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 treatment strategy


A Causal Framework for Evaluating ICU Discharge Strategies

Simha, Sagar Nagaraj, Ortholand, Juliette, Dongelmans, Dave, Workum, Jessica D., Thijssens, Olivier W. M., Abu-Hanna, Ameen, Cinà, Giovanni

arXiv.org Machine Learning

In this applied paper, we address the difficult open problem of when to discharge patients from the Intensive Care Unit. This can be conceived as an optimal stopping scenario with three added challenges: 1) the evaluation of a stopping strategy from observational data is itself a complex causal inference problem, 2) the composite objective is to minimize the length of intervention and maximize the outcome, but the two cannot be collapsed to a single dimension, and 3) the recording of variables stops when the intervention is discontinued. Our contributions are two-fold. First, we generalize the implementation of the g-formula Python package, providing a framework to evaluate stopping strategies for problems with the aforementioned structure, including positivity and coverage checks. Second, with a fully open-source pipeline, we apply this approach to MIMIC-IV, a public ICU dataset, demonstrating the potential for strategies that improve upon current care.


Near-Equivalent Q-learning Policies for Dynamic Treatment Regimes

Yazzourh, Sophia, Moodie, Erica E. M.

arXiv.org Machine Learning

Precision medicine aims to tailor therapeutic decisions to individual patient characteristics. This objective is commonly formalized through dynamic treatment regimes, which use statistical and machine learning methods to derive sequential decision rules adapted to evolving clinical information. In most existing formulations, these approaches produce a single optimal treatment at each stage, leading to a unique decision sequence. However, in many clinical settings, several treatment options may yield similar expected outcomes, and focusing on a single optimal policy may conceal meaningful alternatives. We extend the Q-learning framework for retrospective data by introducing a worst-value tolerance criterion controlled by a hyperparameter $\varepsilon$, which specifies the maximum acceptable deviation from the optimal expected value. Rather than identifying a single optimal policy, the proposed approach constructs sets of $\varepsilon$-optimal policies whose performance remains within a controlled neighborhood of the optimum. This formulation shifts Q-learning from a vector-valued representation to a matrix-valued one, allowing multiple admissible value functions to coexist during backward recursion. The approach yields families of near-equivalent treatment strategies and explicitly identifies regions of treatment indifference where several decisions achieve comparable outcomes. We illustrate the framework in two settings: a single-stage problem highlighting indifference regions around the decision boundary, and a multi-stage decision process based on a simulated oncology model describing tumor size and treatment toxicity dynamics.


medDreamer: Model-Based Reinforcement Learning with Latent Imagination on Complex EHRs for Clinical Decision Support

Xu, Qianyi, Habib, Gousia, Wu, Feng, Perera, Dilruk, Feng, Mengling

arXiv.org Artificial Intelligence

Timely and personalized treatment decisions are essential across a wide range of healthcare settings where patient responses can vary significantly and evolve over time. Clinical data used to support these treatment decisions are often irregularly sampled, where missing data frequencies may implicitly convey information about the patient's condition. Existing Reinforcement Learning (RL) based clinical decision support systems often ignore the missing patterns and distort them with coarse discretization and simple imputation. They are also predominantly model-free and largely depend on retrospective data, which could lead to insufficient exploration and bias by historical behaviors. To address these limitations, we propose medDreamer, a novel model-based reinforcement learning framework for personalized treatment recommendation. medDreamer contains a world model with an Adaptive Feature Integration module that simulates latent patient states from irregular data and a two-phase policy trained on a hybrid of real and imagined trajectories. This enables learning optimal policies that go beyond the sub-optimality of historical clinical decisions, while remaining close to real clinical data. We evaluate medDreamer on both sepsis and mechanical ventilation treatment tasks using two large-scale Electronic Health Records (EHRs) datasets. Comprehensive evaluations show that medDreamer significantly outperforms model-free and model-based baselines in both clinical outcomes and off-policy metrics.


