Kundan Thind

Reza Khanmohammadi, Mohammad M. Ghassemi, Kyle Verdecchia et al.

Natural Language Processing (NLP) is a key technique for developing Medical Artificial Intelligence (AI) systems that leverage Electronic Health Record (EHR) data to build diagnostic and prognostic models. NLP enables the conversion of unstructured clinical text into structured data that can be fed into AI algorithms. The emergence of the transformer architecture and large language models (LLMs) has led to remarkable advances in NLP for various healthcare tasks, such as entity recognition, relation extraction, sentence similarity, text summarization, and question answering. In this article, we review the major technical innovations that underpin modern NLP models and present state-of-the-art NLP applications that employ LLMs in radiation oncology research. However, these LLMs are prone to many errors such as hallucinations, biases, and ethical violations, which necessitate rigorous evaluation and validation before clinical deployment. As such, we propose a comprehensive framework for assessing the NLP models based on their purpose and clinical fit, technical performance, bias and trust, legal and ethical implications, and quality assurance, prior to implementation in clinical radiation oncology. Our article aims to provide guidance and insights for researchers and clinicians who are interested in developing and using NLP models in clinical radiation oncology.

Ujunwa Mgboh, Rafi Ibn Sultan, Joshua Kim et al.

Learning-based fluence map prediction offers a fast alternative to iterative inverse planning in intensity-modulated radiation therapy (IMRT), but its robustness under realistic distribution shifts remains unclear. We study a two-stage transformer pipeline that maps anatomy (CT and contours) to dose and then to beamlet fluence maps. We compare fluence-stage transformer backbones with hierarchical, global, and hybrid attention, trained with a physics-informed loss enforcing energy consistency. Robustness is evaluated under geometric perturbations, radiometric noise, reduced training data, and domain shifts using a prostate IMRT dataset, with additional evaluation of the dose stage on public datasets. Results show smooth degradation under moderate perturbations but sharp failures under severe rotations and noise. Hierarchical transformers (e.g., SwinUNETR) exhibit slower growth in upper-quartile energy error, indicating improved robustness. We further show that SSIM alone fails to capture clinically relevant errors, highlighting the need for physics-informed evaluation.

Reza Khanmohammadi, Ahmed I. Ghanem, Kyle Verdecchia et al.

Large Language Models (LLMs) offer significant potential for clinical symptom extraction, but their deployment in healthcare settings is constrained by privacy concerns, computational limitations, and operational costs. This study investigates the optimization of compact LLMs for cancer toxicity symptom extraction using a novel iterative refinement approach. We employ a student-teacher architecture, utilizing Zephyr-7b-beta and Phi3-mini-128 as student models and GPT-4o as the teacher, to dynamically select between prompt refinement, Retrieval-Augmented Generation (RAG), and fine-tuning strategies. Our experiments on 294 clinical notes covering 12 post-radiotherapy toxicity symptoms demonstrate the effectiveness of this approach. The RAG method proved most efficient, improving average accuracy scores from 0.32 to 0.73 for Zephyr-7b-beta and from 0.40 to 0.87 for Phi3-mini-128 during refinement. In the test set, both models showed an approximate 0.20 increase in accuracy across symptoms. Notably, this improvement was achieved at a cost 45 times lower than GPT-4o for Zephyr and 79 times lower for Phi-3. These results highlight the potential of iterative refinement techniques in enhancing the capabilities of compact LLMs for clinical applications, offering a balance between performance, cost-effectiveness, and privacy preservation in healthcare settings.

Chengyin Li, Hui Zhu, Rafi Ibn Sultan et al.

In the diverse field of medical imaging, automatic segmentation has numerous applications and must handle a wide variety of input domains, such as different types of Computed Tomography (CT) scans and Magnetic Resonance (MR) images. This heterogeneity challenges automatic segmentation algorithms to maintain consistent performance across different modalities due to the requirement for spatially aligned and paired images. Typically, segmentation models are trained using a single modality, which limits their ability to generalize to other types of input data without employing transfer learning techniques. Additionally, leveraging complementary information from different modalities to enhance segmentation precision often necessitates substantial modifications to popular encoder-decoder designs, such as introducing multiple branched encoding or decoding paths for each modality. In this work, we propose a simple Multi-Modal Segmentation (MulModSeg) strategy to enhance medical image segmentation across multiple modalities, specifically CT and MR. It incorporates two key designs: a modality-conditioned text embedding framework via a frozen text encoder that adds modality awareness to existing segmentation frameworks without significant structural modifications or computational overhead, and an alternating training procedure that facilitates the integration of essential features from unpaired CT and MR inputs. Through extensive experiments with both Fully Convolutional Network and Transformer-based backbones, MulModSeg consistently outperforms previous methods in segmenting abdominal multi-organ and cardiac substructures for both CT and MR modalities. The code is available in this {\href{https://github.com/ChengyinLee/MulModSeg_2024}{link}}.

