Benjamin Frey

Thomas Weissmann, Yixing Huang, Stefan Fischer et al.

Background: Deep learning (DL)-based head and neck lymph node level (HN_LNL) autodelineation is of high relevance to radiotherapy research and clinical treatment planning but still underinvestigated in academic literature. Methods: An expert-delineated cohort of 35 planning CTs was used for training of an nnU-net 3D-fullres/2D-ensemble model for autosegmentation of 20 different HN_LNL. A second cohort acquired at the same institution later in time served as the test set (n=20). In a completely blinded evaluation, 3 clinical experts rated the quality of DL autosegmentations in a head-to-head comparison with expert-created contours. For a subgroup of 10 cases, intraobserver variability was compared to the average DL autosegmentation accuracy on the original and recontoured set of expert segmentations. A postprocessing step to adjust craniocaudal boundaries of level autosegmentations to the CT slice plane was introduced and the effect on geometric accuracy and expert rating was investigated. Results: Blinded expert ratings for DL segmentations and expert-created contours were not significantly different. DL segmentations with slice plane adjustment were rated numerically higher (mean, 81.0 vs. 79.6,p=0.185) and DL segmentations without slice plane adjustment were rated numerically lower (77.2 vs. 79.6,p=0.167) than manually drawn contours. DL segmentations with CT slice plane adjustment were rated significantly better than DL contours without slice plane adjustment (81.0 vs. 77.2,p=0.004). Geometric accuracy of DL segmentations was not different from intraobserver variability (mean, 0.76 vs. 0.77, p=0.307). Conclusions: We show that a nnU-net 3D-fullres/2D-ensemble model can be used for highly accurate autodelineation of HN_LNL using only a limited training dataset that is ideally suited for large-scale standardized autodelineation of HN_LNL in the research setting.

Florian Putz, Johanna Grigo, Thomas Weissmann et al.

Background: Tumor segmentation in MRI is crucial in radiotherapy (RT) treatment planning for brain tumor patients. Segment anything (SA), a novel promptable foundation model for autosegmentation, has shown high accuracy for multiple segmentation tasks but was not evaluated on medical datasets yet. Methods: SA was evaluated in a point-to-mask task for glioma brain tumor autosegmentation on 16744 transversal slices from 369 MRI datasets (BraTS 2020). Up to 9 point prompts were placed per slice. Tumor core (enhancing tumor + necrotic core) was segmented on contrast-enhanced T1w sequences. Out of the 3 masks predicted by SA, accuracy was evaluated for the mask with the highest calculated IoU (oracle mask) and with highest model predicted IoU (suggested mask). In addition to assessing SA on whole MRI slices, SA was also evaluated on images cropped to the tumor (max. 3D extent + 2 cm). Results: Mean best IoU (mbIoU) using oracle mask on full MRI slices was 0.762 (IQR 0.713-0.917). Best 2D mask was achieved after a mean of 6.6 point prompts (IQR 5-9). Segmentation accuracy was significantly better for high- compared to low-grade glioma cases (mbIoU 0.789 vs. 0.668). Accuracy was worse using MRI slices cropped to the tumor (mbIoU 0.759) and was much worse using suggested mask (full slices 0.572). For all experiments, accuracy was low on peripheral slices with few tumor voxels (mbIoU, <300: 0.537 vs. >=300: 0.841). Stacking best oracle segmentations from full axial MRI slices, mean 3D DSC for tumor core was 0.872, which was improved to 0.919 by combining axial, sagittal and coronal masks. Conclusions: The Segment Anything foundation model, while trained on photos, can achieve high zero-shot accuracy for glioma brain tumor segmentation on MRI slices. The results suggest that Segment Anything can accelerate and facilitate RT treatment planning, when properly integrated in a clinical application.

Yixing Huang, Ahmed Gomaa, Sabine Semrau et al.

The potential of large language models in medicine for education and decision making purposes has been demonstrated as they achieve decent scores on medical exams such as the United States Medical Licensing Exam (USMLE) and the MedQA exam. In this work, we evaluate the performance of ChatGPT-4 in the specialized field of radiation oncology using the 38th American College of Radiology (ACR) radiation oncology in-training (TXIT) exam and the 2022 Red Journal Gray Zone cases. For the TXIT exam, ChatGPT-3.5 and ChatGPT-4 have achieved the scores of 63.65% and 74.57%, respectively, highlighting the advantage of the latest ChatGPT-4 model. Based on the TXIT exam, ChatGPT-4's strong and weak areas in radiation oncology are identified to some extent. Specifically, ChatGPT-4 demonstrates better knowledge of statistics, CNS & eye, pediatrics, biology, and physics than knowledge of bone & soft tissue and gynecology, as per the ACR knowledge domain. Regarding clinical care paths, ChatGPT-4 performs better in diagnosis, prognosis, and toxicity than brachytherapy and dosimetry. It lacks proficiency in in-depth details of clinical trials. For the Gray Zone cases, ChatGPT-4 is able to suggest a personalized treatment approach to each case with high correctness and comprehensiveness. Importantly, it provides novel treatment aspects for many cases, which are not suggested by any human experts. Both evaluations demonstrate the potential of ChatGPT-4 in medical education for the general public and cancer patients, as well as the potential to aid clinical decision-making, while acknowledging its limitations in certain domains. Because of the risk of hallucination, facts provided by ChatGPT always need to be verified.

Shiyue Zhang, Benjamin Frey, Mohit Bansal

We introduce ChrEnTranslate, an online machine translation demonstration system for translation between English and an endangered language Cherokee. It supports both statistical and neural translation models as well as provides quality estimation to inform users of reliability, two user feedback interfaces for experts and common users respectively, example inputs to collect human translations for monolingual data, word alignment visualization, and relevant terms from the Cherokee-English dictionary. The quantitative evaluation demonstrates that our backbone translation models achieve state-of-the-art translation performance and our quality estimation well correlates with both BLEU and human judgment. By analyzing 216 pieces of expert feedback, we find that NMT is preferable because it copies less than SMT, and, in general, current models can translate fragments of the source sentence but make major mistakes. When we add these 216 expert-corrected parallel texts back into the training set and retrain models, equal or slightly better performance is observed, which indicates the potential of human-in-the-loop learning. Our online demo is at https://chren.cs.unc.edu/ , our code is open-sourced at https://github.com/ZhangShiyue/ChrEnTranslate , and our data is available at https://github.com/ZhangShiyue/ChrEn

Shiyue Zhang, Benjamin Frey, Mohit Bansal

Cherokee is a highly endangered Native American language spoken by the Cherokee people. The Cherokee culture is deeply embedded in its language. However, there are approximately only 2,000 fluent first language Cherokee speakers remaining in the world, and the number is declining every year. To help save this endangered language, we introduce ChrEn, a Cherokee-English parallel dataset, to facilitate machine translation research between Cherokee and English. Compared to some popular machine translation language pairs, ChrEn is extremely low-resource, only containing 14k sentence pairs in total. We split our parallel data in ways that facilitate both in-domain and out-of-domain evaluation. We also collect 5k Cherokee monolingual data to enable semi-supervised learning. Besides these datasets, we propose several Cherokee-English and English-Cherokee machine translation systems. We compare SMT (phrase-based) versus NMT (RNN-based and Transformer-based) systems; supervised versus semi-supervised (via language model, back-translation, and BERT/Multilingual-BERT) methods; as well as transfer learning versus multilingual joint training with 4 other languages. Our best results are 15.8/12.7 BLEU for in-domain and 6.5/5.0 BLEU for out-of-domain Chr-En/EnChr translations, respectively, and we hope that our dataset and systems will encourage future work by the community for Cherokee language revitalization. Our data, code, and demo will be publicly available at https://github.com/ZhangShiyue/ChrEn

Ahmed Gomaa, Yixing Huang, Amr Hagag et al.

Background: This research aims to improve glioblastoma survival prediction by integrating MR images, clinical and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability. Method: We propose and evaluate a transformer-based non-linear and non-proportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with non-imaging data using cross-attention. To demonstrate model generalizability, the model is assessed with the time-dependent concordance index (Cdt) in two training setups using three independent public test sets: UPenn-GBM, UCSF-PDGM, and RHUH-GBM, each comprising 378, 366, and 36 cases, respectively. Results: The proposed transformer model achieved promising performance for imaging as well as non-imaging data, effectively integrating both modalities for enhanced performance (UPenn-GBM test-set, imaging Cdt 0.645, multimodal Cdt 0.707) while outperforming state-of-the-art late-fusion 3D-CNN-based models. Consistent performance was observed across the three independent multicenter test sets with Cdt values of 0.707 (UPenn-GBM, internal test set), 0.672 (UCSF-PDGM, first external test set) and 0.618 (RHUH-GBM, second external test set). The model achieved significant discrimination between patients with favorable and unfavorable survival for all three datasets (logrank p 1.9\times{10}^{-8}, 9.7\times{10}^{-3}, and 1.2\times{10}^{-2}). Conclusions: The proposed transformer-based survival prediction model integrates complementary information from diverse input modalities, contributing to improved glioblastoma survival prediction compared to state-of-the-art methods. Consistent performance was observed across institutions supporting model generalizability.

Ahmed Gomaa, Yixing Huang, Pluvio Stephan et al.

