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1. Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and report

Author

Meade, Angela, Frangou, Elena, Choodari-Oskooei, Babak, Larkin, James, Powles, Tom, Stewart, Grant D., Albiges, Laurence, Bex, Axel, Choueiri, Toni K., Davis, Ian D., Eisen, Tim, Fielding, Alison, Gedye, Craig, Harrison, David J., Kaplan, Rick, Mulhere, Salena, Nathan, Paul, Patel, Grisma, Patel, Jay, Plant, Hannah, Ritchie, Alastair, Rush, Hannah, Shakeshaft, Clare, Stockler, Martin R., Suarez, Cristina, Thompson, Jemima, Thorogood, Nat, Venugopal, Balaji, and Parmar, Mahesh K.B.

Published
2024
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2. A Phase II study of neoadjuvant axitinib for reducing the extent of venous tumour thrombus in clear cell renal cell cancer with venous invasion (NAXIVA)

Author

Stewart, Grant D., Welsh, Sarah J., Ursprung, Stephan, Gallagher, Ferdia A., Jones, James O., Shields, Jacqui, Smith, Christopher G., Mitchell, Thomas J., Warren, Anne Y., Bex, Axel, Boleti, Ekaterini, Carruthers, Jade, Eisen, Tim, Fife, Kate, Hamid, Abdel, Laird, Alexander, Leung, Steve, Malik, Jahangeer, Mendichovszky, Iosif A., Mumtaz, Faiz, Oades, Grenville, Priest, Andrew N., Riddick, Antony C. P., Venugopal, Balaji, Welsh, Michelle, Riddle, Kathleen, Hopcroft, Lisa E. M., and Jones, Robert J.

Published
2022
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3. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis

Author

Field, John K., Vulkan, Daniel, Davies, Michael P.A., Baldwin, David R., Brain, Kate E., Devaraj, Anand, Eisen, Tim, Gosney, John, Green, Beverley A., Holemans, John A., Kavanagh, Terry, Kerr, Keith M., Ledson, Martin, Lifford, Kate J., McRonald, Fiona E., Nair, Arjun, Page, Richard D., Parmar, Mahesh K.B., Rassl, Doris M., Rintoul, Robert C., Screaton, Nicholas J., Wald, Nicholas J., Weller, David, Whynes, David K., Williamson, Paula R., Yadegarfar, Gasham, Gabe, Rhian, and Duffy, Stephen W.

Published
2021
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4. RAMPART: A model for a regulatory-ready academic-led phase III trial in the adjuvant renal cell carcinoma setting

Author

Meade, Angela, Oza, Bhavna, Frangou, Eleni, Smith, Ben, Bryant, Hanna, Kaplan, Rick, Choodari-Oskooei, Babak, Powles, Tom, Stewart, Grant D., Albiges, Laurence, Bex, Axel, Choueiri, Toni K., Davis, Ian D., Eisen, Tim, Fielding, Alison, Harrison, David J., McWhirter, Anita, Mulhere, Salena, Nathan, Paul, Rini, Brian, Ritchie, Alastair, Scovell, Sarah, Shakeshaft, Clare, Stockler, Martin R., Thorogood, Nat, Larkin, James, and Parmar, Mahesh K.B.

Published
2021
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5. RAMPART: A phase III multi-arm multi-stage trial of adjuvant checkpoint inhibitors in patients with resected primary renal cell carcinoma (RCC) at high or intermediate risk of relapse

Author

Oza, Bhavna, Frangou, Eleni, Smith, Ben, Bryant, Hanna, Kaplan, Rick, Choodari-Oskooei, Babak, Powles, Tom, Stewart, Grant D., Albiges, Laurence, Bex, Axel, Choueiri, Toni K., Davis, Ian D., Eisen, Tim, Fielding, Alison, Harrison, David, McWhirter, Anita, Mulhere, Salena, Nathan, Paul, Rini, Brian, Ritchie, Alastair, Scovell, Sarah, Shakeshaft, Clare, Stockler, Martin R., Thorogood, Nat, Parmar, Mahesh K.B., Larkin, James, and Meade, Angela

Published
2021
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6. Temporary treatment cessation compared with continuation of tyrosine kinase inhibitors for adults with renal cancer: the STAR non-inferiority RCT.

