Víctor Hernández

Hospital Universitari Sant Joan de Reus

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Jordi Sáez

Hospital Clínic de Barcelona

Pietro Mancosu

IRCCS Humanitas Research Hospital

N. Jornet

Hospital de Sant Pau

Meritxell Arenas

Hospital Universitari Sant Joan de Reus

Stefano Tomatis

IRCCS Humanitas Research Hospital

Marta Scorsetti

IRCCS Humanitas Research Hospital

M. Esposito

Azienda Usl Toscana Centro

Catharine H. Clark

University College London

L. Vieillevigne

Institut Claudius Regaud

Daniele Loiacono

Politecnico di Milano

Cooperative Institutions

European Society for Therapeutic Radiology and Oncology

Universitat de Barcelona

Hospital Universitari Sant Joan de Reus

Istituti di Ricovero e Cura a Carattere Scientifico

Institut d'Investigació Sanitària Pere Virgili

Universidad Rovira i Virgili

Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Hospital Clínic de Barcelona

Lubbock Christian University

Center for Rheumatology

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Zenodo (CERN European Organization for Nuclear Research) (2023)

Nicola Lambri Damiano Dei Víctor Hernández Isabella Castiglioni Elena Clerici

This record contains raw data related to article "Evaluation of plan complexity and dosimetric plan quality of total marrow and lymphoid irradiation using volumetric modulated arc therapy" Abstract Purpose: To assess the impact of the planner's experience and optimization algorithm on the plan quality and complexity of total marrow and lymphoid irradiation (TMLI) delivered by means of volumetric modulated arc therapy (VMAT) over 2010-2022 at our institute. Methods: Eighty-two consecutive TMLI plans were considered. Three complexity indices were computed to characterize the plans in terms of leaf gap size, irregularity of beam apertures, and modulation complexity. Dosimetric points of the target volume (D2%) and organs at risk (OAR) (Dmean) were automatically extracted to combine them with plan complexity and obtain a global quality score (GQS). The analysis was stratified based on the different optimization algorithms used over the years, including a knowledge-based (KB) model. Patient-specific quality assurance (QA) using Portal Dosimetry was performed retrospectively, and the gamma agreement index (GAI) was investigated in conjunction with plan complexity. Results: Plan complexity significantly reduced over the years (r = -0.50, p < 0.01). Significant differences in plan complexity and plan dosimetric quality among the different algorithms were observed. Moreover, the KB model allowed to achieve significantly better dosimetric results to the OARs. The plan quality remained similar or even improved during the years and when moving to a newer algorithm, with GQS increasing from 0.019 ± 0.002 to 0.025 ± 0.003 (p < 0.01). The significant correlation between GQS and time (r = 0.33, p = 0.01) indicated that the planner's experience was relevant to improve the plan quality of TMLI plans. Significant correlations between the GAI and the complexity metrics (r = -0.71, p < 0.01) were also found. Conclusion: Both the planner's experience and algorithm version are crucial to achieve an optimal plan quality in TMLI plans. Thus, the impact of the optimization algorithm should be carefully evaluated when a new algorithm is introduced and in system upgrades. Knowledge-based strategies can be useful to increase standardization and improve plan quality of TMLI treatments

10.5281/zenodo.10046365

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FRI0110 The impact of seropositivity on the effectiveness of abatacept versus tnf inhibitors in rheumatoid arthritis. real life data from several european registries (THE PAN-ABA STUDY)

Annals of the Rheumatic Diseases (2018)

Delphine S. Courvoisier Denis Mongin Merete Lund Hetland Karel Pavelká Carl Turesson

Background

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are used as diagnostic tools, but may also be used as prognostic factors, as these biomarkers have been associated with better clinical responses to some biologic agents in rheumatoid arthritis (RA).

Objectives

To compare the impact of seropositivity on drug discontinuation and effectiveness for abatacept (ABA) and TNF inhibitors (TNFi) in patients (pts) with RA.

Methods

Pooled analysis of 13 observational RA registries from countries (FR, IT, CZ, DK, NO, PT, RO, ES, SE, CH, NL, JP, CA) where both ABA and TNFi were available concomitantly. Inclusion criteria were RA diagnosis, treatment with ABA or TNFi, and available RF or ACPA status. Main exposure was seropositivity: positive if RF or ACPA were positive, negative if both were negative, and missing if one was missing and the other was negative. Primary endpoint was drug discontinuation, analysed using Cox models, including treatment, seropositivity, and their interaction, adjusting for patient-, treatment-, and disease-characteristics, using strata terms for country and calendar year. We first tested for effect modification by country by additionally including an interaction term between treatment, seropositivity and country. Since we found no effect modification, we took out the interaction term. Effectiveness was analysed using DAS28 remission and low disease activity (LDA) at 1 year, corrected for attrition using Lundex¹.

