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1. Effectiveness of ChatGPT in explaining complex medical reports to patients

Author

Sun, Mengxuan, Reiter, Ehud, Kiltie, Anne E, Ramsay, George, Duncan, Lisa, Murchie, Peter, and Adam, Rosalind

Subjects
Computer Science - Human-Computer Interaction, Computer Science - Computation and Language, Quantitative Biology - Other Quantitative Biology
Abstract

Electronic health records contain detailed information about the medical condition of patients, but they are difficult for patients to understand even if they have access to them. We explore whether ChatGPT (GPT 4) can help explain multidisciplinary team (MDT) reports to colorectal and prostate cancer patients. These reports are written in dense medical language and assume clinical knowledge, so they are a good test of the ability of ChatGPT to explain complex medical reports to patients. We asked clinicians and lay people (not patients) to review explanations and responses of ChatGPT. We also ran three focus groups (including cancer patients, caregivers, computer scientists, and clinicians) to discuss output of ChatGPT. Our studies highlighted issues with inaccurate information, inappropriate language, limited personalization, AI distrust, and challenges integrating large language models (LLMs) into clinical workflow. These issues will need to be resolved before LLMs can be used to explain complex personal medical information to patients., Comment: under review

Published
2024

2. Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity

Author

Then, Chee Kin, Paillas, Salome, Moomin, Aliu, Misheva, Mariya D., Moir, Rachel A., Hay, Susan M., Bremner, David, Roberts (nee Nellany), Kristine S., Smith, Ellen E., Heidari, Zeynab, Sescu, Daniel, Wang, Xuedan, Suárez-Bonnet, Alejandro, Hay, Nadine, Murdoch, Sarah L., Saito, Ryoichi, Collie-Duguid, Elaina S. R., Richardson, Shirley, Priestnall, Simon L., Wilson, Joan M., Gurumurthy, Mahalakshmi, Royle, Justine S., Samuel, Leslie M., Ramsay, George, Vallis, Katherine A., Foster, Kevin R., McCullagh, James S. O., and Kiltie, Anne E.

Published
2024
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7. Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

Author

Figueroa, Jonine D, Middlebrooks, Candace D, Banday, A Rouf, Ye, Yuanqing, Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Koutros, Stella, Kiemeney, Lambertus A, Rafnar, Thorunn, Bishop, Timothy, Furberg, Helena, Matullo, Giuseppe, Golka, Klaus, Gago-Dominguez, Manuela, Taylor, Jack A, Fletcher, Tony, Siddiq, Afshan, Cortessis, Victoria K, Kooperberg, Charles, Cussenot, Olivier, Benhamou, Simone, Prescott, Jennifer, Porru, Stefano, Dinney, Colin P, Malats, Núria, Baris, Dalsu, Purdue, Mark P, Jacobs, Eric J, Albanes, Demetrius, Wang, Zhaoming, Chung, Charles C, Vermeulen, Sita H, Aben, Katja K, Galesloot, Tessel E, Thorleifsson, Gudmar, Sulem, Patrick, Stefansson, Kari, Kiltie, Anne E, Harland, Mark, Teo, Mark, Offit, Kenneth, Vijai, Joseph, Bajorin, Dean, Kopp, Ryan, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Selinski, Silvia, Hengstler, Jan G, Gerullis, Holger, Ovsiannikov, Daniel, Blaszkewicz, Meinolf, Castelao, Jose Esteban, Calaza, Manuel, Martinez, Maria Elena, Cordeiro, Patricia, Xu, Zongli, Panduri, Vijayalakshmi, Kumar, Rajiv, Gurzau, Eugene, Koppova, Kvetoslava, Bueno-De-Mesquita, H Bas, Ljungberg, Börje, Clavel-Chapelon, Françoise, Weiderpass, Elisabete, Krogh, Vittorio, Dorronsoro, Miren, Travis, Ruth C, Tjønneland, Anne, Brennan, Paul, Chang-Claude, Jenny, Riboli, Elio, Conti, David, Stern, Marianna C, Pike, Malcolm C, Van Den Berg, David, Yuan, Jian-Min, Hohensee, Chancellor, Jeppson, Rebecca P, Cancel-Tassin, Geraldine, Roupret, Morgan, Comperat, Eva, Turman, Constance, De Vivo, Immaculata, Giovannucci, Edward, Hunter, David J, Kraft, Peter, Lindstrom, Sara, Carta, Angela, Pavanello, Sofia, Arici, Cecilia, Mastrangelo, Giuseppe, Kamat, Ashish M, Zhang, Liren, Gong, Yilei, Pu, Xia, Hutchinson, Amy, Burdett, Laurie, Wheeler, William A, and Karagas, Margaret R

Subjects
Cancer, Prevention, Human Genome, Genetics, Biotechnology, Urologic Diseases, Aetiology, 2.1 Biological and endogenous factors, Biomarkers, Tumor, Case-Control Studies, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 20, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Polymorphism, Single Nucleotide, Risk Factors, Urinary Bladder Neoplasms, White People, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

Published
2016

15. Combined drug delivery and treatment monitoring using a single high frequency ultrasound system.

Author

Yildiz, Yesna O., Ruan, Jia-Ling, Gray, Michael D., Bau, Luca, Browning, Richard J., Mannaris, Christophoros, Kiltie, Anne E., Vojnovic, Borivoj, and Stride, Eleanor

Subjects
TARGETED drug delivery, DIAGNOSTIC ultrasonic imaging, ULTRASONIC imaging, ULTRASONIC therapy, SPATIAL resolution
Abstract

