Citations

Abstract Purpose Lattice radiation therapy (LRT) is a form of spatially fractionated radiation therapy that allows increased total dose delivery aiming for improved treatment response without an increase in toxicities, commonly utilized for palliation of bulky tumors. The LRT treatment planning process is complex, while eligible patients often have an urgent need for expedited treatment start. In this study, we aimed to develop a simulation‐free workflow for volumetric modulated arc therapy (VMAT)‐based LRT planning via deep learning‐predicted synthetic CT (sCT) to expedite treatment initiation. Methods Two deep learning models were initially trained using 3D U‐Net architecture to generate sCT from diagnostic CTs (dCT) of the thoracic and abdomen regions using a training dataset of 50 patients. The models were then tested on an independent dataset of 15 patients using image similarity analysis assessing mean absolute error (MAE) and structural similarity index measure (SSIM) as metrics. VMAT‐based LRT plans were generated based on sCT and recalculated on the planning CT (pCT) for dosimetric accuracy comparison. Differences in dose volume histogram (DVH) metrics between pCT and sCT plans were assessed using the Wilcoxon signed‐rank test. Results The final sCT prediction model demonstrated high image similarity to pCT, with a MAE and SSIM of 38.93 ± 14.79 Hounsfield Units (HU) and 0.92 ± 0.05 for the thoracic region, and 73.60 ± 22.90 HU and 0.90 ± 0.03 for the abdominal region, respectively. There were no statistically significant differences between sCT and pCT plans in terms of organ‐at‐risk and target volume DVH parameters, including maximum dose (Dmax), mean dose (Dmean), dose delivered to 90% (D90%) and 50% (D50%) of target volume, except for minimum dose (Dmin) and (D10%). Conclusion With demonstrated high image similarity and adequate dose agreement between sCT and pCT, our study is a proof‐of‐concept for using deep learning predicted sCT for a simulation‐free treatment planning workflow for VMAT‐based LRT.

Background/Objectives: The accurate delineation of primary tumors (GTVp) and metastatic lymph nodes (GTVn) in head and neck (HN) cancers is essential for effective radiation treatment planning, yet remains a challenging and laborious task. This study aims to develop a deep-learning-based auto-segmentation (DLAS) model trained on external datasets with false-positive elimination using clinical diagnosis reports. Methods: The DLAS model was trained on a multi-institutional public dataset with 882 cases. Forty-four institutional cases were randomly selected as the external testing dataset. DLAS-generated GTVp and GTVn were validated against clinical diagnosis reports to identify false-positive and false-negative segmentation errors using two large language models: ChatGPT-4 and Llama-3. False-positive ruling out was conducted by matching the centroids of AI-generated contours with the slice locations or anatomical regions described in the reports. Performance was evaluated using the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), and tumor detection precision. Results: ChatGPT-4 outperformed Llama-3 in accurately extracting tumor locations from the diagnostic reports. False-positive contours were identified in 15 out of 44 cases. The DSCmean of the DLAS contours for GTVp and GTVn increased from 0.68 to 0.75 and from 0.69 to 0.75, respectively, after the ruling-out process. Notably, the average HD95 value for GTVn decreased from 18.81 mm to 5.2 mm. Post ruling out, the model achieved 100% precision for GTVp and GTVn when compared with the results of physician-determined contours. Conclusions: The false-positive ruling-out approach based on diagnostic reports effectively enhances the precision of DLAS in the HN region. The model accurately identifies the tumor location and detects all false-negative errors.

Objectives: Identifying patients’ advantageous radiotherapy modalities prior to CT simulation is challenging. This study aimed to develop a workflow using deep learning (DL)-predicted synthetic CT (sCT) for treatment modality comparison based solely on a diagnostic CT (dCT). Methods: A DL network, U-Net, was trained utilizing 46 thoracic cases from a public database to generate sCT images predicting planning CT (pCT) scans based on the latest dCT, and tested on 15 institutional patients. The sCT accuracy was evaluated against the corresponding pCT and a commercial algorithm deformed CT (MdCT) based on Mean Absolute Error (MAE) and Universal Quality Index (UQI). To determine advantageous treatment modality, clinical dose-volume histogram (DVH) metrics and Normal Tissue Complication Probability (NTCP) differences between proton and photon treatment plans were analyzed on the sCTs via concordance correlation coefficient (CCC). Results: The AI-generated sCTs closely resembled those of the commercial deformation algorithm in the tested cases. The differences in MAE and UQI values between the sCT-vs-pCT and MdCT-vs-pCT were 19.38 HU and 0.06, respectively. The mean absolute NTCP deviation between sCT and pCT was 1.54%, 0.21%, and 2.36% for esophagus perforation, lung pneumonitis, and heart pericarditis, respectively. The CCC between sCT and pCT was 0.90 for DVH metrics and 0.97 for NTCP, indicating moderate agreement for DVH metrics and substantial agreement. Conclusions: Radiation oncologists can potentially utilize this personalized sCT based approach as a clinical support tool to rapidly compare the treatment modality benefit during patient consultation and facilitate in-depth discussion on potential toxicities at a patient-specific level.