Results

Using data from 39 266 treatment-courses, in crude analyses, seronegativity was associated with higher drug discontinuation for pts on ABA but not on TNFi (p interaction <0.001), with a hazard ratio (HR) for seropositive vs seronegative of 0.74 (95%CI: 0.66–0.82) for pts on ABA and 0.96 (95%CI: 0.92–1.01) for pts on TNFi. On average, pts on ABA were older and had more prior bDMARDs. Adjusting for potential confounding factors did not modify the results qualitatively (figure 1), with significantly longer time before discontinuation in seropositive vs seronegative pts on ABA (adj. HR: 0.74 (95% CI: 0.67–0.84) but not on TNFi (adj. HR: 0.99 (95% CI: 0.94–1.04)). The proportion of pts reaching DAS28 remission or LDA at 1 year was significantly higher for seropositive vs seronegative pts on ABA (difference in proportion: remission: 5.0%; LDA: 9.7%), but similar for seropositive vs seronegative pts on TNFi (difference in proportion: remission: −2.7%; LDA: −2.3%).

Conclusions

Data from this large pooled registry suggests that seropositivity in RA pts is associated with increased drug retention and effectiveness for ABA but not for TNFi.

Reference

[1] Kristensen, et al. A&R2006;(54):600–6.

Acknowledgements

Unrestricted research grant from BMS

Disclosure of Interest

D. Courvoisier Consultant for: BMS, D. Mongin: None declared, M. Hetland Consultant for: Abbvie, Biogen, BMS, CellTrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB, K. Pavelka Grant/research support from: Ministry of Health, Czech Republic 023728, Consultant for: AbbVie, Roche, MSD, BMS, Amgen, Egis, Medac, UCB, Pfizer, Biogen, C. Turesson Grant/research support from: Abbvie, Bristol Myers-Squibb, Roche. Consultant for: MSD, Bristol Myers-Squibb, Roche, Paid instructor for: Abbvie, Bristol-Myers Squibb, Janssen, MSD, Pfizer, Roche, UCB, S. A. Bergstra: None declared, T. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Epirus, Hospira, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, UCB, M. J. Santos: None declared, V. Hernandez: None declared, F. Iannone Consultant for: BMS, J.-E. Gottenberg Consultant for: BMS, X. Mariette Consultant for: BMS, S. Kubo Speakers bureau: BMS, Pfizer, Takeda, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Bristol-Myers, Chugai, Astellas, Abbvie, Daiichi-Sankyo, Pfizer, Eisai, Ono, Consultant for: Daiichi-Sankyo, Astellas, Pfizer, Mitsubishi-Tanabe, BMS, Chugai, YL Biologics, Eli Lilly, Sanofi, Janssen, UCB, D. Choquette: None declared, R. Ionescu: None declared, A. Finckh Grant/research support from: BMS, Consultant for: BMS, AbbVie, AB2BIO, MSD, Pfizer, Roche, UCB

Abatacept

Discontinuation

TNF inhibitor

Rheumatoid factor

10.1136/annrheumdis-2018-eular.3312

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Citations (1)

Zenodo (CERN European Organization for Nuclear Research) (2023)

Nicola Lambri Víctor Hernández Jordi Sáez M. Pelizzoli Sara Parabicoli

This record contains raw data related to article “Multicentric evaluation of a machine learning model to streamline the radiotherapy patient specific quality assurance process" Purpose: Patient-specific quality assurance (PSQA) is performed to ensure that modulated treatment plans can be delivered as intended, but constitutes a substantial workload that could slow down the radiotherapy process and delay the start of clinical treatments. In this study, we investigated a machine learning (ML) tree-based ensemble model to predict the gamma passing rate (GPR) for volumetric modulated arc therapy (VMAT) plans. Materials and Methods: 5622 VMAT plans from multiple treatment sites were selected from a database of Institution 1 and the ML model trained using 19 metrics. PSQA analyses were performed automatically using criteria 3%/1 mm (global normalization, absolute dose, 10% threshold) and 95% action limit. Model’s performance was evaluated on an out-of-sample test set of Institution 1 and on two independent sets of measurements collected at Institution 2 and Institution 3. Mean absolute error (MAE), as well as the model’s sensitivity and specificity, were computed. Results: The model obtained a MAE of 2.33%, 2.54% and 3.91% for the three Institutions, with a specificity of 0.90, 0.90 and 0.68, and a sensitivity of 0.61, 0.25, and 0.55, respectively. Small positive median values of the residuals (i.e., the difference between measurements and predictions) were observed for each Institution (0.95%, 1.66%, and 3.42%). Thus, the model’s predictions were, on average, close to the real values and provided a conservative estimation of the GPR. Conclusions: ML models can be integrated into clinical practice to streamline the radiotherapy workflow, but they should be center-specific or thoroughly verified within centers before clinical use.

