Nuestros investigadores

Benigno Barbes Fernandez

Índice H
7, (WoS, 19/02/2019)

Publicaciones científicas más recientes (desde 2010)

Autores: Rodriguez, I.; et al.
Revista: MOLECULAR CANCER THERAPEUTICS
ISSN 1535-7163  Vol. 18  Nº 3  2019  págs. 621 - 631
Radiotherapy can be synergistically combined with immunotherapy in mouse models, extending its efficacious effects outside of the irradiated field (abscopal effects). We previously reported that a regimen encompassing local radiotherapy in combination with anti-CD137 plus anti-PD-1 mAbs achieves potent abscopal effects against syngeneic transplanted murine tumors up to a certain tumor size. Knowing that TGF beta expression or activation increases in irradiated tissues, we tested whether TGF beta blockade may further enhance abscopal effects in conjunction with the anti-PD-1 plus anti-CD137 mAb combination. Indeed, TGF beta blockade with 1D11, a TGF beta-neutralizing mAb, markedly enhanced abscopal effects and overall treatment efficacy against subcutaneous tumors of either 4T1 breast cancer cells or large MC38 colorectal tumors. Increases in CD8 T cells infiltrating the nonirradiated lesion were documented upon combined treatment, which intensely expressed Granzyme-B as an indicator of cytotoxic effector capability. Interestingly, tumor tissue but not healthy tissue irradiation results in the presence of higher concentrations of TGF beta in the nonirradiated contralateral tumor that showed smad2/3 phosphorylation increases in infiltrating CD8 T cells. In conclusion, radiotherapy-induced TGF beta hampers abscopal efficacy even upon combination with a potent immunotherapy regimen. Therefore, TGF beta blockade in combination with radioimmunotherapy results in greater efficacy.
Autores: Azcona, Juan Diego, (Autor de correspondencia); Moreno, Marta; et al.
Revista: MEDICAL PHYSICS
ISSN 0094-2405  Vol. 46  Nº 10  2019  págs. 4346 - 4355
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 D-95 and D-min (calculated as D-min,D-0.035cc) metrics. For lung involvement, the mean dose and V-20, V-10, and V-5 were used in the 3D to 4D dose comparison, and D-max (D-0.1cc) 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. D-95 and D-min,D-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.
Autores: Pérez, José Luis; Rodríguez, I.; et al.
Revista: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 29  Nº 5  2018  págs. 1312 - 1319
Background: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. Patients and methods: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24 h with poly-ICLC (Hiltonol), TNF-alpha and IFN-alpha. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m(2) was administered 1 week before. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating peripheral blood mononuclear cell (PBMCs) and serum concentrations of a cytokine panel were sequentially determined before and during treatment. Pre-and posttreatment PBMC from patients achieving durable stable disease (SD) were studied by IFNc ELISPOT-assays responding to tumor-lysate loaded DC and by TCR beta sequencing. Results: Combined treatment was, safe and well tolerated. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR+ immunotherapy. No objective responses were observed, while nine patients presented SD (five of them in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-beta and IFN-alpha mRNA in circulating PBMC. DC vaccination increased serum IL-12 and IL-1 beta concentrations, especially in patients presenting SD. IFNc-ELISPOT reactivity to tumor lysates was observed in two patients experiencing durable SD. Conclusions: This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.
Autores: Azcona, Juan Diego; Moreno, Marta; et al.
Revista: MEDICAL PHYSICS
ISSN 0094-2405  Vol. 45  Nº 6  2018  págs. E523 - E524
Autores: Martin-Martin, G.; Aguilar Redondo, P. B.; Barbes, B; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 127  Nº Supl.1  2018  págs. S461 - S462
Autores: Arbea, Leire; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº Supl. 3  2018  págs. 251 - 252
Autores: Garcia-Consuegra, A.; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº Supl. 3  2018  págs. 253 - 253
Autores: Azcona, Juan Diego; Barbes, B; Morán, Verónica; et al.
