Expanding the use of real-time electromagnetic tracking in radiation oncology.

In the past 10 years, techniques to improve radiotherapy delivery, such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT) for both inter- and intrafraction tumor localization, and hypofractionated delivery techniques such as stereotactic body radiation therapy (SBRT), have evolved tremendously. This review article focuses on only one part of that evolution, electromagnetic tracking in radiation therapy. Electromagnetic tracking is still a growing technology in radiation oncology and, as such, the clinical applications are limited, the expense is high, and the reimbursement is insufficient to cover these costs. At the same time, current experience with electromagnetic tracking applied to various clinical tumor sites indicates that the potential benefits of electromagnetic tracking could be significant for patients receiving radiation therapy. Daily use of these tracking systems is minimally invasive and delivers no additional ionizing radiation to the patient, and these systems can provide explicit tumor motion data. Although there are a number of technical and fiscal issues that need to be addressed, electromagnetic tracking systems are expected to play a continued role in improving the precision of radiation delivery

A margin-based analysis of the dosimetric impact of motion on step-and-shoot IMRT lung plans

PURPOSE: Intrafraction motion during step-and-shoot (SNS) IMRT is known to affect the target dosimetry by a combination of dose blurring and interplay effects. These effects are typically managed by adding a margin around the target. A quantitative analysis was performed, assessing the relationship between target motion, margin size, and target dosimetry with the goal of introducing new margin recipes. METHODS: A computational algorithm was used to calculate 1,174 motion-encoded dose distributions and DVHs within the patient’s CT dataset. Sinusoidal motion tracks were used simulating intrafraction motion for nine lung tumor patients, each with multiple margin sizes. RESULTS: D(95%) decreased by less than 3% when the maximum target displacement beyond the margin experienced motion less than 5 mm in the superior-inferior direction and 15 mm in the anterior-posterior direction. For target displacements greater than this, D(95%) decreased rapidly. CONCLUSIONS: Targets moving in excess of 5 mm outside the margin can cause significant changes to the target. D(95%) decreased by up to 20% with target motion 10 mm outside the margin, with underdosing primarily limited to the target periphery. Multi-fractionated treatments were found to exacerbate target under-coverage. Margins several millimeters smaller than the maximum target displacement provided acceptable motion protection, while also allowing for reduced normal tissue morbidity

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

Real-Time Simulation Of 4D Lung Tumor Radiotherapy Using A Breathing Model

In this paper, we present a real-time simulation and visualization framework that models a deformable surface lung model with tumor, simulates the tumor motion and predicts the amount of radiation doses that would be deposited in the moving lung tumor during the actual delivery of radiation. The model takes as input a subject-specific 4D Computed Tomography (4D CT) of lungs and computes a deformable lung surface model by estimating the deformation properties of the surface model using an inverse dynamics approach. Once computed, the deformable model is used to simulate and visualize lung tumor motion that would occur during radiation therapy accounting for variations in the breathing pattern. A radiation treatment plan for the lung tumor is developed using one of the 4D CT phases. During the simulation of radiation delivery, the dose on the lung tumor is computed for each beam independently. © 2008 Springer Berlin Heidelberg

Expanding the use of real-time electromagnetic tracking in radiation oncology.

In the past 10 years, techniques to improve radiotherapy delivery, such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT) for both inter- and intrafraction tumor localization, and hypofractionated delivery techniques such as stereotactic body radiation therapy (SBRT), have evolved tremendously. This review article focuses on only one part of that evolution, electromagnetic tracking in radiation therapy. Electromagnetic tracking is still a growing technology in radiation oncology and, as such, the clinical applications are limited, the expense is high, and the reimbursement is insufficient to cover these costs. At the same time, current experience with electromagnetic tracking applied to various clinical tumor sites indicates that the potential benefits of electromagnetic tracking could be significant for patients receiving radiation therapy. Daily use of these tracking systems is minimally invasive and delivers no additional ionizing radiation to the patient, and these systems can provide explicit tumor motion data. Although there are a number of technical and fiscal issues that need to be addressed, electromagnetic tracking systems are expected to play a continued role in improving the precision of radiation delivery

