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1. Overview of the Instrumentation for the Dark Energy Spectroscopic Instrument

Author

DESI Collaboration, B. Abareshi, J. Aguilar, S. Ahlen, Shadab Alam, David M. Alexander, R. Alfarsy, L. Allen, C. Allende Prieto, O. Alves, J. Ameel, E. Armengaud, J. Asorey, Alejandro Aviles, S. Bailey, A. Balaguera-Antolínez, O. Ballester, C. Baltay, A. Bault, S. F. Beltran, B. Benavides, S. BenZvi, A. Berti, R. Besuner, Florian Beutler, D. Bianchi, C. Blake, P. Blanc, R. Blum, A. Bolton, S. Bose, D. Bramall, S. Brieden, A. Brodzeller, D. Brooks, C. Brownewell, E. Buckley-Geer, R. N. Cahn, Z. Cai, R. Canning, R. Capasso, A. Carnero Rosell, P. Carton, R. Casas, F. J. Castander, J. L. Cervantes-Cota, S. Chabanier, E. Chaussidon, C. Chuang, C. Circosta, S. Cole, A. P. Cooper, L. da Costa, M.-C. Cousinou, A. Cuceu, T. M. Davis, K. Dawson, R. de la Cruz-Noriega, A. de la Macorra, A. de Mattia, J. Della Costa, P. Demmer, M. Derwent, A. Dey, B. Dey, G. Dhungana, Z. Ding, C. Dobson, P. Doel, J. Donald-McCann, J. Donaldson, K. Douglass, Y. Duan, P. Dunlop, J. Edelstein, S. Eftekharzadeh, D. J. Eisenstein, M. Enriquez-Vargas, S. Escoffier, M. Evatt, P. Fagrelius, X. Fan, K. Fanning, V. A. Fawcett, S. Ferraro, J. Ereza, B. Flaugher, A. Font-Ribera, J. E. Forero-Romero, C. S. Frenk, S. Fromenteau, B. T. Gänsicke, C. Garcia-Quintero, L. Garrison, E. Gaztañaga, F. Gerardi, H. Gil-Marín, S. Gontcho A Gontcho, Alma X. Gonzalez-Morales, G. Gonzalez-de-Rivera, V. Gonzalez-Perez, C. Gordon, O. Graur, D. Green, C. Grove, D. Gruen, G. Gutierrez, J. Guy, C. Hahn, S. Harris, D. Herrera, Hiram K. Herrera-Alcantar, K. Honscheid, C. Howlett, D. Huterer, V. Iršič, M. Ishak, P. Jelinsky, L. Jiang, J. Jimenez, Y. P. Jing, R. Joyce, E. Jullo, S. Juneau, N. G. Karaçaylı, M. Karamanis, A. Karcher, T. Karim, R. Kehoe, S. Kent, D. Kirkby, T. Kisner, F. Kitaura, S. E. Koposov, A. Kovács, A. Kremin, Alex Krolewski, B. L’Huillier, O. Lahav, A. Lambert, C. Lamman, Ting-Wen Lan, M. Landriau, S. Lane, D. Lang, J. U. Lange, J. Lasker, L. Le Guillou, A. Leauthaud, A. Le Van Suu, Michael E. Levi, T. S. Li, C. Magneville, M. Manera, Christopher J. Manser, B. Marshall, Paul Martini, W. McCollam, P. McDonald, Aaron M. Meisner, J. Mena-Fernández, J. Meneses-Rizo, M. Mezcua, T. Miller, R. Miquel, P. Montero-Camacho, J. Moon, J. Moustakas, E. Mueller, Andrea Muñoz-Gutiérrez, Adam D. Myers, S. Nadathur, J. Najita, L. Napolitano, E. Neilsen, Jeffrey A. Newman, J. D. Nie, Y. Ning, G. Niz, P. Norberg, Hernán E. Noriega, T. O’Brien, A. Obuljen, N. Palanque-Delabrouille, A. Palmese, P. Zhiwei, D. Pappalardo, X. PENG, W. J. Percival, S. Perruchot, R. Pogge, C. Poppett, A. Porredon, F. Prada, J. Prochaska, R. Pucha, A. Pérez-Fernández, I. Pérez-Ràfols, D. Rabinowitz, A. Raichoor, S. Ramirez-Solano, César Ramírez-Pérez, C. Ravoux, K. Reil, M. Rezaie, A. Rocher, C. Rockosi, N. A. Roe, A. Roodman, A. J. Ross, G. Rossi, R. Ruggeri, V. Ruhlmann-Kleider, C. G. Sabiu, S. Gaines, K. Said, A. Saintonge, Javier Salas Catonga, L. Samushia, E. Sanchez, C. Saulder, E. Schaan, E. Schlafly, D. Schlegel, J. Schmoll, D. Scholte, M. Schubnell, A. Secroun, H. Seo, S. Serrano, Ray M. Sharples, Michael J. Sholl, Joseph Harry Silber, D. R. Silva, M. Sirk, M. Siudek, A. Smith, D. Sprayberry, R. Staten, B. Stupak, T. Tan, Gregory Tarlé, Suk Sien Tie, R. Tojeiro, L. A. Ureña-López, F. Valdes, O. Valenzuela, M. Valluri, M. Vargas-Magaña, L. Verde, M. Walther, B. Wang, M. S. Wang, B. A. Weaver, C. Weaverdyck, R. Wechsler, Michael J. Wilson, J. Yang, Y. Yu, S. Yuan, Christophe Yèche, H. Zhang, K. Zhang, Cheng Zhao, Rongpu Zhou, Zhimin Zhou, H. Zou, J. Zou, S. Zou, and Y. Zu

Subjects
Dark energy, Spectroscopy, Astronomical instrumentation, Spectrometers, Optical telescopes, Astronomy, QB1-991
Abstract

The Dark Energy Spectroscopic Instrument (DESI) embarked on an ambitious 5 yr survey in 2021 May to explore the nature of dark energy with spectroscopic measurements of 40 million galaxies and quasars. DESI will determine precise redshifts and employ the baryon acoustic oscillation method to measure distances from the nearby universe to beyond redshift z > 3.5, and employ redshift space distortions to measure the growth of structure and probe potential modifications to general relativity. We describe the significant instrumentation we developed to conduct the DESI survey. This includes: a wide-field, 3.°2 diameter prime-focus corrector; a focal plane system with 5020 fiber positioners on the 0.812 m diameter, aspheric focal surface; 10 continuous, high-efficiency fiber cable bundles that connect the focal plane to the spectrographs; and 10 identical spectrographs. Each spectrograph employs a pair of dichroics to split the light into three channels that together record the light from 360–980 nm with a spectral resolution that ranges from 2000–5000. We describe the science requirements, their connection to the technical requirements, the management of the project, and interfaces between subsystems. DESI was installed at the 4 m Mayall Telescope at Kitt Peak National Observatory and has achieved all of its performance goals. Some performance highlights include an rms positioner accuracy of better than 0.″1 and a median signal-to-noise ratio of 7 of the [O ii ] doublet at 8 × 10 ^−17 erg s ^−1 cm ^−2 in 1000 s for galaxies at z = 1.4–1.6. We conclude with additional highlights from the on-sky validation and commissioning, key successes, and lessons learned.

Published
2022
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2. MODUL cohort 2: an adaptable, randomized, signal-seeking trial of fluoropyrimidine plus bevacizumab with or without atezolizumab maintenance therapy for BRAF(wt) metastatic colorectal cancer

Author

J. Tabernero, A. Grothey, D. Arnold, A. de Gramont, M. Ducreux, P. O’Dwyer, A. Tahiri, F. Gilberg, N. Irahara, H.-J. Schmoll, E. Van Cutsem, Institut Català de la Salut, [Tabernero J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain. [Grothey A] West Cancer Center, Germantown, USA. [Arnold D] Asklepios Tumorzentrum Hamburg, AK Altona, Hamburg, Germany. [de Gramont A] Franco-British Hospital, Levallois-Perret, France. [Ducreux M] Gustave Roussy, Université Paris Saclay, Villejuif, France. [O'Dwyer P] Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA, and Vall d'Hebron Barcelona Hospital Campus

Subjects
PD-L1, atezolizumab, Cancer Research, metastatic colorectal cancer, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Medicaments antineoplàstics - Ús terapèutic, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], bevacizumab, Other subheadings::Other subheadings::/drug therapy [Other subheadings], neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Còlon - Càncer - Tractament, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], Oncology, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Recte - Càncer - Tractament
Abstract

Atezolizumab; Bevacizumab; Metastatic colorectal cancer Atezolizumab; Bevacizumab; Cáncer colorrectal metastásico Atezolizumab; Bevacizumab; Càncer colorectal metastàtic Background MODUL is an adaptable, signal-seeking trial designed to test novel agents in predefined patient subgroups in first-line metastatic colorectal cancer (mCRC). Patients and methods Patients with measurable, unresectable, previously untreated mCRC received induction with ≤8 cycles of FOLFOX + bevacizumab followed by randomization to maintenance treatment comprising control [fluoropyrimidine (FP)/bevacizumab: 5-fluorouracil 1600-2400 mg/m2 46-h intravenous (i.v.) infusion day 1 q2 weeks plus leucovorin 400 mg/m2 2-h infusion i.v. day 1 q2 weeks or capecitabine 1000 mg/m2 b.i.d. orally days 1-14 every 21 days; bevacizumab 5 mg/kg 15-30-min i.v. infusion q2 weeks] or experimental treatment in one of four biomarker-driven cohorts. In patients with BRAF wild-type (BRAFwt) tumors (cohort 2), experimental treatment was FP/bevacizumab + atezolizumab (800 mg 60-min i.v. infusion q2 weeks). Primary efficacy endpoint was progression-free survival (PFS; intent-to-treat population). Enrollment is complete; efficacy and safety findings from cohort 2 are presented. Results Four hundred and forty-five patients with BRAFwt mCRC were randomized (2 : 1) to maintenance in cohort 2. At a median follow-up of 10.5 months, PFS outcome hypothesis was not met [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.72-1.17; P = 0.48]; overall survival (OS) was immature. At a median follow-up of 20.3 months (2-year survival follow-up), PFS benefit was also not met (HR 0.95; 95% CI 0.77-1.18; P = 0.666); OS HR with nearly two-thirds of patients with events was 0.83 (95% CI 0.65-1.05; P = 0.117). No new safety signals were identified. The most common grade ≥3 treatment-emergent adverse events (TEAEs) for experimental versus control arms were hypertension (6.1% versus 4.2%), diarrhea (3.1% versus 2.1%), and palmar-plantar erythrodysesthesia syndrome (1.0% versus 2.5%). Four patients experienced TEAEs with fatal outcome, two were study treatment-related: hepatic failure (experimental arm) and large intestine perforation (control arm; bevacizumab-related). Conclusions Adding atezolizumab to FP/bevacizumab as first-line maintenance treatment after FOLFOX + bevacizumab induction for BRAFwt mCRC did not improve efficacy outcomes. This work was supported by F. Hoffmann-La Roche Ltd (no grant number). The sponsor was involved in the study design and was responsible for the overall study management (monitoring), drug supply, data management, statistical analysis, and drug safety process. The Trial Master Files are maintained electronically by the sponsor. The sponsor was involved in the writing of this report, alongside the authors, all of whom had access to the raw data. The corresponding author had full access to all of the data and the final responsibility for submitting the article for publication on behalf of all authors.

Published
2022

3. MODUL cohort 2: an adaptable, randomized, signal-seeking trial of fluoropyrimidine plus bevacizumab with or without atezolizumab maintenance therapy for BRAF

Author

J, Tabernero, A, Grothey, D, Arnold, A, de Gramont, M, Ducreux, P, O'Dwyer, A, Tahiri, F, Gilberg, N, Irahara, H-J, Schmoll, and E, Van Cutsem

Subjects
Bevacizumab, Proto-Oncogene Proteins B-raf, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, Leucovorin, Humans, Fluorouracil, Intestine, Large, Colorectal Neoplasms, Capecitabine
Abstract

MODUL is an adaptable, signal-seeking trial designed to test novel agents in predefined patient subgroups in first-line metastatic colorectal cancer (mCRC).Patients with measurable, unresectable, previously untreated mCRC received induction with ≤8 cycles of FOLFOX + bevacizumab followed by randomization to maintenance treatment comprising control [fluoropyrimidine (FP)/bevacizumab: 5-fluorouracil 1600-2400 mg/mFour hundred and forty-five patients with BRAFAdding atezolizumab to FP/bevacizumab as first-line maintenance treatment after FOLFOX + bevacizumab induction for BRAF

Published
2022

4. Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial

Author

Andrés J M, Ferreri, Kate, Cwynarski, Elisa, Pulczynski, Christopher P, Fox, Elisabeth, Schorb, Claudia, Celico, Monica, Falautano, Alessandro, Nonis, Paul, La Rosée, Mascia, Binder, Alberto, Fabbri, Fiorella, Ilariucci, Mauro, Krampera, Alexander, Roth, Claire, Hemmaway, Peter W, Johnson, Kim M, Linton, Tobias, Pukrop, Jettes Sønderskov, Gørløv, Monica, Balzarotti, Georg, Hess, Ulrich, Keller, Stephan, Stilgenbauer, Jense, Panse, Alessandra, Tucci, Lorella, Orsucci, Francesco, Pisani, Manuela, Zanni, Stefan W, Krause, Hans J, Schmoll, Bernd, Hertenstein, Mathias, Rummel, Jeffery, Smith, Lorenz, Thurner, Giuseppina, Cabras, Elsa, Pennese, Maurilio, Ponzoni, Martina, Deckert, Letterio S, Politi, Jurgen, Finke, Antonella, Ferranti, Kelly, Cozens, Elvira, Burger, Nicoletta, Ielmini, Franco, Cavalli, Emanuele, Zucca, and Gerald, Illerhaus

Subjects
Adult, Cancer Research, Lymphoma, Medizin, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, Combined Modality Therapy, Transplantation, Autologous, Central Nervous System Neoplasms, Methotrexate, Oncology, Antineoplastic Combined Chemotherapy Protocols, Quality of Life, Humans, Rituximab, Thiotepa
Abstract

219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.

