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1. Optimizing Charge Transport Simulation for Hybrid Pixel Detectors

Author

Xie, X., Barten, R., Bergamaschi, A., Braham, B., Brückner, M., Carulla, M., Dinapoli, R., Ebner, S., Ferjaoui, K., Fröjdh, E., Greiffenberg, D., Hasanaj, S., Heymes, J., Hinger, V., King, T., Kozlowski, P., Lopez-Cuenca, C., Mezza, D., Moustakas, K., Mozzanica, A., Paton, K. A., Ruder, C., Schmitt, B., Sieberer, P., Thattil, D., and Zhang, J.

Subjects
Physics - Instrumentation and Detectors
Abstract

To enhance the spatial resolution of the M\"ONCH 25 \textmu m pitch hybrid pixel detector, deep learning models have been trained using both simulation and measurement data. Challenges arise when comparing simulation-based deep learning models to measurement-based models for electrons, as the spatial resolution achieved through simulations is notably inferior to that from measurements. Discrepancies are also observed when directly comparing X-ray simulations with measurements, particularly in the spectral output of single pixels. These observations collectively suggest that current simulations require optimization. To address this, a Monte Carlo simulation was conducted to model the dynamics of charge carriers within the silicon sensor, aiming to refine charge transport modeling. The simulation encompasses the initial generation of the charge cloud, charge cloud drift, charge diffusion and repulsion, and electronic noise. The simulation results were validated with measurements from the M\"ONCH detector for X-rays, and the agreement between measurements and simulations was significantly improved by accounting for the charge repulsion., Comment: Prepared for submission to JINST as a proceeding for 25th International Workshops on Radiation Imaging Detectors

Published
2024

2. Detection of MeV electrons using a charge integrating hybrid pixel detector

Author

Fröjdh, E., Baruffaldi, F., Bergamaschi, A., Carulla, M., Dinapoli, R., Greiffenberg, D., Heymes, J., Hinger, V., Ischebeck, R., Mathisen, S., McKenzie, J., Mezza, D., Moustakas, K., Mozzanica, A., Schmitt, B., and Zhang, J.

Subjects
Physics - Instrumentation and Detectors
Abstract

Electrons are emerging as a strong complement to X-rays for diffraction based studies. In this paper we investigate the performance of a JUNGFRAU detector with 320 um thick silicon sensor at a pulsed electron source. Originally developed for X-ray detection at free electron lasers, JUNGFRAU features a dynamic range of 120 MeV/pixel (implemented with in-pixel gain switching) which translated to about 1200 incident electrons per pixel and frame in the MeV region. We preset basic characteristics such as energy deposited per incident particle, resulting cluster size and spatial resolution along with dynamic (intensity) range scans. Measurements were performed at 4, 10 and 20 MeV/c. We compare the measurements with GEANT4 based simulations and extrapolate the results to different sensor thicknesses using these simulations.

Published
2022
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3. [Artículo traducido] Predictores de las complicaciones postoperatorias en el primer año tras la fijación de fracturas de tobillo de baja energía. Estudio de cohortes retrospectivo sobre 663 fracturas intervenidas consecutivamente en un único centro

Author

Andrés-Peiró, J.-V., Pujol, O., Altayó-Carulla, M., Castellanos-Alonso, S., Reverté-Vinaixa, M.-M., Teixidor-Serra, J., Tomàs-Hernández, J., Selga-Marsà, J., García-Sánchez, Y., Molero-García, V., Joshi-Jubert, N., and Minguell-Monyart, J.

Published
2024
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5. Inverse Low Gain Avalanche Detectors (iLGADs) for precise tracking and timing applications

Author

Currás, E., Carulla, M., Vignali, M. Centis, Duarte-Campderros, J., Fernández, M., Flores, D., García, A., Gómez, G., González, J., Hidalgo, S., Jaramillo, R., Merlos, A., Moll, M., Pellegrini, G., Quirion, D., and Vila, I.

Subjects
Physics - Instrumentation and Detectors, 14J60 (Primary) 14F05, 14J26 (Secondary)
Abstract

Low Gain Avalanche Detector (LGAD) is the baseline sensing technology of the recently proposed Minimum Ionizing Particle (MIP) end-cap timing detectors (MTD) at the Atlas and CMS experiments. The current MTD sensor is designed as a multi-pad matrix detector delivering a poor position resolution, due to the relatively large pad area, around 1 $mm^2$; and a good timing resolution, around 20-30 ps. Besides, in his current technological incarnation, the timing resolution of the MTD LGAD sensors is severely degraded once the MIP particle hits the inter-pad region since the signal amplification is missing for this region. This limitation is named as the LGAD fill-factor problem. To overcome the fill factor problem and the poor position resolution of the MTD LGAD sensors, a p-in-p LGAD (iLGAD) was introduced. Contrary to the conventional LGAD, the iLGAD has a non-segmented deep p-well (the multiplication layer). Therefore, iLGADs should ideally present a constant gain value over all the sensitive region of the device without gain drops between the signal collecting electrodes; in other words, iLGADs should have a 100${\%}$ fill-factor by design. In this paper, tracking and timing performance of the first iLGAD prototypes is presented., Comment: Conference Proceedings of VCI2019, 15th Vienna Conference of Instrumentation, February 18-22, 2019, Vienna, Austria

Published
2019
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6. Beam test measurements of Low Gain Avalanche Detector single pads and arrays for the ATLAS High Granularity Timing Detector

Author

Allaire, C., Benitez, J., Bomben, M., Calderini, G., Carulla, M., Cavallaro, E., Falou, A., Flores, D., Freeman, P., Galloway, Z., Gkougkousis, E. L., Grabas, H., Grinstein, S., Gruey, B., Guindon, S., Correia, A. M. Henriques, Hidalgo, S., Kastanas, A., Labitan, C., Lacour, D., Lange, J., Lanni, F., Lenzi, B., Luce, Z., Makovec, N., Marchiori, G., Masetti, L., Merlos, A., McKinney-Martinez, F., Nikolic-Audit, I., Pellegrini, G., Polifka, R., Quirion, D., Rummler, A., Sadrozinski, H. F-W., Seiden, A., Serin, L., Simion, S., Spencer, E., Trincaz-Duvoid, S., Wilder, M., Zatserklyaniy, A., Zerwas, D., and Zhao, Y.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

For the high luminosity upgrade of the LHC at CERN, ATLAS is considering the addition of a High Granularity Timing Detector (HGTD) in front of the end cap and forward calorimeters at |z| = 3.5 m and covering the region 2.4 < |{\eta}| < 4 to help reducing the effect of pile-up. The chosen sensors are arrays of 50 {\mu}m thin Low Gain Avalanche Detectors (LGAD). This paper presents results on single LGAD sensors with a surface area of 1.3x1.3 mm2 and arrays with 2x2 pads with a surface area of 2x2 mm^2 or 3x3 mm^2 each and different implant doses of the p+ multiplication layer. They are obtained from data collected during a beam test campaign in Autumn 2016 with a pion beam of 120 GeV energy at the CERN SPS. In addition to several quantities measured inclusively for each pad, the gain, efficiency and time resolution have been estimated as a function of the position of the incident particle inside the pad by using a beam telescope with a position resolution of few {\mu}m. Different methods to measure the time resolution are compared, yielding consistent results. The sensors with a surface area of 1.3x1.3 mm^2 have a time resolution of about 40 ps for a gain of 20 and of about 27 ps for a gain of 50 and fulfill the HGTD requirements. Larger sensors have, as expected, a degraded time resolution. All sensors show very good efficiency and time resolution uniformity.

Published
2018
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7. Radiation Hardness of Thin Low Gain Avalanche Detectors

Author

Kramberger, G., Carulla, M., Cavallaro, E., Cindro, V., Flores, D., Galloway, Z., Grinstein, S., Hidalgo, S., Fadeyev, V., Lange, J., Mandic, I., Medin, G., Merlos, A., McKinney-Martinez, F., Mikuz, M., Quirion, D., Pellegrini, G., Petek, M., Sadrozinski, H. F-W., Seiden, A., and Zavrtanik, M.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

Low Gain Avalanche Detectors (LGAD) are based on a n++-p+-p-p++ structure where an appropriate doping of the multiplication layer (p+) leads to high enough electric fields for impact ionization. Gain factors of few tens in charge significantly improve the resolution of timing measurements, particularly for thin detectors, where the timing performance was shown to be limited by Landau fluctuations. The main obstacle for their operation is the decrease of gain with irradiation, attributed to effective acceptor removal in the gain layer. Sets of thin sensors were produced by two different producers on different substrates, with different gain layer doping profiles and thicknesses (45, 50 and 80 um). Their performance in terms of gain/collected charge and leakage current was compared before and after irradiation with neutrons and pions up to the equivalent fluences of 5e15 cm-2. Transient Current Technique and charge collection measurements with LHC speed electronics were employed to characterize the detectors. The thin LGAD sensors were shown to perform much better than sensors of standard thickness (~300 um) and offer larger charge collection with respect to detectors without gain layer for fluences <2e15 cm-2. Larger initial gain prolongs the beneficial performance of LGADs. Pions were found to be more damaging than neutrons at the same equivalent fluence, while no significant difference was found between different producers. At very high fluences and bias voltages the gain appears due to deep acceptors in the bulk, hence also in thin standard detectors.

Published
2017
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8. Gain and time resolution of 45 $\mu$m thin Low Gain Avalanche Detectors before and after irradiation up to a fluence of $10^{15}$ n$_{eq}$/cm$^2$

Author

Lange, J., Carulla, M., Cavallaro, E., Chytka, L., Davis, P. M., Flores, D., Förster, F., Grinstein, S., Hidalgo, S., Komarek, T., Kramberger, G., Mandić, I., Merlos, A., Nozka, L., Pellegrini, G., Quirion, D., and Sykora, T.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

Low Gain Avalanche Detectors (LGADs) are silicon sensors with a built-in charge multiplication layer providing a gain of typically 10 to 50. Due to the combination of high signal-to-noise ratio and short rise time, thin LGADs provide good time resolutions. LGADs with an active thickness of about 45 $\mu$m were produced at CNM Barcelona. Their gains and time resolutions were studied in beam tests for two different multiplication layer implantation doses, as well as before and after irradiation with neutrons up to $10^{15}$ n$_{eq}$/cm$^2$. The gain showed the expected decrease at a fixed voltage for a lower initial implantation dose, as well as for a higher fluence due to effective acceptor removal in the multiplication layer. Time resolutions below 30 ps were obtained at the highest applied voltages for both implantation doses before irradiation. Also after an intermediate fluence of $3\times10^{14}$ n$_{eq}$/cm$^2$, similar values were measured since a higher applicable reverse bias voltage could recover most of the pre-irradiation gain. At $10^{15}$ n$_{eq}$/cm$^2$, the time resolution at the maximum applicable voltage of 620 V during the beam test was measured to be 57 ps since the voltage stability was not good enough to compensate for the gain layer loss. The time resolutions were found to follow approximately a universal function of gain for all implantation doses and fluences., Comment: 17 pages

Published
2017
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9. 3D sensors for the HL-LHC

Author

Furelos, D. Vázquez, Carulla, M., Cavallaro, E., Förster, F., Grinstein, S., Lange, J., Paz, I. López, Manna, M., Pellegrini, G., Quirion, D., and Terzo, S.

Subjects
Physics - Instrumentation and Detectors
Abstract

In order to increase its discovery potential, the Large Hadron Collider (LHC) accelerator will be upgraded in the next decade. The high luminosity LHC (HL-LHC) period demands new sensor technologies to cope with increasing radiation fluences and particle rates. The ATLAS experiment will replace the entire inner tracking detector with a completely new silicon-only system. 3D pixel sensors are promising candidates for the innermost layers of the Pixel detector due to their excellent radiation hardness at low operation voltages and low power dissipation at moderate temperatures. Recent developments of 3D sensors for the HL-LHC are presented., Comment: 8 pages, 5 figures, International Workshops on Radiation Imaging Detectors 2016

Published
2016
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10. Beam test results of a 16 ps timing system based on ultra-fast silicon detectors

Author

Cartiglia, N., Staiano, A., Sola, V., Arcidiacono, R., Cirio, R., Cenna, F., Ferrero, M., Monaco, V., Mulargia, R., Obertino, M., Ravera, F., Sacchi, R., Bellora, A., Durando, S., Mandurrino, M., Minafra, N., Fadeyev, V., Freeman, P., Galloway, Z., Gkougkousis, E., Grabas, H., Gruey, B., Labitan, C. A., Losakul, R., Luce, Z., McKinney-Martinez, F., Sadrozinski, H. F. -W., Seiden, A., Spencer, E., Wilder, M., Woods, N., Zatserklyaniy, A., Pellegrini, G., Hidalgo, S., Carulla, M., Flores, D., Merlos, A., Quirion, D., Cindro, V., Kramberger, G., Mandic, I., Mikuz, M., and Zavrtanik, M.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

In this paper we report on the timing resolution of the first production of 50 micro-meter thick Ultra-Fast Silicon Detectors (UFSD) as obtained in a beam test with pions of 180 GeV/c momentum. UFSD are based on the Low-Gain Avalanche Detectors (LGAD) design, employing n-on-p silicon sensors with internal charge multiplication due to the presence of a thin, low-resistivity diffusion layer below the junction. The UFSD used in this test belongs to the first production of thin (50 {\mu}m) sensors, with an pad area of 1.4 mm2. The gain was measured to vary between 5 and 70 depending on the bias voltage. The experimental setup included three UFSD and a fast trigger consisting of a quartz bar readout by a SiPM. The timing resolution, determined comparing the time of arrival of the particle in one or more UFSD and the trigger counter, for single UFSD was measured to be 35 ps for a bias voltage of 200 V, and 26 ps for a bias voltage of 240 V, and for the combination of 3 UFSD to be 20 ps for a bias voltage of 200 V, and 15 ps for a bias voltage of 240 V., Comment: 7 pages, 8 figures, 1 table, Subm. to NIM A

Published
2016
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11. Recent Technological Developments on LGAD and iLGAD Detectors for Tracking and Timing Applications

Author

Pellegrini, G., Baselga, M., Carulla, M., Fadeyev, V., Fernandez-Martinez, P., Fernandez-Garcia, M., Flores, D., Galloway, Z., Gallrapp, C., Hidalgo, S., Liang, Z., Merlos, A., Moll, M., Quirion, D., Sadrozinski, H., Stricker, M., and Vila, I.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

This paper reports the last technological development on the Low Gain Avalanche Detector (LGAD) and introduces a new architecture of these detectors called inverse-LGAD (iLGAD). Both approaches are based on the standard Avalanche Photo Diodes (APD) concept, commonly used in optical and X-ray detection applications, including an internal multiplication of the charge generated by radiation. The multiplication is inherent to the basic n++-p+-p structure, where the doping profile of the p+ layer is optimized to achieve high field and high impact ionization at the junction. The LGAD structures are optimized for applications such as tracking or timing detectors for high energy physics experiments or medical applications where time resolution lower than 30 ps is required. Detailed TCAD device simulations together with the electrical and charge collection measurements are presented through this work., Comment: Keywords: silicon detectors, avalanche multiplication, timing detectors, tracking detectors. 8 pages. 8 Figures

Published
2015
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12. Ten-Year Probabilities of Death Due to Cancer and Cardiovascular Disease among Breast Cancer Patients Diagnosed in North-Eastern Spain

Author

Universitat Rovira i Virgili, Clèries R; Ameijide A; Buxó M; Vilardell M; Martínez JM; Font R; Marcos-Gragera R; Puigdemont M; Viñas G; Carulla M; Espinàs JA; Galceran J; Izquierdo Á; Borràs JM, Universitat Rovira i Virgili, and Clèries R; Ameijide A; Buxó M; Vilardell M; Martínez JM; Font R; Marcos-Gragera R; Puigdemont M; Viñas G; Carulla M; Espinàs JA; Galceran J; Izquierdo Á; Borràs JM

Abstract

Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR− patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II–III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II–III at an older age, surveillance for preventing late cardiotoxicity is crucial.

Published
2023

13. Long-term survival and cure fraction estimates for childhood cancer in Europe (EUROCARE-6): results from a population-based study

Author

Botta, L, Gatta, G, Capocaccia, R, Stiller, C, Canete, A, Dal Maso, L, Innos, K, Mihor, A, Erdmann, F, Spix, C, Lacour, B, Marcos-Gragera, R, Murray, D, Rossi, S, Hackl, M, Van Eycken, E, Van Damme, N, Valerianova, Z, Sekerija, M, Scoutellas, V, Demetriou, A, Dusek, L, Krejci, D, Storm, H, Magi, M, Paapsi, K, Malila, N, Pitkaniemi, J, Jooste, V, Clavel, J, Poulalhon, C, Desandes, E, Monnereau, A, Katalinic, A, Petridou, E, Markozannes, G, Garami, M, Birgisson, H, Walsh, P, Mazzoleni, G, Vittadello, F, Cuccaro, F, Galasso, R, Sampietro, G, Rosso, S, Gasparotto, C, Maifredi, G, Ferrante, M, Torrisi, A, Sutera Sardo, A, Gambino, M, Lanzoni, M, Ballotari, P, Giacomazzi, E, Ferretti, S, Caldarella, A, Manneschi, G, Sant, M, Baili, P, Berrino, F, Trama, A, Lillini, R, Bernasconi, A, Bonfarnuzzo, S, Vener, C, Didone, F, Lasalvia, P, Del Monego, G, Buratti, L, Serraino, D, Taborelli, M, De Angelis, R, Demuru, E, Di Benedetto, C, Santaquilani, M, Venanzi, S, Tallon, M, Boni, L, Iacovacci, S, Russo, A, Gervasi, F, Spagnoli, G, Cavalieri d'Oro, L, Fusco, M, Vitale, M, Usala, M, Vitale, F, Michiara, M, Chiranda, G, Sacerdote, C, Maule, M, Cascone, G, Spata, E, Mangone, L, Falcini, F, Cavallo, R, Piras, D, Dinaro, Y, Castaing, M, Fanetti, A, Minerba, S, Candela, G, Scuderi, T, Rizzello, R, Stracci, F, Tagliabue, G, Rugge, M, Brustolin, A, Pildava, S, Smailyte, G, Azzopardi, M, Johannesen, T, Didkowska, J, Wojciechowska, U, Bielska-Lasota, M, Pais, A, Ferreira, A, Bento, M, Miranda, A, Safaei Diba, C, Zadnik, V, Zagar, T, Sanchez-Contador Escudero, C, Franch Sureda, P, Lopez de Munain, A, De-La-Cruz, M, Rojas, M, Aleman, A, Vizcaino, A, Almela, F, Sanvisens, A, Sanchez, M, Chirlaque, M, Sanchez-Gil, A, Guevara, M, Ardanaz, E, Canete-Nieto, A, Peris-Bonet, R, Galceran, J, Carulla, M, Kuehni, C, Redmond, S, Visser, O, Karim-Kos, H, Stevens, S, Gavin, A, Morrison, D, Huws, D, Botta L., Gatta G., Capocaccia R., Stiller C., Canete A., Dal Maso L., Innos K., Mihor A., Erdmann F., Spix C., Lacour B., Marcos-Gragera R., Murray D., Rossi S., Hackl M., Van Eycken E., Van Damme N., Valerianova Z., Sekerija M., Scoutellas V., Demetriou A., Dusek L., Krejci D., Storm H., Magi M., Paapsi K., Malila N., Pitkaniemi J., Jooste V., Clavel J., Poulalhon C., Desandes E., Monnereau A., Katalinic A., Petridou E., Markozannes G., Garami M., Birgisson H., Walsh P. M., Mazzoleni G., Vittadello F., Cuccaro F., Galasso R., Sampietro G., Rosso S., Gasparotto C., Maifredi G., Ferrante M., Torrisi A., Sutera Sardo A., Gambino M. L., Lanzoni M., Ballotari P., Giacomazzi E., Ferretti S., Caldarella A., Manneschi G., Sant M., Baili P., Berrino F., Trama A., Lillini R., Bernasconi A., Bonfarnuzzo S., Vener C., Didone F., Lasalvia P., Del Monego G., Buratti L., Serraino D., Taborelli M., De Angelis R., Demuru E., Di Benedetto C., Santaquilani M., Venanzi S., Tallon M., Boni L., Iacovacci S., Russo A. G., Gervasi F., Spagnoli G., Cavalieri d'Oro L., Fusco M., Vitale M. F., Usala M., Vitale F., Michiara M., Chiranda G., Sacerdote C., Maule M., Cascone G., Spata E., Mangone L., Falcini F., Cavallo R., Piras D., Dinaro Y., Castaing M., Fanetti A. C., Minerba S., Candela G., Scuderi T., Rizzello R. V., Stracci F., Tagliabue G., Rugge M., Brustolin A., Pildava S., Smailyte G., Azzopardi M., Johannesen T. B., Didkowska J., Wojciechowska U., Bielska-Lasota M., Pais A., Ferreira A. M., Bento M. J., Miranda A., Safaei Diba C., Zadnik V., Zagar T., Sanchez-Contador Escudero C., Franch Sureda P., Lopez de Munain A., De-La-Cruz M., Rojas M. D., Aleman A., Vizcaino A., Almela F., Sanvisens A., Sanchez M. J., Chirlaque M. D., Sanchez-Gil A., Guevara M., Ardanaz E., Canete-Nieto A., Peris-Bonet R., Galceran J., Carulla M., Kuehni C., Redmond S., Visser O., Karim-Kos H., Stevens S., Gavin A., Morrison D., Huws D. W., Botta, L, Gatta, G, Capocaccia, R, Stiller, C, Canete, A, Dal Maso, L, Innos, K, Mihor, A, Erdmann, F, Spix, C, Lacour, B, Marcos-Gragera, R, Murray, D, Rossi, S, Hackl, M, Van Eycken, E, Van Damme, N, Valerianova, Z, Sekerija, M, Scoutellas, V, Demetriou, A, Dusek, L, Krejci, D, Storm, H, Magi, M, Paapsi, K, Malila, N, Pitkaniemi, J, Jooste, V, Clavel, J, Poulalhon, C, Desandes, E, Monnereau, A, Katalinic, A, Petridou, E, Markozannes, G, Garami, M, Birgisson, H, Walsh, P, Mazzoleni, G, Vittadello, F, Cuccaro, F, Galasso, R, Sampietro, G, Rosso, S, Gasparotto, C, Maifredi, G, Ferrante, M, Torrisi, A, Sutera Sardo, A, Gambino, M, Lanzoni, M, Ballotari, P, Giacomazzi, E, Ferretti, S, Caldarella, A, Manneschi, G, Sant, M, Baili, P, Berrino, F, Trama, A, Lillini, R, Bernasconi, A, Bonfarnuzzo, S, Vener, C, Didone, F, Lasalvia, P, Del Monego, G, Buratti, L, Serraino, D, Taborelli, M, De Angelis, R, Demuru, E, Di Benedetto, C, Santaquilani, M, Venanzi, S, Tallon, M, Boni, L, Iacovacci, S, Russo, A, Gervasi, F, Spagnoli, G, Cavalieri d'Oro, L, Fusco, M, Vitale, M, Usala, M, Vitale, F, Michiara, M, Chiranda, G, Sacerdote, C, Maule, M, Cascone, G, Spata, E, Mangone, L, Falcini, F, Cavallo, R, Piras, D, Dinaro, Y, Castaing, M, Fanetti, A, Minerba, S, Candela, G, Scuderi, T, Rizzello, R, Stracci, F, Tagliabue, G, Rugge, M, Brustolin, A, Pildava, S, Smailyte, G, Azzopardi, M, Johannesen, T, Didkowska, J, Wojciechowska, U, Bielska-Lasota, M, Pais, A, Ferreira, A, Bento, M, Miranda, A, Safaei Diba, C, Zadnik, V, Zagar, T, Sanchez-Contador Escudero, C, Franch Sureda, P, Lopez de Munain, A, De-La-Cruz, M, Rojas, M, Aleman, A, Vizcaino, A, Almela, F, Sanvisens, A, Sanchez, M, Chirlaque, M, Sanchez-Gil, A, Guevara, M, Ardanaz, E, Canete-Nieto, A, Peris-Bonet, R, Galceran, J, Carulla, M, Kuehni, C, Redmond, S, Visser, O, Karim-Kos, H, Stevens, S, Gavin, A, Morrison, D, Huws, D, Botta L., Gatta G., Capocaccia R., Stiller C., Canete A., Dal Maso L., Innos K., Mihor A., Erdmann F., Spix C., Lacour B., Marcos-Gragera R., Murray D., Rossi S., Hackl M., Van Eycken E., Van Damme N., Valerianova Z., Sekerija M., Scoutellas V., Demetriou A., Dusek L., Krejci D., Storm H., Magi M., Paapsi K., Malila N., Pitkaniemi J., Jooste V., Clavel J., Poulalhon C., Desandes E., Monnereau A., Katalinic A., Petridou E., Markozannes G., Garami M., Birgisson H., Walsh P. M., Mazzoleni G., Vittadello F., Cuccaro F., Galasso R., Sampietro G., Rosso S., Gasparotto C., Maifredi G., Ferrante M., Torrisi A., Sutera Sardo A., Gambino M. L., Lanzoni M., Ballotari P., Giacomazzi E., Ferretti S., Caldarella A., Manneschi G., Sant M., Baili P., Berrino F., Trama A., Lillini R., Bernasconi A., Bonfarnuzzo S., Vener C., Didone F., Lasalvia P., Del Monego G., Buratti L., Serraino D., Taborelli M., De Angelis R., Demuru E., Di Benedetto C., Santaquilani M., Venanzi S., Tallon M., Boni L., Iacovacci S., Russo A. G., Gervasi F., Spagnoli G., Cavalieri d'Oro L., Fusco M., Vitale M. F., Usala M., Vitale F., Michiara M., Chiranda G., Sacerdote C., Maule M., Cascone G., Spata E., Mangone L., Falcini F., Cavallo R., Piras D., Dinaro Y., Castaing M., Fanetti A. C., Minerba S., Candela G., Scuderi T., Rizzello R. V., Stracci F., Tagliabue G., Rugge M., Brustolin A., Pildava S., Smailyte G., Azzopardi M., Johannesen T. B., Didkowska J., Wojciechowska U., Bielska-Lasota M., Pais A., Ferreira A. M., Bento M. J., Miranda A., Safaei Diba C., Zadnik V., Zagar T., Sanchez-Contador Escudero C., Franch Sureda P., Lopez de Munain A., De-La-Cruz M., Rojas M. D., Aleman A., Vizcaino A., Almela F., Sanvisens A., Sanchez M. J., Chirlaque M. D., Sanchez-Gil A., Guevara M., Ardanaz E., Canete-Nieto A., Peris-Bonet R., Galceran J., Carulla M., Kuehni C., Redmond S., Visser O., Karim-Kos H., Stevens S., Gavin A., Morrison D., and Huws D. W.

Abstract

Background: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer. Methods: In this population-based study, we analysed 135 847 children (aged 0–14 years) diagnosed during 2000–13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival. Findings: 5-year survival for all childhood cancer combined in Europe in 2010–14 was 81% (95% CI 81–82), showing an increase of three percentage points compared with 2004–06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60–79] to 87% [77–93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010–13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73–75) in 1998–

Published
2022

14. Clear Improvement in Real-World Chronic Myeloid Leukemia Survival: A Comparison With Randomized Controlled Trials

Author

Vener, C., Rossi, S., Minicozzi, P., Marcos-Gragera, R., Poirel, H. A., Maynadie, M., Troussard, X., Pravettoni, G., De Angelis, R., Sant, M., Hackl, M., Van Eycken, E., Valerianova, Z., Sekerija, M., Pavlou, P., Dusek, L., Storm, H., Magi, M., Innos, K., Malila, N., Pitkaniemi, J., Velten, M., Bouvier, A. M., Jooste, V., Guizard, A. V., Launoy, G., Yonli, S. D., Woronoff, A. S., Nousbaum, J. B., Coureau, G., Monnereau, A., Baldi, I., Hammas, K., Tretarre, B., Colonna, M., Plouvier, S., D'Almeida, T., Molinie, F., Cowppli-Bony, A., Bara, S., Schvartz, C., Defossez, G., Lapotre-Ledoux, B., Grosclaude, P., Luttmann, S., Stabenow, R., Nennecke, A., Kieschke, J., Zeissig, S., Holleczek, B., Katalinic, A., Birgisson, H., Murray, D., Walsh, P. M., Mazzoleni, G., Vittadello, F., Cuccaro, F., Galasso, R., Sampietro, G., Rosso, S., Magoni, M., Ferrante, M., Sardo, A. S., Gambino, M. L., Ballotari, P., Giacomazzi, E., Ferretti, S., Caldarella, A., Manneschi, G., Gatta, G., Baili, P., Berrino, F., Botta, L., Trama, A., Lillini, R., Bernasconi, A., Bonfarnuzzo, S., Didone, F., Lasalvia, P., Del Monego, G., Magri, M. C., Buratti, L., Serraino, D., Dal Maso, L., Capocaccia, R., Demuru, E., Di Benedetto, C., Santaquilani, M., Venanzi, S., Filiberti, R. A., Iacovacci, S., Gennaro, V., Russo, A. G., Spagnoli, G., D'Oro, L. C., Fusco, M., Vitale, M. F., Usala, M., Vitale, F., Michiara, M., Chiranda, G., Cascone, G., Spata, E., Mangone, L., Falcini, F., Cavallo, R., Piras, D., Madeddu, A., Bella, F., Fanetti, A. C., Minerba, S., Candela, G., Scuderi, T., Rizzello, R. V., Stracci, F., Tagliabue, G., Rugge, M., Brustolin, A., Pildava, S., Smailyte, G., Azzopardi, M., Johannesen, T. B., Didkowska, J., Wojciechowska, U., Bielska-Lasota, M., Pais, A., Pontes, J. L., Miranda, A., Diba, C. S., Zadnik, V., Zagar, T., Escudero, C. S. -C., Sureda, P. F., de Munain, A. L., De-La-cruz, M., Rojas, M. D., Aleman, A., Vizcaino, A., Sanchez, M. J., Chirlaque, M. D., Eslava, M. G., Ardanaz, E., Galceran, J., Carulla, M., Bergeron, Y., Bouchardy, C., Mousavi, S. M., Bordoni, A., Visser, O., Rashbass, J., Gavin, A., Morrison, D., and Huws, D. W.

Subjects
Cancer Research, Survival, real-world data, randomized controlled trials (RCTs), tyrosine kinase inhibitor (TKI), population-based studies, Tyrosine kinase inhibitor (TKI), Randomized controlled trials (RCTs), survival, Real-world data, Europe, Oncology, cancer registries, chronic myeloid leukemia (CML), Chronic myeloid leukemia (CML), Cancer registries, Population-based studies
Abstract

This study was funded by the Compagnia di San Paolo, the Cariplo Foundation and the European Commission (grant number 801520 HP-JA-2017, Innovative Partnership for Action Against Cancer, iPAAC Joint Action). The sources of the funding played no role in designing the study, collecting, analyzing, or interpreting the data, writing the report, or deciding whether or not to submit the article for publication. This research was (partially) funded by Italian Ministry of Health "Ricerca Corrente" funds. Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15-64 years) diagnosed in 2000-2006 vs. 2007-2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

Published
2022

15. Recommendations on compiling test datasets for evaluating artificial intelligence solutions in pathology

Author

Homeyer, A., Geißler, C., Ole Schwen, L., Zakrzewski, F., Evans, T., Strohmenger, K., Westphal, M., David Bülow, R., Kargl, M., Karjauv, A., Munné-Bertran, I., Orge Retzlaff, C., Romero-López, A., Sołtysiński, T., Plass, M., Carvalho, R., (0000-0002-4974-230X) Steinbach, P., Lan, Y.-C., Bouteldja, N., Haber, D., Rojas-Carulla, M., Vafaei Sadr, A., Kraft, M., Krüger, D., Fick, R., Lang, T., Boor, P., Müller, H., Hufnagl, P., Zerbe, N., Homeyer, A., Geißler, C., Ole Schwen, L., Zakrzewski, F., Evans, T., Strohmenger, K., Westphal, M., David Bülow, R., Kargl, M., Karjauv, A., Munné-Bertran, I., Orge Retzlaff, C., Romero-López, A., Sołtysiński, T., Plass, M., Carvalho, R., (0000-0002-4974-230X) Steinbach, P., Lan, Y.-C., Bouteldja, N., Haber, D., Rojas-Carulla, M., Vafaei Sadr, A., Kraft, M., Krüger, D., Fick, R., Lang, T., Boor, P., Müller, H., Hufnagl, P., and Zerbe, N.

Abstract

Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers, pathologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations on compiling test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help pathologists and regulatory agencies verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future.