Ultrasound-mediated drug delivery is typically performed using transducers with center frequencies ≤ 1 MHz to promote acoustic cavitation. Such frequencies are not commonly used for diagnostic ultrasound due to limited spatial resolution. Therefore, delivery and monitoring of therapeutic ultrasound typically requires two transducers to enable both treatment and imaging. This study investigates the feasibility of using a single commercial ultrasound imaging transducer operating at 5 MHz for both drug delivery and real-time imaging. We compared a single-transducer system (STS) at 5 MHz with a conventional dual-transducer system (DTS) using a 1.1 MHz therapeutic transducer and an imaging probe. in vitro experiments demonstrated that the STS could achieve comparable extravasation depth and area as the DTS, with higher drug deposition observed at 5 MHz. Additionally, extravasation patterns were influenced by peak negative pressure (PNP) and duty cycle, with the narrower beam width at 5 MHz offering potential advantages for targeted drug delivery. in vivo experiments in a murine bladder cancer model confirmed the efficacy of the STS for real-time imaging and drug delivery, with cavitation dose correlating with drug deposition. The results suggest that a single-transducer approach may enhance the precision and efficiency of ultrasound-mediated drug delivery, potentially reducing system complexity and cost. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

Author

Rafnar, Thorunn, Sulem, Patrick, Thorleifsson, Gudmar, Vermeulen, Sita H., Helgason, Hannes, Saemundsdottir, Jona, Gudjonsson, Sigurjon A., Sigurdsson, Asgeir, Stacey, Simon N., Gudmundsson, Julius, Johannsdottir, Hrefna, Alexiusdottir, Kristin, Petursdottir, Vigdis, Nikulasson, Sigfus, Geirsson, Gudmundur, Jonsson, Thorvaldur, Aben, Katja K.H., Grotenhuis, Anne J., Verhaegh, Gerald W., Dudek, Aleksandra M., Witjes, J. Alfred, van der Heijden, Antoine G., Vrieling, Alina, Galesloot, Tessel E., De Juan, Ana, Panadero, Angeles, Rivera, Fernando, Hurst, Carolyn, Bishop, D. Timothy, Sak, Sei C., Choudhury, Ananya, Teo, Mark T.W., Arici, Cecilia, Carta, Angela, Toninelli, Elena, de Verdier, Petra, Rudnai, Peter, Gurzau, Eugene, Koppova, Kvetoslava, van der Keur, Kirstin A., Lurkin, Irene, Goossens, Mieke, Kellen, Eliane, Guarrera, Simonetta, Russo, Alessia, Critelli, Rossana, Sacerdote, Carlotta, Vineis, Paolo, Krucker, Clémentine, Zeegers, Maurice P., Gerullis, Holger, Ovsiannikov, Daniel, Volkert, Frank, Hengstler, Jan G., Selinski, Silvia, Magnusson, Olafur T., Masson, Gisli, Kong, Augustine, Gudbjartsson, Daniel, Lindblom, Annika, Zwarthoff, Ellen, Porru, Stefano, Golka, Klaus, Buntinx, Frank, Matullo, Giuseppe, Kumar, Rajiv, Mayordomo, José I., Steineck, D. Gunnar, Kiltie, Anne E., Jonsson, Eirikur, Radvanyi, François, Knowles, Margaret A., Thorsteinsdottir, Unnur, Kiemeney, Lambertus A., and Stefansson, Kari

Published
2014
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20. MRE11 as a Predictive Biomarker of Outcome After Radiation Therapy in Bladder Cancer

Author

Walker, Alexandra K, Karaszi, Katalin, Valentine, Helen, Strauss, Victoria Y, Choudhury, Ananya, McGill, Shaun, Wen, Kaisheng, Brown, Michael D, Ramani, Vijay, Bhattarai, Selina, Teo, Mark Tw, Yang, Lingjian, Myers, Kevin A, Deshmukh, Nayneeta, Denley, Helen, Browning, Lisa, Love, Sharon B, Iyer, Gopa, Clarke, Noel W, Hall, Emma, Huddart, Robert, James, Nicholas D, Hoskin, Peter J, West, Catharine Ml, and Kiltie, Anne E

Subjects
Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Article
Abstract

Purpose Organ-confined muscle-invasive bladder cancer is treated with cystectomy or bladder preservation techniques, including radiation therapy. There are currently no biomarkers to inform management decisions and aid patient choice. Previously we showed high levels of MRE11 protein, assessed by immunohistochemistry (IHC), predicted outcome after radiation therapy, but not cystectomy. Therefore, we sought to develop the MRE11 IHC assay for clinical use and define its relationship to clinical outcome in samples from 2 major clinical trials. Methods and Materials Samples from the BCON and BC2001 randomized controlled trials and a cystectomy cohort were stained using automated IHC methods and scored for MRE11 in 3 centers in the United Kingdom. Results Despite step-wise creation of scoring cards and standard operating procedures for staining and interpretation, there was poor intercenter scoring agreement (kappa, 0.32; 95% confidence interval, 0.17-0.47). No significant associations between MRE11 scores and cause-specific survival were identified in BCON (n = 132) and BC2001 (n = 221) samples. Reoptimized staining improved agreement between scores from BCON tissue microarrays (n = 116), but MRE11 expression was not prognostic for cause-specific survival. Conclusions Manual IHC scoring of MRE11 was not validated as a reproducible biomarker of radiation-based bladder preservation success. There is a need for automated quantitative methods or a reassessment of how DNA-damage response relates to clinical outcomes.