Abstract Porous nanofibrous microspheres (PNMs) present a versatile and minimally invasive strategy for tissue regeneration, combining biomimetic morphology, tunable structure, and injectability. While self‐assembly and co‐axial electrospray are explored for PNM fabrication, these methods are limited in compositional versatility and production scalability. Here, a 3D‐printed microfluidic platform is presented that enables large‐scale fabrication of PNMs with precise control over size, pore architecture, and morphology. PNMs can be functionalized with bioactive molecules through UV crosslinking, enhancing their regenerative potential by promoting osteogenesis in human bone marrow stromal cells (hBMSCs), angiogenesis in human umbilical vein endothelial cells (HUVECs), and exerting anti‐inflammatory effects on macrophages. Subcutaneous implantation in rats demonstrates that PNMs support cell infiltration, minimize fibrosis, and facilitate tissue integration, achieving complete cell penetration and tissue incorporation within 14 days. These findings establish PNMs as versatile, scalable, and customizable platforms, ideal for applications as injectable drugs or cell carriers, as well as powders, offering promising solutions for wound healing and tissue regeneration.

BACKGROUND: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). METHODS: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. RESULTS: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β–mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. CONCLUSIONS: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.

AbstractBackgroundInaccurate manual organ delineation is one of the high‐risk failure modes in radiation treatment. Numerous automated contour quality assurance (QA) systems have been developed to assess contour acceptability; however, manual inspection of flagged cases is a time‐consuming and challenging process, and can lead to users overlooking the exact error location.PurposeOur aim is to develop and validate a contour QA system that can effectively detect and visualize subregional contour errors, both qualitatively and quantitatively.Methods/MaterialsA novel contour subregion error detection (CSED) system was developed using subregional surface distance discrepancies between manual and deep learning auto‐segmentation (DLAS) contours. A validation study was conducted using a head and neck public dataset containing 339 cases and evaluated according to knowledge‐based pass criteria derived from a clinical training dataset of 60 cases. A blind qualitative evaluation was conducted, comparing the results from the CSED system with manual labels. Subsequently, the CSED‐flagged cases were re‐examined by a radiation oncologist.ResultsThe CSED system could visualize the diverse types of subregional contour errors qualitatively and quantitatively. In the validation dataset, the CSED system resulted in true positive rates (TPR) of 0.814, 0.800, and 0.771; false positive rates (FPR) of 0.310, 0.267, and 0.298; and accuracies of 0.735, 0.759, and 0.730, for brainstem and left and right parotid contours, respectively. The CSED‐assisted manual review caught 13 brainstem, 19 left parotid, and 21 right parotid contour errors missed by conventional human review. The TPR/FPR/accuracy of the CSED‐assisted manual review improved to 0.836/0.253/0.784, 0.831/0.171/0.830, and 0.808/0.193/0.807 for each structure, respectively. Further, the time savings achieved through CSED‐assisted review improved by 75%, with the time for review taking 24.81 ± 12.84, 26.75 ± 10.41, and 28.71 ± 13.72 s for each structure, respectively.ConclusionsThe CSED system enables qualitative and quantitative detection, localization, and visualization of manual segmentation subregional errors utilizing DLAS contours as references. The use of this system has been shown to help reduce the risk of high‐risk failure modes resulting from inaccurate organ segmentation.

