Robustness evaluation of pencil beam scanning proton therapy treatment planning: A systematic review.

Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, at the cost of greater sensitivity to physical, anatomical, and positioning uncertainties. Robust planning, both in terms of plan optimization and evaluation, has gained high visibility in publications on the subject and is part of clinical practice in many centers. However, there is currently no consensus on the methods and parameters to be used for robust optimization or robustness evaluation. We propose to overcome this deficiency by following the modified Delphi consensus method. This method first requires a systematic review of the literature. We performed this review using the PubMed and Web Of Science databases, via two different experts. Potential conflicts were resolved by a third expert. We then explored the different methods before focusing on clinical studies that evaluate robustness on a significant number of patients. Many robustness assessment methods are proposed in the literature. Some are more successful than others and their implementation varies between centers. Moreover, they are not all statistically or mathematically equivalent. The most sophisticated and rigorous methods have seen more limited application due to the difficulty of their implementation and their lack of widespread availability.

Psychometric data of a questionnaire to measure cyberbullying bystander behavior and its behavioral determinants among adolescents.

.This paper describes the items, scale validity and scale reliability of a self-report questionnaire that measures bystander behavior in cyberbullying incidents among adolescents, and its behavioral determinants. Determinants included behavioral intention, behavioral attitudes, moral disengagement attitudes, outcome expectations, self-efficacy, subjective norm and social skills. Questions also assessed (cyber-)bullying involvement. Validity and reliability information is based on a sample of 238 adolescents (M age=13.52 years, SD=0.57). Construct validity was assessed using Confirmatory Factor Analysis (CFA) or Exploratory Factor Analysis (EFA) in Mplus7 software. Reliability (Cronbach Alpha, α) was assessed in SPSS, version 22. Data and questionnaire are included in this article. Further information can be found in DeSmet et al. (2018) [1].

Real time tracking in liver SBRT: comparison of CyberKnife and Vero by planning structure-based γ-evaluation and dose-area-histograms.

The purpose of this study was to evaluate and compare two clinical tracking systems for radiosurgery with regard to their dosimetric and geometrical accuracy in liver SBRT: the robot-based CyberKnife and the gimbal-based Vero. Both systems perform real-time tumour tracking by correlating internal tumour and external surrogate motion. CyberKnife treatment plans were delivered to a high resolution 2D detector array mounted on a 4D motion platform, with the platform simulating (a) tumour motion trajectories extracted from the corresponding CyberKnife predictor log files and (b) the tumour motion trajectories with superimposed baseline-drift. Static reference and tracked dose measurements were compared and dosimetric as well as geometrical uncertainties analyzed by a planning structure-based evaluation. For (a), γ-passing rates inside the CTV (γ-criteria of 1% / 1 mm) ranged from 95% to 100% (CyberKnife) and 98% to 100% (Vero). However, dosimetric accuracy decreases in the presence of the baseline-drift. γ-passing rates for (b) ranged from 26% to 92% and 94% to 99%, respectively; i.e. the effect was more pronounced for CyberKnife. In contrast, the Vero system led to maximum dose deviations in the OAR between +1.5 Gy to +6.0 Gy (CyberKnife: +0.5 Gy to +3.5 Gy). Potential dose shifts were interpreted as motion-induced geometrical tracking errors. Maximum observed shift ranges were -1.0 mm to +0.7 mm (lateral) /-0.6 mm to +0.1 mm (superior-inferior) for CyberKnife and -0.8 mm to +0.2 mm /-0.8 mm to +0.4 mm for Vero. These values illustrate that CyberKnife and Vero provide high precision tracking of regular breathing patterns. Even for the modified motion trajectory, the obtained dose distributions appear to be clinical acceptable with regard to literature QA γ-criteria of 3% / 3 mm.

SU-E-J-140: Initial Clinical Assessment of a Gimbaled Linac Tumor Tracking System in a Patient Simulation Study.