Published
2022

5. Cherenkov Telescope Array : the World’s largest VHE gamma-ray observatory

Author

Roberta Zanin, H. Abdalla, H. Abe, S. Abe, A. Abusleme, F. Acero, A. Acharyya, V. Acin Portella, K. Ackley, R. Adam, C. Adams, S.S. Adhikari, I. Aguado Ruesga, I. Agudo, R. Aguilera, A. Aguirre Santaella, F. Aharonian, A. Alberdi, R. Alfaro, J. Alfaro, C. Alispach, R. Aloisio, R. Alves Batista, J.P. Amans, L. Amati, E. Amato, L. Ambrogi, G. Ambrosi, M. Ambrosio, R. Ammendola, J. Anderson, M. Anduze, E.O. Anguner, L.A. Antonelli, V. Antonuccio, P. Antoranz, R. Anutarawiramkul, J. Aragunde Gutierrez, C. Aramo, A. Araudo, M. Araya, A. Arbet Engels, C. Arcaro, V. Arendt, C. Armand, T. Armstrong, F. Arqueros, L. Arrabito, B. Arsioli, M. Artero, K. Asano, Y. Ascasibar, J. Aschersleben, M. Ashley, P. Attina, P. Aubert, C. B. Singh, D. Baack, A. Babic, M. Backes, V. Baena, S. Bajtlik, A. Baktash, C. Balazs, M. Balbo, O. Ballester, J. Ballet, B. Balmaverde, A. Bamba, R. Bandiera, A. Baquero Larriva, P. Barai, C. Barbier, V. Barbosa Martins, M. Barcelo, M. Barkov, M. Barnard, L. Baroncelli, U. Barres de Almeida, J.A. Barrio, D. Bastieri, P.I. Batista, I. Batkovic, C. Bauer, R. Bautista González, J. Baxter, U. Becciani, J. Becerra González, Y. Becherini, G. Beck, J. Becker Tjus, W. Bednarek, A. Belfiore, L. Bellizzi, R. Belmont, W. Benbow, D. Berge, E. Bernardini, M.I. Bernardos, K. Bernlöhr, A. Berti, M. Berton, B. Bertucci, V. Beshley, N. Bhatt, S. Bhattacharyya, W. Bhattacharyya, B. Y. Bi, G. Bicknell, N. Biederbeck, C. Bigongiari, A. Biland, R. Bird, E. Bissaldi, J. Biteau, M. Bitossi, O. Blanch, M. Blank, J. Blazek, J. Bobin, C. Boccato, F. Bocchino, C. Boehm, M. Bohacova, C. Boisson, J. Boix, J.P. Bolle, J. Bolmont, G. Bonanno, C. Bonavolontà, L. Bonneau Arbeletche, G. Bonnoli, P. Bordas, J. Borkowski, R. Bose, D. Bose, Z. Bosnjak, E. Bottacini, Markus Böttcher, M.T. Botticella, C. Boutonnet, F. Bouyjou, V. Bozhilov, E. Bozzo, L. Brahimi, C. Braiding, S. Brau Nogue, S. Breen, J. Bregeon, M. Breuhaus, A. Brill, W. Brisken, E. Brocato, A.M. Brown, K. Brügge, P. Brun, F. Brun, L. Brunetti, G. Brunetti, P. Bruno, A. Bruno, A. Bruzzese, N. Bucciantini, J. H. Buckley, R. Bühler, A. Bulgarelli, T. Bulik, M. Bünning, M. Bunse, M. Burton, A. Burtovoi, M. Buscemi, S. Buschjager, G. Busetto, J. Buss, K. Byrum, A. Caccianiga, F. Cadoux, A. Calanducci, C. Calderon, J. Calvo Tovar, R. A. Cameron, P. Campana, R. Canestrari, F. Cangemi, B. Cantlay, M. Capalbi, M. Capasso, M. Cappi, A. Caproni, R. Capuzzo Dolcetta, P. Caraveo, V. Cárdenas, L. Cardiel, M. Cardillo, C. Carlile, S. Caroff, R. Carosi, A. Carosi, E. Carquin, M. Carrere, J.M. Casandjian, S. Casanova, F. Cassol, F. Catalani, O. Catalano, D. Cauz, A. Ceccanti, C. Celestino Silva, K. Cerny, M. Cerruti, E. Chabanne, P. Chadwick, Y. Chai, P. Chambery, C. Champion, S. Chaty, A. Chen, K. Cheng, M. Chernyakova, G. Chiaro, A. Chiavassa, M. Chikawa, V.R. Chitnis, J. Chudoba, L. Chytka, S. Cikota, A. Circiello, P. Clark, M. Colak, E. Colombo, S. Colonges, A. Comastri, A. Compagnino, V. Conforti, E. Congiu, R. Coniglione, J. Conrad, F. Conte, J.L. Contreras, P. Coppi, R. Cornat, J. Coronado Blazquez, J. Cortina, A. Costa, H. Costantini, G. Cotter, B. Courty, S. Covino, S. Crestan, P. Cristofari, R. Crocker, J. Croston, K. Cubuk, O. Cuevas, X. Cui, G. Cusumano, S. Cutini, G. D'Amico, F. D'Ammando, P. D'Avanzo, P. Da Vela, M. Dadina, S. Dai, M. Dalchenko, M. Dall'Ora, M.K. Daniel, J. Dauguet, I. Davids, J. Davies, B. Dawson, A. De Angelis, A.E. de Araujo Carvalho, M. de Bony de Lavergne, G. De Cesare, F. de Frondat, I. de la Calle, E. de Gouveia Dal Pino, B. De Lotto, A. De Luca, D. De Martino, M. de Naurois, E. de Ona Wilhelmi, F. De Palma Persio, N. De Simone, V. de Souza Valle, E. Delagnes, G. Deleglise Reznicek, C. Delgado, A.G. Delgado Giler, J. Delgado Mengual Valle, Domenico Della Volpe, D. Depaoli, J. Devin, T. Di Girolamo, C. Di Giulio Pierro, L. Di Venere, C. Díaz, C. Dib, S. Diebold, S. Digel, A. Djannati Atai, J. Djuvsland, A. Dmytriiev, K. Docher, A. Domínguez, D. Dominis Prester, A. Donini, D. Dorner, M. Doro, Rita Cassia dos Anjos, J.L. Dournaux, T. Downes, G. Drake, H. Drass, D. Dravins, C. Duangchan, A. Duara, G. Dubus, L. Ducci, C. Duffy, D. Dumora, K. Dundas Mora, A. Durkalec, V.V. Dwarkadas, J. Ebr, C. Eckner, J. Eder, E. Edy, K. Egberts, S. Einecke, C. Eleftheriadis, D. Elsässer, G. Emery, D. Emmanoulopoulos, J.P. Ernenwein, M. Errando, P. Escarate, J. Escudero, C. Espinoza, S. Ettori, A. Eungwanichayapant, P. Evans, C. Evoli, M. Fairbairn, D. Falceta Goncalves, A. Falcone, V. Fallah Ramazanı, R. Falomo, K. Farakos, G. Fasola, A. Fattorini, Y. Favre, R. Fedora, E. Fedorova, K. Feijen, Q. Feng, G. Ferrand, G. Ferrara, O. Ferreira, M. Fesquet, E. Fiandrini, A. Fiasson, M. Filipovic, D. Fink, J.P. Finley, V. Fioretti, D.F.G. Fiorillo, M. Fiorini, S. Flis, H. Flores, L. Foffano, C. Fohr, M.V. Fonseca, L. Font, G. Fontaine, O. Fornieri, P. Fortin, L. Fortson, N. Fouque, B. Fraga, A. Franceschini, F.J. Franco, L. Freixas Coromina, L. Fresnillo, D. Fugazza, Y. Fujita, S. Fukami, Y. Fukazawa, D. Fulla, S. Funk, A. Furniss, S. Gabici, D. Gaggero, G. Galanti, P. Galdemard, Y. A. Gallant, D. Galloway, S. Gallozzi, V. Gammaldi, R. Garcia, L. E. García-Muñoz, E. Garcia Lopez, F. Gargano, C. Gargano, S. Garozzo, D. Gascon, T. Gasparetto, D. Gasparrini, H. Gasparyan, M. Gaug, N. Geffroy, A. Gent, S. Germani, A. Ghalumyan, A. Ghedina, G. Ghirlanda, F. Gianotti, S. Giarrusso, M. Giarrusso, G. Giavitto, B. Giebels, N. Giglietto, V. Gika, F. Gillardo, R. Gimenes, F. Giordano, E. Giro, M. Giroletti, Andrea Giuliani, M. Gjaja, J.F. Glicenstein, P. Gliwny, H. Goksu, P. Goldoni, J.L. Gomez, M.M. Gonzalez, Juan Manuel Gonzalez, K.S. Gothe, D. Gotz Coelho, T. Grabarczyk, R. Graciani, P. Grandi, G. Grasseau, D. Grasso, D. Green, J. Green, T. Greenshaw, P. Grespan, A. Grillo, M.H. Grondin, J. Grube, V. Guarino, B. Guest, O. Gueta, M. Günduz, S. Gunji, G. Gyuk, J. Hackfeld, D. Hadasch, L. Hagge, A. Hahn, J.E. Hajlaoui, A. Halim, P. Hamal, W. Hanlon, Y. Harada, M.J. Hardcastle, M. Harvey Collado, T. Haubold, A. Haupt, M. Havelka, K. Hayashi, M. Hayashida, H. He, L. Heckmann, M. Heller, F. Henault, Gilles Henri, G. Hermann, S. Hernández Cadena, J. Herrera Llorente, O. Hervet, J. Hinton, A. Hiramatsu, K. Hirotani, B. Hnatyk, R. Hnatyk, J.K. Hoang, D. H.H. Hoffmann, C. Hoischen, J. Holder, M. Holler, B. Hona, D. Horan, Dieter Horns, P. Horvath, J. Houles, M. Hrabovsky, D. Hrupec, Y. Huang, J.‑M. Huet, G. Hughes, G. Hull, T.B. Humensky, M. Hütten, M. Iarlori, J.M. Illa, R. Imazawa, T. Inada, F. Incardona, A. Ingallinera, S. Inoue, T. Inoue, Y. Inoue, F. Iocco, K. Ioka, M. Ionica, S. Iovenitti, A. Iriarte, K. Ishio, W. Ishizaki, Y. Iwamura, J. Jacquemier, M. Jacquemont, M. Jamrozy, P. Janecek, F. Jankowsky, A. JardinBlicq, C. Jarnot, P. Jean Martínez, L. Jocou, N. Jordana, M. Josselin, I. JungRichardt, F.J.P.A. Junqueira, C. Juramy Gilles, P. Kaaret, L.H.S. Kadowaki, M. Kagaya, R. Kankanyan, D. Kantzas, V. Karas, A. Karastergiou, S. Karkar, J. Kasperek, H. Katagiri, J. Kataoka, K. Katarzynski, S. Katsuda, N. Kawanaka, D. Kazanas, D. Kerszberg, B. Khélifi, M.C. Kherlakian, T.P. Kian, D.B. Kieda, T. Kihm, S. Kim, S. Kisaka, R. Kissmann, R. Kleijwegt, G. Kluge, W. Kluźniak, J. Knapp, A. Kobakhidze, Y. Kobayashi, B. Koch, J. Kocot, K. Kohri, N. Komin, A. Kong, K. Kosack, F. Krack, M. Krause, F. Krennrich, H. Kubo, V. N. Kudryavtsev, S. Kunwar, J. Kushida, P. Kushwaha, Barbera Parola, G. La Rosa, R. Lahmann, A. Lamastra, M. Landoni, D. Landriu, R.G. Lang, J. Lapington, P. Laporte, P. Lason, J. Lasuik, J. Lazendic Galloway, T. Le Flour, P. Le Sidaner, S. Leach, S.H. Lee, W.H. Lee, S. Lee Oliveira, A. Lemiere, M. Lemoine Goumard, J.P. Lenain, F. Leone, V. Leray, G. Leto, F. Leuschner, R. Lindemann, E. Lindfors, L. Linhoff, I. Liodakis, A. Lipniacka, M. Lobo, Thomas Lohse, S. Lombardi, A. Lopez, M. Lopez, R. Lopez Coto, F. Louis, M. Louys, F. Lucarelli, H. Ludwig Boudi, P.L. Luque Escamilla, M.C. Maccarone, E. Mach, A.J. Maciejewski, J. Mackey, P. Maeght, C. Maggio, G. Maier, P. Majumdar, M. Makariev, M. Mallamaci, R. Malta Nunes de Almeida, D. Malyshev, D. Mandat, G. Maneva, M. Manganaro, P. Manigot, K. Mannheim, N. Maragos, D. Marano, M. Marconi, A. Marcowith, M. Marculewicz, B. Marcun, J. Marin, N. Marinello, P. Marinos, S. Markoff, P. Marquez, G. Marsella, J. M. Martin, P. G. Martin, M. Martinez, G. Martinez, O. Martinez, H. Martinez Huerta, C. Marty, R. Marx, N. Masetti, P. Massimino, H. Matsumoto, N. Matthews, G. Maurin, W. Max Moerbeck, N. Maxted, M.N. Mazziotta, S.M. Mazzola, J.D. Mbarubucyeye, L. Mc Comb, I. McHardy, S. McKeague, S. McMuldroch, E. Medina, D. Medina Miranda, A. Melandri, C. Melioli, D. Melkumyan, S. Menchiari, S. Mereghetti, G. Merino Arevalo, E. Mestre, J.L. Meunier, T. Meures, S. Micanovic, M. Miceli, M. Michailidis, J. Michalowski, T. Miener, I. Mievre, J. D. Miller, T. Mineo, M. Minev, J.M. Miranda, A. Mitchell, T. Mizuno, B. A. Mode, R. Moderski, L. Mohrmann, E. Molinari, T. Montaruli, I. Monteiro, C. Moore, A. Moralejo, D. Morcuende Parrilla, E. Moretti, K. Mori, P. Moriarty, K. Morik, P. Morris, A. Morselli, K. Mosshammer, R. Mukherjee, J. Muller, C. Mundell, J. Mundet, T. Murach, A. Muraczewski, H. Muraishi, I. Musella, A. Musumarra, A. Nagai, S. Nagataki, T. Naito, T. Nakamori, K. Nakashima, K. Nakayama, N. Nakhjiri, G. Naletto, D. Naumann, L. Nava, M.A. Nawaz, H. Ndiyavala, D. Neise, L. Nellen, R. Nemmen, N. Neyroud, K. Ngernphat, T. Nguyen Trung, L. Nicastro, L. Nickel, J. Niemiec, D. Nieto, C. Nigro, M. Nikołajuk, D. Ninci, K. Noda, Y. Nogami, S. Nolan, R. P. Norris, D. Nosek, M. Nöthe, V. Novotny, S. Nozaki, F. Nunio, P. O'Brien, K. Obara, Y. Ohira, M. Ohishi, S. Ohm, T. Oka, N. Okazaki, A. Okumura, C. Oliver, G. Olivera, B. Olmi, M. Orienti, R. Orito, M. Orlandini, E. Orlando, J.P. Osborne, M. Ostrowski, N. Otte, E. Ovcharov, E. Owen, I. Oya, A. Ozieblo, M. Padovani, A. Pagliaro, A. Paizis, M. Palatiello, M. Palatka, E. Palazzi, J.‑L. Panazol, D. Paneque, S. Panny, Francesca Romana Pantaleo, M. Panter, M. Paolillo, A. Papitto, A. Paravac, J.M. Paredes, G. Pareschi, N. Parmiggiani, R.D. Parsons, P. Paśko, S. R. Patel, B. Patricelli, L. Pavletic, S. Pavy, A. Peer, M. Pecimotika, M.G. Pellegriti, P. Peñil Del Campo, A. Pepato, S. Perard, C. Perennes, M. Peresano, A. Perez Aguilera, J. Perez Romero, M.A. Perez Torres, M. Persic, P. O. Petrucci, O. Petruk, B. Peyaud, K. Pfrang, E. Pian, P. Piatteli, E. Pietropaolo, R. Pillera, D. Pimentel, F. Pintore, C. Pio Garcia, G. Pirola, F. Piron, S. Pita, M. Pohl, V. Poireau, A. Pollo, M. Polo, C. Pongkitivanichkul, J. Porthault, J. Powell, D. Pozo, R.R. Prado, E. Prandini, J. Prast, K. Pressard, G. Principe, N. Produit, D. Prokhorov, H. Prokoph, H. Przybilski, E. Pueschel, G. Pühlhofer, I. Puljak, M.L. Pumo, M. Punch, F. Queiroz, J. Quinn, A. Quirrenbach, P.J. Rajda, R. Rando, S. Razzaque, S. Recchia, P. Reichherzer, O. Reimer, A. Reisenegger, Q. Remy, M. Renaud, T. Reposeur, B. Reville, J.M. Reymond, J. Reynolds, D. Ribeiro, M. Ribo, G. Richards, J. Rico, F. Rieger, L. Riitano, M. Riquelme, D. Riquelme, S. Rivoire, V. Rizi, E. Roache, M. Roche, J. Rodriguez, G. Rodriguez Fernandez, J.C. Rodriguez Ramirez, J.J. Rodriguez Vazquez, G. Rojas, P. Romano, G. Romeo Lobato, C. Romoli, M. Roncadelli, J. Rosado, A. Rosales de Leon, G. Rowell, A. Rugliancich, J.E. Ruiz del Mazo, C. Rulten, C. Russell, F. Russo Hatlen, S. Safi Harb, L. Saha, V. Sahakian, S. Sailer, T. Saito, N. Sakaki, S. Sakurai, G. Salina, H. Salzmann, D. Sanchez, H. Sandaker, A. Sandoval, P. Sangiorgi, M. Sanguillon, H. Sano, M. Santander, A. Santangelo, R. Santos Lima, A. Sanuy, L. Sapozhnikov, T. Saric, S. Sarkar, H. Sasaki, N. Sasaki, Y. Sato, F.G. Saturni, M. Sawada, J. Schaefer, A. Scherer, J. Scherpenberg, P. Schipani, B. Schleicher, J. Schmoll, M. Schneider, H. Schoorlemmer, P. Schovanek, F. Schussler, B. Schwab, U. Schwanke, J. Schwarz, E. Sciacca, S. Scuderi, M. Seglar Arroyo, I. Seitenzahl, D. Semikoz, O. Sergijenko, J.E. Serna Franco, Karol Seweryn, V. Sguera, A. Shalchi, R.Y. Shang, P. Sharma, L. Sidoli, J. Sieiro, H. Siejkowski, A. Sillanpaa, B.B. Singh, K.K. Singh, A. Sinha, C. Siqueira, J. Sitarek, P. Sizun, V. Sliusar, D. Sobczynska, R.W. Sobrinho, H. Sol, G. Sottile, H. Spackman, S. Spencer, G. Spengler, D. Spiga, W. Springer, A. Stamerra, S. Stanic, R. Starling, Ł. Stawarz, Stanislav Stefanik, C. Stegmann, A. Steiner, S. Steinmassl, C. Stella, R. Sternberger, M. Sterzel, C. Stevens, B. Stevenson, T. Stolarczyk, G. Stratta, U. Straumann, J. Striskovic, M. Strzys, R. Stuik, M. Suchenek, Y. Sunada, Tiina Suomijarvi, T. Suric, H. Suzuki, P. Swierk, T. Szepieniec, K. Tachihara, G. Tagliaferri, H. Tajima, N. Tajima, D. Tak, H. Takahashi, M. Takahashi, J. Takata, R. Takeishi, T. Tam, M. Tanaka, T. Tanaka, S. Tanaka, M. Tavani, F. Tavecchio, T. Tavernier, A. Russ Taylor, L.A. Tejedor, P. Temnikov, K. Terauchi, J.C. Terrazas, R. Terrier, T. Terzic, M. Teshima, D. Thibaut, F. Thocquenne, W. Tian, L. Tibaldo, A. Tiengo, M. Tluczykont, C.J. Todero Peixoto, K. Toma, L. Tomankova, J. Tomastik, M. Tornikoski, D.F. Torres, E. Torresi, G. Tosti, L. Tosti, N. Tothill, F. Toussenel, G. Tovmassian, C. Trichard, M. Trifoglio, A. Trois, S. Truzzi, A. Tsiahina, B. Turk, A. Tutone, Y. Uchiyama, P. Utayarat, L. Vaclavek, M. Vacula, V. Vagelli, F. Vagnetti, J.A. Valdivia, M. Valentino, A. Valio, B. Vallage, P. Vallania Quispe, A.M. van den Berg, W. van Driel, C. van Eldik, C. van Rensburg, Brian van Soelen, J. Vandenbroucke, G. Vasileiadis, V. Vassiliev, M. Vazquez Acosta, M. Vecchi, A. Vega, J. Veh, P. Veitch, C. Venter, S. Ventura, S. Vercellone, V. Verguilov, G. Verna, S. Vernetto, V. Verzi, G.P. Vettolani, C. Veyssiere, I. Viale, A. Viana, N. Viaux, J. Vignatti, C.F. Vigorito, J. Villanueva, V. Vitale, V. Vittorini, V. Vodeb, N. Vogel, V. Voisin, S. Vorobiov, M. Vrastil, T. Vuillaume, S.J. Wagner, P. Wagner, K. Wakazono, S.P. Wakely, M. Ward, D. Warren, J. Watson, M. Wechakama, P. Wegner, A. Weinstein, C. Weniger, F. Werner, H. Wetteskind, M. L. White, A. Wierzcholska, S. Wiesand, R. Wijers, M. Wilkinson, M. Will, J. Williams, T. J. Williamson, A. Wolter, Y.W. Wong, M. Wood, T. Yamamoto, H. Yamamoto, Y. Yamane, R. Yamazaki, S. Yanagita, L. Yang, S. Yoo, T. Yoshida, T. Yoshikoshi, P. Yu, A. Yusafzai, Michael Zacharias, B. Zaldivar, L. Zampieri, R. Zanin, R. Zanmar Sanchez, D. Zaric, M. Zavrtanik, D. Zavrtanik, Andrzej Zdziarski, A. Zech, H. Zechlin, A. Zenin, A. Zerwekh, K. Ziętara, A. Zink, J. Ziolkowski, M. Zivec, A. Zmija, Współautorami artykułu są członkowie CTA Observatory, CTA Consortium i LST Collaboration w liczbie 1139, Astronomy, Research unit Nuclear & Hadron Physics, and Research unit Astroparticle Physics

Subjects
Physics, Observatory, Gamma ray, Astronomy
Abstract

Very-high Energy (VHE) gamma-ray astroparticle physics is a relatively young field, and observations over the past decade have surprisingly revealed almost two hundred VHE emitters which appear to act as cosmic particle accelerators. These sources are an important component of the Universe, influencing the evolution of stars and galaxies. At the same time, they also act as a probe of physics in the most extreme environments known - such as in supernova explosions, and around or after the merging of black holes and neutron stars. However, the existing experiments have provided exciting glimpses, but often falling short of supplying the full answer. A deeper understanding of the TeV sky requires a significant improvement in sensitivity at TeV energies, a wider energy coverage from tens of GeV to hundreds of TeV and a much better angular and energy resolution with respect to the currently running facilities. The next generation gamma-ray observatory, the Cherenkov Telescope Array Observatory (CTAO), is the answer to this need. In this talk I will present this upcoming observatory from its design to the construction, and its potential science exploitation. CTAO will allow the entire astronomical community to explore a new discovery space that will likely lead to paradigm-changing breakthroughs. In particular, CTA has an unprecedented sensitivity to short (sub-minute) timescale phenomena, placing it as a key instrument in the future of multi-messenger and multi-wavelength time domain astronomy. I will conclude the talk presenting the first scientific results obtained by the LST-1, the prototype of one CTAO telescope type - the Large-Sized Telescope, that is currently under commission., PoS: Proceedings of Science, 395, ISSN:1824-8039, Proceedings of 37th International Cosmic Ray Conference (ICRC2021)

Published
2022

6. Advance Care Planning in der Onkologie. Ein Beitrag aus klinisch-ethischer Perspektive

Author

Tanja Krones, H J Schmoll, and Jan Schildmann

Subjects
Gynecology, medicine.medical_specialty, business.industry, Medicine, business
Abstract

Bei der Behandlung von an Krebs erkrankten Patienten in der letzten Lebensphase ist der Patientenwille auch in Situationen, in denen der Patient selbst nicht mehr seinen Willen ausern kann, masgebliche Grundlage fur arztliches Handeln. In der klinischen Praxis ist die Feststellung des Patientenwillens selbst bei Vorliegen einer Patientenverfugung haufig schwierig. Die Grunde hierfur liegen einerseits darin, dass bei der Erstellung von Patientenverfugungen haufig Informationen, die fur die Anwendbarkeit der Patientenverfugung wichtig sind, fehlen. Andererseits bestehen auf der Ebene der Umsetzung haufig organisatorische Schwierigkeiten. Advance Care Planning (ACP) umfasst einen kontinuierlichen Erstellungs- und Umsetzungsprozess, der den bekannten Herausforderungen Rechnung tragt und neben Patienten und deren Stellvertretern auch Arzte und Vertreter weiterer Gesundheitsberufe einbezieht. In diesem Beitrag wird das Konzept ACP sowie Auswirkungen auf die Patientenversorgung unter Berucksichtigung der Charakteristika der Versorgung von an Krebs erkrankten Menschen vorgestellt und aus klinisch-ethischer Perspektive diskutiert.

Published
2021

7. O-9 5-FU/LV + cetuximab + vemurafenib as maintenance therapy for BRAF-mutant (BRAFmut) metastatic colorectal cancer: Efficacy, safety, and exploratory biomarker findings from Cohort 1 of the MODUL trial

Author

A. de Gramont, Michel Ducreux, Dirk Arnold, A. Grothey, Maurizio Perdicchio, Zoe June Assaf, Natsumi Irahara, E. Van Cutsem, Peter O'Dwyer, J. Tabernero, H.-J. Schmoll, M. Das Thakur, and A. Tahiri

Subjects
Oncology, medicine.medical_specialty, Cetuximab, Colorectal cancer, business.industry, Mutant, Hematology, medicine.disease, Maintenance therapy, Internal medicine, Cohort, medicine, Biomarker (medicine), Vemurafenib, business, medicine.drug
Published
2021

8. A need to simplify informed consent documents in cancer clinical trials. A position paper of the ARCAD Group

Author

Cathy Eng, G. Decoster, H.-J. Schmoll, Al B. Benson, Annette K. Larsen, Alberto Sobrero, A. de Gramont, Charles S. Fuchs, Harry Bleiberg, Masashi Fujii, John Zalcberg, Jean-Yves Douillard, Dominique Sprumont, Roberto Labianca, Edith P. Mitchell, Ph. Rougier, and Benoist Chibaudel

Subjects
Health Knowledge, Attitudes, Practice, medicine.medical_specialty, good clinical practice, media_common.quotation_subject, education, Legibility, Institution Review Board, Consent Forms, 03 medical and health sciences, 0302 clinical medicine, Documentation, Informed consent, Neoplasms, inform consent, Humans, Medicine, 030212 general & internal medicine, Patient participation, media_common, Clinical Trials as Topic, Medical education, Informed Consent, business.industry, clinical trial, Hematology, ethics, Cancérologie, Clinical trial, Editor's Choice, Oncology, 030220 oncology & carcinogenesis, Family medicine, oncology, Practice Guidelines as Topic, Good clinical practice, Special Articles, Position paper, Patient Participation, business, Autonomy, Hématologie
Abstract

Background: In respect of the principle of autonomy and the right of self-determination, obtaining an informed consent of potential participants before their inclusion in a study is a fundamental ethical obligation. The variations in national laws, regulations, and cultures contribute to complex informed consent documents for patients participating in clinical trials. Currently, only few ethics committees seem willing to address the complexity and the length of these documents and to request investigators and sponsors to revise them in a way to make them understandable for potential participants. The purpose of this work is to focus on the written information in the informed consent documentation for drug development clinical trials and suggests (i) to distinguish between necessary and not essential information, (ii) to define the optimal format allowing the best legibility of those documents., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

9. Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial

Author

A. Reinacher, U. Graeven, H.-J. Schmoll, S.-E. Al-Batran, Julia Quidde, Thoralf Lange, G. Dietrich, S. Hegewisch-Becker, Claus-Christoph Steffens, Dirk Arnold, Norbert Marschner, Axel Hinke, Tanja Trarbach, R. Depenbusch, Andrea Tannapfel, Jan Stoehlmacher, B. Killing, and Christian A. Lerchenmuller

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Randomization, Colorectal cancer, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Quality of life, Surveys and Questionnaires, Internal medicine, Humans, Medicine, In patient, Neoplasm Metastasis, INDUCTION TREATMENT, Aged, business.industry, Hematology, Middle Aged, medicine.disease, humanities, Discontinuation, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Quality of Life, Female, Colorectal Neoplasms, business
Abstract

The unique analysis, the first preplanned HRQOL analysis of the phase III AIO KRK 0207 trial, demonstrates that continuation of active maintenance treatment (FP/Bev or Bev alone) after induction treatment is not associated with a remarkable detrimental effect on HRQOL compared with treatment discontinuation. Median EORTC QLQ-C30 scores and deterioration rates did not differ between maintenance arms. Background First-line maintenance strategies are a current matter of debate in the management of mCRC. Their impact on patient's health-related quality of life (HRQOL) has not yet been evaluated. The objective of this study was to assess whether differences in HRQOL during any active maintenance treatment compared with no maintenance treatment exist. Patient and methods Eight hundred and thirty-seven patients were enrolled in the AIO KRK 0207 trial. Four hundred and seventy-two underwent randomization (after 24 weeks of induction treatment) into one of the maintenance arms: FP plus Bev (arm A), Bev alone (arm B), or no active treatment (arm C). HRQOL were assessed every 6 weeks during induction and maintenance treatment independent from treatment stop, delay, or modification, and also continued after progression, using the EORTC QLQ-C30, QLQ-CR29. The mean value of the global quality of life dimension (GHS/QoL) of the EORTC QLQ-C30, calculated as the average of all available time points after randomization was considered as pre-specified main endpoint. Additionally, EORTC QLQ-C30 response scores were analyzed. Results For HRQOL analysis, 413 patients were eligible (arm A: 136; arm B: 142, arm C: 135). Compliance rate with the HRQOL questionnaires was 95% at time of randomization and remained high during maintenance (98%, 99%, 97% and 97% at week 6, 12, 18 and 24). No significant differences between treatment arms in the mean GHS/QoL scores were observed at any time point. Also, rates of GHS/QoL score deterioration were similar (20.5%; 17.2% and 20.7% of patients), whereas a score improvement occurred in 36.1%; 43.8% and 42.1% (arms A, B and C). Conclusion Continuation of an active maintenance treatment with FP/Bev after induction treatment was neither associated with a detrimental effect on GHS/QoL scores when compared with both, less active treatment with Bev alone or no active treatment. Clinical trials number NCT00973609 (ClinicalTrials.gov).

Published
2016

10. How health-related quality of life assessment should be used in advanced colorectal cancer clinical trials

Author

Tim Maughan, R. Labianca, Jaffer A. Ajani, Christophe Tournigand, C.J.A. Punt, Franck Bonnetain, Al B. Benson, H.-J. Schmoll, Bruce J. Giantonio, Benoist Chibaudel, Miriam Koopman, Richard M. Goldberg, Edith P. Mitchell, J.-Y. Douillard, R. R. Adams, Marc Peeters, Volker Heinemann, Eduardo Díaz-Rubio, Christophe Borg, Annette K. Larsen, A. de Gramont, Charles S. Fuchs, and Harry Bleiberg

Subjects
medicine.medical_specialty, Colorectal cancer, Psychological intervention, Disease, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Health related quality of life, Clinical Trials as Topic, business.industry, Hematology, medicine.disease, Precision medicine, Clinical trial, Clinical research, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Human medicine, Colorectal Neoplasms, business
Abstract

Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival and more recently tumor-based end points such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical end points in current situation if such end points were no validated as surrogate of overall survival to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported end points that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based end points. Health-related quality of life (HRQoL) is effectively an evaluation of quality of life and its relationship with health over time. HRQoL includes the patient report at least of the way a disease or its treatment affects its physical, emotional and social well-being. Over the past few years, several phase III trials in a variety of solid cancers have assessed the incremental value of HRQoL in addition to the traditional end points of tumor response and survival results. HRQoL could provide not only complementary clinical data to the primary outcomes, but also more precise predictive and prognostic value. This end point is useful for both clinicians and patients in order to achieve the dogma of precision medicine. The present article examines the use of HRQoL in phase III metastatic colorectal cancer clinical trials, outlines the importance of HRQoL assessment methods, analysis, and results presentation. Moreover, it discusses the relevance of including HRQoL as a primary/co-primary end point to support the progression-free survival results and to assess efficacy of treatment in the advanced disease setting.

Published
2019

11. Clinicopathological and molecular characteristics of early-onset stage III colon adenocarcinoma: An analysis of 25 studies with 35,713 patients in the Adjuvant Colon Cancer End Points (ACCENT) database

Author

Rachel Kerr, Thierry André, Zhaohui Jin, Hiral D. Parekh, Richard M. Goldberg, Thomas J. George, Greg Yothers, Julien Taieb, Aimery de Gramont, Hans J. Schmoll, Jesse G. Dixon, Eric Van Cutsem, Daniel G. Haller, Naohiro Tomita, Leonard B. Saltz, Qian Shi, Chris Twelves, Takayuki Yoshino, Amit Mahipal, and Frank A. Sinicrope

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Colorectal cancer, business.industry, medicine.medical_treatment, Incidence (epidemiology), medicine.disease, Internal medicine, Stress (linguistics), medicine, Colon adenocarcinoma, Stage (cooking), Young adult, business, Adjuvant, Early onset
Abstract

3597 Background: Colon cancer (CC) incidence and mortality have decreased since the 1970s, but the incidence in young adults (20-49 years) is increasing. There are limited data suggesting that, as a group, patients with early onset CRC (eoCC) may have different phenotypic characteristics compared to those with late onset CRC (loCC, age ≥ 50 years). Methods: Individual patient data on 35,713 subjects with stage III CC from 25 randomized studies (recruiting between 1987 and 2009) in the ACCENT database were pooled. The distributions of demographics, clinicopathological features, biomarkers, and outcome data were summarized by age group. Overall survival (OS), disease-free survival (DFS), recurrence free rate (RFR), and survival after recurrence (SAR) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for gender, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness and molecular markers. Results: Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III eoCC (n = 6246) had similar distributions according to gender, race, PS, risk group, tumor sidedness and T/N stage compared to those with loCC (n = 29467). Patients with eoCC were significantly less likely to be overweight (30.2% vs 36.2%) but more commonly had ≥ 12 lymph nodes resected (69.5% vs 58.7%). The eoCC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%), and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher frequency of Lynch syndrome in eoCC. In univariate analysis, patients with stage III eoCC had significantly better OS, DFS, and SAR; the difference between 3-year DFS and RFR strongly suggests the OS/DFS difference between these the eoCC and loCC may be due to increased competing risks and comorbidities in patients with loCC. In multivariate analysis, age at onset lost its prognostic value when outcome was adjusted for molecular markers. The clear relation between age of onset and KRAS/BRAF status was confirmed in the interaction analysis. Conclusions: Tumor biology was an important determinant of prognosis regardless of patient age. In multivariate analysis age of onset was not a statistically significant determinant of outcome.[Table: see text]

Published
2021

12. Dalotuzumab in chemorefractoryKRASexon 2 mutant colorectal cancer: Results from a randomised phase II/III trial

Author

Tormod Kyrre Guren, Josep Tabernero, Stephen Clarke, Tae Y. Kim, Andrey Loboda, Hans J. Schmoll, Tae W. Kim, Jan Erik Frödin, David Ferry, David Watkins, Mark Ayers, Young Suk Park, Eliza A Hawkes, JaeKyung Roh, David Cunningham, Sun Young Kim, Francesco Sclafani, Clare Peckitt, and Michael Nebozhyn

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Cetuximab, Dalotuzumab, business.industry, Colorectal cancer, Neutropenia, Placebo, medicine.disease, medicine.disease_cause, Irinotecan, 03 medical and health sciences, Exon, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, KRAS, business, medicine.drug
Abstract

Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression-free survival (2.7 vs. 2.6 vs. 1.4 months) and overall survival (7.8 vs. 10.3 vs. 7.8 months) were not statistically significantly different between treatment groups. Most common grade ≥3 treatment-related toxicities included neutropenia, diarrhoea, hyperglycaemia, fatigue and dermatitis acneiform. Expression of IGF-1R, IGF-1, IGF-2 and EREG by quantitative real-time polymerase chain reaction was assessed in 351 patients from the same study with available data on KRAS exon 2 mutational status. Median cycle threshold values for all biomarkers were significantly lower (i.e., higher expression, p

Published
2016

13. Outcome according to KRAS-, NRAS- and BRAF-mutation as well as KRAS mutation variants: pooled analysis of five randomized trials in metastatic colorectal cancer by the AIO colorectal cancer study group

Author

L.F. von Weikersthal, U. Graeven, Thomas Kirchner, Clemens Giessen-Jung, W. Schmiegel, Rainer Porschen, Dominik Paul Modest, S. Hegewisch-Becker, Andrea Tannapfel, Anke Reinacher-Schick, H.-J. Schmoll, Arndt Stahler, Dirk Arnold, Sebastian Stintzing, Ingrid Ricard, Andreas Jung, and Volker Heinemann

Subjects
Male, Proto-Oncogene Proteins B-raf, 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Oncology, medicine.medical_specialty, endocrine system diseases, Colorectal cancer, colorectal cancer, Kaplan-Meier Estimate, medicine.disease_cause, Disease-Free Survival, BRAF, GTP Phosphohydrolases, law.invention, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Exon, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Gastrointestinal Tumors, Humans, Medicine, Neoplasm Metastasis, prognostic factor, neoplasms, Randomized Controlled Trials as Topic, Proportional hazards model, business.industry, Hazard ratio, Membrane Proteins, Original Articles, Hematology, medicine.disease, digestive system diseases, respiratory tract diseases, Treatment Outcome, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Mutation (genetic algorithm), Female, KRAS, Colorectal Neoplasms, business, RAS
Abstract

In this pooled analysis of metastatic colorectal cancer patients, mutations in KRAS, and BRAF were associated with inferior progression-free and overall survival compared with patients with non-mutated tumors. KRAS exon 2 mutation variants were associated with heterogeneous outcome compared with unmutated tumors with KRAS G12C and G13D being associated with rather poor survival., Background To explore the impact of KRAS, NRAS and BRAF mutations as well as KRAS mutation variants in patients with metastatic colorectal cancer (mCRC) receiving first-line therapy. Patients and methods A total of 1239 patients from five randomized trials (FIRE-1, FIRE-3, AIOKRK0207, AIOKRK0604, RO91) were included into the analysis. Outcome was evaluated by the Kaplan–Meier method, log-rank tests and Cox models. Results In 664 tumors, no mutation was detected, 462 tumors were diagnosed with KRAS-, 39 patients with NRAS- and 74 patients with BRAF-mutation. Mutations in KRAS were associated with inferior progression-free survival (PFS) and overall survival (OS) [multivariate hazard ratio (HR) for PFS: 1.20 (1.02–1.42), P = 0.03; multivariate HR for OS: 1.41 (1.17–1.70), P < 0.001]. BRAF mutation was also associated with inferior PFS [multivariate HR: 2.19 (1.59–3.02), P < 0.001] and OS [multivariate HR: 2.99 (2.10–4.25), P < 0.001]. Among specific KRAS mutation variants, the KRAS G12C-variant (n = 28) correlated with inferior OS compared with unmutated tumors [multivariate HR 2.26 (1.25–4.1), P = 0.001]. A similar trend for OS was seen in the KRAS G13D-variant [n = 71, multivariate HR 1.46 (0.96–2.22), P = 0.10]. More frequent KRAS exon 2 variants like G12D [n = 152, multivariate HR 1.17 (0.86–1.6), P = 0.81] and G12V [n = 92, multivariate HR 1.27 (0.87–1.86), P = 0.57] did not have significant impact on OS. Conclusion Mutations in KRAS and BRAF were associated with inferior PFS and OS of mCRC patients compared with patients with non-mutated tumors. KRAS exon 2 mutation variants were associated with heterogeneous outcome compared with unmutated tumors with KRAS G12C and G13D (trend) being associated with rather poor survival.

Published
2016

14. Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials

Author

Muhammad Wasif Saif, H.-J. Schmoll, Steve Lee, Edward McKenna, Michael O’Connell, Thomas H. Cartwright, Greg Yothers, Daniel G. Haller, Chris Twelves, and Weijing Sun

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Colorectal cancer, Comorbidity, law.invention, Capecitabine, Young Adult, FOLFOX, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Aged, Neoplasm Staging, Aged, 80 and over, Clinical Trials as Topic, business.industry, Standard treatment, Hazard ratio, Age Factors, Original Articles, Hematology, Middle Aged, Prognosis, medicine.disease, humanities, digestive system diseases, Oxaliplatin, Survival Rate, Clinical trial, Chemotherapy, Adjuvant, Colonic Neoplasms, Female, business, Follow-Up Studies, medicine.drug
Abstract

Adjuvant oxaliplatin plus capecitabine or leucovorin/5-fluorouracil (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC); however, there is disagreement regarding oxaliplatin benefit in patients aged70. In most analyses, the impact of medical comorbidity (MC) has not been assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were compared with respect to age and MC using pooled data from four randomized, controlled trials, selected for access to patient-level MC data and including commonly endorsed and utilized regimens.Individual data from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were pooled, excluding bevacizumab-treated patients. Patients were grouped by treatment, MC (low versus high), or age (70 versus ≥70), and compared for disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Multivariable Cox proportional hazards regression controlled for gender, T stage, and N stage.DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU regardless of age or MC, although benefits were modestly attenuated for patients aged ≥70. Hazard ratios were 0.68 (P0.0001) and 0.77 (P0.014) for70 and ≥70 age groups; 0.69 (P0.0001) and 0.59 (P0.0001) for Charlson Comorbidity Index ≤1 and1 groups; and 0.70 (P0.0001) and 0.58 (P0.0001) for National Cancer Institute Combined Index ≤1 and1 groups. OS was also significantly improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts and MC scores and higher in patients aged ≥70. Oxaliplatin-relevant grade 3/4 AEs, including neuropathy, were comparable across ages and MC scores.Results further support consideration of XELOX or FOLFOX as standard treatment options for the adjuvant management of stage III CC in all age groups and in patients with comorbidities, consistent with those who were eligible for these clinical trials.

Published
2015

15. A Review of the Evolution of Systemic Chemotherapy in the Management of Colorectal Cancer

Author

Bengt Gustavsson, David MacHover, Kjell Magne Tveit, Göran Carlsson, Hans J. Schmoll, Fernando Gibson, Nicholas J. Petrelli, and Arnaud Roth

Subjects
Oncology, medicine.medical_specialty, Bevacizumab, 5-Fluorouracil, Leucovorin, FOLFIRI, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Adjuvant therapy, Humans, Panitumumab, Molecular Targeted Therapy, neoplasms, Cetuximab, business.industry, 5,10-Methylenetetrahydrofolate, Gastroenterology, Antibodies, Monoclonal, digestive system diseases, Oxaliplatin, Irinotecan, Drug Design, Fluorouracil, Colorectal Neoplasms, business, medicine.drug
Abstract

Herein we present a historical review of the development of systemic chemotherapy for colorectal cancer (CRC) in the metastatic and adjuvant treatment settings. We describe the discovery of 5-fluorouracil (5-FU) by Heidelberger and colleagues in 1957, the potentiation of 5-FU cytotoxicity by the reduced folate leucovorin, and the advent of novel cytotoxic agents, including the topoisomerase I inhibitor irinotecan, the platinum-containing agent oxaliplatin, and the 5-FU prodrug capecitabine. The combination therapies, FOLFOX (5-FU/leucovorin and oxaliplatin) and FOLFIRI (5-FU/leucovorin and irinotecan), have become established as efficacious cytotoxic regimens for the treatment of metastatic CRC, resulting in overall survival times of approximately 2 years. When used as adjuvant therapy, FOLFOX also improves survival and is now the gold standard of care in this setting. Biological agents have been discovered that enhance the effect of cytotoxic therapy, including bevacizumab (a humanized monoclonal antibody that targets vascular endothelial growth factor, a central regulator of angiogenesis) and cetuximab/panitumumab (monoclonal antibodies directed against the epidermal growth factor receptor). Despite the ongoing development of novel antitumor agents and therapeutic principles as we enter the era of personalized cancer medicine, systemic chemotherapy involving infusional 5-FU/leucovorin continues to be the cornerstone of treatment for patients with CRC.

Published
2015

16. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial

Author

Tobias Pukrop, Francesco Pisani, Gerald Illerhaus, Franco Cavalli, Eleonora Minacapelli, Alessandro Levis, Jette Sønderskov Gørløv, Lorella Orsucci, Elisabeth Schorb, Paul La Rosée, Elisa Jacobsen Pulczynski, Francesco Angrilli, Stephan Stilgenbauer, Monica Balzarotti, Georg Hess, Alexander Röth, Jeffery Smith, Claire Hemmaway, Fiorella Ilariucci, Kim Linton, Stefan W. Krause, Alberto Fabbri, Andrés José Maria Ferreri, Mascha Binder, Kate Cwynarski, Maurilio Ponzoni, Jens Panse, Bernd Hertenstein, Martina Deckert, Valter Torri, Hans J. Schmoll, Monica Falautano, Alessandra Tucci, Ulrich Keller, Letterio S. Politi, Emanuele Zucca, Juergen Finke, Christopher P. Fox, Mathias J. Rummel, Giuseppina Cabras, Peter Johnson, Achille Ambrosetti, Michele Reni, Michael Pfreundschuh, Ferreri, A. J. M., Cwynarski, K., Pulczynski, E., Fox, C. P., Schorb, E., La Rosee, P., Binder, M., Fabbri, A., Torri, V., Minacapelli, E., Falautano, M., Ilariucci, F., Ambrosetti, A., Roth, A., Hemmaway, C., Johnson, P., Linton, K. M., Pukrop, T., Sonderskov Gorlov, J., Balzarotti, M., Hess, G., Keller, U., Stilgenbauer, S., Panse, J., Tucci, A., Orsucci, L., Pisani, F., Levis, A., Krause, S. W., Schmoll, H. J., Hertenstein, B., Rummel, M., Smith, J., Pfreundschuh, M., Cabras, G., Angrilli, F., Ponzoni, M., Deckert, M., Politi, L. S., Finke, J., Reni, M., Cavalli, F., Zucca, E., and Illerhaus, G.

Subjects
Oncology, Adult, Male, medicine.medical_specialty, autologous stem cell transplantation, Adolescent, Lymphoma, Medizin, primary CNS lymphoma, whole brain radiotherapy, autologous stem cell transplantation, Phases of clinical research, ThioTEPA, Transplantation, Autologous, Disease-Free Survival, Central Nervous System Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Autologous stem-cell transplantation, primary CNS lymphoma, Chemoimmunotherapy, Internal medicine, Journal Article, Medicine, Humans, Aged, Manchester Cancer Research Centre, Dose-Response Relationship, Drug, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Induction chemotherapy, Brain, Hematology, Middle Aged, Combined Modality Therapy, 3. Good health, Surgery, Transplantation, Regimen, Methotrexate, 030220 oncology & carcinogenesis, whole brain radiotherapy, Rituximab, Female, business, 030215 immunology, medicine.drug, Stem Cell Transplantation
Abstract

Background The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. Methods HIV-negative patients (aged 18–70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0–3 were randomly assigned to receive four courses of methotrexate 3·5 g/m2 on day 1 plus cytarabine 2 g/m2 twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m2 on days −5 and 0 (group B); or the same methotrexate–cytarabine–rituximab combination plus thiotepa 30 mg/m2 on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4–10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine–thiotepa conditioned ASCT (carmustine 400 mg/m2 on day −6, and thiotepa 5 mg/kg every 12 h on days −5 and −4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer-generated randomisation list was used within each stratum. No masking after assignment to intervention was adopted. The primary endpoint was 2-year progression-free survival, with induction group and response to induction chemotherapy as stratification parameters. Analyses were done on a modified intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT01011920. Findings Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited from 53 centres in five countries. 219 of 227 enrolled patients were assessable. Of the 122 patients eligible for the second randomisation, 118 patients were randomly assigned to WBRT or ASCT (59 patients per group) and constitute the study population. WBRT and ASCT were both effective, and achieved the predetermined efficacy threshold of at least 40 progression-free survivors at 2 years among the first 52 patients in both groups D and E. There were no significant differences in 2-year progression-free survival between WBRT and ASCT: 80% (95% CI 70–90) in group D and 69% (59–79) in group E (hazard ratio 1·50, 95% CI 0·83–2·71; p=0·17). Both consolidation therapies were well tolerated. Grade 4 non-haematological toxicity was uncommon; as expected, haematological toxicity was more common in patients treated with ASCT than in those who received WBRT. Two toxic deaths (infections) were recorded, both in patients who received ASCT. Interpretation WBRT and ASCT are both feasible and effective as consolidation therapies after high-dose methotrexate-based chemoimmunotherapy in patients aged 70 years or younger with primary CNS lymphoma. The risks and implications of cognitive impairment after WBRT should be considered at the time of therapeutic decision. Funding Agenzia Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Science Foundation.

Published
2017

17. Treatment of Adolescents and Young Adults (AYA) with Cancer in a Multidisciplinary Setting: On the Way to a Highly Specialized AYA Unit

Author

T. Bernig, R. Huehn, S. Witkowsky, H.-J. Schmoll, Franziska Jahn, A. Hentschel, T. Kegel, and Dieter Körholz

Subjects
medicine.medical_specialty, Pediatrics, Adolescent, Quality Assurance, Health Care, Health Promotion, Medical Oncology, Malignancy, Health Services Accessibility, Young Adult, Multidisciplinary approach, Germany, Neoplasms, Oncology Service, Hospital, Health care, medicine, Humans, Cooperative Behavior, Young adult, Curriculum, Patient Care Team, Clinical Trials as Topic, Health Services Needs and Demand, business.industry, Cancer, medicine.disease, humanities, Survival Rate, Clinical trial, Patient Satisfaction, Family medicine, Pediatrics, Perinatology and Child Health, Quality of Life, Education, Medical, Continuing, Interdisciplinary Communication, business, Psychosocial
Abstract

Further survival improvements of adolescents and young adults (AYA) with cancer are clearly affected by biological characteristics of the malignancies and age-specific needs. Multidisciplinary teams drawing expertice from both pediatric and adult cancer teams as well as clinical trials are required to meet the age specific needs of AYA patients with cancer. In 2011, the first AYA unit was established at the University Hospital Halle (Saale), where patients with newly-diagnosed cancer aged 15-25 are treated interdisciplinary by pediatric and adult oncologists. The enrollment into pediatric or adult clinical trials is controlled by age 18. Over the last 2 years, 19 AYA with cancer have been treated at the unit; and, in turn patients and their relatives reflected a high satisfaction with the offered novel health care approach. In the scope of the future Comprehensive Cancer Center at the University Hospital Halle (Saale), a complete ward is planned for all admitted AYA up to 25 years with cancer. The patients will be treated by a tumor-specialized multidisciplinary team of adult or pediatric oncologists and oncological surgeons. Therefore, we intend to establish a special teaching curriculum for physicians, nurses and psychosocial health care staff. Rather than age, cancer biology of a malignancy, surveillance data of late side effects as well as the age-specific needs of AYA patients will be crucial for best treatment options.

Published
2013

18. Capecitabine/irinotecan or capecitabine/oxaliplatin in combination with bevacizumab is effective and safe as first-line therapy for metastatic colorectal cancer: a randomized phase II study of the AIO colorectal study group

Author

Stefan Kubicka, W. Freier, Anke Reinacher-Schick, Michael Pohl, Axel Hinke, W. Schmiegel, U. Graeven, Dirk Arnold, S. Hegewisch-Becker, H.-J. Schmoll, Andrea Tannapfel, G. Dietrich, and M. Geißler

Subjects
Adult, Diarrhea, Male, Oncology, medicine.medical_specialty, Organoplatinum Compounds, genetic structures, Bevacizumab, Colorectal cancer, Population, Phases of clinical research, Antibodies, Monoclonal, Humanized, Irinotecan, Deoxycytidine, Gastroenterology, Disease-Free Survival, Capecitabine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, CAPOX Regimen, Hematology, Middle Aged, medicine.disease, eye diseases, Oxaliplatin, Treatment Outcome, Camptothecin, Female, Fluorouracil, Colorectal Neoplasms, business, medicine.drug
Abstract

Background This randomized phase II trial investigated the efficacy and safety of capecitabine/oxaliplatin (CapOx) plus bevacizumab and dose-modified capecitabine/irinotecan (mCapIri) plus bevacizumab as first-line therapy in patients with metastatic colorectal cancer (mCRC). Patients and methods Patients received bevacizumab 7.5 mg/kg with oxaliplatin 130 mg/m2/day 1 plus capecitabine 1000 mg/m2 bid/days 1–14 or with irinotecan 200 mg/m2/day 1 plus capecitabine 800 mg/m2 bid/days 1–14 both every 21 days. The primary end point was 6 months progression-free survival (PFS). Results A total of 255 patients were enrolled. The intent-to-treat population comprised 247 patients (CapOx–bevacizumab: n = 127; mCapIri–bevacizumab: n = 120). The six-month PFS rates were 76% (95% CI, 69%–84%) and 84% (95% CI, 77%–90%). Median PFS and OS were 10.4 months (95% CI, 9.0–12.0) and 24.4 months (95% CI, 19.3–30.7) with CapOx–bevacizumab, and 12.1 months (95% CI, 10.8–13.2) and 25.5 months (95% CI, 21.0–31.0) with mCapIri–bevacizumab. Grade 3/4 diarrhea as predominant toxic effect occurred in 22% of patients with CapOx–bevacizumab and in 16% with mCapIri–bevacizumab. Conclusions Both, CapOx–bevacizumab and mCapIri–bevacizumab, show promising activity and an excellent toxic effect profile. Efficacy is in the range of other bevacizumab-containing combination regimen although lower doses of irinotecan and capecitabine were selected for mCapIri.

