematology oncology after treatment, and is increasingly considered as a secondary or exploratory endpoint due to its prognostic potential for traditional clinical trial endpoints such as progression-free survival (PFS) and overall survival (OS). This work aims to evaluate MRD's surrogacy potential across several hematologic cancer indications while keeping the focus on follicular lymphoma (FL), using data from published studies. We examine individual-level and trial-level correlations extracted from previously published studies to elucidate the potential role of MRD in accelerating the drug approval process in hematology oncology trials.
Background: Lung cancer ranks as the leading cause of cancer-related mortality worldwide. The complexity of tumor delineation, crucial for radiation therapy, requires expertise often unavailable in resource-limited settings. Artificial Intelligence(AI), particularly with advancements in deep learning (DL) and natural language processing (NLP), offers potential solutions yet is challenged by high false positive rates. Purpose: The Oncology Contouring Copilot (OCC) system is developed to leverage oncologist expertise for precise tumor contouring using textual descriptions, aiming to increase the efficiency of oncological workflows by combining the strengths of AI with human oversight. Methods: Our OCC system initially identifies nodule candidates from CT scans. Employing Language Vision Models (LVMs) like GPT-4V, OCC then effectively reduces false positives with clinical descriptive texts, merging textual and visual data to automate tumor delineation, designed to elevate the quality of oncology care by incorporating knowledge from experienced domain experts. Results: Deployments of the OCC system resulted in a significant reduction in the false discovery rate by 35.0%, a 72.4% decrea
Objectives: Surrogate endpoints, used to substitute for and predict final clinical outcomes, are increasingly being used to support submissions to health technology assessment agencies. The increase in use of surrogate endpoints has been accompanied by literature describing frameworks and statistical methods to ensure their robust validation. The aim of this review was to assess how surrogate endpoints have recently been used in oncology technology appraisals by the National Institute for Health and Care Excellence (NICE) in England and Wales. Methods: This paper identified technology appraisals in oncology published by NICE between February 2022 and May 2023. Data are extracted on methods for the use and validation of surrogate endpoints. Results: Of the 47 technology appraisals in oncology available for review, 18 (38 percent) utilised surrogate endpoints, with 37 separate surrogate endpoints being discussed. However, the evidence supporting the validity of the surrogate relationship varied significantly across putative surrogate relationships with 11 providing RCT evidence, 7 providing evidence from observational studies, 12 based on clinical opinion and 7 providing no evidence
Unstructured notes within the electronic health record (EHR) contain rich clinical information vital for cancer treatment decision making and research, yet reliably extracting structured oncology data remains challenging due to extensive variability, specialized terminology, and inconsistent document formats. Manual abstraction, although accurate, is prohibitively costly and unscalable. Existing automated approaches typically address narrow scenarios - either using synthetic datasets, restricting focus to document-level extraction, or isolating specific clinical variables (e.g., staging, biomarkers, histology) - and do not adequately handle patient-level synthesis across the large number of clinical documents containing contradictory information. In this study, we propose an agentic framework that systematically decomposes complex oncology data extraction into modular, adaptive tasks. Specifically, we use large language models (LLMs) as reasoning agents, equipped with context-sensitive retrieval and iterative synthesis capabilities, to exhaustively and comprehensively extract structured clinical variables from real-world oncology notes. Evaluated on a large-scale dataset of over 40
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 mu
Introduction: Large language models (LLM) have shown great potential in clinical decision support. GPT-5 is a novel LLM system that has been specifically marketed towards oncology use. Methods: Performance was assessed using two complementary benchmarks: (i) the ACR Radiation Oncology In-Training Examination (TXIT, 2021), comprising 300 multiple-choice items, and (ii) a curated set of 60 authentic radiation oncologic vignettes representing diverse disease sites and treatment indications. For the vignette evaluation, GPT-5 was instructed to generate concise therapeutic plans. Four board-certified radiation oncologists rated correctness, comprehensiveness, and hallucinations. Inter-rater reliability was quantified using Fleiss' \k{appa}. Results: On the TXIT benchmark, GPT-5 achieved a mean accuracy of 92.8%, outperforming GPT-4 (78.8%) and GPT-3.5 (62.1%). Domain-specific gains were most pronounced in Dose and Diagnosis. In the vignette evaluation, GPT-5's treatment recommendations were rated highly for correctness (mean 3.24/4, 95% CI: 3.11-3.38) and comprehensiveness (3.59/4, 95% CI: 3.49-3.69). Hallucinations were rare with no case reaching majority consensus for their presence.
Mathematical oncology is an interdisciplinary research field where the mathematical sciences meet cancer research. Being situated at the intersection of these two fields makes mathematical oncology highly dynamic, as practicing researchers are incentivised to quickly adapt to both technical and medical research advances. Determining the scope of mathematical oncology is therefore not straightforward; however, it is important for purposes related to funding allocation, education, scientific communication, and community organisation. To address this issue, we here conduct a bibliometric analysis of mathematical oncology. We compare our results to the broader field of mathematical biology, and position our findings within theoretical science of science frameworks. Based on article metadata and citation flows, our results provide evidence that mathematical oncology has undergone a significant evolution since the 1960s marked by increased interactions with other disciplines, geographical expansion, larger research teams, and greater diversity in studied topics. The latter finding contributes to the greater discussion on which models different research communities consider to be valuable
Phase I dose escalation trials in oncology generally aim to find the maximum tolerated dose (MTD). However, with the advent of molecular targeted therapies and antibody drug conjugates, dose limiting toxicities are less frequently observed, giving rise to the concept of optimal biological dose (OBD), which considers both efficacy and toxicity. The Estimand framework presented in the addendum of the ICH E9(R1) guidelines strengthens the dialogue between different stakeholders by bringing in greater clarity in the clinical trial objectives and by providing alignment between the targeted estimand under consideration and the statistical analysis methods. However, there lacks clarity in implementing this framework in early phase dose optimization studies. This manuscript aims at discussing the Estimand framework for dose optimization trials in oncology considering efficacy and toxicity through utility functions. Such trials should include Pharmacokinetics (PK) data, toxicity data, and efficacy data. Based on these data, the analysis methods used to identify the optimized dose/s are also described. Focusing on optimizing the utility function to estimate the OBD, the population-level summ