10.5281/zenodo.7844479

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Robotic MLC‐based plans: A study of plan complexity

Medical Physics (2020)

Laura Masi Víctor Hernández Jordi Sáez Raffaela Doro Lorenzo Livi

Purpose The utility of complexity metrics has been assessed for IMRT and VMAT treatment plans, but this analysis has never been performed for CyberKnife (CK) plans. The purpose of this study is to perform a complexity analysis of CK MLC plans, adapting and computing complexity indices previously defined for IMRT plans. Metrics were used to compare the complexity of plans created by two optimization systems and to study correlations between plan complexity and patient‐specific quality assurance (PSQA) results. Relationships between pairs of metrics were also analyzed to get insight into possible interdependencies. Methods Two independent in‐house software platforms were developed to compute six complexity metrics: modulation complexity score (MCS), edge metric (EM), plan irregularity (PI), plan modulation (PM), leaf gap (LG), and small aperture score (SAS10). MCS and PM definitions were adapted to account for CK plans characteristics. The computed metrics were used to compare the existing optimization algorithms (sequential and VOLO) in terms of plan complexity over 24 selected cases. Metrics were then computed over a large number (103) of VOLO SBRT clinical plans from different treatment sites, mainly liver, prostate, pancreas, and spine. Pearson's r was used to study relationships between each pair of metrics. Correlation between complexity indices and PSQA results expressed as gamma index passing rates (GPR) at (3%, 1 mm) and (2%, 1 mm) was finally analyzed. Correlation was regarded as weak for absolute Pearson’s r values in the range 0.2–0.39, moderate 0.4–0.59, strong 0.6−0.79, and very strong 0.8–1. Results When compared to VOLO, sequential plans exhibited a higher complexity degree, showing lower MCS and LG values and higher EM, PM and PI values. Differences were significant for 5/6 metrics (Wilcoxon P < 0.05). The analysis of VOLO clinical plans highlighted different degrees of complexity among plans from different treatment sites, increasing from liver to prostate, pancreas, and finally, spine. Analysis of dependencies between pairs of metrics showed a very strong significant negative correlation ( P < 0.01), respectively, between MCS and PM (r = −0.97), and EM and LG (−0.82). Most of the remaining pairs showed moderate to strong correlations with the exception of PI, which showed weaker correlations with the other metrics. A moderate significant correlation was observed with GPR values both at (3%, 1 mm) and (2%, 1 mm) for all metrics except PI, which showed no correlation. Conclusions Modulation complexity metrics were computed for CK MLC‐based plans for the first time and some metrics' definitions were adapted to CK plans peculiarities. The computed metrics proved a useful tool for comparing optimization algorithms and for characterizing CK clinical plans. Strong and very strong correlations were found between some pairs of metrics. Some significant correlations were found with PSQA GPR, indicating that some indices are promising for rationalizing and reducing PSQA workload. Our results set the basis for evaluating new optimization algorithms and TPS versions in the future, as well as for comparing the complexity of CK MLC‐based plans in multicenter and multiplatform comparisons.

Complexity index

Box plot

Cyberknife

10.1002/mp.14667

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Citations (7)

Great clinical variability of Nance Horan syndrome due to deleterious NHS mutations in two unrelated Spanish families

Ophthalmic Genetics (2019)

Víctor Hernández Isabel Pascual-Camps María José Aparisi Marina Martínez-Matilla Francisco Martı́nez