Published
2013

19. Prognostic and predictive value of VEGF, sVEGFR-2 and CEA in mCRC studies comparing cediranib, bevacizumab and chemotherapy

Author

H.-J. Schmoll, Jane Robertson, Paulo M. Hoff, L Brooks, David Wilson, Shethah Morgan, M Taboada, and Juliane M. Jürgensmeier

Subjects
Vascular Endothelial Growth Factor A, Oncology, Cancer Research, medicine.medical_specialty, Bevacizumab, Colorectal cancer, Enzyme-Linked Immunosorbent Assay, bevacizumab, Antibodies, Monoclonal, Humanized, Cediranib, chemistry.chemical_compound, Carcinoembryonic antigen, FOLFOX, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, cediranib, Neoplasm Metastasis, Molecular Diagnostics, Survival rate, Neoplasm Staging, Retrospective Studies, colorectal, biology, business.industry, Hazard ratio, biomarkers, Prognosis, medicine.disease, VEGF, Vascular Endothelial Growth Factor Receptor-2, Carcinoembryonic Antigen, Surgery, Survival Rate, Vascular endothelial growth factor, chemistry, Quinazolines, biology.protein, Colorectal Neoplasms, business, Follow-Up Studies, medicine.drug
Abstract

Background: The prognostic/predictive value of potential vascular endothelial growth factor (VEGF) signalling biomarkers was evaluated retrospectively using samples from two randomized Phase III studies (HORIZON II and III) investigating cediranib in metastatic colorectal cancer (mCRC). Methods: Baseline levels of VEGF, soluble VEGF receptor-2 (sVEGFR-2) and carcinoembryonic antigen (CEA) were measured in plasma/serum samples collected from patients participating in HORIZON II (n=860; FOLFOX/XELOX plus cediranib 20 mg (n=502) or placebo (n=358)) and HORIZON III (n=1422; mFOLFOX6 plus cediranib 20 mg (n=709) or bevacizumab (n=713)). Median biomarker baseline levels determined cutoff values for the patient subgroups. Results: Baseline data were available for 88–97% of patients/study (>2000 patients). In both the studies, high baseline VEGF and CEA were associated with worse outcomes for progression-free survival (PFS) and overall survival (OS) independent of treatment (HORIZON II OS: VEGF, hazard ratio (HR)=1.35 (95% confidence interval (CI): 1.12–1.63); CEA, HR=1.63 (1.36–1.96); HORIZON III OS: VEGF, HR=1.32 (1.12–1.54); CEA, HR=1.50 (1.29–1.76)). sVEGFR-2 was not prognostic for PFS/OS. Baseline VEGF and CEA were not predictive for PFS/OS outcome to cediranib treatment; low sVEGFR-2 was associated with a trend towards improved cediranib effect in HORIZON II. Conclusion: Baseline VEGF and CEA levels were treatment-independent prognostic biomarkers for PFS and OS in both the studies.

Published
2013

20. The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 10th World Congress on Gastrointestinal Cancer, Barcelona, 2008

Author

Daniel G. Haller, Roberto Labianca, Michel Ducreux, A. de Gramont, Nadir Arber, Atsushi Ohtsu, Josep Tabernero, David Cunningham, Karin Haustermans, C.J.H. van de Velde, Bernard Nordlinger, Malcolm J. Moore, Jordan Berlin, Werner Scheithauer, Paulo M. Hoff, Alberto Sobrero, David J. Kerr, H.-J. Schmoll, E. Van Cutsem, Eduardo Díaz-Rubio, Ph. Rougier, Chris Verslype, Thomas Gruenberger, and Mario Dicato

Subjects
Sorafenib, medicine.medical_specialty, Evidence-based practice, Carcinoma, Hepatocellular, business.industry, General surgery, medicine.medical_treatment, Liver Neoplasms, Hematology, Liver transplantation, medicine.disease, Systemic therapy, digestive system diseases, Clinical trial, Oncology, Hepatocellular carcinoma, medicine, Humans, Gastrointestinal cancer, Liver function, business, neoplasms, medicine.drug
Abstract

This article summarizes the expert discussion on the management of pancreatic cancer, which took place during the 8th World Congress on Gastrointestinal Cancer in June 2006 in Barcelona. A multidisciplinary approach to a patient with pancreatic cancer is essential, in order to guarantee an optimal staging, surgery, selection of the appropriate (neo-)adjuvant strategy and chemotherapeutic choice management. Moreover, optimal symptomatic management requires a dedicated team of health care professionals. Quality control of surgery and pathology is especially important in this disease with a high locoregional failure rate. There is now solid evidence in favour of chemotherapy in both the adjuvant and palliative setting, and gemcitabine combined with erlotinib, capecitabine or platinum compounds seems to be slightly more active than gemcitabine alone in advanced pancreatic cancer. There is a place for chemoradiotherapy in selected patients with locally advanced disease, while the role in the adjuvant setting remains controversial. Those involved in the care for patients with pancreatic cancer should be encouraged to participate in well-designed clinical trials, in order to increase the evidence-based knowledge and to make further progress. © 2007 European Society for Medical Oncology.

Published
2016

21. The management of pancreatic cancer. Current expert opinion and recommendations derived from the 8th World Congress on Gastrointestinal Cancer, Barcelona, 2006

Author

S. Pedrazzoli, David Cunningham, Stefano Cascinu, C. Louvet, Mario Dicato, Arnaud Roth, Paulo M. Hoff, Bengt Glimelius, Bruce D. Minsky, Volker Heinemann, Ph. Rougier, H.-J. Schmoll, Karin Haustermans, Mace L. Rothenberg, C.J.H. van de Velde, Chris Verslype, Malcolm J. Moore, John Zalcberg, Patrick G. Johnston, E. Van Cutsem, Eduardo Díaz-Rubio, Margaret A. Tempero, Josep Tabernero, Daniel G. Haller, David J. Kerr, Bernard Nordlinger, Roberto Labianca, and J-L. van Laethem

Subjects
ddc:616, medicine.medical_specialty, Pancreatic Neoplasms/diagnosis/therapy, Palliative care, business.industry, medicine.medical_treatment, Hematology, medicine.disease, Combined Modality Therapy, Gemcitabine, Surgery, Clinical trial, Radiation therapy, Capecitabine, Oncology, Pancreatic cancer, Medicine, Humans, Erlotinib, business, Intensive care medicine, Chemoradiotherapy, medicine.drug, Neoplasm Staging
Abstract

This article summarizes the expert discussion on the management of pancreatic cancer, which took place during the 8th World Congress on Gastrointestinal Cancer in June 2006 in Barcelona. A multidisciplinary approach to a patient with pancreatic cancer is essential, in order to guarantee an optimal staging, surgery, selection of the appropriate (neo-)adjuvant strategy and chemotherapeutic choice management. Moreover, optimal symptomatic management requires a dedicated team of health care professionals. Quality control of surgery and pathology is especially important in this disease with a high locoregional failure rate. There is now solid evidence in favour of chemotherapy in both the adjuvant and palliative setting, and gemcitabine combined with erlotinib, capecitabine or platinum compounds seems to be slightly more active than gemcitabine alone in advanced pancreatic cancer. There is a place for chemoradiotherapy in selected patients with locally advanced disease, while the role in the adjuvant setting remains controversial. Those involved in the care for patients with pancreatic cancer should be encouraged to participate in well-designed clinical trials, in order to increase the evidence-based knowledge and to make further progress.

Published
2016

22. Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial

Author

Francesco, Sclafani, Tae Y, Kim, David, Cunningham, Tae W, Kim, Josep, Tabernero, Hans J, Schmoll, Jae K, Roh, Sun Y, Kim, Young S, Park, Tormod K, Guren, Eliza, Hawkes, Stephen J, Clarke, David, Ferry, Jan-Erik, Frodin, Mark, Ayers, Michael, Nebozhyn, Clare, Peckitt, Andrey, Loboda, and David J, Watkins

Subjects
Adult, Male, Antibodies, Monoclonal, Cetuximab, Exons, Middle Aged, Antibodies, Monoclonal, Humanized, Irinotecan, Disease-Free Survival, Receptor, IGF Type 1, Proto-Oncogene Proteins p21(ras), Double-Blind Method, Insulin-Like Growth Factor II, Antineoplastic Combined Chemotherapy Protocols, Mutation, Humans, Camptothecin, Female, Insulin-Like Growth Factor I, Colorectal Neoplasms, Aged
Abstract

Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression-free survival (2.7 vs. 2.6 vs. 1.4 months) and overall survival (7.8 vs. 10.3 vs. 7.8 months) were not statistically significantly different between treatment groups. Most common grade ≥3 treatment-related toxicities included neutropenia, diarrhoea, hyperglycaemia, fatigue and dermatitis acneiform. Expression of IGF-1R, IGF-1, IGF-2 and EREG by quantitative real-time polymerase chain reaction was assessed in 351 patients from the same study with available data on KRAS exon 2 mutational status. Median cycle threshold values for all biomarkers were significantly lower (i.e., higher expression, p 0.05) among patients with KRAS wild-type compared to those with KRAS exon 2 mutant tumours. No significant changes were found according to location of the primary tumour with only a trend towards lower expression of IGF-1 in colon compared to rectal cancers (p = 0.06). Albeit limited by the small sample size, this study does not appear to support a potential role for anti-IGF-1R agents in KRAS exon 2 mutant CRC. Data on IGF-1R, IGF-1 and IGF-2 expression here reported may be useful for patient stratification in future trials with inhibitors of the IGF pathway.

Published
2016

23. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial

Author

Michele Reni, Mascha Binder, Angela Ferrari, Roberta Rudà, Ulrich Keller, Tobias Pukrop, Bernd Hertenstein, Georg Hess, Gerald Illerhaus, Peter Johnson, Stephan Stilgenbauer, Claire Hemmaway, Elisabeth Schorb, Paul La Rosée, Francesco Pisani, Jens Panse, Achille Ambrosetti, Monica Balzarotti, Franco Cavalli, Jürgen Finke, Kate Cwynarski, Emanuele Zucca, Martina Deckert, Andrés José Maria Ferreri, Alexander Röth, Alberto Fabbri, Valter Torri, Alessandro Levis, Alessandra Tucci, Letterio S. Politi, Elisa Jacobsen Pulczynski, Kim Linton, Stefan W. Krause, Christopher P. Fox, Maurilio Ponzoni, Hans J. Schmoll, Jette Sønderskov Gørløv, Ferreri, A. J. M., Cwynarski, K., Pulczynski, E., Ponzoni, M., Deckert, M., Politi, L. S., Torri, V., Fox, C. P., Rosee, P. L., Schorb, E., Ambrosetti, A., Roth, A., Hemmaway, C., Ferrari, A., Linton, K. M., Ruda, R., Binder, M., Pukrop, T., Balzarotti, M., Fabbri, A., Johnson, P., Gorlov, J. S., Hess, G., Panse, J., Pisani, F., Tucci, A., Stilgenbauer, S., Hertenstein, B., Keller, U., Krause, S. W., Levis, A., Schmoll, H. J., Cavalli, F., Finke, J., Reni, M., Zucca, E., and Illerhaus, G.

Subjects
Male, Comparative Effectiveness Research, Transplantation Conditioning, Gastrointestinal Diseases, Denmark, Medizin, Kaplan-Meier Estimate, Dexamethasone, Central Nervous System Neoplasms, Death, Sudden, 0302 clinical medicine, Intraocular Lymphoma, Germany, Antineoplastic Combined Chemotherapy Protocols, Medicine, Standard treatment, Optic Nerve Neoplasms, Poisoning, Remission Induction, Cytarabine, Hematopoietic Stem Cell Transplantation, Anemia, Hematology, Induction Chemotherapy, Acute Kidney Injury, Middle Aged, Combined Modality Therapy, Magnetic Resonance Imaging, 3. Good health, Stroke, Treatment Outcome, Tolerability, Italy, 030220 oncology & carcinogenesis, chemoimmunotherapy, Rituximab, Female, Neurotoxicity Syndromes, Chemical and Drug Induced Liver Injury, Switzerland, medicine.drug, Mucositis, medicine.medical_specialty, Lymphoma, B-Cell, Neutropenia, ThioTEPA, Infections, Transplantation, Autologous, Disease-Free Survival, 03 medical and health sciences, primary CNS lymphoma, Chemoimmunotherapy, Internal medicine, Journal Article, primary CNS lymphoma, chemoimmunotherapy, Humans, business.industry, Thrombosis, medicine.disease, Thrombocytopenia, United Kingdom, Surgery, Transplantation, Regimen, Methotrexate, Heart Injuries, Hyperglycemia, Radiotherapy, Adjuvant, business, 030217 neurology & neurosurgery, Febrile neutropenia, Thiotepa, Follow-Up Studies
Abstract

BACKGROUND: Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article.METHODS: For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01011920.FINDINGS: Between Feb 19, 2010, and Aug 27, 2014, 227 eligible patients were recruited. 219 of these 227 enrolled patients were assessable. At median follow-up of 30 months (IQR 22-38), patients treated with rituximab and thiotepa had a complete remission rate of 49% (95% CI 38-60), compared with 23% (14-31) of those treated with methotrexate-cytarabine alone (hazard ratio 0·46, 95% CI 0·28-0·74) and 30% (21-42) of those treated with methotrexate-cytarabine plus rituximab (0·61, 0·40-0·94). Grade 4 haematological toxicity was more frequent in patients treated with methotrexate-cytarabine plus rituximab and thiotepa, but infective complications were similar in the three groups. The most common grade 3-4 adverse events in all three groups were neutropenia, thrombocytopenia, anaemia, and febrile neutropenia or infections. 13 (6%) patients died of toxicity.INTERPRETATION: With the limitations of a randomised phase 2 study design, the IELSG32 trial provides a high level of evidence supporting the use of MATRix combination as the new standard chemoimmunotherapy for patients aged up to 70 years with newly diagnosed primary CNS lymphoma and as the control group for future randomised trials.FUNDING: Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Foundation.

Published
2016

24. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

Author

R. Labianca, Fortunato Ciardiello, J.-Y. Douillard, Alfredo Falcone, André D'Hoore, C.-H. Köhne, Aziz Zaanan, George Pentheroudakis, Dan Aderka, Nicola Normanno, Takayuki Yoshino, Per Pfeiffer, H.-J. Schmoll, Al B. Benson, J.H.J.M. van Krieken, René Adam, Demetris Papamichael, Paulo M. Hoff, Jens Ricke, R. Salazar, György Bodoky, Harpreet Wasan, Josep Tabernero, Timothy J. Price, Dirk Arnold, Michel Ducreux, Alberto Sobrero, Thomas Gruenberger, Brigette B.Y. Ma, Axel Grothey, E. Aranda Aguilar, E. Van Cutsem, Karin Haustermans, Volker Heinemann, Pia Österlund, Kei Muro, Arnaud Roth, Eduardo Díaz-Rubio, Pierre Laurent-Puig, Andrés Cervantes, Alberto Bardelli, Wim J.G. Oyen, Julien Taieb, C.J.A. Punt, Sabine Tejpar, Tim Maughan, Werner Scheithauer, Van Cutsem, E, Cervantes, A, Adam, R, Sobrero, A, Van Krieken, Jh, Aderka, D, Aranda Aguilar, E, Bardelli, A, Benson, A, Bodoky, G, Ciardiello, Fortunato, D'Hoore, A, Diaz Rubio, E, Douillard, Jy, Ducreux, M, Falcone, A, Grothey, A, Gruenberger, T, Haustermans, K, Heinemann, V, Hoff, P, Köhne, Ch, Labianca, R, Laurent Puig, P, Ma, B, Maughan, T, Muro, K, Normanno, N, Österlund, P, Oyen, Wj, Papamichael, D, Pentheroudakis, G, Pfeiffer, P, Price, Tj, Punt, C, Ricke, J, Roth, A, Salazar, R, Scheithauer, W, Schmoll, Hj, Tabernero, J, Taïeb, J, Tejpar, S, Wasan, H, Yoshino, T, Zaanan, A, Arnold, D. 4. 5., and Oncology

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Evidence-based practice, Bevacizumab, Colorectal cancer, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Guidelines as Topic, colorectal cancer, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], 03 medical and health sciences, chemistry.chemical_compound, Clinical practice guidelines, Consensus, ESMO, Hematology, 0302 clinical medicine, Guia de Práctica Clínica, Internal medicine, Biomarkers, Tumor, medicine, Humans, Molecular Targeted Therapy, Neoplasm Metastasis, Intensive care medicine, Tipiracil, Neoplasias Colorrectais/tratamento, FOLFOXIRI, business.industry, clinical practice guidelines, consensus, Cancer, Prognosis, medicine.disease, Debulking, Chemotherapy regimen, digestive system diseases, 3. Good health, 030104 developmental biology, Practice Guideline, chemistry, Colorectal Neoplasms/therapy, 030220 oncology & carcinogenesis, Colorectal Neoplasms, business, clinical practice guideline, medicine.drug
Abstract

Contains fulltext : 165965.pdf (Publisher’s version ) (Closed access) Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.