Published
2022

16. Registration of Urothelial Tumours in Cancer Registries: How to Improve and Make It More Useful?

Author

Medicina i Cirurgia, Universitat Rovira i Virgili, Daubisse-Marliac L; Grosclaude P; Carulla M; Parada D; Vilardell L; Ameijide A; Marcos-Gragera R; Galceran J, Medicina i Cirurgia, Universitat Rovira i Virgili, and Daubisse-Marliac L; Grosclaude P; Carulla M; Parada D; Vilardell L; Ameijide A; Marcos-Gragera R; Galceran J

Abstract

Due to the differences in the definition, criteria of inclusion and coding of urothelial tumours (UTs), data of different cancer registries (CRs) are not comparable. The aim of this work is to study current practices of registration of UT in the European CR of the GRELL countries in order to propose new registration rules to correctly describe incidence and survival of progressive tumours like UT. A questionnaire was sent to 91 CRs to assess whether non-invasive (NI)UT, multiple UTs, UTs occurring outside or before the operating period and time between UTs are currently considered in tumour recording and reporting. All participating CRs (n = 42) record a NI bladder UT in sole occurrence. In case of progressive bladder UT, 98% of the CRs record at least one NIUT but 19% don’t record the invasive progression. 17% of the CRs don’t record an invasive pelvic tumour that occurs after a NI bladder UT. 19% of the CRs don’t record an invasive bladder UT that followed a NI tumour occurring outside the zone or period of time. The recording of two synchronous UTs is carried out with a grouping topography for 36% of the CRs. The same analysis conducted on the reporting of the incidence of UT also shows heterogeneity. We conclude that there is an urgent need to define clear rules for the registration of UT.

Published
2022

17. Predicting Ovarian-Cancer Burden in Catalonia by 2030: An Age–Period–Cohort Modelling

Author

Universitat Rovira i Virgili, Peremiquel-Trillas P; Frias-Gomez J; Alemany L; Ameijide A; Vilardell M; Marcos-Gragera R; Paytubi S; Ponce J; Martínez JM; Pineda M; Brunet J; Matías-Guiu X; Carulla M; Galceran J; Izquierdo Á; Borràs JM; Costas L; Clèries R, Universitat Rovira i Virgili, and Peremiquel-Trillas P; Frias-Gomez J; Alemany L; Ameijide A; Vilardell M; Marcos-Gragera R; Paytubi S; Ponce J; Martínez JM; Pineda M; Brunet J; Matías-Guiu X; Carulla M; Galceran J; Izquierdo Á; Borràs JM; Costas L; Clèries R

Abstract

Ovarian cancer is the most lethal gynaecological cancer in very-high-human-developmentindex regions. Ovarian cancer incidence and mortality rates are estimated to globally rise by 2035, although incidence and mortality rates depend on the region and prevalence of the associated risk factors. The aim of this study is to assess changes in incidence and mortality of ovarian cancer in Catalonia by 2030. Bayesian autoregressive age–period–cohort models were used to predict the burden of OC incidence and mortality rates for the 2015–2030 period. Incidence and mortality rates of ovarian cancer are expected to decline in Catalonia by 2030 in women ≥ 45 years of age. A decrease in ovarian-cancer risk was observed with increasing year of birth, with a rebound in women born in the 1980s. A decrease in mortality was observed for the period of diagnosis and period of death. Nevertheless, ovarian-cancer mortality remains higher among older women compared to other age groups. Our study summarizes the most plausible scenario for ovarian-cancer changes in terms of incidence and mortality in Catalonia by 2030, which may be of interest from a public health perspective for policy implementation.

Published
2022

18. Study of the internal quantum efficiency of FBK sensors with optimized entrance windows

Author

Carulla, M., Centis Vignali, M., Barten, R., Baruffaldi, F., Bergamaschi, A., Borghi, G., Boscardin, M., Brückner, M., Dinapoli, R., Ebner, S., Ficorella, F., Fröjd, E., Greiffenberg, D., Hammad Ali, O., Hasanaj, S., Heymes, J., Hinger, V., King, T., Kozlowski, P., Lopez Cuenca, C., Mezza, D., Moustakas, K., Mozzanica, A., Paternoster, G., Ronchin, S., Ruder, C., Schmitt, B., Thattil, D., and Zhang, J.

Subjects
Instrumentation, Mathematical Physics
Abstract

Single-photon detection of X-rays in the energy range of 250 eV to 1 keV is difficult for hybrid detectors because of the low quantum efficiency and low signal-to-noise ratio. The low quantum efficiency is caused by the absorption of soft X-rays in the entrance window of the silicon sensors. The entrance window consists of an insensitive layer on the surface and a highly doped layer, which is typically from a few hundred nanometers to a couple of micrometers thick and is comparable to the absorption depth of soft X-ray photons (e.g. the attenuation length of 250 eV X-ray photons is ∼100 nm in silicon). The low signal-to-noise ratio is mainly caused by the small signal amplitude (e.g. ca. 70 electrons for 250 eV X-ray photons in silicon) with respect to the electronic noise. To improve the quantum efficiency, the entrance window must be optimized by minimizing the absorption of soft X-rays in the insensitive layer, and reducing charge recombination at the Si-SiO2 interface and in the highly doped region. Low gain avalanche diodes (LGADs) with a multiplication factor between 5 and 10 increase the signal amplitude and therefore improve the signal-to-noise ratio for soft X-rays, enabling single-photon detection down to 250 eV. Combining LGAD technology with an optimized entrance window technology can thus allow hybrid detectors to become a useful tool also for soft X-ray detection. In this work we present the optimization of the entrance window by studying the internal quantum efficiency of eight different process technology variations. The sensors are characterized using light emitting diodes with a wavelength of 405 nm. At this wavelength, the light has an absorption depth of 125 nm, equivalent to that of 276 eV X-rays. The best variation achieves an internal quantum efficiency of 0.992 for 405 nm UV light. Based on this study, further optimization of the quantum efficiency for soft X-rays detection is planned.

Published
2023

19. Incidence of myeloid neoplasms in Spain (2002–2013): a population-based study of the Spanish network of cancer registries

Author

Solans, M., Sanvisens, A., Ameijide, Alberto, Merino, S., Rojas, Dolores, Alemán, A., Banqueri, E., Chico, Matilde, Marcos, A.I., de Castro, Visitación, Gil, L., López de Munain, Arantza, Puigdemont, Montse, Sánchez, M.J., Perucha, J., Ruiz-Armengol, P., Chirlaque, María-Dolores, Guevara, M., Carulla, M., Marcos-Gragera, Rafael, and Universitat Autònoma de Barcelona

Subjects
Adult, Male, Time Factors, Càncer -- Estadístiques, Epidemiology, Science, Leucèmia mieloide, Article, Myeloproliferative disease, Humans, Registries, Aged, Aged, 80 and over, Multidisciplinary, Myeloproliferative Disorders, Cancer -- Statistics, Incidence, Tumors -- Espanya, Middle Aged, Health Surveys, Leukemia, Myeloid, Acute, Tumors -- Spain, Myeloid leukemia, Spain, Myelodysplastic Syndromes, Medicine, Female, Myelodysplastic syndrome
Abstract

This work was partially funded by the Josep Carreras Leukaemia Research Institute (Grant No.: FIJC1100); the Ministry of Science, Innovation and Universities, Carlos III Health Institute (ISCIII), Spain (Grant No.: PI15/00966); the Agency for Management of University and Research Grants, Government of Catalonia (Grant No.: 2017SGR00733); the CIBER of Epidemiology and Public Health (CIBERESP) (`Cohort-Real World Data' subprogram)., Comprehensive population-based data on myeloid neoplasms (MNs) are limited, mainly because some subtypes were not recognized as hematological cancers prior to the WHO publication in 2001, and others are too rare to allow robust estimates within regional studies. Herein, we provide incidence data of the whole spectrum of MNs in Spain during 2002–2013 using harmonized data from 13 population-based cancer registries. Cases (n = 17,522) were grouped following the HAEMACARE groupings and 2013-European standardized incidence rates ( ASRE), incidence trends, and estimates for 2021 were calculated. ASRE per 100,000 inhabitants was 5.14 (95% CI: 5.00–5.27) for myeloproliferative neoplasms (MPN), 4.71 (95% CI: 4.59–4.84) for myelodysplastic syndromes (MDS), 3.91 (95% CI: 3.79–4.02) for acute myeloid leukemia, 0.83 (95% CI: 0.78–0.88) for MDS/MPN, 0.35 (95% CI: 0.32–0.39) for acute leukemia of ambiguous lineage, and 0.58 (95% CI: 0.53–0.62) for nototherwise specified (NOS) cases. This study highlights some useful points for public health authorities, such as the remarkable variability in incidence rates among Spanish provinces, the increasing incidence of MPN, MDS, and MDS/MPN during the period of study, in contrast to a drop in NOS cases, and the number of cases expected in 2021 based on these data (8446 new MNs)., Josep Carreras Leukaemia Research Institute FIJC1100, Ministry of Science, Innovation and Universities, Carlos III Health Institute (ISCIII), Spain PI15/00966, Agency for Management of University and Research Grants, Government of Catalonia 2017SGR00733, CIBER of Epidemiology and Public Health (CIBERESP) ('Cohort-Real World Data' subprogram)

Published
2022

20. Advancing the JUNGFRAU detector toward low-energy X-ray applications

Author

Hinger, V., al Haddad, A., Barten, R., Bergamaschi, A., Brückner, M., Carulla, M., Chiriotti-Alvarez, S., Dinapoli, R., Ebner, S., Fröjdh, E., Greiffenberg, D., Hasanaj, S., King, T., Kozlowski, P., Lopez-Cuenca, C., Mezza, D., Moustakas, K., Mozzanica, A., Ozerov, D., Ruder, C., Schmitt, B., Schnorr, K.A., Thattil, D., and Zhang, J.

Subjects
Instrumentation, Mathematical Physics
Abstract

The charge-integrating hybrid silicon pixel detector JUNGFRAU has found widespread use at free-electron laser and synchrotron facilities. The detector was designed for use with hard X-rays; yet, because of its low noise, high dynamic range, position resolution, and scalable size, JUNGFRAU is of high interest for soft X-ray applications. We discuss improvements of the readout chip and alterations of the entrance window at the back of the sensor that facilitate low-energy X-ray detection. The first use case of the improved system at a low-energy beamline demonstrates single photon sensitivity down to 800 eV. At lower energies, the readout noise of the hybrid detector hinders the resolution of single photons. We propose to couple the JUNGFRAU readout chip with charge-multiplying low-gain avalanche diode (LGAD) sensors to resolve X-ray photons with a minimum energy of 250 eV.

Published
2022

21. Inverse Low Gain Avalanche Detectors (iLGADs) for precise tracking and timing applications

Author

Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Currás, Esteban, Carulla, M., Centis Vignali, M., Duarte Campderros, J., Fernández-García, Marcos, Flores, David, García Alonso, A., Gómez, Gervasio, González, Javier G., Hidalgo, Salvador, Jaramillo, R., Merlos Domingo, Ángel, Moll, Michael, Pellegrini, Giulio, Quirion, David, Vila, Iván, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Currás, Esteban, Carulla, M., Centis Vignali, M., Duarte Campderros, J., Fernández-García, Marcos, Flores, David, García Alonso, A., Gómez, Gervasio, González, Javier G., Hidalgo, Salvador, Jaramillo, R., Merlos Domingo, Ángel, Moll, Michael, Pellegrini, Giulio, Quirion, David, and Vila, Iván

Abstract

Low Gain Avalanche Detector (LGAD) is the baseline sensing technology of the recently proposed Minimum Ionizing Particle (MIP) end-cap timing detectors (MTD) at the Atlas and CMS experiments. The current MTD sensor is designed as a multi-pad matrix detector delivering a poor position resolution, due to the relatively large pad area, around 1 mm2; and a good timing resolution, around 20–30 ps. Besides, in his current technological incarnation, the timing resolution of the MTD LGAD sensors is severely degraded once the MIP particle hits the inter-pad region since the signal amplification is missing for this region. This limitation is named as the LGAD fill-factor problem. To overcome the fill factor problem and the poor position resolution of the MTD LGAD sensors, a p-in-p LGAD (iLGAD) was introduced. Contrary to the conventional LGAD, the iLGAD has a non-segmented deep p-well (the multiplication layer). Therefore, iLGADs should ideally present a constant gain value over all the sensitive region of the device without gain drops between the signal collecting electrodes; in other words, iLGADs should have a 100% fill-factor by design. In this paper, tracking and timing performance of the first iLGAD prototypes is presented.

Published
2020

22. Excess mortality among breast cancer patients in early stages in Tarragona and Gerona (Spain) [Exceso de mortalidad en las pacientes con cáncer de mama en estadios precoces en Tarragona y Gerona (España)]

Author

Universitat Rovira i Virgili, Clèries R., Ameijide A., Buxó M., Vilardell M., Martínez J.M., Marcos-Gragera R., Vilardell M.L., Carulla M., Espinàs J.A., Galceran J., Borràs J.M., Izquierdo Á., Universitat Rovira i Virgili, and Clèries R., Ameijide A., Buxó M., Vilardell M., Martínez J.M., Marcos-Gragera R., Vilardell M.L., Carulla M., Espinàs J.A., Galceran J., Borràs J.M., Izquierdo Á.

Abstract

© 2018 SESPAS Objective: To analyze the population-based survival of breast cancer (CM) diagnosed in early stages estimating the time trends of excess mortality (EM) in the long term in annual and five-year time intervals, and to determine, if possible, a proportion of patients who can be considered cured. Method: We included women diagnosed with BC under the age of 60 years in stages I and II in Girona and Tarragona (N = 2453). The observed (OS) and relative survival (RS) were calculated up to 20 years of follow-up. RS was also estimated at annual (RSI) and in five-year intervals (RS5) to graphically assess the EM. The results are presented by age groups (≤49 and 50-59), stage (I/II) and diagnostic period (1985-1994 and 1995-2004). Results: In stage I, OS and RS were higher during 1995-2004 compared to 1985-1994: 3.5% at 15 years of follow-up and 4.5% at 20-years of follow-up. In 1995-2004, the OS surpassed 80% in stage I patients whereas in stage II it remained below 70%. During 1995-2004, the long-term EM did not level off towards 0 (RSI <1) independently of age group, stage and period of diagnosis. After 15 years of follow-up, the 5-year EM oscillated between 1 and 5% in stage I (RS5 ≥0.95) and between 5 and 10% in stage II. Conclusions: In our cohort, after 15 years of follow-up, it was detected that the annual EM did not disappear and the five-year EM remained between 1 and 10%. Therefore, it was not possible to determine a cure rate of BC during the study period.