Accurate differentiation of pseudoprogression (PsP) from True Progression (TP) following radiotherapy (RT) in glioblastoma (GBM) patients is crucial for optimal treatment planning. However, this task remains challenging due to the overlapping imaging characteristics of PsP and TP. This study therefore proposes a multimodal deep-learning approach utilizing complementary information from routine anatomical MR images, clinical parameters, and RT treatment planning information for improved predictive accuracy. The approach utilizes a self-supervised Vision Transformer (ViT) to encode multi-sequence MR brain volumes to effectively capture both global and local context from the high dimensional input. The encoder is trained in a self-supervised upstream task on unlabeled glioma MRI datasets from the open BraTS2021, UPenn-GBM, and UCSF-PDGM datasets to generate compact, clinically relevant representations from FLAIR and T1 post-contrast sequences. These encoded MR inputs are then integrated with clinical data and RT treatment planning information through guided cross-modal attention, improving progression classification accuracy. This work was developed using two datasets from different centers: the Burdenko Glioblastoma Progression Dataset (n = 59) for training and validation, and the GlioCMV progression dataset from the University Hospital Erlangen (UKER) (n = 20) for testing. The proposed method achieved an AUC of 75.3%, outperforming the current state-of-the-art data-driven approaches. Importantly, the proposed approach relies on readily available anatomical MRI sequences, clinical data, and RT treatment planning information, enhancing its clinical feasibility. The proposed approach addresses the challenge of limited data availability for PsP and TP differentiation and could allow for improved clinical decision-making and optimized treatment plans for GBM patients.

Ugur Dinc, Jibak Sarkar, Philipp Schubert et al.

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. Inter-rater agreement was low (Fleiss' \k{appa} 0.083 for correctness), reflecting inherent variability in clinical judgment. Errors clustered in complex scenarios requiring precise trial knowledge or detailed clinical adaptation. Discussion: GPT-5 clearly outperformed prior model variants on the radiation oncology multiple-choice benchmark. Although GPT-5 exhibited favorable performance in generating real-world radiation oncology treatment recommendations, correctness ratings indicate room for further improvement. While hallucinations were infrequent, the presence of substantive errors underscores that GPT-5-generated recommendations require rigorous expert oversight before clinical implementation.

Ahmed Gomaa, Annette Schwarz, Ludwig Singer et al.

Background: Differentiating radiation necrosis (RN) from tumor progression after stereotactic radiosurgery (SRS) remains a critical challenge in brain metastases. While histopathology represents the gold standard, its invasiveness limits feasibility. Conventional supervised deep learning approaches are constrained by scarce biopsy-confirmed training data. Self-supervised learning (SSL) overcomes this by leveraging the growing availability of large-scale unlabeled brain metastases imaging datasets. Methods: In a two-phase deep learning strategy inspired by the foundation model paradigm, a Vision Transformer (ViT) was pre-trained via SSL on 10,167 unlabeled multi-source T1CE MRI sub-volumes. The pre-trained ViT was then fine-tuned for RN classification using a two-channel input (T1CE MRI and segmentation masks) on the public MOLAB dataset (n=109) using 20% of datasets as same-center held-out test set. External validation was performed on a second-center test cohort (n=28). Results: The self-supervised model achieved an AUC of 0.916 on the same-center test set and 0.764 on the second center test set, surpassing the fully supervised ViT (AUC 0.624/0.496; p=0.001/0.008) and radiomics (AUC 0.807/0.691; p=0.005/0.014). Multimodal integration further improved performance (AUC 0.947/0.821; p=0.073/0.001). Attention map visualizations enabled interpretability showing the model focused on clinically relevant lesion subregions. Conclusion: Large-scale pre-training on increasingly available unlabeled brain metastases datasets substantially improves AI model performance. A two-phase multimodal deep learning strategy achieved high accuracy in differentiating radiation necrosis from tumor progression using only routine T1CE MRI and standard clinical data, providing an interpretable, clinically accessible solution that warrants further validation.

Yixing Huang, Christoph Bert, Philipp Sommer et al.

Brain metastases occur frequently in patients with metastatic cancer. Early and accurate detection of brain metastases is very essential for treatment planning and prognosis in radiation therapy. To improve brain metastasis detection performance with deep learning, a custom detection loss called volume-level sensitivity-specificity (VSS) is proposed, which rates individual metastasis detection sensitivity and specificity in (sub-)volume levels. As sensitivity and precision are always a trade-off in a metastasis level, either a high sensitivity or a high precision can be achieved by adjusting the weights in the VSS loss without decline in dice score coefficient for segmented metastases. To reduce metastasis-like structures being detected as false positive metastases, a temporal prior volume is proposed as an additional input of DeepMedic. The modified network is called DeepMedic+ for distinction. Our proposed VSS loss improves the sensitivity of brain metastasis detection for DeepMedic, increasing the sensitivity from 85.3% to 97.5%. Alternatively, it improves the precision from 69.1% to 98.7%. Comparing DeepMedic+ with DeepMedic with the same VSS loss, 44.4% of the false positive metastases are reduced in the high sensitivity model and the precision reaches 99.6% for the high specificity model. The mean dice coefficient for all metastases is about 0.81. With the ensemble of the high sensitivity and high specificity models, on average only 1.5 false positive metastases per patient needs further check, while the majority of true positive metastases are confirmed. The ensemble learning is able to distinguish high confidence true positive metastases from metastases candidates that require special expert review or further follow-up, being particularly well-fit to the requirements of expert support in real clinical practice.