Published
2016

25. Role of the multidisciplinary team in breast cancer management: results from a large international survey involving 39 countries

Author

Martine Piccart-Gebhart, Cath Taylor, Carlo Palmieri, C. Ghenne, H.-J. Schmoll, Ulf Gunnarsson, Marianne Paesmans, M. Skrzypski, S.M. Dolci, E. de Azambuja, Kamal S Saini, Lieveke Ameye, Otto Metzger-Filho, and Amanda-Jane Ramirez

Subjects
medicine.medical_specialty, Pathology, Decision Making, Alternative medicine, MEDLINE, Breast Neoplasms, Breast cancer, Multidisciplinary approach, medicine, Humans, Disease management (health), Randomized Controlled Trials as Topic, business.industry, International survey, Disease Management, Hematology, medicine.disease, Group Processes, Clinical trial, Clinical Trials, Phase III as Topic, Oncology, Health Care Surveys, Western europe, Family medicine, Female, business
Abstract

Background: The optimal management of patients with breast cancer (BC) requires the expertise of specialists from different disciplines. This has led to the evolution of multidisciplinary teams (MDTs), allowing all key professionals to jointly discuss individual patients and to contribute independently to clinical decisions. Data regarding BC MDTs in different regions and countries are scarce. Methods: The investigators of a large global phase III adjuvant BC trial being conducted by the Breast International Group were invited to respond to a questionnaire about the extent, structure, and function of BC MDTs. Results: One hundred and fifty-two responses from 39 countries were received, and remarkable differences were noted in different geographic regions. Sixty-five percent of the respondents from eastern Europe, 63% from western Europe, 35% from Asia, and 25% from South America declared that MDT was a mandatory part of BC care in their country. Ninety percent of the respondents from Europe stated their MDTs met weekly, compared with only half of the respondents from Asia. Conclusion: This survey is perhaps the first large-scale effort to collect information regarding BC MDTs from different parts of the world and provides objective information of frequency, composition, function, and working mechanism of BC MDTs.

Published
2012

26. Unklares Fieber und B-Symptome bei einem jungen Schwarzafrikaner

Author

Thomas J. Ettrich, H. Ebelt, H.-H. Wolf, Karl Werdan, A. Lindner, A. Oehme, H.-J. Schmoll, Thomas Weber, Maximilian Christopeit, C. Lübbert, Hans-Jürgen Holzhausen, Alexander S. Kekulé, and Dirk Arnold

Subjects
Cytopenia, medicine.medical_specialty, Hemophagocytic lymphohistiocytosis, business.industry, Fulminant, Hepatosplenomegaly, medicine.disease, Pancytopenia, Gastroenterology, B symptoms, Intensive care, Internal medicine, Internal Medicine, medicine, medicine.symptom, business, Rare disease
Abstract

An immunocompetent Nigerian developed a fulminant hemophagocytic lymphohistiocytosis due to Epstein-Barr virus reactivation. The patient initially presented with fever, hepatosplenomegaly and pancytopenia. The clinical status of our patient deteriorated quickly despite treatment with corticoids. Escalation of immunosuppressive treatment was not possible. He died of lung, liver and circulatory failure in our intensive care unit.Hemophagocytic lymphohistiocytosis is a rare disease characterized by inflammation due to prolonged and excessive activation of antigen-presenting cells. High plasma ferritin levels and phagocytosis of hematopoetic cells in bone marrow, spleen and liver lead to the diagnosis. Hemophagocytic lymphohistiocytosis should therefore be included in the differential diagnosis in patients with persistent fever, hepatosplenomegaly and cytopenia.

Published
2011

27. Pancreatic cancer treatment and research: an international expert panel discussion

Author

David Khayat, H.-J. Schmoll, Margaret A. Tempero, Peter Harper, Jordan Berlin, Alberto Sobrero, Daniel G. Haller, E. Van Cutsem, and Michel Ducreux

Subjects
medicine.medical_specialty, Biomedical Research, business.industry, medicine.medical_treatment, Cancer, Antineoplastic Agents, Combination chemotherapy, Hematology, Disease, Congresses as Topic, medicine.disease, Chemotherapy regimen, Surgery, Targeted therapy, Pancreatic Neoplasms, Oncology, Drug development, Pancreatic cancer, medicine, Humans, Intensive care medicine, business, Panel discussion
Abstract

Background Pancreatic cancer has proven extremely challenging to treat. A collaborative effort is needed to advance research and improve treatment. An expert conference was conducted to elicit perspectives regarding the current treatment and future research of pancreatic cancer. Methods The conference comprised an international panel of experts representing five European countries and the United States. Results Adjuvant radiotherapy is used more frequently in the United States than in Europe. In locally advanced disease, there is now more emphasis on early chemotherapy in both Europe and the United States. In metastatic disease, combination chemotherapy is commonly used in Europe and the United States. This varies by country. Advancing pancreatic research will require improving biorepositories and developing a roadmap to prioritize therapeutic targets in different models. Small randomized phase II trials of both non-selected and enriched patient populations will help identify activity of new agents. Phase III trials should only be initiated in appropriate patients based on strong clinical and biological signals. Developing drugs in the adjuvant setting may be preferable to eliminate some of the challenges of drug development in the advanced disease setting. Conclusion Progress in research combined with encouraging improvements from the past offer hope for the future of pancreatic cancer patients.

Published
2011

28. S3-Leitlinie 'Magenkarzinom'

Author

H. Vogelsang, Stefan Mönig, C. Kuhn, Lars Grenacher, Wolfgang Fischbach, Andrea Tannapfel, Markus Moehler, Wh-H. Schmiegel, J. Bernhardt, Michael Stahl, T. Rabenstein, C. Stoll, Hubert J. Stein, Stephan Kanzler, A. Weimann, Manfred P. Lutz, J. Körber, Michael Flentje, P. Rohr, R. Porschen, U. Vanhoefer, Markus Horneber, I. Roetzer, Hj-J. Meyer, J. Fahlke, Bj J. Krause, T. Andus, Pm M. Schlag, Frank Kullmann, P. Baier, K. Ridwelski, W. Schepp, B. Herbst, Helmut Messmann, U. Wedding, Wa A. Diemer, Pr R. Galle, E. Burmester, Ah H. Hölscher, He E. Gabbert, C. Ell, Florian Lordick, S. Groß, H. Boeing, G. Klautke, J. Seraphin, E. Böhle, Cf F. Dietrich, Rd D. Hofheinz, MP Ebert, Dirk Arnold, A. Eickhoff, Christian Jenssen, W. Budach, K. Ludwig, T. Seufferlein, K. Treml, A. Sendler, M. Heike, H. Wilke, R. Tholen, Rainer Fietkau, T. Höhler, H. Feußner, M Vieth, W. Fleig, Michael Selgrad, S. Merkel, Ch. Wittekind, Peter C. Thuss-Patience, Heinz Höfler, Gustavo B. Baretton, Peter Malfertheiner, M. Keller, Carsten Bokemeyer, Ralf Kiesslich, Ines Gockel, Jan Bornschein, Christoph Röcken, Steffen Pistorius, M. Geissler, Kerstin Schütte, G. Schuch, D. Wagner, Christoph Schuhmacher, R. Jakobs, U. Graeven, H. Lang, P. Piso, W. Schwenk, Hj-J. Schmoll, M. Anthuber, Jt T. Hartmann, J. Hübner, S. Höcht, J. R. Izbicki, Volker Heinemann, Daniela Aust, R. Mahlberg, Hartmut Link, Heinz Schmidberger, RM Schmid, P. Reichardt, Se-E. Al-Batran, Martin Stuschke, Thomas Herrmann, K. Caca, and Jann Arends

Subjects
German, medicine.medical_specialty, Esophagogastric cancer, business.industry, General surgery, Gastroenterology, MEDLINE, language, Medicine, Guideline, business, language.human_language
Published
2011

29. Fluoropyrimidine (FP) + bevacizumab (BEV) + atezolizumab vs FP/BEV in BRAFwt metastatic colorectal cancer (mCRC): Findings from Cohort 2 of MODUL – a multicentre, randomized trial of biomarker-driven maintenance treatment following first-line induction therapy

Author

Peter O'Dwyer, J. Tabernero, Ivan Bosanac, Christoph Mancao, A. de Gramont, Dirk Arnold, Stefanie Srock, J. Winter, H.-J. Schmoll, E. Van Cutsem, F. Gilberg, A. Grothey, and Michel Ducreux

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Bevacizumab, Colorectal cancer, medicine.medical_treatment, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Atezolizumab, law, Internal medicine, Induction therapy, medicine, Neoadjuvant therapy, business.industry, Hematology, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, Biomarker (medicine), business, medicine.drug
Published
2018

30. The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (highdose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination

Author

H.-J. Schmoll, J. Ruessel, Patrick Jahn, T. Kegel, Timo Behlendorf, Karin Jordan, Alexander Stein, and Franziska Jahn

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Paclitaxel, Vomiting, Nausea, medicine.drug_class, Morpholines, medicine.medical_treatment, Granisetron, Carboplatin, Young Adult, chemistry.chemical_compound, Neurokinin-1 Receptor Antagonists, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Antiemetic, Ifosfamide, Melphalan, Aprepitant, Etoposide, Transplantation, Chemotherapy, business.industry, Hematology, Middle Aged, Drug Combinations, Regimen, Treatment Outcome, chemistry, Anesthesia, Antiemetics, Female, medicine.symptom, business, medicine.drug
Abstract

Complete protection from nausea/vomiting is currently achieved in a minority of patients receiving high-dose chemotherapy (HDC). Currently the use of 5-HT3-antagonists and dexamethasone (DEX) represents the standard of care. The role of the NK-1-antagonist aprepitant in HDC remains to be better defined. A total of 64 patients undergoing multiple days of HDC received granisetron, DEX plus aprepitant during chemotherapy. After the end of chemotherapy aprepitant plus DEX was given for a further 2 days. Primary end point was CR defined as no vomiting and no use of rescue medication in the overall phase (day 1 until 5 days after end of chemotherapy). Acute/delayed and overall CR were achieved in 83%/70% and 63%, respectively. Acute and delayed nausea were observed in 20 and 38% of the patients. The tolerability of the aprepitant regimen over 4-5 days was comparable with the 3-day antiemetic regimen. In our study, aprepitant demonstrated good tolerability. Taking into account the methodological constraints of comparing our results with those from the available literature, the addition of aprepitant to the antiemetic treatment regimen may provide improved prevention of chemotherapy-induced nausea and vomiting during HDC.

Published
2010

31. PETACC-6: Preop chemoradiation and postop chemotherapy (capecitabine +/- oxaliplatin) in locally advanced rectal cancer: Overall survival after long term follow-up

Author

F. Fauth, H. Reinel, Timothy J. Price, Karin Haustermans, J.F. Daisne, P. Schmidt, John Zalcberg, Murielle Mauer, Jozef Janssens, Baruch Brenner, R.D. Hofheinz, Manfred P. Lutz, Carla Hannig, S. Hollerbach, Sandrine Marreaud, E. Van Cutsem, K. Caca, Niall C. Tebbutt, Bernard Nordlinger, and H.-J. Schmoll

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Chemotherapy, Colorectal cancer, business.industry, Long term follow up, medicine.medical_treatment, Capecitabine/oxaliplatin, Locally advanced, Hematology, 030230 surgery, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Internal medicine, medicine, Overall survival, business
Published
2018

32. FOLFOX/bevacizumab +/- irinotecan in advanced colorectal cancer (CHARTA): Long term outcome

Author

Carla Hannig, Alexander Stein, Axel Florschütz, Fabian Maximilian Meinert, H.-J. Schmoll, Arndt Vogel, Christian Junghanß, Stephan Kanzler, Franziska Cygon, Ulrich Kaiser, and Benjamin Garlipp

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Hematology, Outcome (game theory), Bevacizumab/Irinotecan, Term (time), Advanced colorectal cancer, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, FOLFOX, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, medicine.drug
Published
2018

33. Testicular seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Author

H-J, Schmoll, K, Jordan, R, Huddart, M P Laguna, Pes, A, Horwich, K, Fizazi, V, Kataja, L, Wood, Cancer Center Amsterdam, Amsterdam Public Health, and Urology

Subjects
Male, Salvage Therapy, L-Lactate Dehydrogenase, Radiotherapy, Biopsy, Incidence, Medizin, Hematology, Combined Modality Therapy, Risk Assessment, Seminoma, Europe, Treatment Outcome, Oncology, Testicular Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Secondary Prevention, Humans, Chorionic Gonadotropin, beta Subunit, Human, alpha-Fetoproteins, Neoplasm Metastasis, Orchiectomy, Carcinoma in Situ, Follow-Up Studies, Neoplasm Staging
Published
2010

34. Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in patients with refractory solid tumours: results of a phase I trial

Author

H.-J. Schmoll, Wieland Voigt, S. Lindemann, H. Wiesinger, S. Reif, C. Behrmann, Philipp Kiewe, Eckhard Thiel, M. Giurescu, and Dirk Arnold

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Microtubule bundle formation, Antineoplastic Agents, Epothilone, Pharmacology, Drug Administration Schedule, Refractory, Neoplasms, Clinical Studies, medicine, Humans, epothilone, Benzothiazoles, Adverse effect, refractory solid tumours, Aged, sagopilone, maximum tolerated dose, dose-limiting toxicity, business.industry, Standard treatment, Middle Aged, phase I, medicine.disease, Surgery, Peripheral neuropathy, Oncology, Epothilones, Erythropoietin, Toxicity, Female, business, medicine.drug
Abstract

Background: Epothilones are a novel class of microtubule-stabilising agents, and sagopilone is a fully synthetic epothilone that has shown marked in vivo and in vitro preclinical activity. Methods: This phase I, open-label study investigated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of weekly sagopilone. Twenty-three patients with malignancy resistant or refractory to standard treatment were enrolled into this study evaluating sagopilone doses from 0.6 to 7.0 mg m−2. Results: The incidence of drug-related haematological adverse events (AEs) was low, with two grade 3 events observed. Nonhaematological AEs were generally mild and reversible; increased γ-GT was the only grade 4 event and grade 3 events comprised peripheral neuropathy (n=2), diarrhoea (n=1) and fatigue (n=1). Two grade 3 events were DLTs (diarrhoea and peripheral neuropathy at 7.0 mg m−2). The MTD of weekly sagopilone was therefore established as 5.3 mg m−2. Stable disease was the best overall response (n=3). Microtubule bundle formation in peripheral blood mononuclear cells increased post-treatment, peaking after 1 h. Sagopilone disposition was similar across treatment courses and showed rapidly decreasing serum concentrations after infusion end and a long terminal disposition phase with no obvious accumulation in the serum, probably reflecting a fast uptake into tissues followed by a slow release. Conclusion: Weekly administration of sagopilone could represent an alternative to the 3-weekly administration currently evaluated in phase II trials.

Published
2009

35. Impact of quality of life parameters and coping strategies on postchemotherapy nausea and vomiting

Author

H.-J. Schmoll, C. Lautenschläger, C. Schöber, Axel Grothey, T. Pelz, Karin Jordan, and U. Franke

Subjects
Univariate analysis, medicine.medical_specialty, Multivariate analysis, Nausea, business.industry, Passive coping, Disease, Abdominal pressure, humanities, Surgery, Oncology, Quality of life, Vomiting, medicine, Physical therapy, medicine.symptom, business
Abstract

JORDAN K., GROTHEY A., PELZ T., LAUTENSCHLAGER C., FRANKE U., SCHOBER C. & SCHMOLL H.-J. (2010) European Journal of Cancer Care19, 603–609 Impact of quality of life parameters and coping strategies on postchemotherapy nausea and vomiting To assess whether prechemotherapy quality of life (QoL) factors and certain coping strategies are associated with postchemotherapy nausea and vomiting (PCNV). A total of 43 chemotherapy-naive patients scheduled to receive anti-emetic prophylaxis were enrolled in this study. QoL parameters were measured by a modified EORTC Quality of Life Questionnaire (QLQ-30). In addition, questions regarding active or passive coping strategies were asked 1 day before chemotherapy. Prechemotherapy QoL factors, coping strategies as well as other patient, disease and treatment variables were compared between the groups of patients with or without PCNV. The univariate analysis identified four QoL parameters, ‘tiredness’, ‘impairment of daily life by pain’, ‘sensation of abdominal pressure and fullness’ and ‘impairment of social activities’ as associated with PCNV. No association was found between coping strategies and PCNV. In the multivariate analysis, the factors ‘impairment of social activities’ and ‘sensation of abdominal pressure and fullness’ remained significant. Specific pretreatment QoL parameters are associated with the risk to develop PCNV. Thus, in addition to other established risk factors for PCNV, patients should be screened for these QoL factors in order to improve the control of PCNV and facilitate the selection of appropriate, individualised anti-emetic prophylaxes.