Published
2020

23. Reasons for low cervical cancer survival in new accession European Union countries: a EUROCARE-5 study

Author

Bielska-Lasota, M., Rossi, S., Krzyzak, M., Haelens, A., Domenic, A., De Angelis, R., Maciejczyk, A., Rodriguez-Barranco, M., Zadnik, V., Minicozzi, P., Hackl, M., Ihle, P., Vaneycken, E., Henau, K., Valerianova, Z., Dimitrova, N., Sekerija, M., Cukelj, P., Dusek, L., Zvolsky, M., Magi, M., Aareleid, T., Malila, N., Seppa, K., Velten, M., Guizard, A. V., Faivre, J., Woronoff, A. S., Tretarre, B., Bossard, N., Uhry, Z., Colonna, M., Molinie, F., Cowppli-Bony, A., Bara, S., Lapotre-Ledoux, B., Grosclaude, P., Stabenow, R., Luttmann, S., Eberle, A., Brenner, H., Nennecke, A., Engel, J., Schubert-Fritschle, G., Heidrich, J., Holleczek, B., Katalinic, A., Birgisson, H., Tryggvadottir, L., Clough-Gorr, K., Mazzoleni, G., Bulatko, A., Buzzoni, C., Suterasardo, A., Mancuso, P., Ferretti, S., Barchielli, A., Caldarella, A., Gatta, G., Sant, M., Amati, C., Baili, P., Berrino, F., Bonfarnuzzo, S., Botta, L., Capocaccia, R., Foschi, R., Margutti, C., Meneghini, E., Trama, A., Serraino, D., Dalmaso, L., Deangelis, R., Dibenedetto, C., Caldora, M., Francisci, S., Galati, F., Mallone, S., Pierannunzio, D., Tallon, M., Santaquilani, M., Tavilla, A., Pannozzo, F., Busco, S., Filiberti, R. A., Marani, E., Ricci, P., Spagnoli, G., Cirilli, C., Fusco, M., Vitale, M. F., Usala, M., Vitale, F., Mazzucco, W., Michiara, M., Zanetti, R., Rosso, S., Tumino, R., Mangone, L., Difelice, E., Russo, A. G., Andreano, A., Falcini, F., Caiazzo, A. L., Cesaraccio, R., Piffer, S., Madeddu, A., Tisano, F., Fanetti, A. C., Cometti, I., Candela, P., Scuderi, T., Stracci, F., Bianconi, F., Tagliabue, G., Contiero, P., Rugge, M., Zorzi, M., Pildava, S., Smailyte, G., Azzopardi, M., Calleja, N., Johannesen, T. B., Rachtan, J., Gozdz, S., Macek, P., Blaszczyk, J., Bebenek, M., Forjaz deLacerda, G., Bento, M. J., Antunes, L., Miranda, A., Mayer-da-Silva, A., Safaeidiba, C., Primic-Zakelj, M., Lopez deMunain, A., Gil, L., Diazgarcia, J. M., Marcos-Navarro, A. I., Marcos-Gragera, R., Puigdemont, M., Sanchez, M. J., Chang, D. Y. L., Chirlaque, M. D., Ardanaz, E., Guevara, M., Galceran, J., Carulla, M., Lambe, M., Khan, S., Staehelin, K., Bouchardy, C., Fournier, E., Mousavi, S. M., Ess, S. M., Lorez, M., Mousavi, M., Herrmann, C., Bordoni, A., Spitale, A., Konzelmann, I., Visser, O., Aarts, M., Otter, R., Coleman, M., Allemani, C., Rachet, B., Rashbass, J., Broggio, J., Verne, J., Gavin, A., Donnelly, D., Morrison, D., Black, R., Huws, D. W., Thomas, R., Bielska‑Lasota, M, Rossi, S, Krzyżak, M, Haelens, A, Domenic, A, De Angelis, R, Maciejczyk, A, Rodríguez‑Barranco, M, Zadnik, V, Minicozzi, P, Vitale, F, and Mazzucco, W

Subjects
Morphology, Adult, Male, Stage at diagnosi, Survival, Adolescent, Socio-culturale, Uterine Cervical Neoplasms, Disease, Settore MED/42 - Igiene Generale E Applicata, 03 medical and health sciences, 0302 clinical medicine, Medicine, media_common.cataloged_instance, Humans, European Union, European union, Survival rate, Population-based study, media_common, Aged, Retrospective Studies, Cervical cancer, Aged, 80 and over, Cervical cancer, Europe, Morphology, Population-based study, Stage at diagnosis, Survival, 030219 obstetrics & reproductive medicine, Relative survival, business.industry, Absolute risk reduction, Obstetrics and Gynecology, Retrospective cohort study, Stage at diagnosis, General Medicine, Middle Aged, medicine.disease, Europe, Eastern european, Survival Rate, 030220 oncology & carcinogenesis, Female, business, Demography
Abstract

Purpose: With better access to early diagnosis and appropriate treatment, cervical cancer (CC) burden decreased in several European countries. In Eastern European (EE) countries, which accessed European Union in 2004, CC survival was worse than in the rest of Europe. The present study investigates CC survival differences across five European regions, considering stage at diagnosis (local, regional and metastatic), morphology (mainly squamous versus glandular tumours) and patients’ age. Methods: We analysed 101,714 CC women diagnosed in 2000–2007 and followed-up to December 2008. Age-standardised 5-year relative survival (RS) and the excess risks of cancer death in the 5years after diagnosis were computed. Results: EE women were older and less commonly diagnosed with glandular tumours. Proportions of local stage cancers were similar across Europe, while morphology- and stage-specific RS (especially for non-metastatic disease) were lower in Eastern Europe. Adjusting for age and morphology, excess risk of local stage CC death for EE patients remained higher than that for other European women. Conclusion: Stage, age and morphology alone do not explain worse survival in Eastern Europe: less effective care may play a role, probably partly due to fewer or inadequate resources being allocated to health care in this area, compared to the rest of Europe.

Published
2019

24. Epidemiology of congenital Chagas disease 6 years after implementation of a public health surveillance system, Catalonia, 2010 to 2015

Author

Martin-Nalda, A, Cebollero, A, Carrascon, A, Moreira, A, Requena-Mendez, A, Soto, AT, Martin, A, Ballester, A, Bragulat, A, Soligo, A, Bastarras, AV, Paya, A, Soriano-Arandes, A, Sorni, A, Calvo, A, Mur, A, Colomer, A, Carral, B, Trevino, B, Guarch, B, Orta, C, Rodrigo, C, Galles, C, Garrido, C, Molina, C, Mora, C, Munoz, C, Marti, C, Sanjose, C, Guardia, C, Cortes, C, Gutierrez, C, Martinez, C, Riera, C, Soler, C, Gonzalez, D, Guix, D, Mir, ES, Padilla, E, Sulleiro, E, Llurba, E, Del Amo, E, Moliner, E, Esteba, EP, Coll, E, Rodriguez, E, Monaco, E, Munoz, E, Freixas, E, Dopico, E, Sarda, E, Ballester, F, Gomez, F, Barranco, F, Ripoll, F, Fargas, FJ, Falguera, G, Fernandez-Rivas, G, Ginovart, G, Navarro, G, Garcia-Pardo, G, Lorenzo, G, Ouaarab, H, Caubet, I, Claveria, I, Sanfeliu, I, Molina, I, Blanch, J, Marti, JA, Farre, J, Gascon, J, Costa, J, Prat, JGI, Fulquet, J, Jove, JP, Armengol, J, Riera, JC, Villar, J, Torrent, LS, De La Torre, L, Delgado, L, Valerio, L, Montsant, L, Basile, L, Mayol, L, Valls, ME, Vives, MA, Sauca, MG, Coll, M, Pinazo, MJ, Ferri, MJ, Vidal, MJ, Villegas, ML, Anquela, MAS, Monsonis, M, Blasco, MP, Perez-Moreno, MO, Sabates, MC, Mendez, M, Navarro, M, Urcola, M, Lora, M, Almirall, M, Arasa, M, Alaball, MV, Carulla, M, Jane, M, Ribell-Bachs, M, Abella, M, Gallego, M, Prat, N, Rius, N, Bosh, NP, Garcia, P, Araujo, P, Sole, P, Ciruela, P, Villalobos, P, Almirall, R, Diaz, R, Puigarnau, R, Serra, R, Diez, R, Bosch, ST, Franch, S, Vega, S, Mani, SG, Juncosa, T, Pineda, V, Fumado, V, and Urquizu, X

Abstract

Background: Chagas disease is endemic in Latin America and affects 8 million people worldwide. In 2010, Catalonia introduced systematic public health surveillance to detect and treat congenital Chagas disease. Aim: The objective was to evaluate the health outcomes of the congenital Chagas disease screening programme during the first 6 years (2010-2015) after its introduction in Catalonia. Methods: In a surveillance system, we screened pregnant women and newborns and other children of positive mothers, and treated Chagas-positive newborns and children. Diagnosis was confirmed for pregnant women and children with two positive serological tests and for newborns with microhaematocrit and/or PCR at birth or serology at age 9 months. Results: From 2010 to 2015, the estimated screening coverage rate increased from 68.4% to 88.6%. In this period, 33,469 pregnant women were tested for Trypanosoma cruzi and 937 positive cases were diagnosed. The overall prevalence was 2.8 cases per loo pregnancies per year (15.8 in Bolivian women). We followed 82.8% of newborns until serological testing at age 9-12 months and 28 were diagnosed with Chagas disease (congenital transmission rate: 4.17%). Of 518 siblings, 178 (34.3%) were tested and 14 (7.8%) were positive for T. cruzi. Having other children with Chagas disease and the heart clinical form of Chagas disease were maternal risk factors associated with congenital T. cruzi infection (p < 0.05). Conclusion: The increased screening coverage rate indicates consolidation of the programme in Catalonia. The rate of Chagas disease congenital transmission in Catalonia is in accordance with the range in non-endemic countries.

Published
2019

26. Geographical variability in survival of European children with central nervous system tumours

Author

Storm, H., Engholm, G., Mã¤gi, M., Aareleid, T., Bossard, N., Uhry, Z., Brenner, H., Comber, H., Buzzoni, C., Gatta, G., Sant, M., Amash, H., Amati, C., Baili, P., Berrino, F., Bonfarnuzzo, S., Botta, L., Capocaccia, R., Di Salvo, F., Foschi, R., Margutti, C., Meneghini, E., Minicozzi, P., Trama, A., Tagliabue, G., Contiero, P., Serraino, D., Zucchetto, A., De Angelis, R., Caldora, M., Carrani, E., Francisci, S., Mallone, S., Pierannunzio, D., Roazzi, P., Rossi, S., Santaquilani, M., Tavilla, A., Piffer, S., Calleja, N., Agius, D., Bielska-Lasota, M., Primic-Zakelj, M., Peris-Bonet, R., Pardo Romaguera, E., Lambe, M., Coleman, M., Allemani, C., Rachet, B., Stiller, C., Visser, O., Marcos-Gragera, R., Sã¡nchez, M. -. J., Lacour, B., Kaatsch, P., Rutkowsky, S., Hackl, M., Zielonke, N., Oberaigner, W., Van Eycken, E., Henau, K., Valerianova, Z., Dimitrova, N., Sekerija, M., Malila, N., Seppã¤, K., Faivre, J., Colonna, M., Clavel, J., Desandes, E., Katalinic, A., Garami, M., Jakab, Z., Mazzoleni, G., Bulatko, A., Giacomin, A., Sutera Sardo, A., Mancuso, P., Ferretti, S., Barchielli, A., Caldarella, A., Pannozzo, F., Busco, S., Filiberti, R. A., Marani, E., Ricci, P., Pascucci, C., Autelitano, M., Spagnoli, G., Cirilli, C., Fusco, M., Vitale, M. F., Usala, M., Vitale, F., Ravazzolo, B., Michiara, M., Merletti, F., Maule, M., Tumino, R., Mangone, L., Di Felice, E., Falcini, F., Iannelli, A., Sechi, O., Cesaraccio, R., Madeddu, A., Tisano, F., Maspero, S., Fanetti, A. C., Candela, P., Scuderi, T., Stracci, F., Bianconi, F., Rugge, M., Guzzinati, S., Pildava, S., Smailyte, G., Johannesen, T. B., Rachtan, J., Gã³åºdåº, S., Mężyk, R., BÅ‚aszczyk, J., BÄ™benek, M., Forjaz de Lacerda, G., Bento, M. J., Castro, C., Miranda, A., Mayer-da-Silva, A., Safaei Diba, C., Errezola, M., Bidaurrazaga, J., Vicente Raneda, M., Díaz García, J. M., Marcos-Navarro, A. I., Izquierdo Font, A., Sanchez, M. J., Chang, D. Y. L., Navarro, C., Chirlaque, M. D., Moreno-Iribas, C., Ardanaz, E., Galceran, J., Carulla, M., Mousavi, M., Bouchardy, C., Usel, M., Ess, S. M., Frick, H., Lorez, M., Herrmann, C., Bordoni, A., Spitale, A., Konzelmann, I., Aarts, M., Otter, R., Verne, J., Gavin, A., Donnelly, C., Brewster, D. H., Storm H., Engholm G., Magi M., Aareleid T., Bossard N., Uhry Z., Brenner H., Comber H., Buzzoni C., Gatta G., Sant M., Amash H., Amati C., Baili P., Berrino F., Bonfarnuzzo S., Botta L., Capocaccia R., Di Salvo F., Foschi R., Margutti C., Meneghini E., Minicozzi P., Trama A., Tagliabue G., Contiero P., Serraino D., Zucchetto A., De Angelis R., Caldora M., Carrani E., Francisci S., Mallone S., Pierannunzio D., Roazzi P., Rossi S., Santaquilani M., Tavilla A., Piffer S., Calleja N., Agius D., Bielska-Lasota M., Primic-Zakelj M., Peris-Bonet R., Pardo Romaguera E., Lambe M., Coleman M., Allemani C., Rachet B., Stiller C., Visser O., Marcos-Gragera R., Sanchez M.-J., Lacour B., Kaatsch P., Rutkowsky S., Hackl M., Zielonke N., Oberaigner W., Van Eycken E., Henau K., Valerianova Z., Dimitrova N., Sekerija M., Malila N., Seppa K., Faivre J., Colonna M., Clavel J., Desandes E., Katalinic A., Garami M., Jakab Z., Mazzoleni G., Giacomin A., Sutera Sardo A., Mancuso P., Ferretti S., Barchielli A., Caldarella A., Pannozzo F., Busco S., Filiberti R.A., Marani E., Ricci P., Pascucci C., Autelitano M., Spagnoli G., Cirilli C., Fusco M., Vitale M.F., Usala M., Vitale F., Ravazzolo B., Michiara M., Merletti F., Maule M., Tumino R., Mangone L., Di Felice E., Falcini F., Iannelli A., Sechi O., Cesaraccio R., Madeddu A., Tisano F., Maspero S., Fanetti A.C., Candela P., Scuderi T., Stracci F., Bianconi F., Rugge M., Guzzinati S., Pildava S., Smailyte G., Johannesen T.B., Rachtan J., Gozdz S., Mezyk R., Blaszczyk J., Bebenek M., Forjaz de Lacerda G., Bento M.J., Castro C., Miranda A., Mayer-da-Silva A., Safaei Diba C., Errezola M., Bidaurrazaga J., Vicente Raneda M., Diaz Garcia J.M., Marcos-Navarro A.I., Izquierdo Font A., Sanchez M.J., Chang D.Y.L., Navarro C., Chirlaque M.D., Moreno-Iribas C., Ardanaz E., Galceran J., Carulla M., Mousavi M., Bouchardy C., Usel M., Ess S.M., Frick H., Lorez M., Herrmann C., Bordoni A., Spitale A., Konzelmann I., Aarts M., Otter R., Verne J., Gavin A., Donnelly C., and Brewster D.H.

Subjects
0301 basic medicine, Male, Cancer Research, Pediatrics, medicine.medical_specialty, Childhood cancer survival, Europe, Population-based cancer registries, Disparities, Central nervous system, Adolescent, Population, Population-based cancer registrie, Socio-culturale, Disparities, Central Nervous System Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Epidemiology of cancer, Childhood cancer survival, Medicine, Humans, Preschool, education, Child, Grading (tumors), Survival rate, Survival analysis, education.field_of_study, business.industry, Proportional hazards model, Incidence, Hazard ratio, Central Nervous System Neoplasm, Infant, Population-based cancer registries, Disparitie, Survival Analysis, Europe, 030104 developmental biology, Oncology, Central nervous system, 030220 oncology & carcinogenesis, Child, Preschool, Female, Death certificate, business, Human
Abstract

Survival for childhood central nervous system (CNS) tumours varies across Europe, partly because of the difficulty of distinguishing malignant from non-malignant disease. This study examines bias in CNS tumours survival analysis to obtain the reliable and comparable survival figures. We analysed survival data for about 15, 000 children (age

Published
2017

29. Low gain avalanche detectors

Author

Carulla, M.

Subjects
Advanced hybrid pixel detectors [7], Detectors and Experimental Techniques
Published
2015

30. Recent technological developments on LGAD and iLGAD detectors for tracking and timing applications

Author

European Commission, European Organization for Nuclear Research, Ministerio de Economía y Competitividad (España), Pellegrini, Giulio, Baselga, M., Carulla, M., Fernández Martínez, Patricia, Fernández-García, Marcos, Flores, David, Gallrapp, Christian, Hidalgo, Salvador, Merlos Domingo, Ángel, Moll, Michael, Quirion, David, Vila, Iván, European Commission, European Organization for Nuclear Research, Ministerio de Economía y Competitividad (España), Pellegrini, Giulio, Baselga, M., Carulla, M., Fernández Martínez, Patricia, Fernández-García, Marcos, Flores, David, Gallrapp, Christian, Hidalgo, Salvador, Merlos Domingo, Ángel, Moll, Michael, Quirion, David, and Vila, Iván

Abstract

This paper reports the latest technological development on the Low Gain Avalanche Detector (LGAD) and introduces a new architecture of these detectors called inverse-LGAD (iLGAD). Both approaches are based on the standard Avalanche Photo Diodes (APD) concept, commonly used in optical and X-ray detection applications, including an internal multiplication of the charge generated by radiation. The multiplication is inherent to the basic n–p–p structure, where the doping profile of the p layer is optimized to achieve high field and high impact ionization at the junction. The LGAD structures are optimized for applications such as tracking or timing detectors for high energy physics experiments or medical applications where time resolution lower than 30 ps is required. Detailed TCAD device simulations together with the electrical and charge collection measurements are presented through this work.

