A deep learning-informed interpretation of why and when dose metrics outside the PTV can affect the risk of distant metastasis in SBRT NSCLC patients.

PURPOSE: Recent papers suggested a correlation between the risk of distant metastasis (DM) and dose outside the PTV, though conclusions in different publications conflicted. This study resolves these conflicts and provides a compelling explanation of prognostic factors. MATERIALS AND METHODS: A dataset of 478 NSCLC patients treated with SBRT (IMRT or VMAT) was analyzed. We developed a deep learning model for DM prediction and explainable AI was used to identify the most significant prognostic factors. Subsequently, the prognostic power of the extracted features and clinical details were analyzed using conventional statistical methods. RESULTS: Treatment technique, tumor features, and dosiomic features in a 3 cm wide ring around the PTV (PTV3cm) were identified as the strongest predictors of DM. The Hazard Ratio (HR) for Dmean,PTV3cm was significantly above 1 (p < 0.001). There was no significance of the PTV3cm dose after treatment technique stratification. However, the dose in PTV3cm was found to be a highly significant DM predictor (HR > 1, p = 0.004) when analyzing only VMAT patients with small and spherical tumors (i.e., sphericity > 0.5). CONCLUSIONS: The main reason for conflicting conclusions in previous papers was inconsistent datasets and insufficient consideration of confounding variables. No causal correlation between the risk of DM and dose outside the PTV was found. However, the mean dose to PTV3cm can be a significant predictor of DM in small spherical targets treated with VMAT, which might clinically imply considering larger PTV margins for smaller, more spherical tumors (e.g., if IGTV > 2 cm, then margin ≤ 7 mm, else margin > 7 mm).

Improved outcome models with denoising diffusion.

PURPOSE: Radiotherapy outcome modelling often suffers from class imbalance in the modelled endpoints. One of the main options to address this issue is by introducing new synthetically generated datapoints, using generative models, such as Denoising Diffusion Probabilistic Models (DDPM). In this study, we implemented DDPM to improve performance of a tumor local control model, trained on imbalanced dataset, and compare this approach with other common techniques. METHODS: A dataset of 535 NSCLC patients treated with SBRT (50 Gy/5 fractions) was used to train a deep learning outcome model for tumor local control prediction. The dataset included complete treatment planning data (planning CT images, 3D planning dose distribution and patient demographics) with sparsely distributed endpoints (6-7 % experiencing local failure). Consequently, we trained a novel conditional 3D DDPM model to generate synthetic treatment planning data. Synthetically generated treatment planning datapoints were used to supplement the real training dataset and the improvement in the model's performance was studied. Obtained results were also compared to other common techniques for class imbalanced training, such as Oversampling, Undersampling, Augmentation, Class Weights, SMOTE and ADASYN. RESULTS: Synthetic DDPM-generated data were visually trustworthy, with Fréchet inception distance (FID) below 50. Extending the training dataset with the synthetic data improved the model's performance by more than 10%, while other techniques exhibited only about 4% improvement. CONCLUSIONS: DDPM introduces a novel approach to class-imbalanced outcome modelling problems. The model generates realistic synthetic radiotherapy planning data, with a strong potential to increase performance and robustness of outcome models.

Biodistribution of 125I-MAb 425 in a human glioma xenograft model: effect of chloroquine.

Chloroquine has been shown to increase the cellular retention and nuclear incorporation of 125I-labeled monoclonal antibody (MAb) 425, a murine anti-epidermal growth factor receptor monoclonal antibody, in human high-grade glioma cells in vitro. The objective of this study was to examine the effect of chloroquine on the biodistribution of 125I-MAb 425 in an intracerebral xenogeneic transplant of glioma cells. Nude rats were stereotaxically implanted in the right hemisphere with A1207 human high-grade glioma cells. After 14 days, animals were injected i.v. with chloroquine (40 mg/kg) followed 2 h later by an 125I-MAb 425 (9 MBq) infusion. Tissue distributions were performed up to 168 h post 125I-MAb 425 injection. From 24 to 168 h, tumor-to-contralateral left brain ratios increased from 9 to 15 for 125I-MAb 425 alone, and 7 to 13 for the 125I-MAb 425/chloroquine combination, respectively. A single administration of chloroquine did not result in any significant difference in radiolabeled MAb accumulation in either the tumor site or other tissues. We conclude that chloroquine did not increase the amount of 125I-MAb 425 into the tumor; however, it is safe to administer i.v. at the 40 mg/kg dose. Under these experimental conditions, the increased radioactive accumulation observed for in vitro data did not translate into similar in vivo results.

Administration of a World Wide Web site during a period of rapid growth: the OncoLink experience.

OncoLink is a cancer information resource on the World Wide Web that provides a wide variety of information for both patients and health care providers. Introduced in March 1994, OncoLink has enjoyed a 50-fold increase in use since then, with more than 1.8 million accesses per month as of February 1997. New items are added daily, and the OncoLink Web site currently contains more than 10,000 files. During this period of rapid growth, the complexity of managing and maintaining OncoLink has increased as well. Consequently, we developed administrative procedures to handle our workload, which involves content editing, technical (or production) editing, and Web site maintenance. The new strategies have greatly reduced the need for face-to-face meetings of our editorial and production staffs. The rapid growth of OncoLink would not have been possible without these efficient new strategies for managing its daily operation.

Technical and editorial administration of a World-Wide-Web site during a period of rapid growth: the OncoLink experience.

OncoLink is a cancer information resource on the World-Wide-Web (WWW) that provides a wide variety of information for cancer patients and healthcare providers. Since its introduction in March, 1994 it has enjoyed success as demonstrated by an over 31-fold increase in usage as of February, 1996. Current utilization exceeds 1.1 million accesses per month. The content of OncoLink has also expanded greatly, with new items being added daily. In addition, OncoLink has been the recipient of numerous awards from a variety of agencies and organizations. During this period of rapid growth, the complexity of managing and maintaining OncoLink has likewise increased. This work may be divided into three categories: content editing, technical (or production) editing, and web site maintenance. Consequently, we have developed numerous administrative procedures to handle this workload. After implementing these new administrative strategies, we were able to greatly reduce the need for face-to-face meetings of our Editorial and Production Staffs. This paper describes our experience with developing efficient strategies for managing the daily operation of OncoLink during a period of rapid growth.