AbstractBackgroundDeep learning auto‐segmentation (DLAS) models have been adopted in the clinic; however, they suffer from performance deterioration owing to the clinical practice variability. Some commercial DLAS software provide an incremental retraining function that enables users to train a custom model using their institutional data to account for clinical practice variability.PurposeThis study was performed to evaluate and implement the commercial DLAS software with the incremental retraining function for definitive treatment of patients with prostate cancer in a multi‐user environment.MethodsCT‐based target organs and organs‐at‐risk (OAR) delineation of 215 prostate cancer patients were utilized. The performance of three commercial DLAS software built‐in models was validated with 20 patients. A retrained custom model was developed using 100 patients and evaluated on the remaining data (n = 115). Dice similarity coefficient (DSC), Hausdorff distance (HD), mean surface distance (MSD), and surface DSC (SDSC) were utilized for quantitative evaluation. A multi‐rater qualitative evaluation was blindly performed with a five‐level scale. Visual inspection was performed in consensus and non‐consensus unacceptable cases to identify the failure modes.ResultsThree commercial DLAS vendor built‐in models achieved sub‐optimal performance in 20 patients. The retrained custom model had a mean DSC of 0.82 for prostate, 0.48 for seminal vesicles (SV), and 0.92 for rectum, respectively. This represents a significant improvement over the built‐in model with DSC of 0.73, 0.37, and 0.81 for the corresponding structures. Compared to the acceptance rate of 96.5% and consensus unacceptable rate (i.e., both reviewers rated as unacceptable) of 3.5% achieved by manual contours, the custom model achieved a 91.3% acceptance rate and 8.7% consensus unacceptable rate. The failure modes of retrained custom model were attributed to the following: cystogram (n = 2), hip prosthesis (n = 2), low dose rate brachytherapy seeds (n = 2), air in endorectal balloon(n = 1), non‐iodinated spacer (n = 2), and giant bladder(n = 1).ConclusionThe commercial DLAS software with the incremental retraining function was validated and clinically adopted for prostate patients in a multi‐user environment. AI‐based auto‐delineation of the prostate and OARs is shown to achieve improved physician acceptance, overall clinical utility, and accuracy.

Purpose: Planning target volume (PTV) expansion for post-prostatectomy radiotherapy is typically ≥5 mm. Recent clinical trials have proved the feasibility of a reduced margin of 2–3 mm for treatments on MRI-linac. We aim to study the minimum PTV margin needed using iterative cone-beam CT (iCBCT) as image guidance on conventional linacs. Materials/Methods: Fourteen patients who received post-prostatectomy irradiation (8 with an endorectal balloon and 6 without a balloon) were included in this study. Treatment was delivered with volumetric modulated radiation therapy (VMAT). Fractional dose delivery was evaluated in 165 treatment fractions. The bladder, rectal wall, femoral heads, and prostate bed clinical tumor volume (CTV) were contoured and verified on daily iCBCT. PTV margins (0 mm, 2 mm, and 4 mm) were evaluated on daily iCBCT. CTV coverage and OAR dose parameters were assessed with each PTV margin. Results: CTV D100% was underdosed with a 0 mm margin in 32% of fractions in comparison with 2 mm (6%) and 4 mm (6%) PTV margin (p ≤ 0.001). CTV D95% > 95% was met in 93–94% fractions for all PTV expansions. CTV D95% > 95% was achieved in more patients with an endorectal balloon than those without: 0 mm—90/91 (99%) vs. 63/74 (85%); 2 mm—90/91 (99%) vs. 65/75 (87%); 4 mm—90/90 (100%) vs. 63/73 (86%). There was no difference in absolute median change in CTV D95% (0.32%) for 0-, 2-, and 4 mm margins. The maximum dose remained under 108% for 100% (0 mm), 97% (2 mm), and 98% (4 mm) of images. Rectal wall maximum dose remained under 108% for 100% (0 mm), 100% (2 mm), and 98% (4 mm) of images. Conclusions: With high-quality iCBCT image guidance, PTV margin accounting for inter-fractional uncertainties can be safely reduced for post-prostatectomy radiotherapy. For fractionated radiotherapy, an isotropic expansion of 2 mm and 4 mm may be considered for margin expansion with and without the endorectal balloon. Future application for margin reduction needs to be further evaluated and considered with the advent of shorter post-prostatectomy radiation courses.

In this study, we discovered 3-aminophthalic acid as a new ligand of cereblon (CRBN) E3 ubiquitin ligase and developed a phthalic acid-based O’PROTAC for ERG destruction, expanding the pool of ligands for development of PROTACs, especially O’PROTACs.