Counterfactual Survival Q Learning for Longitudinal Randomized Trials via Buckley James Boosting

Lee, Jeongjin, Kim, Jong-Min

arXiv.org Machine Learning

We propose a Buckley James (BJ) Boost Q learning framework for estimating optimal dynamic treatment regimes under right censored survival data, tailored for longitudinal randomized clinical trial settings. The method integrates accelerated failure time models with iterative boosting techniques, including componentwise least squares and regression trees, within a counterfactual Q learning framework. By directly modeling conditional survival time, BJ Boost Q learning avoids the restrictive proportional hazards assumption and enables unbiased estimation of stage specific Q functions. Grounded in potential outcomes, this framework ensures identifiability of the optimal treatment regime under standard causal assumptions. Compared to Cox based Q learning, which relies on hazard modeling and may suffer from bias under misspecification, our approach provides robust and flexible estimation. Simulation studies and analysis of the ACTG175 HIV trial demonstrate that BJ Boost Q learning yields higher accuracy in treatment decision making, especially in multistage settings where bias can accumulate.


Learning optimal treatment strategies for intraoperative hypotension using deep reinforcement learning

Adiyeke, Esra, Liu, Tianqi, Naganaboina, Venkata Sai Dheeraj, Li, Han, Loftus, Tyler J., Ren, Yuanfang, Shickel, Benjamin, Ruppert, Matthew M., Singh, Karandeep, Fang, Ruogu, Rashidi, Parisa, Bihorac, Azra, Ozrazgat-Baslanti, Tezcan

arXiv.org Artificial Intelligence

Traditional methods of surgical decision making heavily rely on human experience and prompt actions, which are variable. A data-driven system generating treatment recommendations based on patient states can be a substantial asset in perioperative decision-making, as in cases of intraoperative hypotension, for which suboptimal management is associated with acute kidney injury (AKI), a common and morbid postoperative complication. We developed a Reinforcement Learning (RL) model to recommend optimum dose of intravenous (IV) fluid and vasopressors during surgery to avoid intraoperative hypotension and postoperative AKI. We retrospectively analyzed 50,021 surgeries from 42,547 adult patients who underwent major surgery at a quaternary care hospital between June 2014 and September 2020. Of these, 34,186 surgeries were used for model training and 15,835 surgeries were reserved for testing. We developed a Deep Q-Networks based RL model using 16 variables including intraoperative physiologic time series, total dose of IV fluid and vasopressors extracted for every 15-minute epoch. The model replicated 69% of physician's decisions for the dosage of vasopressors and proposed higher or lower dosage of vasopressors than received in 10% and 21% of the treatments, respectively. In terms of IV fluids, the model's recommendations were within 0.05 ml/kg/15 min of the actual dose in 41% of the cases, with higher or lower doses recommended for 27% and 32% of the treatments, respectively. The model resulted in a higher estimated policy value compared to the physicians' actual treatments, as well as random and zero-drug policies. AKI prevalence was the lowest in patients receiving medication dosages that aligned with model's decisions. Our findings suggest that implementation of the model's policy has the potential to reduce postoperative AKI and improve other outcomes driven by intraoperative hypotension.


AI in Oncology: Transforming Cancer Detection through Machine Learning and Deep Learning Applications

Aftab, Muhammad, Mehmood, Faisal, Zhang, Chengjuan, Nadeem, Alishba, Dong, Zigang, Jiang, Yanan, Liu, Kangdongs

arXiv.org Artificial Intelligence

Artificial intelligence (AI) has potential to revolutionize the field of oncology by enhancing the precision of cancer diagnosis, optimizing treatment strategies, and personalizing therapies for a variety of cancers. This review examines the limitations of conventional diagnostic techniques and explores the transformative role of AI in diagnosing and treating cancers such as lung, breast, colorectal, liver, stomach, esophageal, cervical, thyroid, prostate, and skin cancers. The primary objective of this paper is to highlight the significant advancements that AI algorithms have brought to oncology within the medical industry. By enabling early cancer detection, improving diagnostic accuracy, and facilitating targeted treatment delivery, AI contributes to substantial improvements in patient outcomes. The integration of AI in medical imaging, genomic analysis, and pathology enhances diagnostic precision and introduces a novel, less invasive approach to cancer screening. This not only boosts the effectiveness of medical facilities but also reduces operational costs. The study delves into the application of AI in radiomics for detailed cancer characterization, predictive analytics for identifying associated risks, and the development of algorithm-driven robots for immediate diagnosis. Furthermore, it investigates the impact of AI on addressing healthcare challenges, particularly in underserved and remote regions. The overarching goal of this platform is to support the development of expert recommendations and to provide universal, efficient diagnostic procedures. By reviewing existing research and clinical studies, this paper underscores the pivotal role of AI in improving the overall cancer care system. It emphasizes how AI-enabled systems can enhance clinical decision-making and expand treatment options, thereby underscoring the importance of AI in advancing precision oncology


Kolmogorov-Arnold Networks and Evolutionary Game Theory for More Personalized Cancer Treatment

Azimi, Sepinoud, Spekking, Louise, Staňková, Kateřina

arXiv.org Artificial Intelligence

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.


