Genomic evolution of human respiratory syncytial virus during a decade (2013-2023): bridging the path to monoclonal antibody surveillance.

OBJECTIVES: This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023. METHODS: Respiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October 2013 to May 2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes. RESULTS: Analyzing 139,625 samples, 5.3% were HRSV-positive (3008 HRSV-A, 3882 HRSV-B, 56 HRSV-A and -B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified. DISCUSSION: Particularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.

On dosimetric characteristics of detectors for relative dosimetry in small fields: a multicenter experimental study.

Objective. In this multicentric collaborative study, we aimed to verify whether the selected radiation detectors satisfy the requirements of TRS-483 Code of Practice for relative small field dosimetry in megavoltage photon beams used in radiotherapy, by investigating four dosimetric characteristics. Furthermore, we intended to analyze and complement the recommendations given in TRS-483.Approach. Short-term stability, dose linearity, dose-rate dependence, and leakage were determined for 17 models of detectors considered suitable for small field dosimetry. Altogether, 47 detectors were used in this study across ten institutions. Photon beams with 6 and 10 MV, with and without flattening filters, generated by Elekta Versa HDTMor Varian TrueBeamTMlinear accelerators, were used.Main results. The tolerance level of 0.1% for stability was fulfilled by 70% of the data points. For the determination of dose linearity, two methods were considered. Results from the use of a stricter method show that the guideline of 0.1% for dose linearity is not attainable for most of the detectors used in the study. Following the second approach (squared Pearson's correlation coefficientr2), it was found that 100% of the data fulfill the criteriar2> 0.999 (0.1% guideline for tolerance). Less than 50% of all data points satisfied the published tolerance of 0.1% for dose-rate dependence. Almost all data points (98.2%) satisfied the 0.1% criterion for leakage.Significance. For short-term stability (repeatability), it was found that the 0.1% guideline could not be met. Therefore, a less rigorous criterion of 0.25% is proposed. For dose linearity, our recommendation is to adopt a simple and clear methodology and to define an achievable tolerance based on the experimental data. For dose-rate dependence, a realistic criterion of 1% is proposed instead of the present 0.1%. Agreement was found with published guidelines for background signal (leakage).

A protocol for accurate radiochromic film dosimetry using Radiochromic.com.

BACKGROUND: Radiochromic films have many applications in radiology and radiation therapy. Generally, the dosimetry system for radiochromic film dosimetry is composed of radiochromic films, flatbed scanner, and film analysis software. The purpose of this work is to present the effectiveness of a protocol for accurate radiochromic film dosimetry using Radiochromic.com as software for film analysis. MATERIALS AND METHODS: Procedures for image acquisition, lot calibration, and dose calculation are explained and analyzed. Radiochromic.com enables state-of-the-art models and corrections for radiochromic film dosimetry, such as the Multigaussian model for multichannel film dosimetry, and lateral, inter-scan, and re-calibration corrections of the response. RESULTS: The protocol presented here provides accurate dose results by mitigating the sources of uncertainty that affect radiochromic film dosimetry. CONCLUSIONS: Appropriate procedures for film and scanner handling in combination with Radiochromic.com as software for film analysis make easy and accurate radiochromic film dosimetry feasible.

Experimental validation of Monte Carlo based treatment planning system in bone density equivalent media.