A Display Framework For Visualizing Real-Time 3D Lung Tumor Radiotherapy

Medical display systems are valuable tools in enabling the clinicians in the field of radiation therapy to view a patient\u27s multi-modal information and treatment plan details. The effectiveness of display systems is further improved by including computer-based visualization systems that deliver the content comprehensively. In this paper, we present a medical display and visualization framework for radiation therapy that couples a computer-based simulation of real-time lung tumor motion and its dose accumulation during treatment with an Augmented Reality Center (ARC) based display system. The simulation framework provides insights on the variations in the effectiveness of the lung therapy for changes in the patient\u27s breathing conditions. The display system aims to enhance the clinician\u27s understanding by enhancing the 3D depth perception of the dose accumulation in lung tumors. Thus the framework acts as a tool for presenting both pre-operative studies and intra-operative treatment efficacy analysis when coupled with a real-time respiration monitor. A first evaluation of this framework was carried out using six clinical experts. Results show that, using the ARC compared to a 2D monitor, the experts were able to more efficiently perceive the radiation dose delivered to various aspects of the moving tumor and the surrounding normal tissues, as well as more quickly detecting radiation hot spots that are critical to minimizing damage to healthy tissue. © 2008 IEEE

Proposal and Evaluation of a Physician-Free, Real-Time On-Table Adaptive Radiotherapy (PF-ROAR) Workflow for the MRIdian MR-Guided LINAC

With the implementation of MR-LINACs, real-time adaptive radiotherapy has become a possibility within the clinic. However, the process of adapting a patient’s plan is time consuming and often requires input from the entire clinical team, which translates to decreased throughput and limited patient access. In this study, the authors propose and simulate a workflow to address these inefficiencies in staffing and patient throughput. Two physicians, three radiation therapists (RTT), and a research fellow each adapted bladder and bowel contours for 20 fractions from 10 representative patient plans. Contouring ability was compared via calculation of a Dice Similarity Index (DSI). The DSI for bladder and bowel based on each potential physician–therapist pair, as well as an inter-physician comparison, exhibited good overlap amongst all comparisons (p = 0.868). Plan quality was compared through calculation of the conformity index (CI), as well as an evaluation of the plan’s dose to a ‘gold standard’ set of structures. Overall, non-physician plans passed 91.2% of the time. Of the eight non-physician plans that failed their clinical evaluation, six also failed their evaluation against the ‘gold standard’. Another two plans that passed their clinical evaluation subsequently failed in their evaluation against the ‘gold standard’. Thus, the PF-ROAR process has a success rate of 97.5%, with 78/80 plans correctly adapted to the gold standard or halted at treatment. These findings suggest that a physician-free workflow can be well tolerated provided RTTs continue to develop knowledge of MR anatomy and careful attention is given to understanding the complexity of the plan prior to treatment

Enhanced oxidation of nanoparticles through strain-mediated ionic transport

Geometry and confinement effects at the nanoscale can result in substantial modifications to a material’s properties with significant consequences in terms of chemical reactivity, biocompatibility and toxicity. Although benefiting applications across a diverse array of environmental and technological settings, the long-term effects of these changes, for example in the reaction of metallic nanoparticles under atmospheric conditions, are not well understood. Here, we use the unprecedented resolution attainable with aberration-corrected scanning transmission electron microscopy3 to study the oxidation of cuboid Fe nanoparticles. Performing strain analysis at the atomic level, we reveal that strain gradients induced in the confined oxide shell by the nanoparticle geometry enhance the transport of diffusing species, ultimately driving oxide domain formation and the shape evolution of the particle. We conjecture that such a strain-gradient-enhanced mass transport mechanism may prove essential for understanding the reaction of nanoparticles with gases in general, and for providing deeper insight into ionic conductivity in strained nanostructures