Published
2019
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24. EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer—An International Collaborative Multistakeholder Effort †[Formula presented] : Under the Auspices of the EAU-ESMO Guidelines Committees

Author

Witjes, J. Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H. Maxim, de Reijke, Theo M., de Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J., Shariat, Shahrokh F., der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C., Bochner, Bernard H., Bolla, Michel, Boormans, Joost L., Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, de Bari, Berardino, de Blok, Willem, J.l. de Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L., Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J., Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E., Hartmann, Arndt, Hayne, Dickon, Henry, Ann M., Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A., Jones, Rob, Kamat, Ashish M., Khoo, Vincent, Kiltie, Anne E., Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C., Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M. Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R., N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R., Oldenburg, Jan, Osanto, Susanne, J.G. Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I., Pieters, Bradley R., Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E., Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J., Smits, Anita, Stenzl, Arnulf, Thalmann, George N., Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, der Heijden, Antoine G. Van, van Poppel, Hein, Vartolomei, Mihai D., Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A. Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, Horwich, Alan, Urology, APH - Personalized Medicine, APH - Quality of Care, CCA - Cancer Treatment and Quality of Life, and Radiotherapy

Subjects
Consensus, International Cooperation, Follow-up, Urology, education, Bladder cancer, Delphi, Treatment, Diagnosis, Humans, Neoplasm Staging, Urinary Bladder Neoplasms, Journal Article
Abstract

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), and 7–9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach. Patient summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Published
2020

25. EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multistakeholder effort† EU*ACME: under the auspices of the EAU-ESMO guidelines committees

Author

Witjes, J Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H Maxim, De Reijke, Theo M, De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J, Shariat, Shahrokh F, Der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C, Bochner, Bernard H, Bolla, Michel, Boormans, Joost L, Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, J L De Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J, Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E, Hartmann, Arndt, Hayne, Dickon, Henry, Ann M, Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A, Jones, Rob, Kamat, Ashish M, Khoo, Vincent, Kiltie, Anne E, Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C, Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R, N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R, Oldenburg, Jan, Osanto, Susanne, J G Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I, Pieters, Bradley R, Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E, Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J, Smits, Anita, Stenzl, Arnulf, Thalmann, George N, Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Der Heijden, Antoine G Van, Van Poppel, Hein, Vartolomei, Mihai D, Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, and Horwich, Alan

Subjects
education
Abstract

Background: \ud Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.\ud \ud Objective: \ud To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.\ud \ud Design: \ud A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.\ud \ud Setting: \ud Online Delphi survey and consensus conference.\ud \ud Participants: \ud The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.\ud \ud Outcome measurements and statistical analysis: \ud Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), and 7–9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).\ud \ud Results and limitations: \ud Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.\ud \ud Conclusions: \ud These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.\ud \ud Patient summary: \ud This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Published
2020

26. AU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer—An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees

Author

Witjes, J. Alfred, Babjuk, Marek, Bellmunt, Joaquim, Maxim Bruins, H., De Reijke, Theo M., De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J., Shariat, Shahrokh F., Van Der Kwast, Theo, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C., Bochner, Bernard H., Bolla, Michel, Boormans, Joost L., Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, De Visschere, Pieter J.L., Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L., Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J., Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E., Hartmann, Arndt, Hayne, Dickon, Henry, Ann M., Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A., Jones, Rob, Kamat, Ashish M., Khoo, Vincent, Kiltie, Anne E., Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C., Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Carmen Mir, M., Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R., N’dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R., Oldenburg, Jan, Osanto, Susanne, Oyen, Wim J.G., Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I., Pieters, Bradley R., Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E., Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J., Smits, Anita, Stenzl, Arnulf, Thalmann, George N., Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Van Der Heijden, Antoine G., Van Poppel, Hein, Vartolomei, Mihai D., Veskimäe, Erik, Vilaseca, Antoni, Vives Rivera, Franklin A., Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, and Horwich, Alan

Subjects
Medizin
Published
2020

27. Corrigendum to ‘EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer—An International Collaborative Multistakeholder Effort Under the Auspices of the EAU-ESMO Guidelines Committees

Author

Witjes, J. Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H. Maxim, De Reijke, Theo M., De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J., Shariat, Shahrokh F., Van Der Kwast, Theo, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C., Bochner, Bernard H., Bolla, Michel, Boormans, Joost L., Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, De Visschere, Pieter J.L., Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L., Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J., Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E., Hartmann, Arndt, Hayne, Dickon, Henry, Ann M., Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A., Jones, Rob, Kamat, Ashish M., Khoo, Vincent, Kiltie, Anne E., Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C., Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M. Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R., N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R., Oldenburg, Jan, Osanto, Susanne, Oyen, Wim J.G., Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I., Pieters, Bradley R., Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E., Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J., Smits, Anita, Stenzl, Arnulf, Thalmann, George N., Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Van Der Heijden, Antoine G., Van Poppel, Hein, Vartolomei, Mihai D., Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A. Vives, Wiegel, Thomas, Wiklund, Peter, Willemse, Peter-Paul M., Williams, Andrew, Zigeuner, Richard, and Horwich, Alan