Published
2009

36. Neue antiemetische Strategien – nicht nur in der Onkologie

Author

F. Müller, Karin Jordan, and H.-J. Schmoll

Subjects
Gynecology, medicine.medical_specialty, business.industry, Internal Medicine, Medicine, business
Abstract

Ubelkeit und Erbrechen zahlen zu den haufigsten Symptomen im klinischen Alltag. Die korrekte Diagnose ihrer Ursachen setzt die Kenntnis pathophysiologischer Hintergrunde des Erbrechens und haufig eine interdisziplinare Herangehensweise voraus. Das breite Spektrum emetogener Ursachen (labyrinthar, infektios, mechanisch, medikamentos, hormonell) erfordert neben kausalen Therapieansatzen meist auch eine medikamentose symptomorientierte Beschwerdelinderung. Dafur stehen mehrere, im Wirkmechanismus und antiemetischen Potenzial unterschiedliche Substanzklassen zur Verfugung. Die Festlegung der antiemetischen Therapiestrategie erfolgt jeweils individuell und berucksichtigt neben der Ursache des Erbrechens den rezeptorspezifischen Wirkmechanismus der Substanz mit den sich daraus ergebenden Nebenwirkungen. Obwohl in den letzten Jahren neuere Substanzklassen wie 5-HT3-Rezeptor- und Neurokinin-1-Rezeptorantagonisten zunehmend an Bedeutung gewonnen haben, sind herkommliche und langjahrig erfolgreich angewandte Antiemetika weiterhin unverzichtbar.

Published
2009

37. Therapeutische Anwendung mesenchymaler Stromazellen bei Autoimmunerkrankungen

Author

H.-J. Schmoll, Keysser G, M. Schendel, and Lutz P. Müller

Subjects
Autoimmune disease, business.industry, Proliferative capacity, Mesenchymal stem cell, Disease, medicine.disease, Phenotype, Immune system, Rheumatology, In vivo, Immunology, medicine, business, Tropism
Abstract

Mesenchymal stromal cells (MSC) are characterized by their proliferative capacity, their phenotype and their ability to multipotent differentiation. However, little is known about their function and characteristics in vivo. MSC posses a tropism for injured tissues. Numerous investigations of MSC in different model systems suggest an immunosuppressive potential, although the results are in part contradictory. Apparently, MSC exert these effects on nearly all cells in the immune system. However, the relevance and mechanisms of these phenomena in vivo are not clear. The clinical effectiveness of allogeneic MSC in the treatment of refractory graft-versus-host disease has raised hopes that MSC could offer a new concept for the therapy of other immune-mediated disorders. However, before MSC are introduced in clinical practise, several important questions as to their side effects have to be addressed. This includes the possibility that MSC may contribute to the induction of malignant diseases.

Published
2009

40. Keimzelltumoren des Hodens: Epidemiologische und ätiologische Aspekte

Author

C. Bokemeyer, Patrick Schöffski, H. Poliwoda, H.-J. Schmoll, and Andreas Harstrick

Subjects
Gynecology, Disease susceptibility, medicine.medical_specialty, business.industry, Estrogen, medicine.drug_class, Incidence (epidemiology), Medicine, General Medicine, business, Cancer risk
Published
2008

42. Chemoembolisation hepatozellulärer Karzinome mit Lipiodol, Epirubicin und Cisplatin

Author

E. Schmoll, R. Grote, Frank Schmidt, Michael Galanski, B. Bokemeyer, J. Freise, Schüler A, and H.-J. Schmoll

Subjects
Cisplatin, medicine.medical_specialty, business.industry, medicine.medical_treatment, Therapeutic effect, Cancer, General Medicine, medicine.disease, Gastroenterology, Internal medicine, Hepatocellular carcinoma, Lipiodol, Medicine, Embolization, business, Survival rate, Epirubicin, medicine.drug
Abstract

The therapeutic effect of combined chemoembolization with lipiodol, epirubicin and cisplatin in 22 patients with nonresectable tumours, predominantly in livers with cirrhotic transformation, was analysed. Lipiodol was demonstrated in tumour tissue on average three months, maximally six months, after injection. Repeat embolization was done, if possible, after storage had subsided. There were only minor side effects. Quality of life suffered only from the, though delayed, continuing cancer growth. Survival rate was 73% after six months, 54% after one year.

Published
2008

44. Notfälle in Hämatologie und Onkologie

Author

Timo Behlendorf, H.-H. Wolf, K. Jordan, C. Sippel, M. Amoury, and H.-J. Schmoll

Subjects
Emergency Medicine, Critical Care and Intensive Care Medicine
Published
2008

45. Endpoints in Adjuvant Treatment Trials: A Systematic Review of the Literature in Colon Cancer and Proposed Definitions for Future Trials

Author

Marc Buyse, Peter Hohenberger, Cornelis J. A. Punt, Lars Påhlman, Roberto Labianca, Alberto Sobrero, Jean-Yves Douillard, Hans J. Schmoll, Claus Henning Köhne, and Other departments

Subjects
Oncology, Research design, Cancer Research, medicine.medical_specialty, Time Factors, Colorectal cancer, medicine.medical_treatment, Disease-Free Survival, Immune Regulation [NCMLS 2], Translational research [ONCOL 3], Interventional oncology [UMCN 1.5], Internal medicine, Outcome Assessment, Health Care, Clinical endpoint, Humans, Medicine, Treatment Failure, Survival rate, Clinical Trials as Topic, Hereditary cancer and cancer-related syndromes [ONCOL 1], business.industry, Surrogate endpoint, Cancer, medicine.disease, Surgery, Survival Rate, Treatment Outcome, Clinical research, Chemotherapy, Adjuvant, Research Design, Colonic Neoplasms, Disease Progression, business, Adjuvant
Abstract

Item does not contain fulltext Disease-free survival is increasingly being used as the primary endpoint of most trials testing adjuvant treatments in cancer. Other frequently used endpoints include overall survival, recurrence-free survival, and time to recurrence. These endpoints are often defined differently in different trials in the same type of cancer, leading to a lack of comparability among trials. In this Commentary, we used adjuvant studies in colon cancer as a model to address this issue. In a systematic review of the literature, we identified 52 studies of adjuvant treatment in colon cancer published in 1997-2006 that used eight other endpoints in addition to overall survival. Both the definition of these endpoints and the starting point for measuring time to the events that constituted these endpoints varied widely. A panel of experts on clinical research on colorectal cancer then reached consensus on the definition of each endpoint. Disease-free survival--defined as the time from randomization to any event, irrespective of cause--was considered to be the most informative endpoint for assessing the effect of treatment and therefore the most relevant to clinical practice. The proposed guidelines may add to the quality and cross-comparability of future studies of adjuvant treatments for cancer.

Published
2007

46. Comparative activity of antiemetic drugs

Author

Matti Aapro, Hans J. Schmoll, and Karin Jordan

Subjects
Drug, Antiemetic Agent, Vomiting, Nausea, medicine.drug_class, medicine.medical_treatment, media_common.quotation_subject, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Antiemetic, media_common, Antiemetic Drugs, Chemotherapy, Dose-Response Relationship, Drug, business.industry, Hematology, Oncology, Anesthesia, Antiemetics, Serotonin, medicine.symptom, business
Abstract

Nausea and vomiting continues to be an important problem for cancer patients receiving chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) are classified as acute, occurring within the first 24 h, or delayed, occurring after the first 24 h. A number of antiemetic agents are available for the management of nausea and vomiting, including 5-HT3-receptor-antagonists, corticosteroids, NK-1-receptor-antagonists, dopamine-receptor antagonists, benzodiazepines, neuroleptics and cannabinoids. With modern antiemetic therapy, vomiting can be prevented in 70–80% of patients, whereas the control of nausea remains suboptimal. The development of acute emesis is known to depend on serotonin. The pathophysiology of delayed emesis is less well understood, and multiple mechanisms may contribute, including substance P. Here, the most recent developments in the antiemetic therapy, including new antiemetic drugs and the latest guidelines for antiemetic prophylaxis, are reviewed.

Published
2007

47. Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial

Author

Josep Tabernero, Eric Van Cutsem, Filippo de Braud, Timothy J. Price, Karen Rittweger, Hans J. Schmoll, Jean A. Maroun, Daniel G. Haller, Silke Hoersch, and M.E. Hill

Subjects
Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Organoplatinum Compounds, Oxaloacetates, Population, Leucovorin, Kaplan-Meier Estimate, Gastroenterology, Deoxycytidine, Disease-Free Survival, Drug Administration Schedule, Capecitabine, Folinic acid, chemistry.chemical_compound, Bolus (medicine), Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Adjuvant therapy, Humans, education, Aged, Neoplasm Staging, Proportional Hazards Models, education.field_of_study, business.industry, Middle Aged, Oxaliplatin, Treatment Outcome, chemistry, Fluorouracil, Chemotherapy, Adjuvant, Colonic Neoplasms, Female, business, medicine.drug
Abstract

Purpose To report the final efficacy findings and biomarker analysis from the NO16968 trial comparing bolus fluorouracil/folinic acid (FU/FA) with capecitabine plus oxaliplatin (XELOX) in resected stage III colon cancer. Patients and Methods After curative resection, patients were randomly assigned to receive XELOX, as oxaliplatin 130 mg/m2 on day 1 and capecitabine 1,000 mg/m2 twice daily on days 1 to 14 every 3 weeks, or bolus FU/FA, as the Mayo Clinic or Roswell Park regimens, for 6 months. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS). Results The intention-to-treat population comprised 1,886 patients (XELOX, n = 944; FU/FA, n = 942). Seven-year DFS rates were 63% and 56% in the XELOX and FU/FA groups, respectively (hazard ratio [HR], 0.80; 95% CI, 0.69 to 0.93; P = .004). Seven-year OS rates were 73% and 67% in the XELOX and FU/FA groups, respectively (HR, 0.83; 95% CI, 0.70 to 0.99; P = .04). A total of 68% and 77% of patients who experienced relapse or a new colorectal cancer in the XELOX and FU/FA groups, respectively, received drug treatment for metastatic disease. Four hundred ninety-eight patients consented to the biomarker analysis: 242 in the XELOX group and 256 in the FU/FA group. Low tumor expression of dihydropyrimidine dehydrogenase may be predictive for XELOX efficacy; in the XELOX group, for high versus low dihydropyrimidine dehydrogenase expression levels, DFS HR was 2.45 (95% CI, 1.55 to 3.86; P < .001), and OS HR was 2.75 (95% CI, 1.65 to 4.59; P < .001). In the FU/FA group, no statistically significant associations were observed between any tumor biomarker and outcomes. Conclusion XELOX improved OS compared with bolus FU/FA in patients with resected stage III colon cancer after a median follow-up of almost 7 years. XELOX should be considered a standard adjuvant treatment option in patients with stage III disease. Tumoral dihydropyrimidine dehydrogenase expression is a promising predictive, and potentially, highly clinically relevant, biomarker for XELOX efficacy requiring further prospective evaluation.

