3D Dose-Driven, Automatic VMAT Machine Parameter Generation with Deep Learning

Purpose/Objective(s): Recent research efforts utilizing knowledge-based treatment planning for the prediction of 3D radiation dose distributions from planning structure sets have achieved positive results. Most ongoing efforts to generate deliverable plans from the predicted doses rely on full inverse optimizations using dose-volume histogram (DVH) objectives derived from these doses. In this study, we aim to leverage deep learning (DL) to rapidly generate machine delivery parameters for volumetric modulated arc therapy (VMAT) from predicted desired doses. Materials/Methods: Data of 50 previously treated patients at our institution with prostate adenocarcinoma who received definitive radiotherapy were retrospectively obtained. All plans were generated with a one-arc VMAT technique, with conventional fractionation (78 Gy in 39 fx or 79.2 Gy in 44 fx to the prostate gland +/- seminal vesicles). A multi-task U-Net was constructed: it takes the 2D projections of the 3D dose and planning structures as inputs, and it predicts the numerical multi-leaf collimator (MLC) sequence and weights for the 178 control points. Five cases were randomly selected for testing only, and the remaining 45 formed the training set. The algorithm was implemented in Python 3.8 with PyTorch 1.7 as the DL framework. Model training was performed on a GPU. The DL-predicted plans underwent further inverse optimization with the 3D-dose-derived DVH objectives, utilizing only the last step of the Photon Optimizer (PO) in a treatment planning system. The optimization time and plan quality were compared to plans generated with one full PO optimization with the same objectives and clinical plans (all normalized to D95%=100% Rx dose). Results: The DL model was trained for 200 epochs. On average, DL-predicted plans could be optimized in 22% (range, 18-26%) of the time required for full optimization plans. Dosimetric comparison (Table 1) demonstrated that the quality of the DL-predicted plans was comparable with clinical plans and full optimization plans, but the DL-predicted plans tended to have increased dose inhomogeneity within the PTVs. Conclusion: We demonstrated the feasibility of rapidly generating deliverable VMAT plans from desired 3D doses with deep learning. Further work is needed to improve PTV dose homogeneity and generalize the method to multi-arc VMAT delivery

Development and evaluation of a novel MR-compatible pelvic end-to-end phantom

MR-only treatment planning and MR-IGRT leverage MRI\u27s powerful soft tissue contrast for high-precision radiation therapy. However, anthropomorphic MR-compatible phantoms are currently limited. This work describes the development and evaluation of a custom-designed, modular, pelvic end-to-end (PETE) MR-compatible phantom to benchmark MR-only and MR-IGRT workflows. For construction considerations, subject data were assessed for phantom/skeletal geometry and internal organ kinematics to simulate average male pelvis anatomy. Various materials for the bone, bladder, and rectum were evaluated for utility within the phantom. Once constructed, PETE underwent CT-SIM, MR-Linac, and MR-SIM imaging to qualitatively assess organ visibility. Scans were acquired with various bladder and rectal volumes to assess component interactions, filling capabilities, and filling reproducibility via volume and centroid differences. PETE simulates average male pelvis anatomy and comprises an acrylic body oval (height/width = 23.0/38.1 cm) and a cast-mold urethane skeleton, with silicone balloons simulating bladder and rectum, a silicone sponge prostate, and hydrophilic poly(vinyl alcohol) foam to simulate fat/tissue separation between organs. Access ports enable retrofitting the phantom with other inserts including point/film-based dosimetry options. Acceptable contrast was achievable in CT-SIM and MR-Linac images. However, the bladder was challenging to distinguish from background in CT-SIM. The desired contrast for T1-weighted and T2-weighted MR-SIM (dark and bright bladders, respectively) was achieved. Rectum and bone exhibited no MR signal. Inputted volumes differed by(CT-SIM) and bladder (MR-SIM) volumes. Increasing bladder and rectal volumes induced organ displacements and shape variations. Reproduced volumes differed b