Introduction Advanced, Monte Carlo (MC) based dose calculation algorithms, determine absorbed dose as dose to medium-in-medium (Dm,m) or dose to water-in-medium (Dw,m). Some earlier studies identified the differences in the absorbed doses related to the calculation mode, especially in the bone density equivalent (BDE) media. Since the calculation algorithms built in the treatment planning systems (TPS) should be dosimetrically verified before their use, we analyzed dose differences between two calculation modes for the Elekta Monaco TPS. We compared them with experimentally determined values, aiming to define a supplement to the existing TPS verification methodology. Materials and methods In our study, we used a 6 MV photon beam from a linear accelerator. To evaluate the accuracy of the TPS calculation approaches, measurements with a Farmer type chamber in a semi-anthropomorphic phantom were compared to those obtained by two calculation options. The comparison was made for three parts of the phantom having different densities, with a focus on the BDE part. Results Measured and calculated doses were in agreement for water and lung equivalent density materials, regardless of the calculation mode. However, in the BDE part of the phantom, mean dose differences between the calculation options ranged from 5.7 to 8.3%, depending on the method used. In the BDE part of the phantom, neither of the two calculation options were consistent with experimentally determined absorbed doses. Conclusions Based on our findings, we proposed a supplement to the current methodology for the verification of commercial MC based TPS by performing additional measurements in BDE material.

Output correction factors for small static fields in megavoltage photon beams for seven ionization chambers in two orientations - perpendicular and parallel.

PURPOSE: The goal of the present work was to provide a large set of detector-specific output correction factors for seven small volume ionization chambers on two linear accelerators in four megavoltage photon beams utilizing perpendicular and parallel orientation of ionization chambers in the beam for nominal field sizes ranging from 0.5 cm2  × 0.5 cm2 to 10 cm2  × 10 cm2 . The present study is the second part of an extensive research conducted by our group. METHODS: Output correction factors k Q clin , Q ref f clin , f ref were experimentally determined on two linacs, Elekta Versa HD and Varian TrueBeam for 6 and 10 MV beams with and without flattening filter for nine square fields ranging from 0.5 cm2  × 0.5 cm2 to 10 cm2  × 10 cm2 , for seven mini and micro ionization chambers, IBA CC04, IBA Razor, PTW 31016 3D PinPoint, PTW 31021 3D Semiflex, PTW 31022 3D PinPoint, PTW 31023 PinPoint, and SI Exradin A16. An Exradin W1 plastic scintillator and EBT3 radiochromic films were used as the reference detectors. RESULTS: For all ionization chambers, values of output correction factors k Q clin , Q ref f clin , f ref were lower for parallel orientation compared to those obtained in the perpendicular orientation. Five ionization chambers from our study set, IBA Razor, PTW 31016 3D PinPoint, PTW 31022 3D PinPoint, PTW 31023 PinPoint, and SI Exradin A16, fulfill the requirement recommended in the TRS-483 Code of Practice, that is, 0.95 < k Q clin , Q ref f clin , f ref < 1.05 , down to the field size 0.8 cm2  × 0.8 cm2 , when they are positioned in parallel orientation; two of the ionization chambers, IBA Razor and PTW 31023 PinPoint, satisfy this condition down to the field size of 0.5 cm2  × 0.5 cm2 . CONCLUSIONS: The present paper provides experimental results of detector-specific output correction factors for seven small volume ionization chambers. Output correction factors were determined in 6 and 10 MV photon beams with and without flattening filter down to the square field size of 0.5 cm2  × 0.5 cm2 for two orientations of ionization chambers - perpendicular and parallel. Our main finding is that output correction factors are smaller if they are determined in a parallel orientation compared to those obtained in a perpendicular orientation for all ionization chambers regardless of the photon beam energy, filtration, or linear accelerator being used. Based on our findings, we recommend using ionization chambers in parallel orientation, to minimize corrections in the experimental determination of field output factors. Latter holds even for field sizes below 1.0 cm2  × 1.0 cm2 , whenever necessary corrections remain within 5%, which was the case for several ionization chambers from our set. TRS-483 recommended perpendicular orientation of ionization chambers for the determination of field output factors. The present study presents results for both perpendicular and parallel orientation of ionization chambers. When validated by other researchers, the present results for parallel orientation can be considered as a complementary dataset to those given in TRS-483.

A novel method for the determination of field output factors and output correction factors for small static fields for six diodes and a microdiamond detector in megavoltage photon beams.

PURPOSE: The goal of this work is to provide a large and consistent set of data for detector-specific output correction factors, k Q clin , Q ref f clin , f ref , for small static fields for seven solid-state detectors and to determine field output factors, Ω Q clin , Q ref f clin , f ref , using EBT3 radiochromic films and W1 plastic scintillator as reference detectors on two different linear accelerators and four megavoltage photon beams. Consistent measurement conditions and recommendations given in the International Code of Practice TRS-483 for small-field dosimetry were followed throughout the study. METHODS: Ω Q clin , Q ref f clin , f ref were determined on two linacs, Elekta Versa HD and Varian TrueBeam, for 6 and 10 MV beams with and without flattening filter and for nine fields ranging from 0.5 × 0.5 cm2 to 10 × 10 cm2 . Signal readings obtained with EBT3 radiochromic films and W1 plastic scintillator were fitted by an analytical function. Volume averaging correction factors, determined from two-dimensional (2D) dose matrices obtained with EBT3 films and fitted to bivariate Gaussian function, were used to correct measured signals. k Q clin , Q ref f clin , f ref were determined empirically for six diodes, IBA SFD, IBA Razor, PTW 60008 P, PTW 60012 E, PTW 60018 SRS, and SN EDGE, and a PTW 60019 microDiamond detector. RESULTS: Field output factors and detector-specific k Q clin , Q ref f clin , f ref are presented in the form of analytical functions as well as in the form of discrete values. It is found that in general, for a given linac, small-field output factors need to be determined for every combination of beam energy and filtration (WFF or FFF) and field size as the differences between them can be statistically significant (P < 0.05). For different beam energies, the present data for k Q clin , Q ref f clin , f ref are found to differ significantly (P < 0.05) from the corresponding data published in TRS-483 mostly for the smallest fields (<1.5 cm). For the PTW microDiamond detector, statistically significant differences (P < 0.05) between k Q clin , Q ref f clin , f ref values were found for all investigated beams on an Elekta Versa HD linac for field sizes 0.5 × 0.5 cm2 and 0.8 × 0.8 cm2 . Significant differences in k Q clin , Q ref f clin , f ref between beams of a given energy but with and without flattening filters are found for measurements made in small fields (<1.5 cm) at a given linac. Differences in k Q clin , Q ref f clin , f ref are also found when measurements are made at different linacs using the same beam energy filtration combination; for the PTW microDiamond detector, these differences were found to be around 6% and were considered as significant. CONCLUSIONS: Selection of two reference detectors, EBT3 films and W1 plastic scintillator, and use of an analytical function, is a novel approach for the determination of Ω Q clin , Q ref f clin , f ref for small static fields in megavoltage photon beams. Large set of k Q clin , Q ref f clin , f ref data for seven solid-state detectors and four beam energies determined on two linacs by a single group of researchers can be considered a valuable supplement to the literature and the TRS-483 dataset.

Treating lung cancer with dynamic conformal arc therapy: a dosimetric study.

BACKGROUND: Lung cancer patients are often in poor physical condition, and a shorter treatment time would reduce their discomfort. Dynamic conformal arc therapy (DCAT) offers a shorter treatment time than conventional 3D conformal radiotherapy (3D CRT) and is usually available even in departments without inverse planning possibilities. We examined its suitability as a treatment modality for lung cancer patients. METHODS: On a cohort of 35 lung cancer patients, relevant dosimetric parameters were compared in respective DCAT and 3D CRT treatment plans. Radiochromic film dosimetry in an anthropomorphic phantom was used to compare both DCAT and 3D CRT dose distributions against their planned counterparts. RESULTS: In comparison with their 3D CRT counterparts, DCAT plans equal or exceed the agreement between the calculated dose and the dose measured using film dosimetry. In dosimetric comparison, DCAT performed significantly better than 3D CRT in dose conformity to PTV and the number of monitor units used per plan, and significantly worse in dose homogeneity, mean lung dose and lung volume exposed to 5 Gy or more (V5Gy). No significant difference was found in the V20Gy value to lung, dose to 1 cm3 of spinal cord, and the mean dose to oesophagus. Improvements in V20Gy and V5Gy were found to be negatively correlated. DCAT plans differ from 3D CRT by exhibiting a moderate negative correlation between target volume sphericity and dose homogeneity. CONCLUSIONS: With respect to the agreement between the planned and the irradiated dose distribution, DCAT appears at least as reliable as 3D CRT. In specific conditions concerning the patient anatomy and treatment prescription, DCAT may yield more favourable dosimetric parameters. On average, however, conventional 3D CRT usually obtains better dosimetric parameters. We can thus only recommend DCAT as a complementary technique to the conventional 3D CRT.

Influence of the Integral Quality Monitor transmission detector on high energy photon beams: A multi-centre study.

PURPOSE: The influence of the Integral Quality Monitor (IQM) transmission detector on photon beam properties was evaluated in a preclinical phase, using data from nine participating centres: (i) the change of beam quality (beam hardening), (ii) the influence on surface dose, and (iii) the attenuation of the IQM detector. METHODS: For 6 different nominal photon energies (4 standard, 2 FFF) and square field sizes from 1×1cm2 to 20×20cm2, the effect of IQM on beam quality was assessed from the PDD20,10 values obtained from the percentage dose depth (PDD) curves, measured with and without IQM in the beam path. The change in surface dose with/without IQM was assessed for all available energies and field sizes from 4×4cm2 to 20×20cm2. The transmission factor was calculated by means of measured absorbed dose at 10cm depth for all available energies and field sizes. RESULTS: (i) A small (0.11-0.53%) yet statistically significant beam hardening effect was observed, depending on photon beam energy. (ii) The increase in surface dose correlated with field size (p<0.01) for all photon energies except for 18MV. The change in surface dose was smaller than 3.3% in all cases except for the 20×20cm2 field and 10MV FFF beam, where it reached 8.1%. (iii) For standard beams, transmission of the IQM showed a weak dependence on the field size, and a pronounced dependence on the beam energy (0.9412 for 6MV to 0.9578 for 18MV and 0.9440 for 6MV FFF; 0.9533 for 10MV FFF). CONCLUSIONS: The effects of the IQM detector on photon beam properties were found to be small yet statistically significant. The magnitudes of changes which were found justify treating IQM either as tray factors within the treatment planning system (TPS) for a particular energy or alternatively as modified outputs for specific beam energy of linear accelerators, which eases the introduction of the IQM into clinical practice.

Reducing the dosimetric impact of positional errors in field junctions for craniospinal irradiation using VMAT.

AIM: To improve treatment plan robustness with respect to small shifts in patient position during the VMAT treatment by ensuring a linear ramp-like dose profile in treatment field overlap regions. BACKGROUND: Craniospinal irradiation (CSI) is considered technically challenging because the target size exceeds the maximal field size, which necessitates using abutted or overlapping treatment fields. Volumetric modulated arc therapy (VMAT) is increasingly being examined for CSI, as it offers both better dose homogeneity and better dose conformance while also offering a possibility to create field junctions which are more robust towards small shifts in patient position during the treatment. MATERIALS AND METHODS: A VMAT treatment plan with three isocenters was made for a test case patient. Three groups of overlapping arc field pairs were used; one for the cranial and two for the spinal part. In order to assure a ramp-like dose profile in the field overlap region, the upper spinal part was optimised first, with dose prescription explicitly enforcing a ramp-like dose profile. The cranial and lower spinal part were done afterwards, taking into account the dose contribution of the upper spinal fields. RESULTS: Using simple geometrical reasoning, we demonstrated that hot- and cold spots which arise from small displacement of one treatment field relative to the other treatment field can be reduced by taking two precautions: (a) widening the field overlap region, and (b) reducing the field gradient across the overlap region. The function with the smallest maximal gradient is a linear ramp. We present a treatment planning technique which yields the desired dose profile of the two contributing fields, and minimises dosimetric dependence on minor positional errors in patient set-up.