Published
2015

48. Introducing the CTA concept

Author

A. Mathieu, R. G. Wagner, K. Panagiotidis, S Rosier Lees, Julien Rousselle, M. Gómez Berisso, Michela Uslenghi, Stephen Maxfield, R. C. Shellard, Ivica Puljak, T. Le Flour, Thomas Schanz, Tobias C. Walther, Juanan Aguilar, Pierre Colin, M. Chikawa, N. Fouque, Mosè Mariotti, G. Fontaine, Merja Tornikoski, V. Diez-Blanco, Enrico Giro, A. Krepps, G. Koss, J. M. Martin, Sergio Billotta, E. de Oña Wilhelmi, Keitaro Takahashi, S. Buson, P. Brook, S. Steiner, M. Dyrda, Joseph Silk, Sera Markoff, P. Lubinski, U. Schwanke, Sauvik Bhattacharyya, J. Ripken, T. Haubold, C. Zurbach, H. Wetteskind, R. Hermel, J. Darling, J. Nicolau-Kukliński, Konstancja Satalecka, M. Videla, Stefan Funk, P. Conconi, S. Bajtlik, Lukasz Stawarz, J. M. Paredes, K. Reitberger, Stefan Wagner, Teresa Mineo, David Kieda, G. Pareschi, Shigeto Kabuki, Makoto Sawada, Antonio Stamerra, Rodolfo Canestrari, N. Baby, G. Crimi, P. Kostka, J. Grube, R. Zanin, I. K. Kominis, L. Mc Comb, R. Sternberger, M. Fesquet, M. Tokarz, David Fink, Daniela Dorner, N. Hamer Heras, A. Moralejo Olaizola, M. de Naurois, Diego F. Torres, Claes Fransson, K. Nishijima, Yutaka Fujita, L. Fresnillo, B. García, R. Kossakowski, A. Masserot, H. von Gunten, Alkiviadis F. Bais, Ciro Bigongiari, A. Saggion, G. Papyan, I. Mrusek, K. Farakos, J. Michałowski, A. Franckowiak, Fernando Martinez, M. Doert, R. Wawrzaszek, Michele Doro, L. Sapozhnikov, Claudia Lavalley, D. Thuermann, A.A. Zdziarski, Cristina Knapic, Karen Byrum, N. Neyroud, Petr Schovanek, W. Domainko, D. Kastana, E. Birsin, Adrian Biland, F. Sánchez, Alexandre Marcowith, M. Errando, R. L. C. Starling, J. Schultze, A. Weinstein, B. B. Singh, Yassir Moudden, Jelena Aleksić, C. L. Naumann, V. Waegebaert, M. Shayduk, U. F. Katz, Gianpiero Tagliaferri, M. Schroedter, A. Vollhardt, O. Reimann, Hideyuki Ohoka, Vincenzo Testa, C. Jablonski, Tsuguya Naito, J. Schäfer, Stavros Maltezos, A. Wierzcholska, P. Wawer, L. Nellen, F. Mirabel, Tatsuo Yoshida, P. H. Carton, Nina Nowak, L. Platos, Riccardo Rando, P. P. Krueger, R. Wischnewski, W. Romaszkan, E. Fede, Martino Marisaldi, Markus Gaug, Richard Willingale, J. H. Buckley, U. De AlmeidaBarres, J. Knapp, Saverio Lombardi, D. della Volpe, A. Herrero, A. Bottani, E. Delagnes, Martin J. Hardcastle, C. Morello, Anna Lipniacka, T. Greenshaw, M. Renaud, Giancarlo Cusumano, Jonathan Biteau, M. Sowiński, J. R. T. de Mello Neto, T. B. Humensky, Michael G. Richer, G. Parks, G. Grasseau, H. Baba, Gino Tosti, Damir Lelas, H. Krawzcynski, David Paneque, M. Barcelo, R. Dickherber, P. Ferrando, Shinji Hara, D. Florin, Hideaki Katagiri, T. Shibata, Fuyuki Tokanai, N. A. McCubbin, J. Gomez-Ortega, D. Nakajima, A. Liolios, P. Laporte, Orjan Dale, A. Sillanpää, Dainis Dravins, Timothée Grégoire, Nu. Komin, A. Mihailidis, L. Sidoli, Shiu-Hang Lee, A. W. Chen, J. M. Illa, A. Kuznetsov, P. Munar-Adrover, D. Dominis Prester, Marcos Daniel Actis, Abraham D. Falcone, L. Journet, D. Hadasch, N. Galante, A. Murphy, C. J. Todero Peixoto, S. Wiesand, A. Aravantinos, A. C. Rovero, J. L. Dournaux, P. Romano, M. Hrabovsky, R. de los Reyes Lopez, M. Ostrowski, J. Pallota, Geza Gyuk, Petar Temnikov, R. Dubois, Jan Ebr, R. Koul, David J. Smith, S. Schwarzburg, P. Manigot, Chad Finley, Tarek M. Hassan, Giuseppe Sottile, Evgeni Ovcharov, P. J. Rajda, F. Krennrich, Peter L. Moore, W. B. Focke, W. Bednarek, Elena Amato, Kazunori Kohri, J. Gamez-Garcia, I. Oya, A. Shibuya, German Hermann, William H. Lee, Dorota Sobczyńska, X. Zhou, C. Balkowski, G. Vallejo, M. Hayashida, M. Bitossi, Loukas Vlahos, H. Lockart, N. Geffroy, L. Tibaldo, Marek Jamrozy, Luke O'c. Drury, Pratik Majumdar, P. Sutcliffe, S. Schlenstedt, M. Palatka, Christophe Champion, H. Ueno, M. Rupiński, P. Giommi, J. Schwarz, G. Pühlhofer, Takashi Saito, W. van Driel, C. van Eldik, Q. Xiong, Yasuo Fukui, A. Donat, A. Ibarra, R. S. Warwick, Michiko Ohishi, A. W. Smith, J.-P. Lenain, Aion Viana, Terry Ashton, Guillaume Dubus, Jacek Niemiec, K. Kodani, Luis Ángel Tejedor, A. Wörnlein, Takanori Yoshikoshi, Masahiro Teshima, W. Gäbele, Ll. Font, Olaf Reimer, J. F. Valdés-Galicia, Lucy Fortson, J. P. Osborne, Mattia Fornasa, Keith Bechtol, Masayuki Tanaka, Shigehiro Nagataki, M. Rataj, M. Ribordy, Emmanuel Moulin, I. de la Calle, K. Winiarski, C. Jeanney, I. Mognet, I. Vegas, C. Juffroy, Yutaka Ohira, A. Jacholkowska, Matthew Wood, A. E. Suárez, J. Bähr, K. M. Schure, J. Maya, M. Dafonseca, J. Tasan, R. Sugawara, M. Bourgeat, A. Mancilla, D. Pelat, Olga Botner, D. Nedbal, G. Depaola, Robert Wagner, T. Okuda, H. Arnaldi, Josep Martí, P. Corona, T. Bonev, D. Yelos, J. Sieiro, V. Scalzotto, Jacco Vink, D. Languignon, Marco Ajello, J. Vandenbrouke, Philipp Mertsch, M. Mordalska, P. Wegner, P. Ziółkowski, P. T. O'Brien, A. Nozato, Robert D. Preece, B. Huber, Matteo Balbo, J.R. Bogart, R. Kankanyan, K. Mori, T. Jogler, Seth Digel, Claudio Vuerli, Hiromitsu Takahashi, Thomas Lohse, K. Saito, A. W. Borgland, Elisa Prandini, Helene Sol, Ryan Heller, M. Bogdan, D. Dumas, M. Stodulski, Y. Awane, Piercarlo Bonifacio, Pedro L. Luque-Escamilla, Judith H. Croston, Fabio Pizzolato, P. M. Chadwick, M. K. Daniel, Riccardo Paoletti, Reiko Orito, Katsuaki Asano, R. Frei, G. Disset, Valerie Connaughton, Juhani Huovelin, Hiroyasu Tajima, S. Vercellone, F. Feinstein, G. Decerprit, Riccardo Smareglia, S. Spyrou, Gustavo E. Romero, J. Shi, J. Carr, N. Girard, Dirk L. Hoffmann, Andreas Zech, Markus Boettcher, Osvaldo Catalano, Akira Okumura, M. Dohmke, C. Föhr, Sabrina Casanova, R. A. Cameron, Jan Conrad, K. Umehara, K. K. Yadav, A. Paizis, John L. Quinn, L. Pogosyan, C. Farnier, William J. Potter, Domenico Impiombato, Tadashi Kifune, Jonathan Granot, Gernot Maier, M. Cieślar, S. Palanque, G.W. Fraser, J. Prast, R. Bose, Heidi Sandaker, G. Lamanna, Dusan Mandat, J.F. Glicenstein, J. Harris, D. Naumann, J. Ziolkowski, Michał Szanecki, C. Delgado, J. Kocot, W. Lustermann, Sabine Elles, J. Schmoll, L. Gérard, M. López, Norita Kawanaka, V. Gika, B. Lieunard, A. Pichel, Martin Pohl, Mariusz Sterzel, S. Vincent, Paolo De Coppi, J. Lande, O. Blanch Bigas, Gianluca Giavitto, Yusuke Konno, Julian Sitarek, M. Panter, P.-O. Petrucci, F. Henault, M. Prouza, Philip Kaaret, Josep Colomé, Luciano Nicastro, German Martinez, L. Gebremedhin, J. M. Yebras, Apostolos Mastichiadis, A. S. Madhavan, Thomas J. Maccarone, K. Berger, R. Buehler, P. Jean, N. Sartore, F. Toussenel, Aris Karastergiou, W. Kluźniak, A. Djannati-Ataï, S. J. Fegan, Louis Antonelli, A. González Muñoz, J. Berdugo, S. S. Upadhya, M. Sidz, F. Mottez, Patrick Vogler, F. Di Pierro, Wystan Benbow, B. Sacco, L. Chiappetti, J. Dumm, R. Firpo Curcoll, David Gascon, V. Boccone, J. Krause, J. P. Avernet, B. Peyaud, B. De Lotto, Ana Babić, T. O. B. Schmidt, I. M. McHardy, T. Schweizer, S. P. Wakely, Daniel Gall, Frank M. Rieger, E. Sant'Ambrogio, M. Kagaya, P. Vincent, R. C. Rannot, Sandro Mereghetti, A. De Angelis, M. Scarcioffolo, R. White, G. H. Sembroski, Takeshi Nakamori, C. Medina, M. A. De Oliveira Leigui, Subir Sarkar, A. Marszałek, Reshmi Mukherjee, K. Nakayama, A. Fiasson, S. Giarrusso, T. Bernardino, J. P. Finley, D. Neise, L. O. Takalo, F. Grañena, Nikola Godinovic, H. Sasaki, P. Zychowski, Francesco Dazzi, B. Courty, A. Basili, Vitaly Neustroev, B. Khélifi, T. Glanzman, M. Trifoglio, Regis Terrier, R. A. Ong, E. M. Santos, M. Minuti, Thomas Bretz, R. Moderski, J. Kushida, S. Royer, Emilio Molinari, Etienne Lyard, J. Houles, Juan Abel Barrio, T. Lerch, S. Rivoire, T. Kishimoto, M. Cailles, M. Casiraghi, Nikolaos Stergioulas, J. Gaweda, S. Koyama, Ingomar Allekotte, E. Ismailova, Elina Giannakaki, S. Schwemmer, Ryo Yamazaki, G. Fasola, Christoph Deil, Jose Luis Contreras, T. Bird, Miguel A. Sánchez-Conde, J. Dick, E. Edy, D. Parsons, R. Pyzioł, R. Mirzoyan, Manjuli R. Sharma, J. Borkowski, Jonathan S. Lapington, Cameron B Rulten, Rino Bandiera, Volker Beckmann, Jun Kakuwa, Dimitris Balis, Kenji Toma, Anna Barnacka, Andrea Santangelo, L. Padilla, Peter Eger, G. Decock, Karol Seweryn, N. Sakaki, Darko Veberič, Andrea Bulgarelli, B. Rudak, M. Pérez, H. Koppel, Felix Spanier, M. I. Martínez, D. Horville, Marco Molinaro, R. Walter, P. Ramon, S. Brau-Nogue, J. Camprecios, K. Kärcher, John H. Seiradakis, S. Criswell, D. J. Leopold, V. J. Guarino, R. Gredig, S. Vorobiov, Viktor Gruev, Gareth Hughes, Daniele Spiga, Quirin Weitzel, N. Håkansson, Susumu Inoue, U. Straumann, Juan Cortina, B. Behera, Jürgen Knödlseder, Daniel Nieto, Tomasz Szepieniec, H. Prokoph, Jerzy Grygorczuk, G. De La Vega, Jim Hinton, E. Chabanne, M. Mahabir, R. Krobot, M. Capalbi, Miroslav Pech, C. Díaz, J. Ludwin, F. Gianotti, Garret Cotter, Claudio Melioli, Hiroaki Yamamoto, C. Veyssiere, Kunihito Ioka, S. Sun, J. M. Parraud, L. Rob, Felix Aharonian, G. Maneva, D. Melkumyan, T. Schwab, J. Kasperek, J. M. Huet, E. Lorenz, S. Tanaka, Y. A. Gallant, S. Couturier, B.W. Favill, J. Boix Gargallo, Andrea Tiengo, Leszek Bogacz, Andreu Sanuy, Christian Fruck, J. Sykes, C. Martens, A. Yoshida, Marek Sikora, E. Racero, G. Rouaix, N. Bhat, A. Salini, A. S. Barber, Mauro Ghigo, Jan Ridky, K. Kosack, Konrad Bernlöhr, C. Tenzer, Alice Allafort, M. Torres, Catherine Boisson, Grzegorz Kowal, M. Karczewski, G. Agnetta, Victor Stamatescu, Anthony H. Gonzalez, S. Rousselle, Giovanni Bonanno, A. Zajczyk, A. Gadola, P. Martin, V. Zitelli, I. Manthos, N. Maragos, A. Dettlaff, F. Profeti, S. Colonges, S. Gunji, S. Cazaux, S. Colafrancesco, M. Paz Arribas, Rika Hagiwara, Darell Engelhaupt, Nestor Mirabal, Johann Cohen-Tanugi, S. Grunewald, Abby M. Green, I. D. Davids, D. Nosek, T. Yamamoto, Gagik Tovmassian, R. Sakonaka, Miguel Alcubierre, C. Baixeras, T. L. Usher, Kazufumi Torii, H. Lüdecke, L. Wiśniewski, B. Kellner-Leidel, P. Demange, F. Gonzalez, B. Moal, V. De Caprio, V. Golev, K. Katarzyński, V. Bugaev, A. Reimer, J. Koziol, G. Pojmanski, Alessandro Carosi, J. Bolmont, A. Nikolaidis, R. J. García López, V. A. Kudryavtsev, C. Stegmann, J.-P. Ernenwein, M. Fiorini, Ivone F. M. Albuquerque, Marco Tavani, P. Korohoda, A. Giuliani, E. Carmona, C. Bauer, Kostas D. Kokkotas, O. Tibolla, G. Deleglise, Pierre Brun, Dinko Dimitrov, I. Jung, R. Steenkamp, Marc Ribó, Kathrin Egberts, P. Reardon, Adriano Ghedina, Stefan Rosén, N. Hidaka, Trygve Buanes, A. Segreto, H. Huan, Juri Poutanen, Ruben Lopez-Coto, S. Cavazzani, Massimiliano Belluso, A. Kretzschmann, F. De Frondat, A. Riviere, J. F. Olive, Tsunefumi Mizuno, Serena Mattiazzo, M. González, D. Fantinel, Matteo Cerruti, S. Vergani, Sabrina Einecke, N. La Palombara, Reinhard Schlickeiser, P. Antoranz, Pol Bordas, D. Paillot, V. de Souza, Yasushi Fukazawa, Phil Evans, Werner Hofmann, Hugh Dickinson, F. Roy, Yvonne Becherini, E. O. Angüner, D. Corti, T. C. Arlen, Francesco Russo, V. R. Chitnis, D. Ross, R. Gabriele, Massimo Persic, E. Fokitis, A. Bonardi, D. Garrido, A. Niedźwiecki, L. Cossio, Hidetoshi Kubo, Y. de Oliveira, F. Mattana, Anna Szostek, M. Compin, S. Blake, F. Lucarelli, Petter Hofverberg, Felix Ryde, M. Gougerot, C. Boutonnet, Dimitrios Emmanoulopoulos, A. Mangano, P. Vallania, Jose Miguel Miranda, A. Manalaysay, M. Raue, A. Bouvier, Shohei Yanagita, Nektarios Vlahakis, Joni Tammi, M. Naumann-Godo, Kohta Murase, E. Fillin-Martino, Jiri Chudoba, K. Hatanaka, A. Lopatin, N. Otte, G. Rojas, Tomonori Totani, K. S. Gothe, J. P. Vialle, D. Kolitzus, K. Warda, Hironori Matsumoto, J. Rico, P. Ringegni, James Chiang, R. McKay, A. Bobkov, Aya Bamba, H. Takami, B. Giebels, O. Grimm, S. Basso, F. Dubois, Victor Zabalza, A. Förster, Pasquale Blasi, Alexandros Papayannis, A. G. Akhperjanian, Eckhard Kendziorra, James A. Anderson, Giuseppe Malaguti, R. Welsing, S. Pita, A. Ozieblo, Heide Costantini, D. Tezier, J.-H. Köhne, M. Tluczykont, Ll. Garrido, Alexander Varón Sandoval, Matthew R. Orr, Dominique Durand, F. Chollet, O. 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K., Yadav, H., Yamamoto, T., Yamamoto, R., Yamazaki, S., Yanagita, J. M., Yebra, D., Yelo, A., Yoshida, T., Yoshida, T., Yoshikoshi, V., Zabalza, M., Zacharia, A., Zajczyk, R., Zanin, A., Zdziarski, A., Zech, A., Zhao, X., Zhou, K., Zietara, J., Ziolkowski, P., Ziolkowski, V., Zitelli, C., Zurbach, P., Zychowski, Laboratoire d'Annecy de Physique des Particules (LAPP/Laboratoire d'Annecy-le-Vieux de Physique des Particules), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), AstroParticule et Cosmologie (APC (UMR_7164)), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7), APC - Astrophysique des Hautes Energies (APC - AHE), PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Dipartimento di Astronomia, Universita degli Studi di Bologna, Università di Bologna [Bologna] (UNIBO)-Università di Bologna [Bologna] (UNIBO), Centre de Physique des Particules de Marseille (CPPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Aix Marseille Université (AMU), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CTA, Laboratoire Univers et Théories (LUTH (UMR_8102)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Laboratoire d'Annecy de Physique des Particules (LAPP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Dipartimento di Astronomia, Universita degli Studi di Bologna, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), and High Energy Astrophys. & Astropart. Phys (API, FNWI)

Subjects
Next generation Cherenkov telescopes, Ciencias Físicas, 01 natural sciences, 7. Clean energy, TeV GAMMA-RAY ASTRONOMY, Observatory, Air showers, HESS, Cherenkov Telescopes, 010303 astronomy & astrophysics, MISSION, SUPERNOVA REMNANT W44, TELESCOPE, ASTRONOMY, EMISSION, Physics, ta213, [SDU.ASTR.HE]Sciences of the Universe [physics]/Astrophysics [astro-ph]/High Energy Astrophysical Phenomena [astro-ph.HE], Settore FIS/01 - Fisica Sperimentale, Astrophysics::Instrumentation and Methods for Astrophysics, TeV gamma-ray astronomy, ddc:540, CIENCIAS NATURALES Y EXACTAS, [PHYS.ASTR.HE]Physics [physics]/Astrophysics [astro-ph]/High Energy Astrophysical Phenomena [astro-ph.HE], [PHYS.ASTR.IM]Physics [physics]/Astrophysics [astro-ph]/Instrumentation and Methods for Astrophysic [astro-ph.IM], Air shower, AIR SHOWERS, Astrophysics::High Energy Astrophysical Phenomena, 0103 physical sciences, Preparatory phase, ta115, TeV gamma-ray astronomy Air showers Cherenkov Telescopes, 010308 nuclear & particles physics, business.industry, CHERENKOV TELESCOPES, Física, Astronomy, Institut für Physik und Astronomie, Astronomy and Astrophysics, ASTROFÍSICA, Cherenkov Telescope Array, [SDU.ASTR.IM]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Instrumentation and Methods for Astrophysic [astro-ph.IM], Astronomía, Design study, Telecommunications, business
Abstract

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project., La lista completa de autores puede consultarse en el documento o en la página web de la revista., Facultad de Ingeniería

Published
2013

49. 5-Fluorouracil/folinic acid plus oxaliplatin (FUFOX, arm A) versus capecitabine plus oxaliplatin (CAPOX, arm B) in the treatment of advanced colorectal carcinoma (ACRC)

Author

Hendrik-Tobias Arkenau, Peter Reichardt, A. Grothey, Gail K. Adler, B Petershagen, Axel Hinke, Ullrich Graeven, Rainer Porschen, H.-J. Schmoll, and W. Schmiegel

Subjects
medicine.medical_specialty, Colorectal cancer, business.industry, Gastroenterology, medicine.disease, Oxaliplatin, Capecitabine, Folinic acid, Fluorouracil, Internal medicine, medicine, business, medicine.drug
Published
2015

50. Significance of Tamm-Horsfall Protein Excretion in Diabetes mellitus and Cisplatin Nephrotoxicity1

Author

M Soose, H J Schmoll, Petzoldt R, Hilmar Stolte, Wilfried Gwinner, Jäckle-Meyer I, and M Baum

Subjects
Cisplatin, medicine.medical_specialty, Kidney, Tamm–Horsfall protein, Proteinuria, biology, business.industry, Mucoproteins, Pharmacology, medicine.disease, Nephrotoxicity, Excretion, Endocrinology, medicine.anatomical_structure, Internal medicine, Diabetes mellitus, biology.protein, Medicine, medicine.symptom, business, medicine.drug
Published
2015

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