Revista: MEDICAL DOSIMETRY
ISSN 0958-3947  Vol. 42  Nº 4  2017  págs. 282 - 288
This study aimed to describe the commissioning of small field size radiosurgery cones in a 6-MV flattening filter free (FFF) beam and report our measured values. Four radiosurgery cones of diameters 5, 10, 12.5, and 15¿mm supplied by Elekta Medical were commissioned in a 6-MV FFF beam from an Elekta Versa linear accelerator. The extraction of a reference signal for measuring small fields in scanning mode is challenging. A transmission chamber was attached to the lower part of the collimators and used for percentage depth dose (PDD) and profile measurements in scanning mode with a stereotactic diode. Tissue-maximum ratios (TMR) and output factors (OF) for all collimators were measured with a stereotactic diode (IBA). TMR and the OF for the largest collimator were also acquired on a polystyrene phantom with a microionization chamber of 0.016¿cm3 volume (PTW Freiburg PinPoint 3D). Measured TMR with diode and PinPoint microionization chamber agreed very well with differences smaller than 1% for depths below 20¿cm, except for the smaller collimator, for which differences were always smaller than 2%. Calculated TMR were significantly different (up to 7%) from measured TMR. OF measured with diode and chamber showed a difference of 3.5%. The use of a transmission chamber allowed the measurement of the small-field dosimetric properties with a simple setup. The commissioning of radiosurgery cones in FFF beams has been performed with essentially the same procedures and recommended ...
Autores: Garasa, S.; Rodriguez, I.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 97  Nº 2  2017  págs. 389 - 400
Purpose/Objectives: The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Materials/Methods: Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGF beta in this process anti-TGF beta blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGF beta and /or anti-ICAM1 blocking mAb. Results: We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGF beta. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Conclusion: Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to immunotherapy. (C) 2016 Elsevier Inc. All rights reserved.
Autores: T Monserrat; Prieto, Elena; Barbes, B; et al.
Revista: ACTA RADIOLOGICA
ISSN 0284-1851  Vol. 59  Nº 6  2017  págs. 649-56
CDMAM phantom images were acquired for various PMMA thicknesses and inverse Image Quality Figure (IQFinv) was calculated. Values of incident entrance surface air kerma (ESAK) and average glandular dose (AGD) were obtained from the DICOM header for a total of 1088 pairs of clinical cases. Two experienced radiologists compared subjectively the image quality of a total of 149 pairs of clinical cases. Results CNR values were higher and doses were lower in PRIME mode for all thicknesses. IQFinv values in PRIME mode were lower for all thicknesses except for 40¿mm of PMMA equivalent, in which IQFinv was slightly greater in PRIME mode. A mean reduction of 10% in ESAK and 12% in AGD in PRIME mode with respect to standard mode was obtained. The clinical image quality in PRIME and standard acquisitions resulted to be similar in most of the cases (84% for the first radiologist and 67% for the second one). Conclusion The use of PRIME software reduces, in average, the dose of radiation to the breast without affecting image quality. This reduction is greater for thinner and denser breasts
Autores: Rodríguez, I.; Barbes, B; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 16  Nº 6  2017  págs. 1246 - 1251
PURPOSE/OBJECTIVES: Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory monoclonal antibodies (mAb) to act both on irradiated tumor lesions and on tumors at distant, nonirradiated sites. We have recently reported that external beam radiotherapy achieves abscopal effects when combined with antagonist anti-PD1 mAbs and agonist anti-CD137 (4-1BB) mAbs. The goal of this work is to study the abscopal effects of radiotherapy instigated by brachytherapy techniques. METHODS AND MATERIALS: Mice bearing a subcutaneous colorectal carcinoma, MC38 (colorectal cancer), in both flanks were randomly assigned to receive brachytherapy or not (8 Gy × three fractions) to only one of the two grafted tumors, in combination with intraperitoneal immunostimulatory monoclonal antibodies (anti-PD1, anti-CD137, and/or their respective isotype controls). To study the abscopal effects of brachytherapy, we established an experimental set up that permits irradiation of mouse tumors sparing a distant site resembling metastasis. Such second nonirradiated tumor was used as indicator of abscopal effect. Tumor size was monitored every 2 days. RESULTS: Abscopal effects on distant nonirradiated subcutaneous tumor lesions of transplanted MC38-derived tumors only took place when brachytherapy was combined with immunostimulatory anti-PD1 and/or anti-CD137 mAbs. CONCLUSIONS: Our results demonstrate that immunotherapy-potentiated abscopal effects can be attained by brachytherapy. Accordingly, immunotherapy plus brachytherapy combinations are suitable for clinical translation.