Published
2016

31. Time trends of cancer incidence and mortality in Catalonia during 1993-2007

Author

Medicina i Cirurgia, Universitat Rovira i Virgili, Ribes, J, Gispert, R, Izquierdo, A, Puigdefabregas, A, Buxo, M, Carulla, M, Freitas, A, Marcos-Gragera, R, Borras, J, Esteban, L, Cleries, R, GALCERAN PADRÓS, JAUME JOSEP MARIA, BORRAS BALADA, JOAN LLUÍS, Medicina i Cirurgia, Universitat Rovira i Virgili, Ribes, J, Gispert, R, Izquierdo, A, Puigdefabregas, A, Buxo, M, Carulla, M, Freitas, A, Marcos-Gragera, R, Borras, J, Esteban, L, Cleries, R, GALCERAN PADRÓS, JAUME JOSEP MARIA, and BORRAS BALADA, JOAN LLUÍS

Abstract

To describe time trends of cancer in Catalonia, Spain, during the period 1993-2007.Data have been provided by two population-based cancer registries, Girona and Tarragona, and the Catalan mortality registry. Cancer incidence in Catalonia has been estimated through modeling methods using data from these health structures.During 2003-2007, there were 20,042 cancer cases and 9,842 deaths per year among men and 13,673 new cancer cases and 5,882 deaths among women. The most frequent incident cancers among men were prostate (N = 4,258), lung (N = 3,021), colorectal (N = 3,007) and bladder (N = 2,238), whereas among women they were breast (N = 3,907), colorectal (N = 2,088), corpus uteri (N = 734) and lung (N = 527). During 1993-2007, age-standardized incidence rates (ASIRs) rose 1.2 % per year among men [prostate (6.3 %), testis (5.7 %), kidney (2.9 %), liver (2.2 %) and colorectal (2.1 %)]. ASIRs decreased for stomach (-2.9 %), oral cavity and pharynx (-2.8 %), larynx (-2.7 %) and esophagus (-2 %). Among women, ASIRs only rose for lung (5.2 %), kidney (3.1 %), oral cavity and pharynx (2.6 %) and thyroid (1.6 %). ASIRs decreased for corpus uteri (-2.3 %), stomach (-1.7 %) and ovary (-1.6 %). Cancer mortality decreased -1.3 % per year among men and -2.1 % among women during the same period.Among men, the decrease of incidence/mortality of tobacco-related tumors was related to a reduction of smoking prevalence. Among women, the stabilization of breast cancer incidence and the rise of lung cancer incidence are similar to that observed in most European regions. These results allow assessing the effectiveness of public health strategies and they pose new frontiers for cancer control in Catalonia.

Published
2014

32. Dermoscopy of pyogenic granuloma: a morphological study.

Author

Universitat Rovira i Virgili, Zaballos P, Carulla M, Ozdemir F, Zalaudek I, Bañuls J, Llambrich A, Puig S, Argenziano G, Malvehy J, Universitat Rovira i Virgili, and Zaballos P, Carulla M, Ozdemir F, Zalaudek I, Bañuls J, Llambrich A, Puig S, Argenziano G, Malvehy J

Abstract

Pyogenic granuloma is a common, benign, vascular lesion of the skin and mucous membranes which is a simulator of amelanotic/hypomelanotic melanoma and other tumours.To determine the diagnostic significance of dermoscopic structures and patterns associated with pyogenic granulomas in a large series of cases.Digital dermoscopic images of histopathologically proven cases of 122 pyogenic granulomas and 140 other tumours (28 amelanotic melanomas, seven melanoma metastases, 22 basal cell carcinomas and 83 other tumours) were collected from university hospitals in Spain, Italy, Austria and Turkey. The frequency, sensitivity, specificity, positive predictive value, negative predictive value, intraobserver agreement and interobserver agreement of the dermoscopic structures and patterns associated with pyogenic granulomas were calculated.Vascular structures were observed in 45% of pyogenic granulomas (sensitivity of 45·1% and specificity of 17·9%; both P < 0·001). Seven exclusive patterns were made up from the combination of the structures 'reddish homogeneous area' (RHA), 'white collarette' (WC), 'white rail lines' (WRL) and 'vascular structures' (VS). The pattern composed of RHA, WC and WRL showed the highest sensitivity (22·1%; P < 0·001) and a specificity of 100% (P < 0·001) for pyogenic granulomas. Two other patterns (RHA + WC and RHA + WC +?WRL + VS) showed 100% specificity when compared with melanoma (P < 0·001 and P < 0·05, respectively).Even though some dermoscopic patterns are useful in the recognition of pyogenic granulomas, dermoscopy is not a substitute for histology, mostly when vessels are present, as melanoma cannot be ruled out.© 2010 The Authors. BJD © 2010 British Association of Dermatologists.

Published
2010

34. High-spatial resolution measurements with a GaAs:Cr sensor using the charge integrating MÖNCH detector with a pixel pitch of 25 μm

Author

Chiriotti, Sabina, Barten, Rebecca, Bergamaschi, Anna, Carulla, M., Chsherbakov, Ivan, Dinapoli, Roberto, Fröjdh, Erik, Greiffenberg, Dominic, Hasanaj, Shqipe, Hinger, V., King, T., Kozlowski, Pawel, López-Cuenca, Carlos, Lozinskaya, Anastassiya D., Marone, F., Mezza, Davide, Moustakas, K., Mozzanica, Aldo, Ruder, Christian, Schmitt, Bernd, Thattil, Dhanya, Tolbanov, Oleg P., Tyazhev, Anton V., Zarubin, Andrei N., Zhang, J., and Brückner, Martin

Subjects
детекторы рентгеновского излучения, обработка изображения, Physics::Instrumentation and Detectors, Instrumentation, гибридные детекторы, Mathematical Physics
Abstract

The aim of this project is to determine the imaging capabilities of a 25 μm pixel pitch GaAs:Cr sensor of 500 μm thickness bump-bonded to the charge integrating MÖNCH 03 readout chip (also called GaAs-MÖNCH assembly) and to assess the possibility to improve the spatial resolution by applying a position interpolation algorithm developed at PSI. Measurements were performed at the TOMCAT beamline of the Swiss Light Source (SLS) using photon beams in the energy range of 10–30 keV. The imaging experiments indicate the possibility to enhance the spatial resolution of the detector beyond its actual physical pixel pitch. We have quantified the spatial resolution of a GaAs-MÖNCH assembly by means of the modulation transfer function (MTF), achieving 10 μm at 10 keV and 12 μm at 20 keV photon energies. By applying a modified interpolation algorithm, a spatial resolution of ∼5 μm was obtained for 16 keV when binning to 2.5 μm virtual pixels, while with the silicon-MÖNCH assembly, we achieved a spatial resolution of 3.5 μm, which serves as gold standard. The results are promising because they open new possibilities to perform imaging measurements using the GaAs-MÖNCH assembly at photon energies above 15 keV, where silicon sensors suffer from a diminishing quantum efficiency.

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35. First case of bacteraemia due to Acinetobacter schindleri harbouring blaNDM-1 in an immunocompromised patient.

Author

Montaña, S., Palombarani, S., Carulla, M., Kunst, A., Rodriguez, C.H., Nastro, M., Vay, C., Ramirez, M.S., and Almuzara, M.

Subjects
*ACINETOBACTER, *IMMUNOCOMPROMISED patients, *STRAIN rate, *CRYPTOCOCCUS neoformans, *BACTERIA
Abstract

Clinically significant NDM-1-producing Acinetobacter schindleri has not yet been described in the literature. We report the first case of bacteraemia due to an A. schindleri strain harbouring bla NDM-1 recovered from an immunocompromised patient. Our report reinforces the fact that NDM-1 can easily be acquired by Acinetobacter species. [ABSTRACT FROM AUTHOR]

Published
2018
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36. ORIGINAL ARTICLE Mechanisms of reduced susceptibility to amoxycillin–clavulanic acid in Escherichia coli strains from the health region of Tortosa (Catalonia, Spain).

Author

Pérez-Moreno, M. O., Pérez-Moreno, M., Carulla, M., Rubio, C., Jardí, A. M., and Zaragoza, J.

Subjects
*CLAVULANIC acid, *ESCHERICHIA coli, *DRUG resistance in microorganisms
Abstract

This study investigated the mechanisms involved in reduced susceptibility to amoxycillin–clavulanic acid and the prevalence of enzymes compatible with inhibitor-resistant TEM (IRT) β-lactamases produced by Escherichia coli isolates from patients in north-eastern Spain. The resistance mechanisms of 158 strains showing resistance or intermediate resistance to amoxycillin–clavulanic acid among 1122 ampicillin-resistant clinical isolates of E. coli were assessed on the basis of their β-lactam resistance phenotypes. β-Lactamases produced by strains showing resistant phenotypes suggestive of inhibitor-resistant penicillinase production were characterised by their isoelectric point. Specific activity and the concentration of clavulanic acid required to inhibit β-lactamase activity by 50% (IC50) were determined in strains harbouring enzymes that focused at pI 5.2 or 5.4 in order to achieve presumptive identification of IRT β-lactamases. Resistance phenotypes were consistent with overproduction of TEM-1, TEM-2 or SHV-1 β-lactamases in 56 strains, with AmpC cephalosporinase hyperproduction in 46 strains, and with production of inhibitor-resistant penicillinases in 49 strains. Of the latter isolates, 17 produced moderately high or high levels of enzymes co-focusing with TEM-1, 17 produced enzymes co-focusing with OXA-1 ( n = 12) or with PSE-1 ( n = 5), either alone or in association with TEM-1, while only 15 produced enzymes with a phenotype characteristic of IRT β-lactamases. It was concluded that resistance to amoxycillin–clavulanic acid in E. coli isolates from this area was mainly associated with presumptive overproduction of TEM-1, TEM-2 or SHV-1 β-lactamases (46%) or of AmpC cephalosporinase (29%), while the occurrence of enzymes categorised as IRT β-lactamases was unusual (9.5%). [ABSTRACT FROM AUTHOR]

Published
2004
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37. Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours

Author

Panagis M. Lykoudis, Stefano Partelli, Francesca Muffatti, Martyn Caplin, Massimo Falconi, Giuseppe K. Fusai, Monika Hackl, Elizabeth Van Eycken, Kris Henau, Nadya Dimitrova, Mario Sekerija, Ladislav Dušek, Margit Mägi, Nea Malila, Maarit Leinonen, Michel Velten, Xavier Troussard, Veronique Bouvier, Anne-Valérie Guizard, Anne-Marie Bouvier, Patrick Arveux, Marc Maynadié, Anne-Sophie Woronoff, Michel Robaszkiewicz, Isabelle Baldi, Alain Monnereau, Brigitte Tretarre, Marc Colonna, Florence Molinié, Simona Bara, Claire Schvartz, Bénédicte Lapôtre-Ledoux, Pascale Grosclaude, Roland Stabenow, Sabine Luttmann, Alice Nennecke, Jutta Engel, Gabriele Schubert-Fritschle, Jan Heidrich, Bernd Holleczek, Jón Gunnlaugur Jónasson, Kerri Clough-Gorr, Harry Comber, Guido Mazzoleni, Adriano Giacomin, Antonella Sutera Sardo, Alessandro Barchielli, Diego Serraino, Roberta De Angelis, Sandra Mallone, Andrea Tavilla, Daniela Pierannunzio, Silvia Rossi, Mariano Santaquilani, Arnold Knijn, Fabio Pannozzo, Valerio Gennaro, Lucia Benfatto, Paolo Ricci, Mariangela Autelitano, Gianbattista Spagnoli, Mario Fusco, Mario Usala, Francesco Vitale, Maria Michiara, Rosario Tumino, Lucia Mangone, Fabio Falcini, Stefano Ferretti, Rosa Angela Filiberti, Enza Marani, Arturo Iannelli, Flavio Sensi, Silvano Piffer, Maria Gentilini, Anselmo Madeddu, Antonio Ziino, Sergio Maspero, Pina Candela, Fabrizio Stracci, Giovanna Tagliabue, Massimo Rugge, Annalisa Trama, Gemma Gatta, Laura Botta, Riccardo Capocaccia, Santa Pildava, Giedre Smailyte, Neville Calleja, Tom Børge Johannesen, Jadwiga Rachtan, Stanisław Góźdź, Jerzy Błaszczyk, Kamila Kępska, Gonçalo Forjaz de Lacerda, Maria José Bento, Ana Miranda, Chakameh Safaei Diba, Enrique Almar, Nerea Larrañaga, Arantza Lopez de Munain, Ana Torrella-Ramos, José María Díaz García, Rafael Marcos-Gragera, Maria Josè Sanchez, Carmen Navarro, Diego Salmeron, Conchi Moreno-Iribas, Jaume Galceran, Marià Carulla, Mohsen Mousavi, Christine Bouchardy, Silvia M. Ess, Andrea Bordoni, Isabelle Konzelmann, Jem Rashbass, Anna Gavin, David H. Brewster, Dyfed Wyn Huws, Otto Visser, Magdalena Bielska-Lasota, Maja Primic-Zakelj, Ian Kunkler, Ellen Benhamou, Lykoudis, P. M., Partelli, S., Muffatti, F., Caplin, M., Falconi, M., Fusai, G. K., Hackl, M., Van Eycken, E., Henau, K., Dimitrova, N., Sekerija, M., Dusek, L., Magi, M., Malila, N., Leinonen, M., Velten, M., Troussard, X., Bouvier, V., Guizard, A. -V., Bouvier, A. -M., Arveux, P., Maynadie, M., Woronoff, A. -S., Robaszkiewicz, M., Baldi, I., Monnereau, A., Tretarre, B., Colonna, M., Molinie, F., Bara, S., Schvartz, C., Lapotre-Ledoux, B., Grosclaude, P., Stabenow, R., Luttmann, S., Nennecke, A., Engel, J., Schubert-Fritschle, G., Heidrich, J., Holleczek, B., Jonasson, J. G., Clough-Gorr, K., Comber, H., Mazzoleni, G., Giacomin, A., Sardo, A. S., Barchielli, A., Serraino, D., De Angelis, R., Mallone, S., Tavilla, A., Pierannunzio, D., Rossi, S., Santaquilani, M., Knijn, A., Pannozzo, F., Gennaro, V., Benfatto, L., Ricci, P., Autelitano, M., Spagnoli, G., Fusco, M., Usala, M., Vitale, F., Michiara, M., Tumino, R., Mangone, L., Falcini, F., Ferretti, S., Filiberti, R. A., Marani, E., Iannelli, A., Sensi, F., Piffer, S., Gentilini, M., Madeddu, A., Ziino, A., Maspero, S., Candela, P., Stracci, F., Tagliabue, G., Rugge, M., Trama, A., Gatta, G., Botta, L., Capocaccia, R., Pildava, S., Smailyte, G., Calleja, N., Johannesen, T. B., Rachtan, J., Gozdz, S., Blaszczyk, J., Kepska, K., de Lacerda, G. F., Bento, M. J., Miranda, A., Diba, C. S., Almar, E., Larranaga, N., de Munain, A. L., Torrella-Ramos, A., Diaz Garcia, J. M., Marcos-Gragera, R., Sanchez, M. J., Navarro, C., Salmeron, D., Moreno-Iribas, C., Galceran, J., Carulla, M., Mousavi, M., Bouchardy, C., Ess, S. M., Bordoni, A., Konzelmann, I., Rashbass, J., Gavin, A., Brewster, D. H., Huws, D. W., Visser, O., Bielska-Lasota, M., Primic-Zakelj, M., Kunkler, I., Benhamou, E., Lykoudis P.M., Partelli S., Muffatti F., Caplin M., Falconi M., Fusai G.K., Hackl M., Van Eycken E., Henau K., Dimitrova N., Sekerija M., Dusek L., Magi M., Malila N., Leinonen M., Velten M., Troussard X., Bouvier V., Guizard A.-V., Bouvier A.-M., Arveux P., Maynadie M., Woronoff A.-S., Robaszkiewicz M., Baldi I., Monnereau A., Tretarre B., Colonna M., Molinie F., Bara S., Schvartz C., Lapotre-Ledoux B., Grosclaude P., Stabenow R., Luttmann S., Nennecke A., Engel J., Schubert-Fritschle G., Heidrich J., Holleczek B., Jonasson J.G., Clough-Gorr K., Comber H., Mazzoleni G., Giacomin A., Sardo A.S., Barchielli A., Serraino D., De Angelis R., Mallone S., Tavilla A., Pierannunzio D., Rossi S., Santaquilani M., Knijn A., Pannozzo F., Gennaro V., Benfatto L., Ricci P., Autelitano M., Spagnoli G., Fusco M., Usala M., Vitale F., Michiara M., Tumino R., Mangone L., Falcini F., Ferretti S., Filiberti R.A., Marani E., Iannelli A., Sensi F., Piffer S., Gentilini M., Madeddu A., Ziino A., Maspero S., Candela P., Stracci F., Tagliabue G., Rugge M., Trama A., Gatta G., Botta L., Capocaccia R., Pildava S., Smailyte G., Calleja N., Johannesen T.B., Rachtan J., Gozdz S., Blaszczyk J., Kepska K., de Lacerda G.F., Bento M.J., Miranda A., Diba C.S., Almar E., Larranaga N., de Munain A.L., Torrella-Ramos A., Diaz Garcia J.M., Marcos-Gragera R., Sanchez M.J., Navarro C., Salmeron D., Moreno-Iribas C., Galceran J., Carulla M., Mousavi M., Bouchardy C., Ess S.M., Bordoni A., Konzelmann I., Rashbass J., Gavin A., Brewster D.H., Huws D.W., Visser O., Bielska-Lasota M., Primic-Zakelj M., Kunkler I., and Benhamou E.