Deep Learning Methods for the Noniterative Conditional Expectation G-Formula for Causal Inference from Complex Observational Data

Rein, Sophia M, Li, Jing, Hernan, Miguel, Beam, Andrew

arXiv.org Machine Learning

The g-formula can be used to estimate causal effects of sustained treatment strategies using observational data under the identifying assumptions of consistency, positivity, and exchangeability. The non-iterative conditional expectation (NICE) estimator of the g-formula also requires correct estimation of the conditional distribution of the time-varying treatment, confounders, and outcome. Parametric models, which have been traditionally used for this purpose, are subject to model misspecification, which may result in biased causal estimates. Here, we propose a unified deep learning framework for the NICE g-formula estimator that uses multitask recurrent neural networks for estimation of the joint conditional distributions. Using simulated data, we evaluated our model's bias and compared it with that of the parametric g-formula estimator. We found lower bias in the estimates of the causal effect of sustained treatment strategies on a survival outcome when using the deep learning estimator compared with the parametric NICE estimator in settings with simple and complex temporal dependencies between covariates. These findings suggest that our Deep Learning g-formula estimator may be less sensitive to model misspecification than the classical parametric NICE estimator when estimating the causal effect of sustained treatment strategies from complex observational data.


Large Language Models-Enabled Digital Twins for Precision Medicine in Rare Gynecological Tumors

Lammert, Jacqueline, Pfarr, Nicole, Kuligin, Leonid, Mathes, Sonja, Dreyer, Tobias, Modersohn, Luise, Metzger, Patrick, Ferber, Dyke, Kather, Jakob Nikolas, Truhn, Daniel, Adams, Lisa Christine, Bressem, Keno Kyrill, Lange, Sebastian, Schwamborn, Kristina, Boeker, Martin, Kiechle, Marion, Schatz, Ulrich A., Bronger, Holger, Tschochohei, Maximilian

arXiv.org Machine Learning

Rare gynecological tumors (RGTs) present major clinical challenges due to their low incidence and heterogeneity. The lack of clear guidelines leads to suboptimal management and poor prognosis. Molecular tumor boards accelerate access to effective therapies by tailoring treatment based on biomarkers, beyond cancer type. Unstructured data that requires manual curation hinders efficient use of biomarker profiling for therapy matching. This study explores the use of large language models (LLMs) to construct digital twins for precision medicine in RGTs. Our proof-of-concept digital twin system integrates clinical and biomarker data from institutional and published cases (n=21) and literature-derived data (n=655 publications with n=404,265 patients) to create tailored treatment plans for metastatic uterine carcinosarcoma, identifying options potentially missed by traditional, single-source analysis. LLM-enabled digital twins efficiently model individual patient trajectories. Shifting to a biology-based rather than organ-based tumor definition enables personalized care that could advance RGT management and thus enhance patient outcomes.


G-Transformer: Counterfactual Outcome Prediction under Dynamic and Time-varying Treatment Regimes

Xiong, Hong, Wu, Feng, Deng, Leon, Su, Megan, Lehman, Li-wei H

arXiv.org Artificial Intelligence

In the context of medical decision making, counterfactual prediction enables clinicians to predict treatment outcomes of interest under alternative courses of therapeutic actions given observed patient history. Prior machine learning approaches for counterfactual predictions under time-varying treatments focus on static time-varying treatment regimes where treatments do not depend on previous covariate history. In this work, we present G-Transformer, a Transformer-based framework supporting g-computation for counterfactual prediction under dynamic and time-varying treatment strategies. G-Transfomer captures complex, long-range dependencies in time-varying covariates using a Transformer architecture. G-Transformer estimates the conditional distribution of relevant covariates given covariate and treatment history at each time point using an encoder architecture, then produces Monte Carlo estimates of counterfactual outcomes by simulating forward patient trajectories under treatment strategies of interest. We evaluate G-Transformer extensively using two simulated longitudinal datasets from mechanistic models, and a real-world sepsis ICU dataset from MIMIC-IV. G-Transformer outperforms both classical and state-of-the-art counterfactual prediction models in these settings. To the best of our knowledge, this is the first Transformer-based architecture for counterfactual outcome prediction under dynamic and time-varying treatment strategies.