PURPOSE: A simulation study was conducted on patients to evaluate the workflow and quantify the performance of the BrainLab/MHI Vero dynamic tumor tracking system in clinical circumstances. METHODS: The gimbals hold the linac-MLC assembly which enables tracking of moving tumors. Two kV imaging systems are attached at ±45° from the 6MV beam allowing simultaneous X-rays. A simulation study was conducted on 5 lung-liver patients. The procedure involved quantification of tumor motion based on localization of Visicoil gold markers implanted in the tumor. Except for switching on the treatment beam, the entire tumor tracking workflow was executed involving patient positioning, synchronized acquisition of skin marker motion and X-ray images, fiducial marker detection, external-internal correlation model calculation, skin marker surrogate guided tracking and monitoring imaging. Tracking error was calculated from gimbals log-files and the acquired monitoring X-rays. Imaging dose was measured with TLD on phantoms and on the patients. RESULTS: Imaging for correlation model building resulted in 17.6mGy skin dose. Taking the treatment duration of a 3×20Gy lung SBRT treatment, depending on the treatment fields orientation an additional maximal exposure of 28.8mGy was estimated for acquiring 1Hz X-ray monitoring during tracking. A mean absolute tracking error of 1.1 mm was measured, with a 90% percentile of 2.1 mm. The average time to set up the patient entering the room to the first MV beam-on was 9min. From the acquisition of the modeling images sequence up to beam-on took 3min. CONCLUSIONS: A clinical version of the Vero tumor tracking system has been installed, including automatic detection of fiducial markers implanted in the tumor. An initial assessment has shown that the tracking system is functional and its performance adequate to move forward to final commissioning and initiation of patient treatments. This collaborative work was supported by the Flemish government through the Hercules foundation and the â€Å“Fonds voor Wetenschappelijk Onderzoek - Vlaanderen†grants G.0486.06 and G.0412.08, and corporate funding from BrainLab AG. There are no other conflicts of interest.

WE-G-213CD-03: A Dual Complementary Verification Method for Dynamic Tumor Tracking on Vero SBRT.

PURPOSE: to use complementary cine EPID and gimbals log file analysis for in-vivo tracking accuracy monitoring. METHODS: A clinical prototype of dynamic tracking (DT) was installed on the Vero SBRT system. This prototype version allowed tumor tracking by gimballed linac rotations using an internal-external correspondence model. The DT prototype software allowed the detailed logging of all applied gimbals rotations during tracking. The integration of an EPID on the vero system allowed the acquisition of cine EPID images during DT. We quantified the tracking error on cine EPID (E-EPID) by subtracting the target center (fiducial marker detection) and the field centroid. Dynamic gimbals log file information was combined with orthogonal x-ray verification images to calculate the in-vivo tracking error (E-kVLog). The correlation between E-kVLog and E-EPID was calculated for validation of the gimbals log file. Further, we investigated the sensitivity of the log file tracking error by introducing predefined systematic tracking errors. As an application we calculate gimbals log file tracking error for dynamic hidden target tests to investigate gravity effects and decoupled gimbals rotation from gantry rotation. Finally, calculating complementary cine EPID and log file tracking errors evaluated the clinical accuracy of dynamic tracking. RESULTS: A strong correlation was found between log file and cine EPID tracking error distribution during concurrent measurements (R=0.98). We found sensitivity in the gimbals log files to detect a systematic tracking error up to 0.5 mm. Dynamic hidden target tests showed no gravity influence on tracking performance and high degree of decoupled gimbals and gantry rotation during dynamic arc dynamic tracking. A submillimetric agreement between clinical complementary tracking error measurements was found. CONCLUSIONS: Redundancy of the internal gimbals log file with x-ray verification images with complementary independent cine EPID images was implemented to monitor the accuracy of gimballed tumor tracking on Vero SBRT. Research was financially supported by the Flemish government (FWO), Hercules Foundation and BrainLAB AG.

Selecting an appropriate biomonitoring strategy to evaluate dermal exposure to opioid narcotic analgesics in pharmaceutical production workers.

