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In this manuscript, we draw on the insights from Kahneman, Sibony, and Sunsteins influential nonfiction book Noise: A Flaw in Human Judgment to explore the concept of unwanted variability in judgment (i.e., noise). We introduce key terms and connect these insights to the field of radiation oncology by illustrating how noise contributes to errors in clinically relevant areas such as contouring. Additionally, we propose practical strategies to reduce noise in radiation oncology, such as through judgment aggregation and the use of artificial intelligence tools, building on the principles outlined in the book.

Magnetic resonance (MR)-guided radiation therapy (RT) is enhancing head and neck cancer (HNC) treatment through superior soft tissue contrast and longitudinal imaging capabilities. However, manual tumor segmentation remains a significant challenge, spurring interest in artificial intelligence (AI)-driven automation. To accelerate innovation in this field, we present the Head and Neck Tumor Segmentation for MR-Guided Applications (HNTS-MRG) 2024 Challenge, a satellite event of the 27th International Conference on Medical Image Computing and Computer Assisted Intervention. This challenge addresses the scarcity of large, publicly available AI-ready adaptive RT datasets in HNC and explores the potential of incorporating multi-timepoint data to enhance RT auto-segmentation performance. Participants tackled two HNC segmentation tasks: automatic delineation of primary gross tumor volume (GTVp) and gross metastatic regional lymph nodes (GTVn) on pre-RT (Task 1) and mid-RT (Task 2) T2-weighted scans. The challenge provided 150 HNC cases for training and 50 for testing, hosted on Grand Challenge using a Docker submission framework. In total, 19 independent teams from across the world qualified by submitting both their algorithms and corresponding papers, resulting in 18 submissions for Task 1 and 15 submissions for Task 2. Evaluation using the mean aggregated Dice Similarity Coefficient showed top-performing AI methods achieved scores of 0.825 in Task 1 and 0.733 in Task 2. These results surpassed clinician interobserver variability benchmarks, marking significant strides in automated tumor segmentation for MR-guided RT applications in HNC., Comment: For HNTS-MRG 2024 volume of Lecture Notes in Computer Science

The Dice Similarity Coefficient (DSC) is the current de facto standard to determine agreement between a reference segmentation and one generated by manual / auto-contouring approaches. This metric is useful for non-spatially important images; however, radiation therapy requires consideration of nearby Organs-at-Risk (OARs) and their radiosensitivity which are currently unaccounted for with the traditional DSC. In this work, we introduce the OAR-DSC which accounts for nearby OARs and their radiosensitivity when computing the DSC. We illustrate the importance of this through cases where two proposed contours have similar DSC, but lower OAR-DSC when one contour expands closer to the surrounding OARs. This work is important because the OAR-DSC may be used by deep learning auto-contouring algorithms in a radiation therapy specific loss function, thereby progressing on the current disregard for the importance of these differences on the final radiation dose plan generation, delivery, and risks of patient toxicity., Comment: Proceedings of the XX-th international conference on the use of computers in radiation therapy (ICCR)

Deep learning has significantly advanced the potential for automated contouring in radiotherapy planning. In this manuscript, guided by contemporary literature, we underscore three key insights: (1) High-quality training data is essential for auto-contouring algorithms; (2) Auto-contouring models demonstrate commendable performance even with limited medical image data; (3) The quantitative performance of auto-contouring is reaching a plateau. Given these insights, we emphasize the need for the radiotherapy research community to embrace data-centric approaches to further foster clinical adoption of auto-contouring technologies., Comment: 13 pages, 4 figures

Purpose: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. Methods: A total of 245 VMAT HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included CT images, target prescriptions, and contours for targets and organs at risk (OARs). The model's performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared to manual flags by 3 HN radiation oncologists. Results: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D1%, D95%, and D99% across the targets were within -2.53%(SD=1.34%), -0.42%(SD=1.27%), and -0.12%(SD=1.97%), respectively, and the OAR mean and maximum doses were within -0.33Gy(SD=1.40Gy) and -0.96Gy(SD=2.08Gy). For the plan quality assessment study, radiation oncologists flagged 47 OARs for possible plan improvement. There was high interphysician variability; 83% of physician-flagged OARs were flagged by only one of 3 physicians. The comparative dose prediction model flagged 63 OARs, including 30 of 47 physician-flagged OARs. Conclusion: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality., Comment: updated to reflect the published peer-reviewed article