Subjects
Liver metastase, medicine.medical_specialty, Pathology, Socio-culturale, 03 medical and health sciences, Liver metastases, Rare Diseases, 0302 clinical medicine, Neuroendocrine tumours, Pancreas, Rare cancers, Multidisciplinary approach, Rare Disease, Neuroendocrine tumour, Humans, Medicine, Pancrea, Precision Medicine, Intensive care medicine, Liver metastases, Neuroendocrine tumours, Pancreas, Rare cancers, Patient Care Team, business.industry, Pancreatic Neoplasm, Rare cancer, General Medicine, Pancreatic Neoplasms, Survival Rate, Neuroendocrine Tumors, Surgery, Oncology, 030220 oncology & carcinogenesis, Mandate, 030211 gastroenterology & hepatology, business, Neuroendocrine Tumor, Delivery of Health Care, Human
Abstract

Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network.

Published
2019

38. Testicular germ-cell tumours and penile squamous cell carcinoma: Appropriate management makes the difference

Author

Nicola Nicolai, Davide Biasoni, Mario A. Catanzaro, Maurizio Colecchia, Annalisa Trama, Monika Hackl, Elizabeth Van Eycken, Kris Henau, Nadya Dimitrova, Mario Sekerija, Ladislav Dušek, Margit Mägi, Nea Malila, Maarit Leinonen, Michel Velten, Xavier Troussard, Veronique Bouvier, Anne-Valérie Guizard, Anne-Marie Bouvier, Patrick Arveux, Marc Maynadié, Anne-Sophie Woronoff, Michel Robaszkiewic, Isabelle Baldi, Alain Monnereau, Brigitte Tretarre, Marc Colonna, Florence Molinié, Simona Bara, Claire Schvartz, Bénédicte Lapôtre-Ledoux, Pascale Grosclaude, Roland Stabenow, Sabine Luttmann, Alice Nennecke, Jutta Engel, Gabriele Schubert-Fritschle, Jan Heidrich, Bernd Holleczek, Jón Gunnlaugur Jónasson, Kerri Clough-Gorr, Harry Comber, Guido Mazzoleni, Adriano Giacomin, Antonella Sutera Sardo, Alessandr Barchielli, Diego Serraino, Roberta De Angelis, Sandra Mallone, Andrea Tavilla, Daniela Pierannunzio, Silvia Rossi, Mariano Santaquilani, Arnold Knijn, Fabio Pannozzo, Valerio Gennaro, Lucia Benfatto, Paolo Ricci, Mariangela Autelitano, Gianbattista Spagnoli, Mario Fusco, Mario Usala, Francesco Vitale, Maria Michiara, Rosario Tumino, Lucia Mangone, Fabio Falcini, Stefano Ferretti, Rosa Angela Filiberti, Enza Marani, Arturo Iannelli, Flavio Sensi, Silvano Piffer, Maria Gentilini, Anselmo Madeddu, Antonio Ziino, Sergio Maspero, Pina Candela, Fabrizio Stracci, Giovanna Tagliabue, Massimo Rugge, Gemma Gatta, Laura Botta, Riccardo Capocaccia, Santa Pildava, Giedre Smailyte, Neville Calleja, Tom Børge Johannesen, Jadwiga Rachtan, Stanisław Góźdź, Jerzy Błaszczyk, Kamila Kępska, Gonçalo Forjaz de Lacerda, Maria José Bento, Ana Miranda, Chakameh Safaei Diba, Enrique Almar, Nerea Larrañaga, Arantza Lopez de Munain, Ana Torrella-Ramos, José María Díaz García, Rafael Marcos-Gragera, Maria Josè Sanchez, Carmen Navarro, Diego Salmeron, Conchi Moreno-Iribas, Jaume Galceran, Marià Carulla, Mohsen Mousavi, Christine Bouchardy, Silvia M. Ess, Andrea Bordoni, Isabelle Konzelmann, Jem Rashbass, Anna Gavin, David H. Brewster, Dyfed Wyn Huws, Otto Visser, Magdalena Bielska-Lasota, Maja Primic-Zakelj, Ian Kunkler, Ellen Benhamou, Nicolai N., Biasoni D., Catanzaro M.A., Colecchia M., Trama A., Hackl M., Eycken E.V., Henau K., Dimitrova N., Sekerija M., Dusek L., Magi M., Malila N., Leinonen M., Velten M., Troussard X., Bouvier V., Guizard A.-V., Bouvier A.-M., Arveux P., Maynadie M., Woronoff A.-S., Robaszkiewic M., Baldi I., Monnereau A., Tretarre B., Colonna M., Molinie F., Bara S., Schvartz C., Lapotre-Ledoux B., Grosclaude P., Stabenow R., Luttmann S., Nennecke A., Engel J., Schubert-Fritschle G., Heidrich J., Holleczek B., Jonasson J.G., Clough-Gorr K., Comber H., Mazzoleni G., Giacomin A., Sutera Sardo A., Barchielli A., Serraino D., De Angelis R., Mallone S., Tavilla A., Pierannunzio D., Rossi S., Santaquilani M., Knijn A., Pannozzo F., Gennaro V., Benfatto L., Ricci P., Autelitano M., Spagnoli G., Fusco M., Usala M., Vitale F., Michiara M., Tumino R., Mangone L., Falcini F., Ferretti S., Filiberti R.A., Marani E., Iannelli A., Sensi F., Piffer S., Gentilini M., Madeddu A., Ziino A., Maspero S., Candela P., Stracci F., Tagliabue G., Rugge M., Gatta G., Botta L., Capocaccia R., Pildava S., Smailyte G., Calleja N., Johannesen T.B., Rachtan J., Gozdz S., Blaszczyk J., Kepska K., de Lacerda G.F., Bento M.J., Miranda A., Diba C.S., Almar E., Larranaga N., de Munain A.L., Torrella-Ramos A., Diaz Garcia J.M., Marcos-Gragera R., Sanchez M.J., Navarro C., Salmeron D., Moreno-Iribas C., Galceran J., Carulla M., Mousavi M., Bouchardy C., M. Ess S., Bordoni A., Konzelmann I., Rashbass J., Gavin A., Brewster D.H., Huws D.W., Visser O., Bielska-Lasota M., Primic-Zakelj M., Kunkler I., Benhamou E., Nicolai, N, Biasoni, D, Catanzaro, Ma, Colecchia, M, Trama, A, Hackl, M, Van Eycken, E, Henau, K, Dimitrova, N, Sekerija, M, Dusek, L, Maagi, M, Malila, N, Leinonen, M, Velten, M, Troussard, X, Bouvier, V, Guizard, Av, Bouvier, Am, Arveux, P, Maynadie, M, Woronoff, A, Robaszkiewicz, M, Baldi, I, Monnereau, A, Tretarre, B, Colonna, M, Molinie, F, Bara, S, Schvartz, C, Lapotre-Ledoux, B, Grosclaude, P, Stabenow, R, Luttmann, S, Nennecke, A, Engel, J, Schubert-Fritschle, G, Heidrich, J, Holleczek, B, Jonasson, Jg, Clough-Gorr, K, Comber, H, Mazzoleni, G, Giacomin, A, Sardo, A, Barchielli, A, Serraino, D, De Angelis, R, Mallone, S, Tavilla, A, Pierannunzio, D, Rossi, S, Santaquilani, M, Knijn, A, Pannozzo, F, Gennaro, V, Benfatto, L, Ricci, P, Autelitano, M, Spagnoli, G, Fusco, M, Usala, M, Vitale, F, Michiara, M, Tumino, R, Mangone, L, Falcini, F, Ferretti, S, Filiberti, Ra, Marani, E, Iannelli, A, Sensi, F, Puffer, S, Gentilini, M, Madeddu, A, Ziino, A, Maspero, S, Candela, P, Stracci, F, Tagliabue, G, Rugge, M, Gatta, G, Botta, L, Capocaccia, R, Pildava, S, Smailyte, G, Calleja, N, Johannesen, Tb, Rachtan, J, Gozdz, S, Blaszczyk, J, Kepska, K, de Lacerda, Gf, Bento, Mj, Miranda, A, Diba, C, Almar, E, Larranaga, N, de Munain, Al, Torrella-Ramos, M, Garcia, Jmd, Marcos-Gragera, R, Sanchez, Mj, Navarro, C, Salmeron, D, Moreno-Iribas, C, Galceran, J, Carulla, M, Mousavi, M, Bouchardy, C, Ess, Sm, Bordoni, A, Konzelmann, I, Rashbass, J, Gavin, A, Brewster, Dh, Huws, Dw, Visser, O, Bielska-Lasota, M, Primic-Zakelj, M, Kunkler, I, and Benhamou, E

Subjects
Oncology, Male, Survival, 030232 urology & nephrology, Disease, Carcinoma, Community network, Europe, Germ cell and embryonal, Neoplasms, Penis neoplasms, Rare diseases, Squamous cell, Tertiary care centres, Testicular neoplasms, Surgery, 0302 clinical medicine, Epidemiology, Testicular neoplasm, Referral and Consultation, General Medicine, Neoplasms, Germ Cell and Embryonal, Tertiary care centre, Survival Rate, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Carcinoma, Squamous Cell, Human, medicine.medical_specialty, Penile squamous cell carcinoma, Socio-culturale, Cancer Care Facilities, 03 medical and health sciences, Penis neoplasm, Rare Disease, Internal medicine, medicine, Humans, Penile Neoplasms, Neoplasm Staging, Penis Neoplasms, business.industry, Cancer Care Facilitie, Lymphatic Metastasi, medicine.disease, Testicular germ cell, Adult life, Penile Neoplasm, Proper treatment, Neoplasm, Lymph Node Excision, business, Delivery of Health Care
Abstract

Germ-cell tumours (GCT) of the testis and penile squamous cell carcinoma (PeSCC) are a rare and a very rare uro-genital cancers, respectively. Both tumours are well defined entities in terms of management, where specific recommendations - in the form of continuously up-to-dated guide lines- are provided. Impact of these tumour is relevant. Testicular GCT affects young, healthy men at the beginning of their adult life. PeSCC affects older men, but a proportion of these patients are young and the personal consequences of the disease may be devastating. Deviation from recommended management may be a reason of a significant prognostic worsening, as proper treatment favourably impacts on these tumours, dramatically on GCT and significantly on PeSCC. RARECAREnet data may permit to analyse how survivals may vary according to geographical areas, histology and age, leading to assume that non-homogeneous health-care resources may impact the cure and definitive outcomes. In support of this hypothesis, some epidemiologic datasets and clinical findings would indicate that survival may improve when appropriate treatments are delivered, linked to a different accessibility to the best health institutions, as a consequence of geographical, cultural and economic barriers. Finally, strong clues based on epidemiological and clinical data support the hypothesis that treatment delivered at reference centres or under the aegis of a qualified multi-institutional network is associated with a better prognosis of patients with these malignancies. The ERN EURACAN represents the best current European effort to answer this clinical need.

Published
2018

39. Treatment challenges in and outside a network setting: Head and neck cancers

Author

Ester Orlandi, Salvatore Alfieri, Christian Simon, Annalisa Trama, Lisa Licitra, Monika Hackl, Elizabeth Van Eycken, Kris Henau, Nadya Dimitrova, Mario Sekerija, Ladislav Dušek, Margit Mägi, Nea Malila, Maarit Leinonen, Michel Velten, Xavier Troussard, Veronique Bouvier, Anne-Valérie Guizard, Anne-Marie Bouvier, Patrick Arveux, Marc Maynadié, Anne-Sophie Woronoff, Michel Robaszkiewic, Isabelle Baldi, Alain Monnereau, Brigitte Tretarre, Marc Colonna, Florence Molinié, Simona Bara, Claire Schvartz, Bénédicte Lapôtre-Ledoux, Pascale Grosclaude, Roland Stabenow, Sabine Luttmann, Alice Nennecke, Jutta Engel, Gabriele Schubert-Fritschle, Jan Heidrich, Bernd Holleczek, Jón Gunnlaugur Jónasson, Kerri Clough-Gorr, Harry Comber, Guido Mazzoleni, Adriano Giacomin, Antonella Sutera Sardo, Alessandr Barchielli, Diego Serraino, Roberta De Angelis, Sandra Mallone, Andrea Tavilla, Daniela Pierannunzio, Silvia Rossi, Mariano Santaquilani, Arnold Knijn, Fabio Pannozzo, Valerio Gennaro, Lucia Benfatto, Paolo Ricci, Mariangela Autelitano, Gianbattista Spagnoli, Mario Fusco, Mario Usala, Francesco Vitale, Maria Michiara, Rosario Tumino, Lucia Mangone, Fabio Falcini, Stefano Ferretti, Rosa Angela Filiberti, Enza Marani, Arturo Iannelli, Flavio Sensi, Silvano Piffer, Maria Gentilini, Anselmo Madeddu, Antonio Ziino, Sergio Maspero, Pina Candela, Fabrizio Stracci, Giovanna Tagliabue, Massimo Rugge, Gemma Gatta, Laura Botta, Riccardo Capocaccia, Santa Pildava, Giedre Smailyte, Neville Calleja, Tom Børge Johannesen, Jadwiga Rachtan, Stanisław Góźdź, Jerzy Błaszczyk, Kamila Kępska, Gonçalo Forjaz de Lacerda, Maria José Bento, Ana Miranda, Chakameh Safaei Diba, Enrique Almar, Nerea Larrañaga, Arantza Lopez de Munain, Ana Torrella-Ramos, José María Díaz García, Rafael Marcos-Gragera, Maria Josè Sanchez, Carmen Navarro, Diego Salmeron, Conchi Moreno-Iribas, Jaume Galceran, Marià Carulla, Mohsen Mousavi, Christine Bouchardy, Silvia M. Ess, Andrea Bordoni, Isabelle Konzelmann, Jem Rashbass, Anna Gavin, David H. Brewster, Dyfed Wyn Huws, Otto Visser, Magdalena Bielska-Lasota, Maja Primic-Zakelj, Ian Kunkler, Ellen Benhamou, Orlandi E., Alfieri S., Simon C., Trama A., Licitra L., Hackl M., Eycken E.V., Henau K., Dimitrova N., Sekerija M., Dusek L., Magi M., Malila N., Leinonen M., Velten M., Troussard X., Bouvier V., Guizard A.-V., Bouvier A.-M., Arveux P., Maynadie M., Woronoff A.-S., Robaszkiewic M., Baldi I., Monnereau A., Tretarre B., Colonna M., Molinie F., Bara S., Schvartz C., Lapotre-Ledoux B., Grosclaude P., Stabenow R., Luttmann S., Nennecke A., Engel J., Schubert-Fritschle G., Heidrich J., Holleczek B., Jonasson J.G., Clough-Gorr K., Comber H., Mazzoleni G., Giacomin A., Sutera Sardo A., Barchielli A., Serraino D., De Angelis R., Mallone S., Tavilla A., Pierannunzio D., Rossi S., Santaquilani M., Knijn A., Pannozzo F., Gennaro V., Benfatto L., Ricci P., Autelitano M., Spagnoli G., Fusco M., Usala M., Vitale F., Michiara M., Tumino R., Mangone L., Falcini F., Ferretti S., Filiberti R.A., Marani E., Iannelli A., Sensi F., Piffer S., Gentilini M., Madeddu A., Ziino A., Maspero S., Candela P., Stracci F., Tagliabue G., Rugge M., Gatta G., Botta L., Capocaccia R., Pildava S., Smailyte G., Calleja N., Johannesen T.B., Rachtan J., Gozdz S., Blaszczyk J., Kepska K., de Lacerda G.F., Bento M.J., Miranda A., Diba C.S., Almar E., Larranaga N., de Munain A.L., Torrella-Ramos A., Diaz Garcia J.M., Marcos-Gragera R., Sanchez M.J., Navarro C., Salmeron D., Moreno-Iribas C., Galceran J., Carulla M., Mousavi M., Bouchardy C., Ess S.M., Bordoni A., Konzelmann I., Rashbass J., Gavin A., Brewster D.H., Huws D.W., Visser O., Bielska-Lasota M., Primic-Zakelj M., Kunkler I., and Benhamou E.