Dosimetric Evaluation of Fractionated Stereotactic Radiation Therapy for Skull Base Meningiomas Using HyperArc and Multicriteria Optimization

Purpose: Treatment planning of skull based meningiomas can be difficult due to the irregular shaped target volumes and proximity to critical optic structures. This study evaluated the use of HyperArc (HA) radiosurgery optimization and delivery in conjunction with multicriteria optimization (MCO) to create conformal and efficient treatment plans for conventionally fractionated radiation therapy to difficult base-of-skull (BOS) lesions. Methods and Materials: Twelve patients with BOS meningioma were retrospectively planned with HA-specific optimization algorithm, stereotactic normal tissue objective (SRS-NTO), and conventional automatic normal tissue objective to evaluate normal brain sparing (mean dose and V20 Gy). MCO was used on both SRS-NTO and automatic normal tissue objective plans to further decrease organ-at-risk doses and target dose maximum to within clinically acceptable constraints. Delivery efficiency was evaluated based on planned monitor units. Results: The SRS-NTO in HA can be used to improve the mid- and low-dose spread to normal brain tissue in the irradiation of BOS meningiomas. Improvement in normal brain sparing can be seen in larger, more irregular shaped lesions and less so in smaller spherical targets. MCO can be used in conjunction with the SRS-NTO to reduce target dose maximum and dose to organ at risk without sacrificing the gain in normal brain sparing. Conclusions: HA can be beneficial both in treatment planning by using the SRS-NTO and in delivery efficiency through the decrease in monitor units and automated delivery

Commissioning, clinical implementation, and initial experience with a new brain tumor treatment package on a low-field MR-linac

To evaluate the image quality, dosimetric properties, setup reproducibility, and planar cine motion detection of a high-resolution brain coil and integrated stereotactic brain immobilization system that constitute a new brain treatment package (BTP) on a low-field magnetic resonance imaging (MRI) linear accelerator (MR-linac). Image quality of the high-resolution brain coil was evaluated with the 17 cm diameter spherical phantom and the American College of Radiology (ACR) Large MRI Phantom. Patient imaging studies approved by the institutional review board (IRB) assisted in selecting image acquisition parameters. Radiographic and dosimetric evaluation of the high-resolution brain coil and the associated immobilization devices was performed using dose calculations and ion chamber measurements. End-to-end testing was performed simulating a cranial lesion in a phantom. Inter-fraction setup variability and motion detection tests were evaluated on four healthy volunteers. Inter-fraction variability was assessed based on three repeat setups for each volunteer. Motion detection was evaluated using three-plane (axial, coronal, and sagittal) MR-cine imaging sessions, where volunteers were asked to perform a set of specific motions. The images were post-processed and evaluated using an in-house program. Contrast resolution of the high-resolution brain coil is superior to the head/neck and torso coils. The BTP receiver coils have an average HU value of 525 HU. The most significant radiation attenuation (3.14%) of the BTP, occurs through the lateral portion of the overlay board where the high-precision lateral-profile mask clips attach to the overlay. The greatest inter-fraction setup variability occurred in the pitch (average 1.08 degree) and translationally in the superior/inferior direction (average 4.88 mm). Three plane cine imaging with the BTP was able to detect large and small motions. Small voluntary motions, sub-millimeter in magnitude (maximum 0.9 mm), from motion of external limbs were detected. Imaging tests, inter-fraction setup variability, attenuation, and end-to-end measurements were quantified and performed for the BTP. Results demonstrate better contrast resolution and low contrast detectability that allows for better visualization of soft tissue anatomical changes relative to head/neck and torso coil systems

Prediction of cis-regulatory elements controlling genes differentially expressed by retinal and choroidal vascular endothelial cells

Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two endothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., glucocorticoid receptor, high mobility group AT-hook 1, heat shock transcription factor 1, p53, vitamin D receptor) or choroidal (i.e., transcription factor E2F, Yin Yang 1, zinc finger 5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination