PULSAR (personalized, ultra-fractionated stereotactic adaptive radiotherapy) is the adaptation of stereotactic ablative radiotherapy towards personalized cancer management. For the first time, we applied a transformer-based attention mechanism to investigate the underlying interactions between combined PULSAR and PD-L1 blockade immunotherapy based on a murine cancer model (Lewis Lung Carcinoma, LLC). The proposed approach is able to predict the trend of tumor volume change semi-quantitatively, and excels in identifying the potential causal relationships through both self-attention and cross-attention scores. Introduction The field of combining radiotherapy and immunotherapy is rapidly evolving, and one aspect of particular interest is determination of optimal timing and sequence to harness the potential synergy between radiation therapy and immune checkpoint blockade.

Estimating the uncertainty of deep learning models in a reliable and efficient way has remained an open problem, where many different solutions have been proposed in the literature. Most common methods are based on Bayesian approximations, like Monte Carlo dropout (MCDO) or Deep ensembling (DE), but they have a high inference time (i.e. require multiple inference passes) and might not work for out-of-distribution detection (OOD) data (i.e. similar uncertainty for in-distribution (ID) and OOD). In safety critical environments, like medical applications, accurate and fast uncertainty estimation methods, able to detect OOD data, are crucial, since wrong predictions can jeopardize patients safety. In this study, we present an alternative direct uncertainty estimation method and apply it for a regression U-Net architecture. The method consists in the addition of a branch from the bottleneck which reconstructs the input. The input reconstruction error can be used as a surrogate of the model uncertainty. For the proof-of-concept, our method is applied to proton therapy dose prediction in head and neck cancer patients. Accuracy, time-gain, and OOD detection are analyzed for our method in this particular application and compared with the popular MCDO and DE. The input reconstruction method showed a higher Pearson correlation coefficient with the prediction error (0.620) than DE and MCDO (between 0.447 and 0.612). Moreover, our method allows an easier identification of OOD (Z-score of 34.05). It estimates the uncertainty simultaneously to the regression task, therefore requires less time or computational resources.

The primary aim of this research was to address the limitations observed in the medical knowledge of prevalent large language models (LLMs) such as ChatGPT, by creating a specialized language model with enhanced accuracy in medical advice. We achieved this by adapting and refining the large language model meta-AI (LLaMA) using a large dataset of 100,000 patient-doctor dialogues sourced from a widely used online medical consultation platform. These conversations were cleaned and anonymized to respect privacy concerns. In addition to the model refinement, we incorporated a self-directed information retrieval mechanism, allowing the model to access and utilize real-time information from online sources like Wikipedia and data from curated offline medical databases. The fine-tuning of the model with real-world patient-doctor interactions significantly improved the model's ability to understand patient needs and provide informed advice. By equipping the model with self-directed information retrieval from reliable online and offline sources, we observed substantial improvements in the accuracy of its responses. Our proposed ChatDoctor, represents a significant advancement in medical LLMs, demonstrating a significant improvement in understanding patient inquiries and providing accurate advice. Given the high stakes and low error tolerance in the medical field, such enhancements in providing accurate and reliable information are not only beneficial but essential.

Typically, the current dose prediction models are limited to small amounts of data and require re-training for a specific site, often leading to suboptimal performance. We propose a site-agnostic, 3D dose distribution prediction model using deep learning that can leverage data from any treatment site, thus increasing the total data available to train the model. Applying our proposed model to a new target treatment site requires only a brief fine-tuning of the model to the new data and involves no modifications to the model input channels or its parameters. Thus, it can be efficiently adapted to a different treatment site, even with a small training dataset.

In tumor segmentation, inter-observer variation is acknowledged to be a significant problem. This is even more significant in clinical target volume (CTV) segmentation, specifically, in post-operative settings, where a gross tumor does not exist. In this scenario, CTV is not an anatomically established structure but rather one determined by the physician based on the clinical guideline used, the preferred trade off between tumor control and toxicity, their experience, training background etc... This results in high inter-observer variability between physicians. Inter-observer variability has been considered an issue, however its dosimetric consequence is still unclear, due to the absence of multiple physician CTV contours for each patient and the significant amount of time required for dose planning. In this study, we analyze the impact that these physician stylistic variations have on organs-at-risk (OAR) dose by simulating the clinical workflow using deep learning. For a given patient previously treated by one physician, we use DL-based tools to simulate how other physicians would contour the CTV and how the corresponding dose distributions should look like for this patient. To simulate multiple physician styles, we use a previously developed in-house CTV segmentation model that can produce physician style-aware segmentations. The corresponding dose distribution is predicted using another in-house deep learning tool, which, averaging across all structures, is capable of predicting dose within 3% of the prescription dose on the test data. For every test patient, four different physician-style CTVs are considered and four different dose distributions are analyzed. OAR dose metrics are compared, showing that even though physician style variations results in organs getting different doses, all the important dose metrics except Maximum Dose point are within the clinically acceptable limit.

The use of neural networks to directly predict three-dimensional dose distributions for automatic planning is becoming popular. However, the existing methods only use patient anatomy as input and assume consistent beam configuration for all patients in the training database. The purpose of this work is to develop a more general model that, in addition to patient anatomy, also considers variable beam configurations, to achieve a more comprehensive automatic planning with a potentially easier clinical implementation, without the need of training specific models for different beam settings.

With the advancement of treatment modalities in radiation therapy for cancer patients, outcomes have improved, but at the cost of increased treatment plan complexity and planning time. The accurate prediction of dose distributions would alleviate this issue by guiding clinical plan optimization to save time and maintain high quality plans. We have modified a convolutional deep network model, U-net (originally designed for segmentation purposes), for predicting dose from patient image contours. We show that, as an example, we are able to accurately predict the dose of intensity-modulated radiation therapy (IMRT) for prostate cancer patients, where the average dice similarity coefficient is 0.91 when comparing the predicted vs. true isodose volumes between 0% and 100% of the prescription dose. The average value of the absolute differences in [max, mean] dose is found to be under 5% of the prescription dose, specifically for each structure is [1.80%, 1.03%](PTV), [1.94%, 4.22%](Bladder), [1.80%, 0.48%](Body), [3.87%, 1.79%](L Femoral Head), [5.07%, 2.55%](R Femoral Head), and [1.26%, 1.62%](Rectum) of the prescription dose. We thus managed to map a desired radiation dose distribution from a patient's PTV and OAR contours. As an additional advantage, relatively little data was used in the techniques and models described in this paper.