Subjects
Medizin
Abstract

Korrektur zu 10.1016/j.eururo.2019.09.035

Published
2020

28. EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees

Author

Witjes, J. Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H. Maxim, De Reijke, Theo M., De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J., Shariat, Shahrokh F., Van Der Kwast, Theo, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C., Bochner, Bernard H., Bolla, Michel, Boormans, Joost L., Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, De Visschere, Pieter J. L ., Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J., Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E., Hartmann, Arndt, Hayne, Dickon, Henry, Ann M., Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A., Jones, Rob, Kamat, Ashish M., Khoo, Vincent, Kiltie, Anne E., Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C., Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M. Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R., N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R., Oldenburg, Jan, Osanto, Susanne, Oyen, Wim J.G., Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I., Pieters, Bradley R., Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E., Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J., Smits, Anita, Stenzl, Arnulf, Thalmann, George N., Tombal, Bertrand, Turkbey, Baris, Vahr Lauridsen, Susanne, Valdagni, Riccardo, Van Der Heijden, Antoine G., Van Poppel, Hein, Vartolomei, Mihai D., Veskimäe, Erik, Vilaseca, Antoni, Vives Rivera, Franklin A., Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, Horwich, Alan, Witjes, J. Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H. Maxim, De Reijke, Theo M., De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J., Shariat, Shahrokh F., Van Der Kwast, Theo, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C., Bochner, Bernard H., Bolla, Michel, Boormans, Joost L., Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, De Visschere, Pieter J. L ., Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J., Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E., Hartmann, Arndt, Hayne, Dickon, Henry, Ann M., Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A., Jones, Rob, Kamat, Ashish M., Khoo, Vincent, Kiltie, Anne E., Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C., Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M. Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R., N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R., Oldenburg, Jan, Osanto, Susanne, Oyen, Wim J.G., Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I., Pieters, Bradley R., Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E., Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J., Smits, Anita, Stenzl, Arnulf, Thalmann, George N., Tombal, Bertrand, Turkbey, Baris, Vahr Lauridsen, Susanne, Valdagni, Riccardo, Van Der Heijden, Antoine G., Van Poppel, Hein, Vartolomei, Mihai D., Veskimäe, Erik, Vilaseca, Antoni, Vives Rivera, Franklin A., Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, and Horwich, Alan

Abstract

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus stateme, Errata: Witjes JA, Babjuk M, Bellmunt J, et al. Corrigendum to 'EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort Under the Auspices of the EAU-ESMO Guidelines Committees' [European Urology 77 (2020) 223-250]. Eur Urol. 2020;78(1):e48-e50. doi:10.1016/j.eururo.2020.03.017

Published
2020
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29. EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer—An International Collaborative Multistakeholder Effort †[Formula presented] : Under the Auspices of the EAU-ESMO Guidelines Committees

Author

Witjes, J Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H Maxim, De Reijke, Theo M, De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J, Shariat, Shahrokh F, Der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C, Bochner, Bernard H, Bolla, Michel, Boormans, Joost L, Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, J L De Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J, Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E, Hartmann, Arndt, Hayne, Dickon, Henry, Ann M, Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A, Jones, Rob, Kamat, Ashish M, Khoo, Vincent, Kiltie, Anne E, Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C, Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R, N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R, Oldenburg, Jan, Osanto, Susanne, J G Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I, Pieters, Bradley R, Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E, Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J, Smits, Anita, Stenzl, Arnulf, Thalmann, George N, Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Der Heijden, Antoine G Van, Van Poppel, Hein, Vartolomei, Mihai D, Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, Horwich, Alan, Witjes, J Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H Maxim, De Reijke, Theo M, De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J, Shariat, Shahrokh F, Der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C, Bochner, Bernard H, Bolla, Michel, Boormans, Joost L, Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, J L De Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J, Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E, Hartmann, Arndt, Hayne, Dickon, Henry, Ann M, Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A, Jones, Rob, Kamat, Ashish M, Khoo, Vincent, Kiltie, Anne E, Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C, Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R, N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R, Oldenburg, Jan, Osanto, Susanne, J G Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I, Pieters, Bradley R, Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E, Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J, Smits, Anita, Stenzl, Arnulf, Thalmann, George N, Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Der Heijden, Antoine G Van, Van Poppel, Hein, Vartolomei, Mihai D, Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, and Horwich, Alan

Published
2020

30. EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort: Under the Auspices of the EAU-ESMO Guidelines Committees.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Witjes, J Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H Maxim, De Reijke, Theo M, De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J, Shariat, Shahrokh F, Der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C, Bochner, Bernard H, Bolla, Michel, Boormans, Joost L, Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, J L De Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J, Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E, Hartmann, Arndt, Hayne, Dickon, Henry, Ann M, Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A, Jones, Rob, Kamat, Ashish M, Khoo, Vincent, Kiltie, Anne E, Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C, Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R, N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R, Oldenburg, Jan, Osanto, Susanne, J G Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I, Pieters, Bradley R, Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E, Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J, Smits, Anita, Stenzl, Arnulf, Thalmann, George N, Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Der Heijden, Antoine G Van, Van Poppel, Hein, Vartolomei, Mihai D, Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, Horwich, Alan, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Witjes, J Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H Maxim, De Reijke, Theo M, De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J, Shariat, Shahrokh F, Der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C, Bochner, Bernard H, Bolla, Michel, Boormans, Joost L, Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, J L De Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J, Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E, Hartmann, Arndt, Hayne, Dickon, Henry, Ann M, Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A, Jones, Rob, Kamat, Ashish M, Khoo, Vincent, Kiltie, Anne E, Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C, Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R, N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R, Oldenburg, Jan, Osanto, Susanne, J G Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I, Pieters, Bradley R, Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E, Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J, Smits, Anita, Stenzl, Arnulf, Thalmann, George N, Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Der Heijden, Antoine G Van, Van Poppel, Hein, Vartolomei, Mihai D, Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, and Horwich, Alan

Abstract

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus stateme

Published
2020

31. EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer—An International Collaborative Multistakeholder Effort †[Formula presented]: Under the Auspices of the EAU-ESMO Guidelines Committees