Author

Collinson, Fiona, Royle, Kara-Louise, Swain, Jayne, Ralph, Christy, Maraveyas, Anthony, Eisen, Tim, Nathan, Paul, Jones, Robert, Meads, David, Wah, Tze Min, Martin, Adam, Bestall, Janine, Kelly-Morland, Christian, Linsley, Christopher, Oughton, Jamie, Chan, Kevin, Theodoulou, Elisavet, Arias-Pinilla, Gustavo, Kwan, Amy, and Daverede, Luis

Published
2024
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8. The WIRE study a phase II, multi-arm, multi-centre, non-randomised window-of-opportunity clinical trial platform using a Bayesian adaptive design for proof-of-mechanism of novel treatment strategies in operable renal cell cancer – a study protocol

Author

Ursprung, Stephan, Mossop, Helen, Gallagher, Ferdia A., Sala, Evis, Skells, Richard, Sipple, Jamal A. N., Mitchell, Thomas J., Chhabra, Anita, Fife, Kate, Matakidou, Athena, Young, Gemma, Walker, Amanda, Thomas, Martin G., Ortuzar, Mireia Crispin, Sullivan, Mark, Protheroe, Andrew, Oades, Grenville, Venugopal, Balaji, Warren, Anne Y., Stone, John, Eisen, Tim, Wason, James, Welsh, Sarah J., and Stewart, Grant D.

Published
2021
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15. Metastatic chromophobe renal cell carcinoma treated with targeted therapies: A Renal Cross Channel Group study

Author

Colomba, Emeline, Le Teuff, Gwénaël, Eisen, Tim, Stewart, Grant D., Fife, Kate, Larkin, James, Biondo, Andrea, Pickering, Lisa, Srinivasan, Anandagopal, Boyle, Helen, Derosa, Lisa, Sternberg, Cora N., Recine, Federica, Ralph, Christy, Saldana, Carolina, Barthélémy, Philippe, Bernhard, Jean Christophe, Gurney, Howard, Verhoest, Gregory, Vauleon, Elodie, Bigot, Pierre, Berger, Julien, Pfister, Christian, Gravis, Gwenaelle, Rodier, Jean-Michel, Culine, Stéphane, Caty, Armelle, Rolland, Frederic, Priou, Franck, Escudier, Bernard, and Albiges, Laurence

Published
2017
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17. Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors

Author

Smith, Christopher G., Moser, Tina, Mouliere, Florent, Field-Rayner, Johanna, Eldridge, Matthew, Riediger, Anja L., Chandrananda, Dineika, Heider, Katrin, Wan, Jonathan C. M., Warren, Anne Y., Morris, James, Hudecova, Irena, Cooper, Wendy N., Mitchell, Thomas J., Gale, Davina, Ruiz-Valdepenas, Andrea, Klatte, Tobias, Ursprung, Stephan, Sala, Evis, Riddick, Antony C. P., Aho, Tevita F., Armitage, James N., Perakis, Samantha, Pichler, Martin, Seles, Maximilian, Wcislo, Gabriel, Welsh, Sarah J., Matakidou, Athena, Eisen, Tim, Massie, Charles E., Rosenfeld, Nitzan, Heitzer, Ellen, and Stewart, Grant D.

