Definition of a framework for volumetric modulated arc therapy plan quality assessment with integration of dose-, complexity-, and robustness metrics.

Background And Purpose: Conventionally, the quality of radiotherapy treatment plans is assessed through visual inspection of dose distributions and dose-volume histograms. This study developed a framework to evaluate plan quality using dose, complexity, and robustness metrics. Additionally, a method for predicting plan robustness metrics using dose and complexity metrics was introduced for cases where plan robustness evaluation is unavailable or impractical.

Cardiac stereotactic body radiotherapy to treat malignant ventricular arrhythmias directly affects the cardiomyocyte electrophysiology.

Background: Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood.

Objective: We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression.

Feasibility of Optical Surface-Guidance for Position Verification and Monitoring of Stereotactic Body Radiotherapy in Deep-Inspiration Breath-Hold.

Background: Reductions in tumor movement allow for more precise and accurate radiotherapy with decreased dose delivery to adjacent normal tissue that is crucial in stereotactic body radiotherapy (SBRT). Deep inspiration breath-hold (DIBH) is an established approach to mitigate respiratory motion during radiotherapy. We assessed the feasibility of combining modern optical surface-guided radiotherapy (SGRT) and image-guided radiotherapy (IGRT) to ensure and monitor reproducibility of DIBH and to ensure accurate tumor localization for SBRT as an imaging-guided precision medicine.

Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

Background: [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs.

Patients And Methods: In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years.

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions.

Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout.

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice.

The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP).

Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases : Plan comparison and early clinical evaluation.

Background: Radiosurgical treatment of brain metastases is well established in daily clinical routine. Utilization of flattening-filter-free beams (FFF) may allow for more rapid delivery of treatment doses and improve clinical comfort. Hence, we compared plan quality and efficiency of radiosurgery in FFF mode to FF techniques.

Establishing stereotactic body radiotherapy with flattening filter free techniques in the treatment of pulmonary lesions - initial experiences from a single institution.

Background: Stereotactic body radiotherapy (SBRT) using flattening filter free (FFF)-techniques has been increasingly applied during the last years. However, clinical studies investigating this emerging technique are still rare. Hence, we analyzed toxicity and clinical outcome of pulmonary SBRT with FFF-techniques and performed dosimetric comparison to conventional techniques using flattening filters (FF).

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry.

Unlabelled: Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain.

Interferon-γ Inhibits Ebola Virus Infection.

Ebola virus outbreaks, such as the 2014 Makona epidemic in West Africa, are episodic and deadly. Filovirus antivirals are currently not clinically available. Our findings suggest interferon gamma, an FDA-approved drug, may serve as a novel and effective prophylactic or treatment option.

Ebola virus entry into host cells: identifying therapeutic strategies.

Filoviruses cause severe hemorrhagic fever in humans. The archetypal virus of this group, Ebola virus, is responsible for the current filovirus epidemic in West Africa. Filoviruses infect most mammalian cells, resulting in broad species tropism and likely contributing to rapid spread of virus throughout the body.

Comprehensive functional analysis of N-linked glycans on Ebola virus GP1.

Unlabelled: Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans.

Dosimetric integration of daily mega-voltage cone-beam CT for image-guided intensity-modulated radiotherapy.

Purpose: The goal of this work was to compare different methods of incorporating the additional dose of mega-voltage cone-beam CT (MV-CBCT) for image-guided intensity modulated radiotherapy (IMRT) of different tumor entities.

Material And Methods: The absolute dose delivered by the MV-CBCT was calculated and considered by creating a scaled IMRT plan (scIMRT) by renormalizing the clinically approved plan (orgIMRT) so that the sum with the MV-CBCT dose yields the same prescribed dose. In the other case, a newly optimized plan (optIMRT) was generated by including the dose distribution of the MV-CBCT as pre-irradiation.

Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide.

Recent reports postulate that the dual oxidase (DUOX) proteins function as part of a multicomponent oxidative pathway used by the respiratory mucosa to kill bacteria. The other components include epithelial ion transporters, which mediate the secretion of the oxidizable anion thiocyanate (SCN(-)) into airway surface liquid, and lactoperoxidase (LPO), which catalyzes the H(2)O(2)-dependent oxidation of the pseudohalide SCN(-) to yield the antimicrobial molecule hypothiocyanite (OSCN(-)). We hypothesized that this oxidative host defense system is also active against respiratory viruses.

New multileaf collimator with a leaf width of 5 mm improves plan quality compared to 10 mm in step-and-shoot IMRT of HNC using integrated boost procedure.