Author

MS Urologische Oncologie, Cancer, Urologie Medisch volwassenen, Witjes, J Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H Maxim, De Reijke, Theo M, De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J, Shariat, Shahrokh F, Der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C, Bochner, Bernard H, Bolla, Michel, Boormans, Joost L, Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, J L De Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J, Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E, Hartmann, Arndt, Hayne, Dickon, Henry, Ann M, Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A, Jones, Rob, Kamat, Ashish M, Khoo, Vincent, Kiltie, Anne E, Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C, Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R, N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R, Oldenburg, Jan, Osanto, Susanne, J G Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I, Pieters, Bradley R, Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E, Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J, Smits, Anita, Stenzl, Arnulf, Thalmann, George N, Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Der Heijden, Antoine G Van, Van Poppel, Hein, Vartolomei, Mihai D, Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, Horwich, Alan, MS Urologische Oncologie, Cancer, Urologie Medisch volwassenen, Witjes, J Alfred, Babjuk, Marek, Bellmunt, Joaquim, Bruins, H Maxim, De Reijke, Theo M, De Santis, Maria, Gillessen, Silke, James, Nicholas, Maclennan, Steven, Palou, Juan, Powles, Tom, Ribal, Maria J, Shariat, Shahrokh F, Der Kwast, Theo Van, Xylinas, Evanguelos, Agarwal, Neeraj, Arends, Tom, Bamias, Aristotle, Birtle, Alison, Black, Peter C, Bochner, Bernard H, Bolla, Michel, Boormans, Joost L, Bossi, Alberto, Briganti, Alberto, Brummelhuis, Iris, Burger, Max, Castellano, Daniel, Cathomas, Richard, Chiti, Arturo, Choudhury, Ananya, Compérat, Eva, Crabb, Simon, Culine, Stephane, De Bari, Berardino, De Blok, Willem, J L De Visschere, Pieter, Decaestecker, Karel, Dimitropoulos, Konstantinos, Dominguez-Escrig, Jose L, Fanti, Stefano, Fonteyne, Valerie, Frydenberg, Mark, Futterer, Jurgen J, Gakis, Georgios, Geavlete, Bogdan, Gontero, Paolo, Grubmüller, Bernhard, Hafeez, Shaista, Hansel, Donna E, Hartmann, Arndt, Hayne, Dickon, Henry, Ann M, Hernandez, Virginia, Herr, Harry, Herrmann, Ken, Hoskin, Peter, Huguet, Jorge, Jereczek-Fossa, Barbara A, Jones, Rob, Kamat, Ashish M, Khoo, Vincent, Kiltie, Anne E, Krege, Susanne, Ladoire, Sylvain, Lara, Pedro C, Leliveld, Annemarie, Linares-Espinós, Estefania, Løgager, Vibeke, Lorch, Anja, Loriot, Yohann, Meijer, Richard, Mir, M Carmen, Moschini, Marco, Mostafid, Hugh, Müller, Arndt-Christian, Müller, Christoph R, N'Dow, James, Necchi, Andrea, Neuzillet, Yann, Oddens, Jorg R, Oldenburg, Jan, Osanto, Susanne, J G Oyen, Wim, Pacheco-Figueiredo, Luís, Pappot, Helle, Patel, Manish I, Pieters, Bradley R, Plass, Karin, Remzi, Mesut, Retz, Margitta, Richenberg, Jonathan, Rink, Michael, Roghmann, Florian, Rosenberg, Jonathan E, Rouprêt, Morgan, Rouvière, Olivier, Salembier, Carl, Salminen, Antti, Sargos, Paul, Sengupta, Shomik, Sherif, Amir, Smeenk, Robert J, Smits, Anita, Stenzl, Arnulf, Thalmann, George N, Tombal, Bertrand, Turkbey, Baris, Lauridsen, Susanne Vahr, Valdagni, Riccardo, Der Heijden, Antoine G Van, Van Poppel, Hein, Vartolomei, Mihai D, Veskimäe, Erik, Vilaseca, Antoni, Rivera, Franklin A Vives, Wiegel, Thomas, Wiklund, Peter, Williams, Andrew, Zigeuner, Richard, and Horwich, Alan

Published
2020

34. Functional assays to determine the significance of two common XPC 3'UTR variants found in bladder cancer patients

Author

Bishop D, Hall Janet, Bentley Johanne, Vaslin Laurence, Elliott Faye, Scott Gina B, Qiao Boling, Knowles Margaret A, and Kiltie Anne E

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background XPC is involved in the nucleotide excision repair of DNA damaged by carcinogens known to cause bladder cancer. Individuals homozygous for the variant allele of XPC c.1496C > T (p.Ala499Val) were shown in a large pooled analysis to have an increased bladder cancer risk, and we found two 3'UTR variants, *611T > A and c.*618A > G, to be in strong linkage disequilibrium with c.1496T. Here we determined if these two 3'UTR variants can affect mRNA stability and assessed the impact of all three variants on mRNA and protein expression. Methods In vitro mRNA stability assays were performed and mRNA and protein expression measured both in plasmid-based assays and in lymphocytes and lymphoblastoid cell lines from bladder and breast cancer patients. Results The two 3'UTR variants were associated with reduced protein and mRNA expression in plasmid-based assays, suggesting an effect on mRNA stability and/or transcription/translation. A near-significant reduction in XPC protein expression (p = 0.058) was detected in lymphoblastoid cell lines homozygous for these alleles but no differences in mRNA stability in these lines was found or in mRNA or protein levels in lymphocytes heterozygous for these alleles. Conclusion The two 3'UTR variants may be the variants underlying the association of c.1496C > T and bladder cancer risk acting via a mechanism modulating protein expression.

Published
2011
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35. High-throughput DNA Sequencing Identifies Novel CtIP (RBBP8)Variants in Muscle-invasive Bladder Cancer Patients

Author

Jevons, Sarah J., Green, Angela, Lunter, Gerton, Kartsonaki, Christiana, Buck, David, Piazza, Paolo, and Kiltie, Anne E.

Abstract

Germline mutations in DNA damage signalling and repair genes predispose individuals to cancer. Rare germline variants may also increase cancer risk and be predictive of outcomes following cancer treatments, but require high-throughput sequencing (HTS) for detection in large cohorts. To use a dual indexing system on a HTS platform to detect novel variants in CtIP (RBBP8) which may be associated with clinical outcomes following radiotherapy treatment for bladder cancer. All exons and flanking introns of CtIP were amplified from germline DNA from bladder cancer patients using seven primer pairs by automated long-range PCR. Amplicons were pooled, fragmented and ligated to adaptor sequences. One of 96 tag sequences was introduced at each end by PCR. Sequencing was performed on a single flow cell of an Illumina MiSeq. Reads were mapped by Stampy and variants called by Platypus. For phasing experiments, target regions were amplified and cloned for Sanger sequencing. Of 201 samples, 160 were successfully amplified. Eleven CtIP variants were called, within the exons and 15 bp adjacent intronic DNA, including eight known variants from the 1000 Genomes project, plus three previously unreported variants now confirmed by Sanger sequencing. In two individuals, phasing experiments showed two variants of interest to be on separate alleles, likely to result in stronger impairment of gene function. We have demonstrated proof of principle for dual indexing on 160 samples on one MiSeq flow cell sequencing surface, and show that for the CtIP gene multiplexing of up to 720 samples would provide sufficient coverage to achieve >98% detection power for rare germline variation, reducing HTS costs substantially.

Published
2022
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36. Analysis of variants in DNA damage signalling genes in bladder cancer

Author

Bishop D Timothy, Bristow Robert G, Churchman Michael, Iles Mark M, Elliott Faye, Choudhury Ananya, and Kiltie Anne E

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Chemicals from occupational exposure and components of cigarette smoke can cause DNA damage in bladder urothelium. Failure to repair DNA damage by DNA repair proteins may result in mutations leading to genetic instability and the development of bladder cancer. Immunohistochemistry studies have shown DNA damage signal activation in precancerous bladder lesions which is lost on progression, suggesting that the damage signalling mechanism acts as a brake to further tumorigenesis. Single nucleotide polymorphisms (SNPs) in DSB signalling genes may alter protein function. We hypothesized that SNPs in DSB signalling genes may modulate predisposition to bladder cancer and influence the effects of environmental exposures. Methods We recruited 771 cases and 800 controls (573 hospital-based and 227 population-based from a previous case-control study) and interviewed them regarding their smoking habits and occupational history. DNA was extracted from a peripheral blood sample and genotyping of 24 SNPs in MRE11, NBS1, RAD50, H2AX and ATM was undertaken using an allelic discrimination method (Taqman). Results Smoking and occupational dye exposure were strongly associated with bladder cancer risk. Using logistic regression adjusting for age, sex, smoking and occupational dye exposure, there was a marginal increase in risk of bladder cancer for an MRE11 3'UTR SNP (rs2155209, adjusted odds ratio 1.54 95% CI (1.13–2.08, p = 0.01) for individuals homozygous for the rare allele compared to those carrying the common homozygous or heterozygous genotype). However, in the hospital-based controls, the genotype distribution for this SNP deviated from Hardy-Weinberg equilibrium. None of the other SNPs showed an association with bladder cancer and we did not find any significant interaction between any of these polymorphisms and exposure to smoking or dye exposure. Conclusion Apart from a possible effect for one MRE11 3'UTR SNP, our study does not support the hypothesis that SNPs in DSB signaling genes modulate predisposition to bladder cancer.

Published
2008
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37. DNA repair gene XRCC1 polymorphisms and bladder cancer risk

Author

Bishop D Timothy, Paul Alan B, Barrett Jennifer H, Sak Sei, and Kiltie Anne E

Subjects
Genetics, QH426-470
Abstract

Abstract Background Cigarette smoking and chemical occupational exposure are the main known risk factors for bladder transitional cell carcinoma (TCC). Oxidative DNA damage induced by carcinogens present in these exposures requires accurate base excision repair (BER). The XRCC1 protein plays a crucial role in BER by acting as a scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein structure or function or create alternatively spliced proteins which may influence BER efficiency and hence affect individual susceptibility to bladder cancer. Recent epidemiological studies have shown inconsistent associations between these polymorphisms and bladder cancer. To clarify the situation, we conducted a comprehensive analysis of 14 XRCC1 polymorphisms in a case-control study involving more than 1100 subjects. Results We found no evidence of an association between any of the 14 XRCC1 polymorphisms and bladder cancer risk. However, we found carriage of the variant Arg280His allele to be marginally associated with increased bladder cancer risk compared to the wild-type genotype (adjusted odds ratio [95% confidence interval], 1.50 [0.98–2.28], p = 0.06). The association was stronger for current smokers such that individuals carrying the variant 280His allele had a two to three-fold increased risk of bladder cancer compared to those carrying the wildtype genotype (p = 0.09). However, the evidence for gene-environment interaction was not statistically significant (p = 0.45). Conclusion We provide no evidence of an association between polymorphisms in XRCC1 and bladder cancer risk, although our study had only limited power to detect the association for low frequency variants, such as Arg280His.