Published
2020
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20. IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial

Author

Rini, Brian I, Stenzl, Arnulf, Zdrojowy, Romauld, Kogan, Mikhail, Shkolnik, Mikhail, Oudard, Stephane, Weikert, Steffen, Bracarda, Sergio, Crabb, Simon J, Bedke, Jens, Ludwig, Joerg, Maurer, Dominik, Mendrzyk, Regina, Wagner, Claudia, Mahr, Andrea, Fritsche, Jens, Weinschenk, Toni, Walter, Steffen, Kirner, Alexandra, Singh-Jasuja, Harpreet, Reinhardt, Carsten, and Eisen, Tim

Published
2016
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21. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial

Author

Armstrong, Andrew J, Halabi, Susan, Eisen, Tim, Broderick, Samuel, Stadler, Walter M, Jones, Robert J, Garcia, Jorge A, Vaishampayan, Ulka N, Picus, Joel, Hawkins, Robert E, Hainsworth, John D, Kollmannsberger, Christian K, Logan, Theodore F, Puzanov, Igor, Pickering, Lisa M, Ryan, Christopher W, Protheroe, Andrew, Lusk, Christine M, Oberg, Sadie, and George, Daniel J

Published
2016
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23. The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort

Author

Klatte, Tobias, Gallagher, Kevin M., Afferi, Luca, Volpe, Alessandro, Kroeger, Nils, Ribback, Silvia, McNeill, Alan, Riddick, Antony C. P., Armitage, James N., ‘Aho, Tevita F., Eisen, Tim, Fife, Kate, Bex, Axel, Pantuck, Allan J., and Stewart, Grant D.

Published
2019
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25. Data from The UK Lung Screen (UKLS): Demographic Profile of First 88,897 Approaches Provides Recommendations for Population Screening

Author

McRonald, Fiona E., primary, Yadegarfar, Ghasem, primary, Baldwin, David R., primary, Devaraj, Anand, primary, Brain, Kate E., primary, Eisen, Tim, primary, Holemans, John A., primary, Ledson, Martin, primary, Screaton, Nicholas, primary, Rintoul, Robert C., primary, Hands, Christopher J., primary, Lifford, Kate, primary, Whynes, David, primary, Kerr, Keith M., primary, Page, Richard, primary, Parmar, Mahesh, primary, Wald, Nicholas, primary, Weller, David, primary, Williamson, Paula R., primary, Myles, Jonathan, primary, Hansell, David M., primary, Duffy, Stephen W., primary, and Field, John K., primary

Published
2023
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26. Supplementary Figures 1 - 2, Tables 1 - 3 from The UK Lung Screen (UKLS): Demographic Profile of First 88,897 Approaches Provides Recommendations for Population Screening

Author

McRonald, Fiona E., primary, Yadegarfar, Ghasem, primary, Baldwin, David R., primary, Devaraj, Anand, primary, Brain, Kate E., primary, Eisen, Tim, primary, Holemans, John A., primary, Ledson, Martin, primary, Screaton, Nicholas, primary, Rintoul, Robert C., primary, Hands, Christopher J., primary, Lifford, Kate, primary, Whynes, David, primary, Kerr, Keith M., primary, Page, Richard, primary, Parmar, Mahesh, primary, Wald, Nicholas, primary, Weller, David, primary, Williamson, Paula R., primary, Myles, Jonathan, primary, Hansell, David M., primary, Duffy, Stephen W., primary, and Field, John K., primary

Published
2023
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27. Data from Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group

Author

Manola, Judith, primary, Royston, Patrick, primary, Elson, Paul, primary, McCormack, Jennifer Bacik, primary, Mazumdar, Madhu, primary, Négrier, Sylvie, primary, Escudier, Bernard, primary, Eisen, Tim, primary, Dutcher, Janice, primary, Atkins, Michael, primary, Heng, Daniel Y.C., primary, Choueiri, Toni K., primary, Motzer, Robert, primary, and Bukowski, Ronald, primary

Published
2023
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28. supplementary data from A Genetic Polymorphism in CTLA-4 Is Associated with Overall Survival in Sunitinib-Treated Patients with Clear Cell Metastatic Renal Cell Carcinoma

Author

Liu, Xiaoyan, primary, Swen, Jesse J., primary, Diekstra, Meta H.M., primary, Boven, Epie, primary, Castellano, Daniel, primary, Gelderblom, Hans, primary, Mathijssen, Ron H.J., primary, Vermeulen, Sita H., primary, Oosterwijk, Egbert, primary, Junker, Kerstin, primary, Roessler, Max, primary, Alexiusdottir, Kristin, primary, Sverrisdottir, Asgerdur, primary, Radu, Marius T., primary, Ambert, Valentin, primary, Eisen, Tim, primary, Warren, Anne, primary, Rodríguez-Antona, Cristina, primary, García-Donas, Jesus, primary, Böhringer, Stefan, primary, Koudijs, Karel K.M., primary, Kiemeney, Lambertus A.L.M., primary, Rini, Brian I., primary, and Guchelaar, Henk-Jan, primary