OBJECTIVES: In a follow-up study of previous research, in which exposure pathways for opioid narcotic analgesics were identified in pharmaceutical workers involved in drug synthesis, the current research focused on the selection of an appropriate biomonitoring strategy. METHODS: Six opioid narcotic production workers were intensively monitored during a (1 week) fentanyl production campaign. A systematic sampling scheme was followed that provided information about hand contamination and biomarker levels at multiple time points. RESULTS: Linear mixed-effects models, incorporating half-shift and end-of-shift hand contamination levels, showed a positive and significant correlation with fentanyl urinary excretion occurring at many of the 4 h time lags investigated (4-28 h). Optimum model characteristics, including both minimal between- and within-worker variability, were obtained at lag times of 24 h and 20 h, respectively, advocating a pre-shift urine sampling strategy on the following day. In addition, for these lag times the portion of the variability explained by the model was maximal. Furthermore, using a distributed lag model, it was demonstrated that urinary fentanyl levels were positively correlated with hand contamination levels measured at the preceding four 8 h time lags (8-32 h), although statistical significance was only shown for a lag time of 24 h. CONCLUSION: Fentanyl levels in pre-shift urine samples reflect dermal exposure to the compound during the previous day. Thus, in the specific working environment investigated, a biological monitoring protocol evaluating pre-shift urinary fentanyl levels could provide an adequate risk estimate in individual workers.

Identification of exposure pathways for opioid narcotic analgesics in pharmaceutical production workers.

The protection of workers from the potential harmful effects of active pharmaceutical ingredients (APIs) poses a significant challenge for the drug manufacturing industry. The actual pathways through which pharmaceutical production workers are exposed to potent drugs and the processes resulting in actual uptake are up till now virtually unknown. In this study, a detailed exposure assessment survey was conducted in a pharmaceutical 'primary manufacturing' production facility during which environmental and biological exposure monitoring for potent opioid narcotic drugs was performed. On the occasion of multiple consecutive production days, personal half-shift air samples were collected and hand wipes were taken at the end of each half-shift and analysed for fentanyl. All environmental samples showed detectable amounts of fentanyl (>0.1 ng per sample), indicating a potential for both inhalation and dermal exposure. Spatial distribution of fentanyl dermal contamination was further investigated by means of patch samplers placed on five anatomical regions of the body. Body locations showing the highest level of fentanyl contamination were identified as the hands, the neck and lower arms. The effective uptake of fentanyl was demonstrated by the detection of this opioid in urine samples of the workers involved. Individual and group-level analysis of combined external and internal fentanyl exposure measures revealed a positive and significant correlation between fentanyl hand exposure and urinary excretion, while it seemed that the effect of inhalation exposure was largely due to its correlation with dermal exposure. The results of the established individual linear and mixed effects models strongly suggest that in most workers the dermal pathway is actually the primary route of fentanyl exposure.

Microprobe speciation analysis of inorganic solids by fourier transform laser mass spectrometry.

Fourier transform (FT) laser microprobe mass spectrometry (LMMS) aims at the characterization of local constituents at the surface of solids. Signals from structural fragments specify the main building blocks of the analyte while adduct ions, consisting of one or two intact analyte molecules and a stable ion, allow specific identification of the molecule. A series of inorganic reference compounds including binary salts, oxides, and oxy salts was analyzed to assess the FT LMMS capabilities for the determination of the inorganic molecular composition. Compounds from different classes can be tentatively identified by deductive reasoning while those with the same elements in different stoichiometries require comparison with reference spectra.

Molecular identification of foreign inclusions in inflammatory tissue surrounding metal implants by Fourier transform laser microprobe mass spectrometry.

Fourier transform laser microprobe mass spectrometry (FT LMMS) is a novel technique for micro-analysis of solids with a lateral resolution in the 5 microns range. One of the major advantages of the technique is the capability to perform characterisation of the molecular composition of both organic and inorganic compounds. The information is directly deduced from the signals without the aid of reference spectra. FT LMMS was applied to the characterisation of black tissue fragments in a biopsy from a patient, in which a constrained condylar nodular knee system was implanted ten years ago. The tissue contained numerous foreign giant cells with a black non-birefringent pigment in their cytoplasm. FT LMMS analysis allowed us to detect directly by means of molecular signals, that the debris consisted primarily of titanium oxide and not metallic titanium, while the implant itself only contained titanium.

Laser microprobe mass spectrometry: principle and applications in biology and medicine.

Laser microprobe mass spectrometry (LMMS) is an interesting technique for micro- and surface analysis. It employs local ionization by a focused laser under high power density conditions and subsequent mass analysis of the generated ions. This paper surveys the main LMMS instruments and their operational principles. Sample preparation is discussed in the context of biological materials. The problem of quantification is addressed. Selected examples show the way that precise information on the molecular composition can be deduced from the detected signals. Both inorganic and organic substances can be identified, even without reference spectra, from in-situ analysis with a lateral resolution in the order of 1 to 5 micrograms.