Chemotherapy is one of the primary modalities of cancer treatment. Chemotherapy drug administration is a complex problem that often requires expensive clinical trials to evaluate potential regimens. One way to alleviate this burden and better inform future trials is to build reliable models for drug administration. Previous chemotherapy optimization models have mainly relied on optimal control, which does not lend itself to capturing complex and vital operational constraints in chemotherapy planning involving discrete decisions, such as doses via pills and rest periods. In addition, most of the existing models for chemotherapy optimization lack an explicit toxicity measure and impose toxicity constraints primarily through (fixed) limits on drug concentration. The existing stochastic optimization models also focus on maximizing the probability of cure when tumor heterogeneity is uncertain. In this paper, we develop a mixed-integer program for combination chemotherapy (utilization of multiple drugs) optimization that incorporates various important operational constraints and, besides dose and concentration limits, controls treatment toxicity based on its effect on the count of white blood cells. To address the uncertainty of tumor heterogeneity, we propose chance constraints that guarantee reaching an operable tumor size with a high probability in a neoadjuvant setting. We present analytical results pertinent to the accuracy of the model in representing biological processes of chemotherapy and establish its merit for clinical applications through a numerical study of breast cancer.

MRI offers outstanding soft tissue contrast that may reduce uncertainties in target and organ-at-risk delineation and enable online adaptive image-guided treatment. Spatial distortions resulting from non-linearities in the gradient fields and non-uniformity in the main magnetic field must be accounted for across the imaging field-of-view to prevent systematic errors during treatment delivery. This work presents a modular phantom and software application to characterize geometric distortion (GD) within the large field-of-view MRI images required for radiation therapy simulation. The modular phantom is assembled from a series of rectangular foam blocks containing high-contrast fiducial markers in a known configuration. The modular phantom design facilitates transportation of the phantom between different MR scanners and MR-guided linear accelerators and allows the phantom to be adapted to fit different sized bores or coils. The phantom was evaluated using a 1.5T MR-guided linear accelerator (MR-Linac) and 1.5T and 3.0T diagnostic scanners. Performance was assessed by varying acquisition parameters to induce image distortions in a known manner. Imaging was performed using T1 and T2 weighted pulse sequences with 2D and 3D distortion correction algorithms and the receiver bandwidth (BW) varied as 250-815 Hz/pixel. Phantom set-up reproducibility was evaluated across independent set-ups. The software was validated by comparison with a non-modular phantom. Average geometric distortion was 0.94+/-0.58 mm for the MR-Linac, 0.90+/-0.53 mm for the 1.5 T scanner, and 1.15+/-0.62 mm for the 3.0T scanner, for a 400 mm diameter volume-of-interest. GD increased, as expected, with decreasing BW, and with the 2D versus 3D correction algorithm. Differences in GD attributed to phantom set-up were 0.13 mm or less. Differences in GD for the two software applications were less than 0.07 mm., Comment: 25 pages

In the context of a binary classification problem, the optimal linear combination of continuous predictors can be estimated by maximizing an empirical estimate of the area under the receiver operating characteristic (ROC) curve (AUC). For multi-category responses, the optimal predictor combination can similarly be obtained by maximization of the empirical hypervolume under the manifold (HUM). This problem is particularly relevant to medical research, where it may be of interest to diagnose a disease with various subtypes or predict a multi-category outcome. Since the empirical HUM is discontinuous, non-differentiable, and possibly multi-modal, solving this maximization problem requires a global optimization technique. Estimation of the optimal coefficient vector using existing global optimization techniques is computationally expensive, becoming prohibitive as the number of predictors and the number of outcome categories increases. We propose an efficient derivative-free black-box optimization technique based on pattern search to solve this problem. Through extensive simulation studies, we demonstrate that the proposed method achieves better performance compared to existing methods including the step-down algorithm. Finally, we illustrate the proposed method to predict swallowing difficulty after radiation therapy for oropharyngeal cancer based on radiation dose to various structures in the head and neck.