Purpose: To investigate whether a new multileaf collimator with a leaf width of 5 mm (MLC-5) over the entire field size of 40 x 40 cm(2) improves plan quality compared to a leaf width of 10 mm (MLC-10) in intensity-modulated radiotherapy (IMRT) with integrated boost for head and neck cancer.

Patients And Methods: A plan comparison was performed for ten patients with head and neck cancer. For each patient, seven plans were calculated: one plan with MLC-10 and nine beams, four plans with MLC-5 and nine beams (with different intensity levels and two-dimensional median filter sizes [2D-MFS]), and one seven-beam plan with MLC-5 and MLC-10, respectively.

4D-CT-based target volume definition in stereotactic radiotherapy of lung tumours: comparison with a conventional technique using individual margins.

Purpose: To investigate the dosimetric benefit of integration of 4D-CT in the planning target volume (PTV) definition process compared to conventional PTV definition using individual margins in stereotactic body radiotherapy (SBRT) of lung tumours.

Material And Methods: Two different PTVs were defined: PTV(conv) consisting of the helical-CT-based clinical target volume (CTV) enlarged isotropically for each spatial direction by the individually measured amount of motion in the 4D-CT, and PTV(4D) encompassing the CTVs defined in the 4D-CT phases displaying the extremes of the tumour position. Tumour motion as well as volumetric and dosimetric differences and relations of both PTVs were evaluated.

The design, physical properties and clinical utility of an iris collimator for robotic radiosurgery.

Robotic radiosurgery using more than one circular collimator can improve treatment plan quality and reduce total monitor units (MU). The rationale for an iris collimator that allows the field size to be varied during treatment delivery is to enable the benefits of multiple-field-size treatments to be realized with no increase in treatment time due to collimator exchange or multiple traversals of the robotic manipulator by allowing each beam to be delivered with any desired field size during a single traversal. This paper describes the Iris variable aperture collimator (Accuray Incorporated, Sunnyvale, CA, USA), which incorporates 12 tungsten-copper alloy segments in two banks of six.

Uncertainty estimation in intensity-modulated radiotherapy absolute dosimetry verification.

Purpose: Intensity-modulated radiotherapy (IMRT) represents an important method for improving RT. The IMRT relative dosimetry checks are well established; however, open questions remain in reference dosimetry with ionization chambers (ICs). The main problem is the departure of the measurement conditions from the reference ones; thus, additional uncertainty is introduced into the dose determination.

Correction of patient positioning errors based on in-line cone beam CTs: clinical implementation and first experiences.

Background: The purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy.

Patients And Methods: For evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT).

The influence of breathing motion on intensity modulated radiotherapy in the step-and-shoot technique: phantom measurements for irradiation of superficial target volumes.

For intensity modulated radiotherapy (IMRT) of deep-seated tumours, dosimetric variations of the original static dose profiles due to breathing motion can be primarily considered as blurring effects known from conventional radiotherapy. The purpose of this dosimetric study was to clarify whether these results are transferable to superficial targets and to quantify the additional effect of fractionation. A solid polystyrene phantom and an anthropomorphic phantom were used for film and ion chamber dose measurements.

Measurements of characteristics of time pattern in dose delivery in step-and-shoot IMRT.

Background And Purpose: Although intensity-modulated radiotherapy (IMRT) has already shown its clinical benefit, there are some issues which are not yet fully understood. Among these is the question whether the protracted dose delivery due to the lowered dose rate has any radiobiological consequences. To investigate this question, an exact characterization of dose rate profiles in typical clinical plans is needed.

Radiobiological investigation of dose-rate effects in intensity-modulated radiation therapy.

Background And Purpose: Intensity-modulated radiation therapy (IMRT) has proven extraordinary capability in physical terms such as target conformity, dose escalation in the target volume, and sparing of neighboring organs at risk. The radiobiological consequences of the protracted dose delivery for cell survival and cell cycle progression are still unclear and shall be examined in this study.

Material And Methods: Human lymphoblasts (TK6) and human melanoma cells (MeWo) were irradiated with protocols of increasing dose protraction.

Concomitant radiochemotherapy or accelerated radiotherapy: analysis of two randomized trials of the French Head and Neck Cancer Group (GORTEC).

In the early 1990s, when conventional radiotherapy (RT) was the standard of care in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), two main options were being tested to improve the efficacy and the therapeutic ratio of RT. The first approach evaluated the effect of adding chemotherapy (CT) simultaneously to RT (RT-CT), while the second approach assessed the effect of modified fractionated RT. To answer these two questions, in 1994, the French Group for Head and Neck Oncology Radiotherapy (GORTEC) initiated two randomized trials.