Published
2023
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29. Supplementary Figure 1 from Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group

Author

Manola, Judith, primary, Royston, Patrick, primary, Elson, Paul, primary, McCormack, Jennifer Bacik, primary, Mazumdar, Madhu, primary, Négrier, Sylvie, primary, Escudier, Bernard, primary, Eisen, Tim, primary, Dutcher, Janice, primary, Atkins, Michael, primary, Heng, Daniel Y.C., primary, Choueiri, Toni K., primary, Motzer, Robert, primary, and Bukowski, Ronald, primary

Published
2023
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30. Supplementary Tables and Figures from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma

Author

Armstrong, Andrew J., primary, Nixon, Andrew B., primary, Carmack, Andrea, primary, Yang, Qian, primary, Eisen, Tim, primary, Stadler, Walter M., primary, Jones, Robert J., primary, Garcia, Jorge A., primary, Vaishampayan, Ulka N., primary, Picus, Joel, primary, Hawkins, Robert E., primary, Hainsworth, John D., primary, Kollmannsberger, Christian K., primary, Logan, Theodore F., primary, Puzanov, Igor, primary, Pickering, Lisa M., primary, Ryan, Christopher W., primary, Protheroe, Andrew, primary, George, Daniel J., primary, and Halabi, Susan, primary

Published
2023
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31. Supplementary Figure 2 from Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group

Author

Manola, Judith, primary, Royston, Patrick, primary, Elson, Paul, primary, McCormack, Jennifer Bacik, primary, Mazumdar, Madhu, primary, Négrier, Sylvie, primary, Escudier, Bernard, primary, Eisen, Tim, primary, Dutcher, Janice, primary, Atkins, Michael, primary, Heng, Daniel Y.C., primary, Choueiri, Toni K., primary, Motzer, Robert, primary, and Bukowski, Ronald, primary

Published
2023
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32. Supplementary Figure 4a from Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma

Author

Armstrong, Andrew J., primary, Nixon, Andrew B., primary, Carmack, Andrea, primary, Yang, Qian, primary, Eisen, Tim, primary, Stadler, Walter M., primary, Jones, Robert J., primary, Garcia, Jorge A., primary, Vaishampayan, Ulka N., primary, Picus, Joel, primary, Hawkins, Robert E., primary, Hainsworth, John D., primary, Kollmannsberger, Christian K., primary, Logan, Theodore F., primary, Puzanov, Igor, primary, Pickering, Lisa M., primary, Ryan, Christopher W., primary, Protheroe, Andrew, primary, George, Daniel J., primary, and Halabi, Susan, primary

Published
2023
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33. Supplementary Tables 1-7 from Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group

Author

Manola, Judith, primary, Royston, Patrick, primary, Elson, Paul, primary, McCormack, Jennifer Bacik, primary, Mazumdar, Madhu, primary, Négrier, Sylvie, primary, Escudier, Bernard, primary, Eisen, Tim, primary, Dutcher, Janice, primary, Atkins, Michael, primary, Heng, Daniel Y.C., primary, Choueiri, Toni K., primary, Motzer, Robert, primary, and Bukowski, Ronald, primary

Published
2023
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34. Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project

Author

Kramar, Andrew, Sylvester, Richard, Filleron, Thomas, Negrier, Sylvie, Joniau, Steven, Mulders, Peter, Powles, Thomas, Escudier, Bernard, Bex, Axel, Bonnetain, Franck, Bossi, Alberto, Braccarda, Sergio, Bukowski, Ronald, Catto, James, Choueiri, Toni, Crabb, Simon, Eisen, Tim, El Demery, Mounira, