Azcona-Armendariz, J.D. (Juan Diego)

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    Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution
    (Springer, 2023) Aguilar, B. (Borja); Suarez, V. (Victor); Cabello, P. (Pablo); Sancho, L. (Lidia); Pedrero, D. (Diego); Aristu-Mendioroz, J.J. (José Javier); Lassaletta, Á. (Álvaro); Fernández-de-Miguel, J.M. (José María); Álvarez-de-Sierra, B. (Beatriz); Panizo, E. (Elena); Alonso, A. (Alberto); Meiriño, R. (Rosa); Palma, J. (Jacobo); Gallardo-Madueño, G. (Guillermo); Calvo, F.A. (Felipe A.); Moran, V. (Verónica); Cambeiro, M. (Mauricio); Serrano-Andreu, J. (Javier); Azcona-Armendariz, J.D. (Juan Diego); Martin, S. (Santiago); Alcázar, A. (Andrés); Viñals, A. (Alberto); Delgado, J.M. (José Miguel); Gibert, C. (Carlota)
    Introduction A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efcient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. Methods A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities’ recommendations. The temporary trends of patients care and research projects proposals were registered. Results 3 out of 14 members of the professional staf involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientifc production was adapted to the pandemic evolution and its infuence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. Conclusions Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefts of online learning will shape the future of proton therapy education.
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    A novel concept to include uncertainties in the evaluation of stereotactic body radiation therapy after 4D dose accumulation using deformable image registration
    (Wiley, 2019) Aristu-Mendioroz, J.J. (José Javier); Barbes-Fernandez, B. (Benigno); Burguete, J. (Javier); Azcona-Armendariz, J.D. (Juan Diego); Moreno-Jimenez, M. (Marta); Huesa-Berral, C. (Carlos)
    Purpose: To use four-dimensional (4D) dose accumulation based on deformable image registration (DIR) to assess dosimetric uncertainty in lung stereotactic body radiation therapy (SBRT) treatment planning. A novel concept, the Evaluation Target Volume (ETV), was introduced to achieve this goal. Methods: The internal target volume (ITV) approach was used for treatment planning for 11 patients receiving lung SBRT. Retrospectively, 4D dose calculation was done in Pinnacle v9.10. Total dose was accumulated in the reference phase using DIR with MIM. DIR was validated using landmarks introduced by an expert radiation oncologist. The 4D and three-dimensional (3D) dose distributions were compared within the gross tumor volume (GTV) and the planning target volume (PTV) using the D95 and Dmin (calculated as Dmin,0.035cc ) metrics. For lung involvement, the mean dose and V20 , V10 , and V5 were used in the 3D to 4D dose comparison, and Dmax (D0.1cc ) was used for all other organs at risk (OAR). The new evaluation target volume (ETV) was calculated by expanding the GTV in the reference phase in order to include geometrical uncertainties of the DIR, interobserver variability in the definition of the tumor, and uncertainties of imaging and delivery systems. D95 and Dmin,0.035cc metrics were then calculated on the basis of the ETV for 4D accumulated dose distributions, and these metrics were compared with those calculated from the PTV for 3D planned dose distributions. Results: The target registration error (TRE) per spatial component was below 0.5 ± 2.1mm for all our patients. For five patients, dose degradation above 2% (>4% in 2 patients) was found in the PTV after 4D accumulation and attributed to anatomical variations due to breathing. Comparison of D95 and Dmin,0.035cc metrics showed that the ETV (4D accumulated dose) estimated substantially lower coverage than the PTV (3D planning dose): in six out of the 11 cases, and for at least for one of the two metrics, coverage estimated by ETV was at least 5% lower than that estimated by PTV. Furthermore, the ETV approach revealed hot and cold spots within its boundaries. Conclusions: A workflow for 4D dose accumulation based on DIR has been devised. Dose degradation was attributed to respiratory motion. To overcome limitations in the PTV for the purposes of evaluating DIR-based 4D accumulated dose distributions, a new concept, the ETV, was proposed. This concept appears to facilitate more reliable dose evaluation and a better understanding of dosimetric uncertainties due to motion and deformation.
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    Detailed dosimetric evaluation of inter-fraction and respiratory motion in lung stereotactic body radiation therapy based on daily 4D cone beam CT images
    (IOP Publishing, 2022) Rossi, M. (Maddalena); Belderbos, J. (José); Kranen, S. (Simon) van; Burguete, J. (Javier); Juan-Cruz, C. (Celia); Azcona-Armendariz, J.D. (Juan Diego); Sonke, J.J. (Jan-Jakob); Huesa-Berral, C. (Carlos)
    Objective. Periodic respiratory motion and inter-fraction variations are sources of geometric uncertainty in stereotactic body radiation therapy (SBRT) of pulmonary lesions. This study extensively evaluates and validates the separate and combined dosimetric effect of both factors using 4D-CT and daily 4D-cone beam CT (CBCT) dose accumulation scenarios.Approach. A first cohort of twenty early stage or metastatic disease lung cancer patients were retrospectively selected to evaluate each scenario. The planned-dose (3DRef) was optimized on a 3D mid-position CT. To estimate the dosimetric impact of respiratory motion (4DRef), inter-fractional variations (3DAcc) and the combined effect of both factors (4DAcc), three dose accumulation scenarios based on 4D-CT, daily mid-cone beam CT (CBCT) position and 4D-CBCT were implemented via CT-CT/CT-CBCT deformable image registration (DIR) techniques. Each scenario was compared to 3DRef.A separate cohort of ten lung SBRT patients was selected to validate DIR techniques. The distance discordance metric (DDM) was implemented per voxel and per patient for tumor and organs at risk (OARs), and the dosimetric impact for CT-CBCT DIR geometric errors was calculated.Main results.Median and interquartile range (IQR) of the dose difference per voxel were 0.05/2.69 Gy and -0.12/2.68 Gy for3DAcc-3DRefand4DAcc-3DRef.For4DRef-3DRefthe IQR was considerably smaller -0.15/0.78 Gy. These findings were confirmed by dose volume histogram parameters calculated in tumor and OARs. For CT-CT/CT-CBCT DIR validation, DDM (95th percentile) was highest for heart (6.26 mm)/spinal cord (8.00 mm), and below 3 mm for tumor and the rest of OARs. The dosimetric impact of CT-CBCT DIR errors was below 2 Gy for tumor and OARs.Significance. The dosimetric impact of inter-fraction variations were shown to dominate those of periodic respiration in SBRT for pulmonary lesions. Therefore, treatment evaluation and dose-effect studies would benefit more from dose accumulation focusing on day-to-day changes then those that focus on respiratory motion.
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    Quality assurance in IMRT: Importance of the transmission through the jaws for an accurate calculation of absolute doses and relative distributions
    (2002-02-08) Siochi, R.A. (R. Alfredo); Azinovic, I. (Ignacio); Azcona-Armendariz, J.D. (Juan Diego)
    The goal of IMRT is to achieve an isodose distribution conformed to the tumor while avoiding the organs at risk. For these tasks several gantry angles are selected, each one containing a series of different leaf configurations for the multileaf collimator ~MLC! ~segments!. Verifying the relative distributions as well as the absolute doses is an important step for quality assurance issues. We have observed that an accurate modeling of the transmission of the primary x-ray fluence through the jaws and MLC as well as the head scatter is crucial for a precise calculation of relative doses and monitor units. Also, an inaccurate calculation of the output factor for small size segments can lead to important differences in the absolute dose for points under these segments. Incorrect models could lead to systematic errors of around 5% to 10% in the calculated monitor units and a shift in the isodose curves. © 2002 American Association of Physicists in Medicine.
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    A novel concept to include uncertainties in the evaluation of stereotactic body radiation therapy after 4D dose accumulation using deformable image registration
    (Wiley, 2019) Burguete-Mas, F.J. (Francisco Javier); Aristu-Mendioroz, J.J. (José Javier); Barbes-Fernandez, B. (Benigno); Azcona-Armendariz, J.D. (Juan Diego); Moreno-Jimenez, M. (Marta); Huesa-Berral, C. (Carlos)
    Purpose: To use four-dimensional (4D) dose accumulation based on deformable image registration (DIR) to assess dosimetric uncertainty in lung stereotactic body radiation therapy (SBRT) treatment planning. A novel concept, the Evaluation Target Volume (ETV), was introduced to achieve this goal. Methods: The internal target volume (ITV) approach was used for treatment planning for 11 patients receiving lung SBRT. Retrospectively, 4D dose calculation was done in Pinnacle v9.10. Total dose was accumulated in the reference phase using DIR with MIM. DIR was validated using landmarks introduced by an expert radiation oncologist. The 4D and three-dimensional (3D) dose distributions were compared within the gross tumor volume (GTV) and the planning target volume (PTV) using the D95 and Dmin (calculated as Dmin,0.035cc ) metrics. For lung involvement, the mean dose and V20 , V10 , and V5 were used in the 3D to 4D dose comparison, and Dmax (D0.1cc ) was used for all other organs at risk (OAR). The new evaluation target volume (ETV) was calculated by expanding the GTV in the reference phase in order to include geometrical uncertainties of the DIR, interobserver variability in the definition of the tumor, and uncertainties of imaging and delivery systems. D95 and Dmin,0.035cc metrics were then calculated on the basis of the ETV for 4D accumulated dose distributions, and these metrics were compared with those calculated from the PTV for 3D planned dose distributions. Results: The target registration error (TRE) per spatial component was below 0.5 ± 2.1mm for all our patients. For five patients, dose degradation above 2% (>4% in 2 patients) was found in the PTV after 4D accumulation and attributed to anatomical variations due to breathing. Comparison of D95 and Dmin,0.035cc metrics showed that the ETV (4D accumulated dose) estimated substantially lower coverage than the PTV (3D planning dose): in six out of the 11 cases, and for at least for one of the two metrics, coverage estimated by ETV was at least 5% lower than that estimated by PTV. Furthermore, the ETV approach revealed hot and cold spots within its boundaries. Conclusions: A workflow for 4D dose accumulation based on DIR has been devised. Dose degradation was attributed to respiratory motion. To overcome limitations in the PTV for the purposes of evaluating DIR-based 4D accumulated dose distributions, a new concept, the ETV, was proposed. This concept appears to facilitate more reliable dose evaluation and a better understanding of dosimetric uncertainties due to motion and deformation.
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    Precise dosimetric comparison between GAMOS and the collapsed cone convolution algorithm of 4D DOSE accumulated in lung SBRT treatments
    (Elsevier, 2023) Arce, P. (Pedro); Burguete, J. (Javier); Azcona-Armendariz, J.D. (Juan Diego); Lagares, J.I. (Juan Ignacio); Huesa-Berral, C. (Carlos)
    Background: It is widely accepted that Monte Carlo dose calculations offers a higher precision that the commercially available dose calculation algorithms. This advantage may be especially relevant for lung Stereotactic Body Radiation Therapy (SBRT), as this is a precise technique applied to an area of big inhomogeneity. Purpose: We conducted a comparative study to reveal the differences between the doses calculated using the Collapsed Cone Convolution algorithm and the GAMOS/Geant4 Monte Carlo calculation for lung cancer patients treated with Stereotactic Body Radiation Therapy on an Elekta Versa HD linac. Methods: For this study a set of ten patient treatments carried out at the Clínica Universidad de Navarra was selected. Theanalysis is based on the comparison of several dosimetric quantities for the Gross Tumor Volume (GTV) and several OrgansAt Risk (OARs), and also a gamma index calculation with distance-to-agreement set to 2 mm and dose difference to 3%, as recommended by ICRU to assess clinical impact. In order to guarantee a small uncertainty in the Monte Carlo calculation of the dosimetric quantities, we studied in detail the validity of different methods that may be used to determine this uncertainty. To compensate for lung movements, a 4D-Cone-beam Computed Tomography (CBCT) was acquired before treatment, whichallowed us to identify eight respiratory phases using a temporal binning. Using commercial MIM software®, we performed a deformable image registration between the eight CT respiration phases to construct the 4D doses. The same procedure was applied for the Treatment Planning System (TPS) dose files and for the Monte Carlo dose files. Results: The differences between the two algorithms reveal the known weaknesses of the Collapsed Cone Convolution (CCC) algorithm for the calculation of lateral doses and in regions of large density change. The comparison between the two algorithms for individual phase doses shows differences up to 5% of the GTV D95 or 3–4 Gy in some OARs, which may have a clinical impact. Nevertheless these differences are reduced for the 4D dose in most quantities under study. Conclusions: Comparing the dose calculated with a Collapsed Cone Convolution algorithm with GAMOS/Geant4 for ten patients and eight respiratory phases, we found some differences that could have a clinical impact. When combining the eight temporal phases into a 4D dose using the MIM Deformable Image Registration software, the differences diminished substantially. Our statistical analysis concludes that dose uncertainty in the voxels with a maximum dose below a given percentage guarantees uncertainty in the dosimetric quantities below that figure.
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    A method using 4D dose accumulation to quantify the interplay effect in lung stereotactic body radiation therapy
    (IOP Publishing, 2021) Burguete, J. (Javier); Azcona-Armendariz, J.D. (Juan Diego); Moreno-Jimenez, M. (Marta); Huesa-Berral, C. (Carlos)
    The purpose of this study was to devise and evaluate a method to quantify the dosimetric uncertainty produced by the interplay between the movement of multileaf collimator and respiratory motion in lung stereotactic body radiation therapy. The method calculates the dose distribution for all control points from a dynamic treatment in all respiratory phases. The methodology includes some characteristics of a patient's irregular breathing patterns. It selects, for each control point, the phases with maximum and minimum mean dose over the tumor and their corresponding adjacent phases, whenever necessary. According to this selection, the dose matrices from each control point are summed up to obtain two dose distributions in each phase, which are accumulated in the reference phase subsequently by deformable image registration (DIR). D 95 and [Formula: see text] were calculated over those accumulated dose distributions for Gross Tumor Volume (GTV), Planning Target Volume-based on Internal Target Volume approach-and Evaluation Target Volume (ETV), a novel concept that applies to 4D dose accumulation. With the ETV, DIR and interplay uncertainties are separated. The methodology also evaluated how variations in the breathing rate and field size affects the mean dose received by the GTV. The method was applied retrospectively in five patients treated with intensity modulated radiotherapy-minimum area defined by the leaves configuration at any control point was at least 4 cm2. Uncertainties in tumor coverage were small (in most patients, changes on D 95 and [Formula: see text] were below 2% for GTV and ETV) but significant over- and under-dosages near ETV, which can be accentuated by highly irregular breathing. Uncertainties in mean dose for GTV tended to decrease exponentially with increasing field size and were reduced by an increase of breathing rate. The implementation of this method would be helpful to assess treatment quality in patients with irregular breathing. Furthermore, it could be used to study interplay uncertainties when small field sizes are used.
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    Accuracy of the recombination correction factor (ks) in FFF beams for three ion chamber types
    (Elsevier, 2018) Martin-Martin, G. (G.); Barbes-Fernandez, B. (Benigno); Aguilar, P.B. (P. B.); Azcona-Armendariz, J.D. (Juan Diego)
    Flattening filter free (FFF) beams pose particular considerations for absolute dosimetry. • These beams are capable to deliver high doses per pulse (DPP) which implies special consideration regarding recombination effects in ionization chambers. • We wanted to know which type of ionization chamber (Farmer, Semiflex or Pinpoint) would be more appropriate for commisioning our new FFF beam.
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    Commissioning of a synchrotron-based proton beam therapy system for use with a Monte Carlo treatment planning system
    (Elsevier, 2023) Burguete-Mas, F.J. (Francisco Javier); Aguilar, B. (Borja); Cabello, P. (Pablo); Pedrero, D. (Diego); Fayos-Solá, R. (Roser); Polo, R. (Ramón); Zucca, D. (Daniel); Bermúdez, R. (Rocío); Irazola, L. (Leticia); Azcona-Armendariz, J.D. (Juan Diego); Viñals, A. (Alberto); Delgado, J.M. (José Miguel); Huesa-Berral, C. (Carlos); Perales-Molina, A. (Álvaro)
    This work tackles the commissioning and validation of a novel combination of a synchrotron-based proton beam therapy system (Hitachi, Ltd.) for use with a Monte Carlo treatment planning system (TPS). Four crucial aspects in this configuration have been investigated: (1) Monte Carlo-based correction performed by the TPS to the measured integrated depth-dose curves (IDD), (2) circular spot modelling with a single Gaussian function to characterize the synchrotron physical spot, which is elliptical, (3) the modelling of the range shifter that enables using only one set of measurements in open beams, and (4) the Monte Carlo dose calculation model in small fields. Integrated depth-dose curves were measured with a PTW Bragg peak chamber and corrected, with a Monte Carlo model, to account for energy absorbed outside the detector. The elliptical spot was measured by IBA Lynx scintillator, EBT3 films and PTW microDiamond. The accuracy of the TPS (RayStation, RaySearch Laboratories) at spot modelling with a circular Gaussian function was assessed. The beam model was validated using spread-out Bragg peak (SOBP) fields. We took single-point doses at several depths through the central axis using a PTW Farmer chamber, for fields between 2 × 2cm and 30 × 30cm. We checked the range-shifter modelling from open-beam data. We tested clinical cases with film and an ioni- zation chamber array (IBA Matrix). Sigma differences for spots fitted using 2D images and 1D profiles to elliptical and circular Gaussian models were below 0.22 mm. Differences between SOBP measurements at single points and TPS calculations for all fields between 5 × 5 and 30 × 30cm were below 2.3%. Smaller fields had larger differences: up to 3.8% in the 2 × 2cm field. Mean differences at several depths along the central axis were generally below 1%. Differences in range- shifter doses were below 2.4%. Gamma test (3%, 3 mm) results for clinical cases were generally above 95% for Matrix and film. Approaches for modelling synchrotron proton beams have been validated. Dose values for open and range- shifter fields demonstrate accurate Monte Carlo correction for IDDs. Elliptical spots can be successfully modelled using a circular Gaussian, which is accurate for patient calculations and can be used for small fields. A double-Gaussian spot can improve small-field calculations. The range-shifter modelling approach, which reduces clinical commissioning time, is adequate
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    Intensity modulated dose calculation with an improved experimental pencil-beam kernel
    (2010-08-11) Azcona-Armendariz, J.D. (Juan Diego)
    This article presents an improved pencil-beam dose calculation formalism based on an experimental kernel obtained by deconvolution. The new algorithm makes it possible to calculate the absorbed dose for all field sizes. Methods: The authors have enhanced