Reza Khanmohammadi, Erfan Miahi, Simerjot Kaur et al.

The miscalibration of Large Reasoning Models (LRMs) undermines their reliability in high-stakes domains, necessitating methods to accurately estimate the confidence of their long-form, multi-step outputs. To address this gap, we introduce the Reasoning Model Confidence estimation Benchmark (RMCB), a public resource of 347,496 reasoning traces from six popular LRMs across different architectural families. The benchmark is constructed from a diverse suite of datasets spanning high-stakes domains, including clinical, financial, legal, and mathematical reasoning, alongside complex general reasoning benchmarks, with correctness annotations provided for all samples. Using RMCB, we conduct a large-scale empirical evaluation of over ten distinct representation-based methods, spanning sequential, graph-based, and text-based architectures. Our central finding is a persistent trade-off between discrimination (AUROC) and calibration (ECE): text-based encoders achieve the best AUROC (0.672), while structurally-aware models yield the best ECE (0.148), with no single method dominating both. Furthermore, we find that increased architectural complexity does not reliably outperform simpler sequential baselines, suggesting a performance ceiling for methods relying solely on chunk-level hidden states. This work provides the most comprehensive benchmark for this task to date, establishing rigorous baselines and demonstrating the limitations of current representation-based paradigms.

Ujunwa Mgboh, Rafi Ibn Sultan, Joshua Kim et al.

Fluence map prediction is central to automated radiotherapy planning but remains an ill-posed inverse problem due to the complex relationship between volumetric anatomy and beam-intensity modulation. Convolutional methods in prior work often struggle to capture long-range dependencies, which can lead to structurally inconsistent or physically unrealizable plans. We introduce \textbf{FluenceFormer}, a backbone-agnostic transformer framework for direct, geometry-aware fluence regression. The model uses a unified two-stage design: Stage~1 predicts a global dose prior from anatomical inputs, and Stage~2 conditions this prior on explicit beam geometry to regress physically calibrated fluence maps. Central to the approach is the \textbf{Fluence-Aware Regression (FAR)} loss, a physics-informed objective that integrates voxel-level fidelity, gradient smoothness, structural consistency, and beam-wise energy conservation. We evaluate the generality of the framework across multiple transformer backbones, including Swin UNETR, UNETR, nnFormer, and MedFormer, using a prostate IMRT dataset. FluenceFormer with Swin UNETR achieves the strongest performance among the evaluated models and improves over existing benchmark CNN and single-stage methods, reducing Energy Error to $\mathbf{4.5\%}$ and yielding statistically significant gains in structural fidelity ($p < 0.05$).

Reza Khanmohammadi, Erfan Miahi, Simerjot Kaur et al.

Large vision-language models suffer from visual ungroundedness: they can produce a fluent, confident, and even correct response driven entirely by language priors, with the image contributing nothing to the prediction. Existing confidence estimation methods cannot detect this, as they observe model behavior under normal inference with no mechanism to determine whether a prediction was shaped by the image or by text alone. We introduce BICR (Blind-Image Contrastive Ranking), a model-agnostic confidence estimation framework that makes this contrast explicit during training by extracting hidden states from a frozen LVLM twice: once with the real image-question pair, and once with the image blacked out while the question is held fixed. A lightweight probe is trained on the real-image hidden state and regularized by a ranking loss that penalizes higher confidence on the blacked-out view, teaching it to treat visual grounding as a signal of reliability at zero additional inference cost. Evaluated across five modern LVLMs and seven baselines on a benchmark covering visual question answering, object hallucination detection, medical imaging, and financial document understanding, BICR achieves the best cross-LVLM average on both calibration and discrimination simultaneously, with statistically significant discrimination gains robust to cluster-aware analysis at 4-18x fewer parameters than the strongest probing baseline.

Humza Nusrat, Luke Francisco, Bing Luo et al.