Published
2007
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41. Developing Ultrasound-Activated Gemcitabine Delivery Systems for Chemoradiation Therapy in Muscle-Invasive Bladder Cancer

Author

Ruan, Jia-Ling, primary, Browning, Richard, additional, Yildiz, Yesna, additional, Bau, Luca, additional, Thompson, James, additional, Elliott, Amy, additional, Smart, Sean, additional, Folkes, Lisa, additional, Hampson, Alix, additional, Beguin, Estelle, additional, Gray, Michael, additional, Vojnovic, Borivoj, additional, Stride, Eleanor, additional, and Kiltie, Anne, additional

Published
2019
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43. Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity

Author

Groselj, Blaz, primary, Ruan, Jia-Ling, additional, Scott, Helen, additional, Gorrill, Jessica, additional, Nicholson, Judith, additional, Kelly, Jacqueline, additional, Anbalagan, Selvakumar, additional, Thompson, James, additional, Stratford, Michael R.L., additional, Jevons, Sarah J., additional, Hammond, Ester M., additional, Scudamore, Cheryl L., additional, Kerr, Martin, additional, and Kiltie, Anne E., additional

Published
2018
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45. Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

Author

Figueroa, Jonine D. Middlebrooks, Candace D. Banday, A. Rouf and Ye, Yuanqing Garcia-Closas, Montserrat Chatterjee, Nilanjan and Koutros, Stella Kiemeney, Lambertus A. Rafnar, Thorunn and Bishop, Timothy Furberg, Helena Matullo, Giuseppe Golka, Klaus Gago-Dominguez, Manuela Taylor, Jack A. Fletcher, Tony and Siddiq, Afshan Cortessis, Victoria K. Kooperberg, Charles and Cussenot, Olivier Benhamou, Simone Prescott, Jennifer and Porru, Stefano Dinney, Colin P. Malats, Nuria Baris, Dalsu and Purdue, Mark P. Jacobs, Eric J. Albanes, Demetrius Wang, Zhaoming Chung, Charles C. Vermeulen, Sita H. Aben, Katja K. and Galesloot, Tessel E. Thorleifsson, Gudmar Sulem, Patrick and Stefansson, Kari Kiltie, Anne E. Harland, Mark Teo, Mark and Offit, Kenneth Vijai, Joseph Bajorin, Dean Kopp, Ryan and Fiorito, Giovanni Guarrera, Simonetta Sacerdote, Carlotta and Selinski, Silvia Hengstler, Jan G. Gerullis, Holger and Ovsiannikov, Daniel Blaszkewicz, Meinolf Esteban Castelao, Jose and Calaza, Manuel Martinez, Maria Elena Cordeiro, Patricia and Xu, Zongli Panduri, Vijayalakshmi Kumar, Rajiv Gurzau, Eugene Koppova, Kvetoslava Bueno-De-Mesquita, H. Bas and Ljungberg, Borje Clavel-Chapelon, Francoise Weiderpass, Elisabete Krogh, Vittorio Dorronsoro, Miren Travis, Ruth C. and Tjonneland, Anne Brennan, Paul Chang-Claude, Jenny and Riboli, Elio Conti, David Stern, Marianna C. Pike, Malcolm C. Van den Berg, David Yuan, Jian-Min Hohensee, Chancellor and Jeppson, Rebecca P. Cancel-Tassin, Geraldine Roupret, Morgan and Comperat, Eva Turman, Constance De Vivo, Immaculata and Giovannucci, Edward Hunter, David J. Kraft, Peter Lindstrom, Sara Carta, Angela Pavanello, Sofia Arici, Cecilia and Mastrangelo, Giuseppe Kamat, Ashish M. Zhang, Liren Gong, Yilei Pu, Xia Hutchinson, Amy Burdett, Laurie Wheeler, William A. Karagas, Margaret R. Johnson, Alison Schned, Alan and Hosain, G. M. Monawar Schwenn, Molly Kogevinas, Manolis and Tardon, Adonina Serra, Consol Carrato, Alfredo and Garcia-Closas, Reina Lloreta, Josep Andriole, Jr., Gerald and Grubb, III, Robert Black, Amanda Diver, W. Ryan Gapstur, Susan M. Weinstein, Stephanie Virtamo, Jarmo Haiman, Christopher A. Landi, Maria Teresa Caporaso, Neil E. and Fraumeni, Jr., Joseph F. Vineis, Paolo Wu, Xifeng Chanock, Stephen J. Silverman, Debra T. Prokunina-Olsson, Ludmila and Rothman, Nathaniel

Abstract

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1x 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 x 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 x 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P

Published
2016

49. Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

Author

Figueroa, Jonine D., Middlebrooks, Candace D., Banday, A. Rouf, Ye, Yuanqing, Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Koutros, Stella, Kiemeney, Lambertus A., Rafnar, Thorunn, Bishop, Timothy, Furberg, Helena, Matullo, Giuseppe, Golka, Klaus, Gago-Dominguez, Manuela, Taylor, Jack A., Fletcher, Tony, Siddiq, Afshan, Cortessis, Victoria K., Kooperberg, Charles, Cussenot, Olivier, Benhamou, Simone, Prescott, Jennifer, Porru, Stefano, Dinney, Colin P., Malats, Nuria, Baris, Dalsu, Purdue, Mark P., Jacobs, Eric J., Albanes, Demetrius, Wang, Zhaoming, Chung, Charles C., Vermeulen, Sita H., Aben, Katja K., Galesloot, Tessel E., Thorleifsson, Gudmar, Sulem, Patrick, Stefansson, Kari, Kiltie, Anne E., Harland, Mark, Teo, Mark, Offit, Kenneth, Vijai, Joseph, Bajorin, Dean, Kopp, Ryan, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Selinski, Silvia, Hengstler, Jan G., Gerullis, Holger, Ovsiannikov, Daniel, Blaszkewicz, Meinolf, Esteban Castelao, Jose, Calaza, Manuel, Martinez, Maria Elena, Cordeiro, Patricia, Xu, Zongli, Panduri, Vijayalakshmi, Kumar, Rajiv, Gurzau, Eugene, Koppova, Kvetoslava, Bueno-De-Mesquita, H. Bas, Ljungberg, Börje, Clavel-Chapelon, Francoise, Weiderpass, Elisabete, Krogh, Vittorio, Dorronsoro, Miren, Travis, Ruth C., Tjonneland, Anne, Brennan, Paul, Chang-Claude, Jenny, Riboli, Elio, Conti, David, Stern, Marianna C., Pike, Malcolm C., Van den Berg, David, Yuan, Jian-Min, Hohensee, Chancellor, Jeppson, Rebecca P., Cancel-Tassin, Geraldine, Roupret, Morgan, Comperat, Eva, Turman, Constance, De Vivo, Immaculata, Giovannucci, Edward, Hunter, David J., Kraft, Peter, Lindstrom, Sara, Carta, Angela, Pavanello, Sofia, Arici, Cecilia, Mastrangelo, Giuseppe, Kamat, Ashish M., Zhang, Liren, Gong, Yilei, Pu, Xia, Hutchinson, Amy, Burdett, Laurie, Wheeler, William A., Karagas, Margaret R., Johnson, Alison, Schned, Alan, Hosain, G. M. Monawar, Schwenn, Molly, Kogevinas, Manolis, Tardon, Adonina, Serra, Consol, Carrato, Alfredo, Garcia-Closas, Reina, Lloreta, Josep, Andriole, Gerald, Jr., Grubb, Robert, III, Black, Amanda, Diver, W. Ryan, Gapstur, Susan M., Weinstein, Stephanie, Virtamo, Jarmo, Haiman, Christopher A., Landi, Maria Teresa, Caporaso, Neil E., Fraumeni, Joseph F., Jr., Vineis, Paolo, Wu, Xifeng, Chanock, Stephen J., Silverman, Debra T., Prokunina-Olsson, Ludmila, Rothman, Nathaniel, Figueroa, Jonine D., Middlebrooks, Candace D., Banday, A. Rouf, Ye, Yuanqing, Garcia-Closas, Montserrat, Chatterjee, Nilanjan, Koutros, Stella, Kiemeney, Lambertus A., Rafnar, Thorunn, Bishop, Timothy, Furberg, Helena, Matullo, Giuseppe, Golka, Klaus, Gago-Dominguez, Manuela, Taylor, Jack A., Fletcher, Tony, Siddiq, Afshan, Cortessis, Victoria K., Kooperberg, Charles, Cussenot, Olivier, Benhamou, Simone, Prescott, Jennifer, Porru, Stefano, Dinney, Colin P., Malats, Nuria, Baris, Dalsu, Purdue, Mark P., Jacobs, Eric J., Albanes, Demetrius, Wang, Zhaoming, Chung, Charles C., Vermeulen, Sita H., Aben, Katja K., Galesloot, Tessel E., Thorleifsson, Gudmar, Sulem, Patrick, Stefansson, Kari, Kiltie, Anne E., Harland, Mark, Teo, Mark, Offit, Kenneth, Vijai, Joseph, Bajorin, Dean, Kopp, Ryan, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Selinski, Silvia, Hengstler, Jan G., Gerullis, Holger, Ovsiannikov, Daniel, Blaszkewicz, Meinolf, Esteban Castelao, Jose, Calaza, Manuel, Martinez, Maria Elena, Cordeiro, Patricia, Xu, Zongli, Panduri, Vijayalakshmi, Kumar, Rajiv, Gurzau, Eugene, Koppova, Kvetoslava, Bueno-De-Mesquita, H. Bas, Ljungberg, Börje, Clavel-Chapelon, Francoise, Weiderpass, Elisabete, Krogh, Vittorio, Dorronsoro, Miren, Travis, Ruth C., Tjonneland, Anne, Brennan, Paul, Chang-Claude, Jenny, Riboli, Elio, Conti, David, Stern, Marianna C., Pike, Malcolm C., Van den Berg, David, Yuan, Jian-Min, Hohensee, Chancellor, Jeppson, Rebecca P., Cancel-Tassin, Geraldine, Roupret, Morgan, Comperat, Eva, Turman, Constance, De Vivo, Immaculata, Giovannucci, Edward, Hunter, David J., Kraft, Peter, Lindstrom, Sara, Carta, Angela, Pavanello, Sofia, Arici, Cecilia, Mastrangelo, Giuseppe, Kamat, Ashish M., Zhang, Liren, Gong, Yilei, Pu, Xia, Hutchinson, Amy, Burdett, Laurie, Wheeler, William A., Karagas, Margaret R., Johnson, Alison, Schned, Alan, Hosain, G. M. Monawar, Schwenn, Molly, Kogevinas, Manolis, Tardon, Adonina, Serra, Consol, Carrato, Alfredo, Garcia-Closas, Reina, Lloreta, Josep, Andriole, Gerald, Jr., Grubb, Robert, III, Black, Amanda, Diver, W. Ryan, Gapstur, Susan M., Weinstein, Stephanie, Virtamo, Jarmo, Haiman, Christopher A., Landi, Maria Teresa, Caporaso, Neil E., Fraumeni, Joseph F., Jr., Vineis, Paolo, Wu, Xifeng, Chanock, Stephen J., Silverman, Debra T., Prokunina-Olsson, Ludmila, and Rothman, Nathaniel

Abstract

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

Published
2016
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50. Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays

Author

Lawson, Jonathan, primary, Robinson-Vyas, Rupesh J, additional, McQuillan, Janette P, additional, Paterson, Andy, additional, Christie, Sarah, additional, Kidza-Griffiths, Matthew, additional, McDuffus, Leigh-Anne, additional, Moutasim, Karwan A, additional, Shaw, Emily C, additional, Kiltie, Anne E, additional, Howat, William J, additional, Hanby, Andrew M, additional, Thomas, Gareth J, additional, and Smittenaar, Peter, additional

Published
2016
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