Autores: Pérez, José Luis; et al.
Revista: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 28  Nº Supl. 11  2017  págs. 48P
Autores: Morán, Verónica; Prieto, Elena; García, Berta; et al.
Revista: REVISTA ESPAÑOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN 2253-654X  Vol. 35  Nº 3  2016  págs. 175-85
It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions
Autores: Morán, Verónica; Prieto, Elena; García, Berta; et al.
Revista: REVISTA ESPANOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
ISSN 2253-654X  Vol. 35  Nº 3  2016  págs. 175 - 185
Objectives: The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. Material and methods: A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0 m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). Results: During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 mu Sv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. Conclusion: It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.
Autores: Rodriguez, I.; Garasa, S.; et al.
Revista: CANCER RESEARCH
ISSN 0008-5472  Vol. 76  Nº 20  2016  págs. 5994 - 6005
Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions and on distant, nonirradiated tumor sites. The combination of radiotherapy with immunostimulatory anti-PD1 and anti-CD137 mAbs was conducive to favorable effects on distant nonirradiated tumor lesions as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), and 4T1 (breast cancer) models. The therapeutic activity was crucially performed by CD8 T cells, as found in selective depletion experiments. Moreover, the integrities of BATF-3-dependent dendritic cells specialized in crosspresentation/crosspriming of antigens to CD8+ T cells and of the type I IFN system were absolute requirements for the antitumor effects to occur. The irradiation regimen induced immune infiltrate changes in the irradiated and nonirradiated lesions featured by reductions in the total content of effector T cells, Tregs, and myeloid-derived suppressor cells, while effector T cells expressed more intracellular IFN¿ in both the irradiated and contralateral tumors. Importantly, 48 hours after irradiation, CD8+ TILs showed brighter expression of CD137 and PD1, thereby displaying more target molecules for the corresponding mAbs. Likewise, PD1 and CD137 were induced on tumor-infiltrating lymphocytes from surgically excised human carcinomas that were irradiated ex vivo These mechanisms involving crosspriming and CD8 T cells advocate clinical development of immunotherapy combinations with anti-PD1 plus anti-CD137 mAbs that can be synergistically accompanied by radiotherapy strategies, even if the disease is left outside the field of irradiation.
Autores: Morán, Verónica; Prieto, Elena; Zubiria, A.; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 43  Nº Supl 1  2016  págs. S410
Autores: Prieto, Elena; Marti-Climent, JM; Morán, Verónica; et al.
Revista: PHYSICA MEDICA
ISSN 1120-1797  Vol. 31  Nº 8  2015  págs. 948-955
Optimization of reconstruction algorithm and parameters has been performed to take particular advantage of the last generation PET scanner, recommending specific settings for different brain PET radiotracers.
Autores: Azcona, Juan Diego; Barbes, B; Wang, L.; et al.
Revista: PHYSICS IN MEDICINE AND BIOLOGY
ISSN 0031-9155  Vol. 61  Nº 1  2015  págs. 50 - 66
This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac's head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was demonstrated.
Autores: Barbes, B; Azcona, Juan Diego; Prieto, Elena; et al.