Stereotactic radiosurgery (SRS) demands precise dose shaping around critical structures, yet black-box AI systems have limited clinical adoption due to opacity concerns. We tested whether chain-of-thought reasoning improves agentic planning in a retrospective cohort of 41 patients with brain metastases treated with 18 Gy single-fraction SRS. We developed SAGE (Secure Agent for Generative Dose Expertise), an LLM-based planning agent for automated SRS treatment planning. Two variants generated plans for each case: one using a non-reasoning model, one using a reasoning model. The reasoning variant showed comparable plan dosimetry relative to human planners on primary endpoints (PTV coverage, maximum dose, conformity index, gradient index; all p > 0.21) while reducing cochlear dose below human baselines (p = 0.022). When prompted to improve conformity, the reasoning model demonstrated systematic planning behaviors including prospective constraint verification (457 instances) and trade-off deliberation (609 instances), while the standard model exhibited none of these deliberative processes (0 and 7 instances, respectively). Content analysis revealed that constraint verification and causal explanation concentrated in the reasoning agent. The optimization traces serve as auditable logs, offering a path toward transparent automated planning.

Reza Khanmohammadi, Ahmed I Ghanem, Kyle Verdecchia et al.

This study introduces a novel teacher-student architecture utilizing Large Language Models (LLMs) to improve prostate cancer radiotherapy symptom extraction from clinical notes. Mixtral, the student model, initially extracts symptoms, followed by GPT-4, the teacher model, which refines prompts based on Mixtral's performance. This iterative process involved 294 single symptom clinical notes across 12 symptoms, with up to 16 rounds of refinement per epoch. Results showed significant improvements in extracting symptoms from both single and multi-symptom notes. For 59 single symptom notes, accuracy increased from 0.51 to 0.71, precision from 0.52 to 0.82, recall from 0.52 to 0.72, and F1 score from 0.49 to 0.73. In 375 multi-symptom notes, accuracy rose from 0.24 to 0.43, precision from 0.6 to 0.76, recall from 0.24 to 0.43, and F1 score from 0.20 to 0.44. These results demonstrate the effectiveness of advanced prompt engineering in LLMs for radiation oncology use.

Humza Nusrat, Bing Luo, Ryan Hall et al.

Radiotherapy treatment planning is a complex and time-intensive process, often impacted by inter-planner variability and subjective decision-making. To address these challenges, we introduce Dose Optimization Language Agent (DOLA), an autonomous large language model (LLM)-based agent designed for optimizing radiotherapy treatment plans while rigorously protecting patient privacy. DOLA integrates the LLaMa3.1 LLM directly with a commercial treatment planning system, utilizing chain-of-thought prompting, retrieval-augmented generation (RAG), and reinforcement learning (RL). Operating entirely within secure local infrastructure, this agent eliminates external data sharing. We evaluated DOLA using a retrospective cohort of 18 prostate cancer patients prescribed 60 Gy in 20 fractions, comparing model sizes (8 billion vs. 70 billion parameters) and optimization strategies (No-RAG, RAG, and RAG+RL) over 10 planning iterations. The 70B model demonstrated significantly improved performance, achieving approximately 16.4% higher final scores than the 8B model. The RAG approach outperformed the No-RAG baseline by 19.8%, and incorporating RL accelerated convergence, highlighting the synergy of retrieval-based memory and reinforcement learning. Optimal temperature hyperparameter analysis identified 0.4 as providing the best balance between exploration and exploitation. This proof of concept study represents the first successful deployment of locally hosted LLM agents for autonomous optimization of treatment plans within a commercial radiotherapy planning system. By extending human-machine interaction through interpretable natural language reasoning, DOLA offers a scalable and privacy-conscious framework, with significant potential for clinical implementation and workflow improvement.

Reza Khanmohammadi, Erfan Miahi, Mehrsa Mardikoraem et al.

Miscalibration in Large Language Models (LLMs) undermines their reliability, highlighting the need for accurate confidence estimation. We introduce CCPS (Calibrating LLM Confidence by Probing Perturbed Representation Stability), a novel method analyzing internal representational stability in LLMs. CCPS applies targeted adversarial perturbations to final hidden states, extracts features reflecting the model's response to these perturbations, and uses a lightweight classifier to predict answer correctness. CCPS was evaluated on LLMs from 8B to 32B parameters (covering Llama, Qwen, and Mistral architectures) using MMLU and MMLU-Pro benchmarks in both multiple-choice and open-ended formats. Our results show that CCPS significantly outperforms current approaches. Across four LLMs and three MMLU variants, CCPS reduces Expected Calibration Error by approximately 55% and Brier score by 21%, while increasing accuracy by 5 percentage points, Area Under the Precision-Recall Curve by 4 percentage points, and Area Under the Receiver Operating Characteristic Curve by 6 percentage points, all relative to the strongest prior method. CCPS delivers an efficient, broadly applicable, and more accurate solution for estimating LLM confidence, thereby improving their trustworthiness.