Background: Nance-Horan syndrome (NHS) is an X-linked rare congenital disorder caused by mutations in the NHS gene. Clinical manifestations include congenital cataracts, facial and dental dysmorphism and, in some cases, intellectual disability. The aim of the present work was to identify the genetic cause of this disease in two unrelated Spanish NHS families and to determine the relative involvement of this gene in the pathogenesis.Materials and methods: Four members of a two-generation family, three males and one female (Family 1), and seven members of a three-generation family, two males and five females (Family 2) were recruited and their index cases were screened for mutations in the NHS gene and 26 genes related with ocular congenital anomalies by NGS (Next Generation Sequencing).Results: Two pathogenic variants were found in the NHS gene: a nonsense mutation (p.Arg373X) and a frameshift mutation (p.His669ProfsX5). These mutations were found in the two unrelated NHS families with different clinical manifestations.Conclusions: In the present study, we identified two truncation mutations (one of them novel) in the NHS gene, associated with NHS. Given the wide clinical variability of this syndrome, NHS may be difficult to detect in individuals with subtle clinical manifestations or when congenital cataracts are the primary clinical manifestation which makes us suspect that it can be underdiagnosed. Combination of genetic studies and clinical examinations are essential for the clinical diagnosis optimization.

Nonsense

Nonsense mutation

10.1080/13816810.2019.1692362

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Plan quality improvement by DVH sharing and planner’s experience: Results of a SBRT multicentric planning study on prostate

Physica Medica (2019)

E. Villaggi Víctor Hernández M. Fusella E. Moretti S. Russo

Planner

10.1016/j.ejmp.2019.05.003

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Citations (34)

Resultados de la encuesta de la Sociedad Española de Física Médica sobre de control de calidad de sistemas de planificación de tratamientos en el ámbito de haces de fotones y electrones de radioterapia externa

Revista de Física Médica (2021)

Alejandro García Romero Víctor Hernández Montserrat Baeza Trujillo Antonio Teijeiro García F. Clemente Gutiérrez

El grupo de trabajo de control de calidad de sistemas de planificación de tratamientos se formó a finales de 2020 con el objetivo de actualizar las recomendaciones existentes dentro del ámbito del cálculo de haces de fotones y electrones. Una vez perfilados los objetivos del grupo, conocer la manera en la que trabajan los servicios de radiofísica al respecto en 2021 se determinó como uno de los primordiales y se decidió la elaboración de una encuesta que recogiera la práctica habitual en este ámbito y permitiera elaborar un mapa de situación a nivel nacional. Se presentan los resultados de la encuesta, contestada por el 55% de los centros españoles según la estimación realizada.

10.37004/sefm/2021.22.2.006

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501 MLC modelling and configuration in TPSs: Current challenges and new methodologies

Radiotherapy and Oncology (2024)

Víctor Hernández Jordi Sáez

10.1016/s0167-8140(24)04209-9

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Recommendation on the technical and dosimetric data to be included in stereotactic body radiation therapy clinical trial publications based on a systematic review

Radiotherapy and Oncology (2023)

Nicholas Hardcastle Mirjana Josipović E. Clementel Víctor Hernández G. Smyth

10.1016/j.radonc.2023.110042

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A new method for modelling the tongue-and-groove in treatment planning systems

Physics in Medicine and Biology (2018)

Víctor Hernández Juan Antonio Vera‐Sánchez L. Vieillevigne C. Khamphan Jordi Sáez

Commercial TPSs typically model the tongue-and-groove (TG) by extending the projections of the leaf sides by a certain constant width. However, this model may produce discrepancies of as much as 7%-10% in the calculated average doses, especially for the High Definition multi-leaf collimator (MLC) (Hernandez et al 2017 Phys. Med. Biol. 62 6688-707). The purpose of the present study is to introduce and validate a new method for modelling the TG that uses a non constant TG width. We provide the theoretical background and a detailed methodology to determine the optimal shape of this TG width from measurements and we fit an empirical function to the TG width that depended on two parameters [Formula: see text] and [Formula: see text]. Parameter [Formula: see text] represents the TG width and [Formula: see text] introduces a curvature correction in the width near the leaf tip end. The new TG model was implemented in MATLAB and when the curvature correction was zero ([Formula: see text]) it caused the same discrepancies as the constant width model used by the Eclipse TPS. On the other hand, when the experimentally determined [Formula: see text] was used the new model's calculations were in close agreement with measurements, with all differences in average doses [Formula: see text]1%. Additionally, film dosimetry was used to successfully validate the potential of the new TG model to recreate the fine spatial details associated to TG effects. We also showed that the parameters [Formula: see text], [Formula: see text] depend solely on the MLC design by evaluating three different linear accelerators for each MLC model considered, namely Varian's High Definition and Millennium120 MLCs. In conclusion, a new method was presented that greatly improves the TG modelling. The present method can be easily implemented in commercial TPSs and has the potential to further increase their accuracy, especially for MLCs with rounded leaf ends.

Collimator

Constant (computer programming)

10.1088/1361-6560/aaf098

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Citations (11)