Revista: JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS
ISSN 1526-9914  Vol. 16  Nº 5  2015  págs. 306-321
Autores: Barbes, B; Paramo, R.; Blanco, E.; et al.
Revista: JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
ISSN 1388-6150  Vol. 115  Nº 2  2014  págs. 1883 - 1891
A study of thermal properties of CuO dispersed in water and ethylene glycol as a function of the particle volume fraction and at temperatures between 298 and 338 K has been performed. Thermal conductivities have been studied by the steady-state coaxial cylinders method, using a C80D microcalorimeter (Setaram, France) equipped with special calorimetric vessels. Heat capacities have been measured with a Micro DSC II microcalorimeter (Setaram, France) with batch cells designed in our laboratory and the "scanning or continuous method." Results for thermal conductivities can be well justified using a classical model (Hamilton-Crosser), and experimental measurements of heat capacities can be justified with a model of particles in thermal equilibrium with the base fluid.
Autores: Barbes, B; Azcona, Juan Diego; Burguete, Javier; et al.
Revista: MEDICAL PHYSICS
ISSN 0094-2405  Vol. 41  Nº 1  2014  págs. 12102-11
Autores: Barbes, B; Paramo, R.; Blanco, E.; et al.
Revista: JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
ISSN 1388-6150  Vol. 111  Nº 2  2013  págs. 1615 - 1625
Thermal conductivities and specific heat capacities of nanoparticles of Al2O3 dispersed in water and ethylene glycol as a function of the particle volume fraction and at temperatures between 298 and 338 K were measured. The steady-state coaxial cylinders method, using a C80D microcalorimeter (Setaram, France) equipped with special calorimetric vessels, was used for the thermal conductivities measurements. The heat capacities were measured with a Micro DSC II microcalorimeter (Setaram, France) with batch cells designed in our laboratory and the "scanning or continuous method." The Hamilton-Crosser model properly accounts for the thermal conductivity of the studied nanofluids. Assuming that the nanoparticles and the base fluid are in thermal equilibrium, the experimental specific heat capacities of nanofluids are correctly justified.
Autores: Barbes, B; Paramo, R.; Sobron, F.; et al.
Revista: JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
ISSN 1388-6150  Vol. 104  Nº 2  2011  págs. 805 - 812
A study has been carried out of calorimetric cells based on the coaxial cylinder method suitable for the thermal conductivity measurements in a C80D micro-calorimeter from Setaram (France). On the hypothesis of a pure conductive process, it has been possible to obtain the equation expressing the thermal conductivity k of a liquid sample in function of the heat flow measured by the calorimeter, and the relative thermal conductivity uncertainty has been analysed. To justify the hypothesis of practical absence of convection and negligible temperature differences during experimentation, a CFD (Computational Fluid Dynamics) study has been performed. With a view to testing our equipment and calibration method, the thermal conductivities of some pure liquids (toluene, n-decane) and systems (water + ethanol and nanofluid water/Al2O3), which cover a wide range, have been measured.
Autores: Barbes, B; Blanco, E.; Casanova, C.; et al.
Revista: MEASUREMENT SCIENCE AND TECHNOLOGY
ISSN 0957-0233  Vol. 22  Nº 4  2011  págs. 045401
A study of a steady-state method for thermal conductivity measurements of liquids has been carried out. It uses a C80D differential micro-calorimeter from Setaram (France), with special designed vessels containing a heating resistance. The thermal conductivity k of a liquid sample is determined as a function of the heat flow measured by the calorimeter, using an expression whose coefficients are found through the calibration with three reference liquids. These coefficients change with the calorimeter temperature, so the calibration has to be performed at each temperature. In this work, it has been verified that the coefficients' temperature variations can be justified by the thermal properties of the calorimeter components. A new model valid for all temperatures has been developed, taking into account those factors. This new model confirms the physical meaning of the procedure, brings down the number of measurements required for the calibration, and slightly reduces the uncertainty of the results.

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