Subjects
0301 basic medicine, medicine.medical_specialty, Socio-culturale, Social issues, Multidisciplinary team, 03 medical and health sciences, Therapeutic approach, 0302 clinical medicine, Rare Diseases, Multidisciplinary approach, medicine, Humans, Adverse effect, Intensive care medicine, Head and neck cancer, Referral and Consultation, Patient Care Team, European reference networks joint action of rare cancers, Rare disease, business.industry, Head and Neck Neoplasm, General Medicine, medicine.disease, Europe, 030104 developmental biology, Clinical research, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, European reference networks joint action of rare cancer, Surgery, business, Delivery of Health Care, Human
Abstract

Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lead to improved survival rates. This result is likely due to improved diagnostic and staging accuracy, a more efficacious therapeutic approach and enhanced communication across disciplines. Despite the benefit of MTD, it must be noted that this approach requires considerable time, effort and financial resources and is usually more frequent in highly organized and high-volume centers. Literature data on clinical research suggest that patients treated in high-accrual centers report better treatment outcomes compared to patients treated in low-volume centers, where a lower radiotherapy-compliance and worst overall survival have been reported. There is general agreement that treatment of rare cancers such as HNC should be concentrated in high volume, specialized and multidisciplinary centers. In order to achieve this goal, the creation of international collaboration network is fundamental. The European Reference Networks for example aim to create an international virtual advisory board, whose objectives are the exchange of expertise, training, clinical collaboration and the reduction of disparities and enhancement of rationalize migration across Europe. The purpose of our work is to review all aspects and challenges in and outside this network setting planned for the management of HNC patients.

Published
2017

40. Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet—a population-based study

Author

Fabio Falcini, Charles A. Stiller, Diego Serraino, Antonella Sutera Sardo, Kerri Clough-Gorr, Mario Fusco, Véronique Bouvier, Silvia Francisci, Alain Monnereau, Carmen Navarro, Alessandro Barchielli, Annalisa Trama, Bénédicte Lapôtre-Ledoux, Stanislaw Gózdz, Isabelle Konzelmann, J. Błaszczyk, Laura Botta, Simona Bara, Flavio Sensi, Gonçalo Forjaz de Lacerda, Nadya Dimitrova, Lucia Mangone, Pamela Minicozzi, Maria Michiara, Neville Calleja, M Usala, E Marani, Innos Kaire, Tom Børge Johannesen, Ladislav Dušek, Sabine Luttmann, M Autelitano, Anne Sophie Woronoff, Vincent K Y Ho, Francesco Vitale, Silvano Piffer, Jan Maarten van der Zwan, Dyfed Wyn Huws, David H. Brewster, Margit Mägi, Zdravka Valerianova, Anna Luisa Caiazzo, Maja Primic Žakelj, Adriano Giacomin, E. Almar, F Bella, Ellen Benhamou, Arantza Lopez de Munain, Patrick Arveux, Claire Schvartz, José María Díaz García, M. Robaszkiewicz, Isabelle Baldi, Otto Visser, Mohsen Mousavi, Maria José Bento, Lesley A. Anderson, Chakameh Safaei Diba, Mariano Santaquilani, Gemma Gatta, Tina Žagar, Pina Candela, Jadwiga Rachtan, María José Sánchez, Andrea Bordoni, Monika Hackl, Gabriele Schubert-Fritschle, Nea Malila, Diego Salmerón, Massimo Rugge, Carmen Tereanu, Maarit K. Leinonen, Jem Rashbass, Arturo Iannelli, Milena Sant, Antonino Ziino Colanino, Marià Carulla, Christine Bouchardy, Keiu Paapsi, Marc Colonna, Jon G. Jonasson, Brigitte Trétarre, A.V. Guizard, Riccardo Capocaccia, Xavier Troussard, Jan Heidrich, Dominic Agius, Kamila Kepska, Daniela Pierannunzio, Santa Pildava, Stefano Ferretti, Silvia Rossi, Guido Mazzoleni, Rafael Marcos-Gragera, Giedre Smailyte, Gianbattista Spagnoli, Nancy Van Damme, Roland Stabenow, Anna Gavin, Paolo Baili, Anselmo Madeddu, Fabio Pannozzo, M. Sekerija, Silvia Ess, Sandra Mallone, Rosa Filiberti, Pascale Grosclaude, Florence Molinié, S Maspero, Alice Nennecke, Rosario Tumino, Renée Otter, Ana Torrella-Ramos, Fabrizio Stracci, Giovanna Tagliabue, Michel Velten, Andrea Tavilla, Marc Maynadié, Arnold Knijn, Conchi Moreno-Iribas, Eva Ardanaz, M.A. Gentilini, Paolo Ricci, Liesbet Van Eycken, Ana Miranda, Sabine Siesling, Nerea Larrañaga, Roberta De Angelis, Harry Comber, Paolo Collarile, K. Henau, Bernd Holleczek, Anne Marie Bouvier, Jutta Engel, Jaume Galceran, Gatta G., Capocaccia R., Botta L., Mallone S., De Angelis R., Ardanaz E., Comber H., Dimitrova N., Leinonen M.K., Siesling S., van der Zwan J.M., Van Eycken L., Visser O., Zakelj M.P., Anderson L.A., Bella F., Kaire I., Otter R., Stiller C.A., Trama A., Hackl M., Henau K., Van Damme N., Valerianova Z., Sekerija M., Dusek L., Magi M., Paapsi K., Malila N., Velten M., Troussard X., Bouvier V., Guizard A.-V., Bouvier A.-M., Arveux P., Maynadie M., Woronoff A.-S., Robaszkiewicz M., Baldi I., Monnereau A., Tretarre B., Colonna M., Molinie F., Bara S., Schvartz C., Lapotre-Ledoux B., Grosclaude P., Stabenow R., Luttmann S., Nennecke A., Engel J., SchubertFritschle G., Heidrich J., Holleczek B., Jonasson J.G., Clough-Gorr K., Mazzoleni G., Giacomin A., Sardo A.S., Barchielli A., Serraino D., Collarile P., Pannozzo F., Ricci P., Autelitano M., Spagnoli G., Fusco M., Usala M., Vitale F., Michiara M., Tumino R., Mangone L., Falcini F., Ferretti S., Filiberti R.A., Marani E., Caiazzo A.L., Iannelli A., Sensi F., Piffer S., Gentilini M., Madeddu A., Colanino A.Z., Maspero S., Candela P., Stracci F., Tagliabue G., Rugge M., Baili P., Minicozzi P., Sant M., Tereanu C., Francisci S., Tavilla A., Pierannunzio D., Rossi S., Santaquilani M., Knijn A., Pildava S., Smailyte G., Calleja N., Agius D., Johannesen T.B., Rachtan J., Gozdz S., Blaszczyk J., Kepska K., Lacerda G.F.D., Bento M.J., Miranda A., Diba C.S., Zagar T., Almar E., Larranaga N., Munain A.L.D., Torrella-Ramos A., Garcia J.M.D., Marcos-Gragera R., Sanchez M.J., Navarro C., Salmeron D., Moreno-Iribas C., Galceran J., Carulla M., Mousavi M., Bouchardy C., Ess S.M., Bordoni A., Konzelmann I., Rashbass J., Gavin A., Brewster D.H., Huws D.W., Ho V.K., and Benhamou E.

Subjects
Male, 0301 basic medicine, Pathology, population-based registries, Cancer Care Facilities, Delivery of Health Care, Europe, Female, Hospitalization, Humans, Incidence, Neoplasms, Rare Diseases, Registries, Survival Rate, Oncology, 0302 clinical medicine, Medicine, media_common, Tumors -- Treatment -- Europe, education.field_of_study, Relative survival, Incidence (epidemiology), RARECARE project, 030220 oncology & carcinogenesis, medicine.medical_specialty, Health surveys, Population, Socio-culturale, 03 medical and health sciences, SDG 3 - Good Health and Well-being, media_common.cataloged_instance, Cancer -- Mortality, Risk factor, European union, education, Survival rate, Oncology, cancer burden, incidence, rare cancer,population-based registries, rare cancers, cancer registry, RARECARE, business.industry, Rare cancer, Cancer -- Patients -- Long-term care, Cancer registry, 030104 developmental biology, cancer burden, business, Demography, Rare disease
Abstract

Background: Rare cancers pose challenges for diagnosis, treatments, and clinical decision making. Information about rare cancers is scant. The RARECARE project defined rare cancers as those with an annual incidence of less than six per 100 000 people in European Union (EU). We updated the estimates of the burden of rare cancers in Europe, their time trends in incidence and survival, and provide information about centralisation of treatments in seven European countries. Methods: We analysed data from 94 cancer registries for more than 2 million rare cancer diagnoses, to estimate European incidence and survival in 2000–07 and the corresponding time trends during 1995–2007. Incidence was calculated as the number of new cases divided by the corresponding total person-years in the population. 5-year relative survival was calculated by the Ederer-2 method. Seven registries (Belgium, Bulgaria, Finland, Ireland, the Netherlands, Slovenia, and the Navarra region in Spain) provided additional data for hospitals treating about 220 000 cases diagnosed in 2000–07. We also calculated hospital volume admission as the number of treatments provided by each hospital rare cancer group sharing the same referral pattern. Findings: Rare cancers accounted for 24% of all cancers diagnosed in the EU during 2000–07. The overall incidence rose annually by 0.5% (99·8% CI 0·3–0·8). 5-year relative survival for all rare cancers was 48·5% (95% CI 48·4 to 48·6), compared with 63·4% (95% CI 63·3 to 63·4) for all common cancers. 5-year relative survival increased (overall 2·9%, 95% CI 2·7 to 3·2), from 1999–2001 to 2007–09, and for most rare cancers, with the largest increases for haematological tumours and sarcomas. The amount of centralisation of rare cancer treatment varied widely between cancers and between countries. The Netherlands and Slovenia had the highest treatment volumes. Interpretation: Our study benefits from the largest pool of population-based registries to estimate incidence and survival of about 200 rare cancers. Incidence trends can be explained by changes in known risk factors, improved diagnosis, and registration problems. Survival could be improved by early diagnosis, new treatments, and improved case management. The centralisation of treatment could be improved in the seven European countries we studied., peer-reviewed

Published
2017

41. Survival of 86,690 patients with thyroid cancer: A population-based study in 29 European countries from EUROCARE-5

Author

L. Dal Maso, A. Tavilla, F. Pacini, D. Serraino, B.A.C. van Dijk, M.D. Chirlaque, R. Capocaccia, N. Larrañaga, M. Colonna, D. Agius, E. Ardanaz, J. Rubió-Casadevall, A. Kowalska, S. Virdone, S. Mallone, H. Amash, R. De Angelis, M. Hackl, N. Zielonke, E. Van Eycken, K. Henau, Z. Valerianova, N. Dimitrova, M. Sekerija, L. Dušek, M. Zvolský, H. Storm, G. Engholm, M. Mägi, T. Aareleid, N. Malila, K. Seppä, M. Velten, A.V. Guizard, J. Faivre, A.S. Woronoff, B. Tretarre, N. Bossard, Z. Uhry, F. Molinié, S. Bara, C. Schvartz, B. Lapôtre-Ledoux, P. Grosclaude, R. Stabenow, S. Luttmann, A. Eberle, H. Brenner, A. Nennecke, J. Engel, G. Schubert-Fritschle, J. Heidrich, B. Holleczek, A. Katalinic, J.G. Jónasson, L. Tryggvadóttir, H. Comber, G. Mazzoleni, A. Bulatko, C. Buzzoni, A. Giacomin, A. Sutera Sardo, A. Mazzei, S. Ferretti, A. Barchielli, A. Caldarella, G. Gatta, M. Sant, C. Amati, P. Baili, F. Berrino, S. Bonfarnuzzo, L. Botta, F. Di Salvo, R. Foschi, C. Margutti, E. Meneghini, P. Minicozzi, A. Trama, A. Zucchetto, M. Caldora, E. Carrani, S. Francisci, D. Pierannunzio, P. Roazzi, S. Rossi, M. Santaquilani, F. Pannozzo, S. Busco, R.A. Filiberti, M. Vercelli, P. Ricci, M. Autelitano, G. Spagnoli, C. Cirilli, M. Fusco, M.F. Vitale, M. Usala, F. Vitale, B. Ravazzolo, M. Michiara, R. Tumino, L. Mangone, M. Vicentini, F. Falcini, A. Iannelli, O. Sechi, R. Cesaraccio, S. Piffer, A. Madeddu, F. Tisano, S. Maspero, A.C. Fanetti, R. Zanetti, S. Rosso, P. Candela, T. Scuderi, F. Stracci, A. Rocca, G. Tagliabue, P. Contiero, M. Rugge, S. Tognazzo, S. Pildava, G. Smailyte, N. Calleja, T.B. Johannesen, J. Rachtan, S. Góźdź, R. Mężyk, J. Błaszczyk, M. Bębenek, M. Bielska-Lasota, G. Forjaz de Lacerda, M.J. Bento, C. Castro, A. Miranda, A. Mayer-da-Silva, C. Safaei Diba, M. Primic-Zakelj, M. Errezola, J. Bidaurrazaga, J.M. Díaz García, A.I. Marcos-Navarro, R. Marcos-Gragera, A. Izquierdo Font, M.J. Sanchez, E. Molina, C. Navarro, C. Moreno-Iribas, J. Galceran, M. Carulla, M. Lambe, S. Khan, M. Mousavi, C. Bouchardy, M. Usel, S.M. Ess, H. Frick, M. Lorez, C. Herrmann, A. Bordoni, A. Spitale, I. Konzelmann, O. Visser, V. Ho, R. Otter, M. Coleman, C. Allemani, B. Rachet, J. Rashbass, J. Broggio, J. Verne, A. Gavin, C. Donnelly, D.H. Brewster, D.W. Huws, C. White, Registre des cancers du Tarn, France, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Registre général des cancers du Tarn, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Dal Maso L., Tavilla A., Pacini F., Serraino D., van Dijk B.A.C., Chirlaque M.D., Capocaccia R., Larranaga N., Colonna M., Agius D., Ardanaz E., Rubio-Casadevall J., Kowalska A., Virdone S., Mallone S., Amash H., De Angelis R., Hackl M., Zielonke N., Van Eycken E., Henau K., Valerianova Z., Dimitrova N., Sekerija M., Dusek L., Zvolsky M., Storm H., Engholm G., Magi M., Aareleid T., Malila N., Seppa K., Velten M., Guizard A.V., Faivre J., Woronoff A.S., Tretarre B., Bossard N., Uhry Z., Molinie F., Bara S., Schvartz C., Lapotre-Ledoux B., Grosclaude P., Stabenow R., Luttmann S., Eberle A., Brenner H., Nennecke A., Engel J., Schubert-Fritschle G., Heidrich J., Holleczek B., Katalinic A., Jonasson J.G., Tryggvadottir L., Comber H., Mazzoleni G., Bulatko A., Buzzoni C., Giacomin A., Sutera Sardo A., Ferretti S., Mazzei A., Caldarella A., Gatta G., Sant M., Amati C., Baili P., Berrino F., Bonfarnuzzo S., Botta L., Di Salvo F., Foschi R., Margutti C., Meneghini E., Minicozzi P., Trama A., Zucchetto A., Caldora M., Carrani E., Francisci S., Pierannunzio D., Roazzi P., Rossi S., Santaquilani M., Pannozzo F., Busco S., Filiberti R.A., Vercelli M., Ricci P., Autelitano M., Spagnoli G., Cirilli C., Fusco M., Vitale M.F., Usala M., Vitale F., Ravazzolo B., Michiara M., Tumino R., Mangone L., Vicentini M., Falcini F., Iannelli A., Sechi O., Cesaraccio R., Piffer S., Madeddu A., Tisano F., Maspero S., Fanetti A.C., Zanetti R., Rosso S., Candela P., Scuderi T., Stracci F., Rocca A., Tagliabue G., Contiero P., Rugge M., Tognazzo S., Pildava S., Smailyte G., Calleja N., Johannesen T.B., Rachtan J., Gozdz S., Mezyk R., Blaszczyk J., Bebenek M., Bielska-Lasota M., Forjaz de Lacerda G., Bento M.J., Castro C., Miranda A., Mayer-da-Silva A., Safaei Diba C., Primic-Zakelj M., Errezola M., Bidaurrazaga J., Diaz Garcia J.M., Marcos-Navarro A.I., Marcos-Gragera R., Izquierdo Font A., Sanchez M.J., Molina E., Navarro C., Moreno-Iribas C., Galceran J., Carulla M., Lambe M., Khan S., Mousavi M., Bouchardy C., Usel M., Ess S.M., Frick H., Lorez M., Herrmann C., Bordoni A., Spitale A., Konzelmann I., Visser O., Ho V., Otter R., Coleman M., Allemani C., Rachet B., Rashbass J., Broggio J., Verne J., Gavin A., Donnelly C., Brewster D.H., Huws D.W., and White C.

Subjects
Registrie, Male, Cancer Research, IMPACT, Cancer registrie, [SDV]Life Sciences [q-bio], Papillary, 0302 clinical medicine, QUALITY-OF-LIFE, Residence Characteristics, Adenocarcinoma, Follicular, Cancer registries, Registries, Thyroid cancer, Thyroid Neoplasm, education.field_of_study, Relative survival, Incidence (epidemiology), Mortality rate, Incidence, Diagnosis-Related Group, EUROCARE, Europe, Adolescent, Adult, Aged, Carcinoma, Carcinoma, Papillary, Diagnosis-Related Groups, Female, Humans, Middle Aged, Sex Distribution, Thyroid Neoplasms, Young Adult, Oncology, PREVALENCE, 3. Good health, Thyroid Cancer, Papillary, 030220 oncology & carcinogenesis, Cohort, Human, medicine.medical_specialty, Population, GEOGRAPHICAL-DISTRIBUTION, UNITED-STATES, Socio-culturale, 030209 endocrinology & metabolism, Adenocarcinoma, RECENT TRENDS, 03 medical and health sciences, MANAGEMENT, medicine, education, Survival rate, business.industry, MORTALITY, Follicular, medicine.disease, Cancer registry, Surgery, MICROCARCINOMA, Residence Characteristic, business, Demography
Abstract

Background: Incidence rates of thyroid cancer (TC) increased in several countries during the last 30 years, while mortality rates remained unchanged, raising important questions for treatment and follow-up of TC patients. This study updates population-based estimates of relative survival (RS) after TC diagnosis in Europe by sex, country, age, period and histology.Methods: Data from 87 cancer registries in 29 countries were extracted from the EUROCARE-5 dataset. One-and 5-year RS were estimated using the cohort approach for 86,690 adult TC patients diagnosed in 2000-2007 and followed-up to 12/31/2008. RS trends in 1999-2007 and 10-year RS in 2005-2007 were estimated using the period approach.Results: In Europe 2000-2007, 5-year RS after TC was 88% in women and 81% in men. Survival rates varied by country and were strongly correlated (Pearson rho = 75%) with country-specific incidence rates. Five-year RS decreased with age (in women from > 95% at age 15-54 to 57% at age 75+), from 98% in women and 94% in men with papillary TC to 14% in women and 12% in men with anaplastic TC. Proportion of papillary TC varied by country and increased over time, while survival rates were similar across areas and periods. In 1999-2007, 5-year RS increased by five percentage points for all TCs but only by two for papillary and by four for follicular TC. Ten-year RS in 2005-2007 was 89% in women and 79% in men.Conclusions: The reported increasing TC survival trend and differences by area are mainly explained by the varying histological case-mix of cases. (C) 2017 Elsevier Ltd. All rights reserved.

Published
2017

42. Quantum Efficiency Measurement and Modeling of Silicon Sensors Optimized for Soft X-ray Detection.

Author

Carulla M, Barten R, Baruffaldi F, Bergamaschi A, Borghi G, Boscardin M, Brückner M, Butcher TA, Centis Vignali M, Dinapoli R, Ebner S, Ficorella F, Fröjdh E, Greiffenberg D, Hammad Ali O, Hasanaj S, Heymes J, Hinger V, King T, Kozlowski P, Lopez Cuenca C, Mezza D, Moustakas K, Mozzanica A, Paternoster G, Paton KA, Ronchin S, Ruder C, Schmitt B, Sieberer P, Thattil D, Vogelsang K, Xie X, and Zhang J

Abstract

Hybrid pixel detectors have become indispensable at synchrotron and X-ray free-electron laser facilities thanks to their large dynamic range, high frame rate, low noise, and large area. However, at energies below 3 keV, the detector performance is often limited because of the poor quantum efficiency of the sensor and the difficulty in achieving single-photon resolution due to the low signal-to-noise ratio. In this paper, we address the quantum efficiency of silicon sensors by refining the design of the entrance window, mainly by passivating the silicon surface and optimizing the dopant profile of the n + region. We present the measurement of the quantum efficiency in the soft X-ray energy range for silicon sensors with several process variations in the fabrication of planar sensors with thin entrance windows. The quantum efficiency for 250 eV photons is increased from almost 0.5% for a standard sensor to up to 62% as a consequence of these developments, comparable to the quantum efficiency of backside-illuminated scientific CMOS sensors. Finally, we discuss the influence of the various process parameters on quantum efficiency and present a strategy for further improvement.

Published
2024
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43. Getting personal with epigenetics: towards individual-specific epigenomic imputation with machine learning.

Author

Hawkins-Hooker A, Visonà G, Narendra T, Rojas-Carulla M, Schölkopf B, and Schweikert G

Subjects
Humans, Machine Learning, Epigenome, Precision Medicine methods, DNA Methylation genetics, Epigenomics methods, Epigenesis, Genetic
Abstract

Epigenetic modifications are dynamic mechanisms involved in the regulation of gene expression. Unlike the DNA sequence, epigenetic patterns vary not only between individuals, but also between different cell types within an individual. Environmental factors, somatic mutations and ageing contribute to epigenetic changes that may constitute early hallmarks or causal factors of disease. Epigenetic modifications are reversible and thus promising therapeutic targets for precision medicine. However, mapping efforts to determine an individual's cell-type-specific epigenome are constrained by experimental costs and tissue accessibility. To address these challenges, we developed eDICE, an attention-based deep learning model that is trained to impute missing epigenomic tracks by conditioning on observed tracks. Using a recently published set of epigenomes from four individual donors, we show that transfer learning across individuals allows eDICE to successfully predict individual-specific epigenetic variation even in tissues that are unmapped in a given donor. These results highlight the potential of machine learning-based imputation methods to advance personalized epigenomics., (© 2023. Springer Nature Limited.)

Published
2023
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44. Ten-Year Probabilities of Death Due to Cancer and Cardiovascular Disease among Breast Cancer Patients Diagnosed in North-Eastern Spain.

Author

Clèries R, Ameijide A, Buxó M, Vilardell M, Martínez JM, Font R, Marcos-Gragera R, Puigdemont M, Viñas G, Carulla M, Espinàs JA, Galceran J, Izquierdo Á, and Borràs JM

Subjects
Humans, Female, Spain epidemiology, Early Detection of Cancer, Probability, Breast Neoplasms diagnosis, Cardiovascular Diseases epidemiology
Abstract

Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR- patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II-III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II-III at an older age, surveillance for preventing late cardiotoxicity is crucial.

Published
2022
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45. Recommendations on compiling test datasets for evaluating artificial intelligence solutions in pathology.

Author

Homeyer A, Geißler C, Schwen LO, Zakrzewski F, Evans T, Strohmenger K, Westphal M, Bülow RD, Kargl M, Karjauv A, Munné-Bertran I, Retzlaff CO, Romero-López A, Sołtysiński T, Plass M, Carvalho R, Steinbach P, Lan YC, Bouteldja N, Haber D, Rojas-Carulla M, Vafaei Sadr A, Kraft M, Krüger D, Fick R, Lang T, Boor P, Müller H, Hufnagl P, and Zerbe N

Subjects
Humans, Forecasting, Datasets as Topic, Artificial Intelligence, Pathology
Abstract

Artificial intelligence (AI) solutions that automatically extract information from digital histology images have shown great promise for improving pathological diagnosis. Prior to routine use, it is important to evaluate their predictive performance and obtain regulatory approval. This assessment requires appropriate test datasets. However, compiling such datasets is challenging and specific recommendations are missing. A committee of various stakeholders, including commercial AI developers, pathologists, and researchers, discussed key aspects and conducted extensive literature reviews on test datasets in pathology. Here, we summarize the results and derive general recommendations on compiling test datasets. We address several questions: Which and how many images are needed? How to deal with low-prevalence subsets? How can potential bias be detected? How should datasets be reported? What are the regulatory requirements in different countries? The recommendations are intended to help AI developers demonstrate the utility of their products and to help pathologists and regulatory agencies verify reported performance measures. Further research is needed to formulate criteria for sufficiently representative test datasets so that AI solutions can operate with less user intervention and better support diagnostic workflows in the future., (© 2022. The Author(s).)

Published
2022
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46. Publisher Correction to: Recommendations on compiling test datasets for evaluating artificial intelligence solutions in pathology.

Author

Homeyer A, Geißler C, Schwen LO, Zakrzewski F, Evans T, Strohmenger K, Westphal M, Bülow RD, Kargl M, Karjauv A, Munné-Bertran I, Retzlaff CO, Romero-López A, Sołtysiński T, Plass M, Carvalho R, Steinbach P, Lan YC, Bouteldja N, Haber D, Rojas-Carulla M, Vafaei Sadr A, Kraft M, Krüger D, Fick R, Lang T, Boor P, Müller H, Hufnagl P, and Zerbe N

Published
2022
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47. Incidence and survival of lymphoid neoplasms in Spain, 2002-2013: A population-based study from the Spanish Network of Cancer Registries (REDECAN).

Author

Pla C, Solans M, Ameijide A, Sanvisens A, Carulla M, Rojas MD, Alemán MA, Sáez-Lloret I, Díaz-Del-Campo C, Marcos-Navarro AI, Sainz-de-Aja L, Aizpurua-Atxega A, Lopez-de-Munain A, Sánchez MJ, Perucha J, Franch P, Chirlaque MD, Guevara M, Galceran J, Merino S, and Marcos-Gragera R

Abstract

Introduction: The aim of this study was to describe incidence, incidence trends and survival patterns of lymphoid neoplasms (LNs) and its subtypes in Spain in the period 2002-2013 using data from the Spanish Network of Cancer Registries (REDECAN)., Materials and Methods: Data were extracted from 13 Spanish population-based cancer registries. LNs incident cases were codified using the International Classification of Diseases for Oncology, third edition (ICD-O-3) and grouped according to the WHO 2008 classification. Age-standardized incidence rates to the 2013 European standard population (ASIRe) were obtained. Poisson regression models were used to analyze trends in incidence rates and estimate the annual percentage change (APC) for each subtype. The number of cases in Spain for 2023 was estimated by applying the estimated age-specific rates for the year 2023 to the 2023 Spanish population. Observed survival (OS) was estimated by the Kaplan-Meier method and net survival (NS) by the Pohar-Perme method. Sex- and age-specific estimates of 5-year NS were calculated, as well as its changes according to two periods of diagnosis (2002-2007 and 2008-2013)., Results: LNs accounted for 69% (n=39,156) of all hematological malignancies (n=56,751) diagnosed during the period of study. Median age at diagnosis was 67 years (interquartile range (IQR) = 52-77). The overall ASIRe was 34.23 (95% confidence interval (CI): 33.89, 34.57) and showed a marked male predominance in almost all subtypes (global sex ratio = 1.45). During the study period, incidence trends of LNs remained stable (APC: 0.3; 95% CI: -0.1, 0.6), nevertheless some subtypes showed statistically significant variations, such as LNs NOS category (APC: -5.6; 95% CI: -6.8, -4.3). Around 17,926 new cases of LNs will be diagnosed in 2023 in Spain. Survival rates differed considerably across age-groups, while they were similar between men and women. Five- year NS was 62.81% (95% CI: 62.1, 63.52) for all LNs, and varied widely across LNs subtypes, ranging from 39.21% to 90.25%. NS for all LNs improved from the first period of diagnosis to the second one, being 61.57% (95% CI: 60.56, 62.61) in 2002-2007 and 64.17% (95% CI: 63.29, 65.07) in 2008-2013., Conclusions: This study presents the first complete and extensive population-based analysis of LNs incidence and survival in Spain. These population-based data provide relevant information to better understand the epidemiology of LNs in Southern Europe and it features some useful points for public health authorities and clinicians. However, additional improvements regarding the registration of these hematological neoplasms can be implemented., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pla, Solans, Ameijide, Sanvisens, Carulla, Rojas, Alemán, Sáez-Lloret, Díaz-del-Campo, Marcos-Navarro, Sainz-de-Aja, Aizpurua-Atxega, Lopez-de-Munain, Sánchez, Perucha, Franch, Chirlaque, Guevara, Galceran, Merino, Marcos-Gragera and REDECAN working group.)

Published
2022
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48. Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Author

Cardoso R, Guo F, Heisser T, De Schutter H, Van Damme N, Nilbert MC, Christensen J, Bouvier AM, Bouvier V, Launoy G, Woronoff AS, Cariou M, Robaszkiewicz M, Delafosse P, Poncet F, Walsh PM, Senore C, Rosso S, Lemmens VEPP, Elferink MAG, Tomšič S, Žagar T, Marques ALM, Marcos-Gragera R, Puigdemont M, Galceran J, Carulla M, Sánchez-Gil A, Chirlaque MD, Hoffmeister M, and Brenner H

Abstract

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries., Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method., Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country., Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians., Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid., Competing Interests: HDS and NVD are employed by the Belgian Cancer Registry, which is financed by regional and federal authorities for collecting data regarding new cancer diagnoses and cancer screening in Belgium, and for disseminating associated epidemiological parameters., (© 2022 The Authors.)

Published
2022
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49. Using population-based data to evaluate the impact of adherence to endocrine therapy on survival in breast cancer through the web-application BreCanSurvPred.

Author

Font R, Buxó M, Ameijide A, Martínez JM, Marcos-Gragera R, Carulla M, Puigdemont M, Vilardell M, Civit S, Viñas G, Espinàs JA, Galceran J, Izquierdo Á, Borràs JM, and Clèries R

Subjects
Cohort Studies, Female, Humans, Neoplasm Staging, Prognosis, Proportional Hazards Models, Receptor, ErbB-2, Software, Spain epidemiology, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Patient Compliance statistics & numerical data
Abstract

We show how the use and interpretation of population-based cancer survival indicators can help oncologists talk with breast cancer (BC) patients about the relationship between their prognosis and their adherence to endocrine therapy (ET). The study population comprised a population-based cohort of estrogen receptor positive BC patients (N = 1268) diagnosed in Girona and Tarragona (Northeastern Spain) and classified according to HER2 status (+ / -), stage at diagnosis (I/II/III) and five-year cumulative adherence rate (adherent > 80%; non-adherent ≤ 80%). Cox regression analysis was performed to identify significant prognostic factors for overall survival, whereas relative survival (RS) was used to estimate the crude probability of death due to BC (P BC ). Stage and adherence to ET were the significant factors for predicting all-cause mortality. Compared to stage I, risk of death increased in stage II (hazard ratio [HR] 2.24, 95% confidence interval [CI]: 1.51-3.30) and stage III (HR 5.11, 95% CI 3.46-7.51), and it decreased with adherence to ET (HR 0.57, 95% CI 0.41-0.59). P BC differences were higher in non-adherent patients compared to adherent ones and increased across stages: stage I: 6.61% (95% CI 0.05-13.20); stage II: 9.77% (95% CI 0.59-19.01), and stage III: 22.31% (95% CI 6.34-38.45). The age-adjusted survival curves derived from this modeling were implemented in the web application BreCanSurvPred ( https://pdocomputation.snpstats.net/BreCanSurvPred ). Web applications like BreCanSurvPred can help oncologists discuss the consequences of non-adherence to prescribed ET with patients., (© 2022. The Author(s).)

Published
2022
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50. Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN).

Author

Guevara M, Molinuevo A, Salmerón D, Marcos-Gragera R, Carulla M, Chirlaque MD, Rodríguez Camblor M, Alemán A, Rojas D, Vizcaíno Batllés A, Chico M, Jiménez Chillarón R, López de Munain A, de Castro V, Sánchez MJ, Ramalle-Gómara E, Franch P, Galceran J, and Ardanaz E

Abstract

The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectiveness.

Published
2022
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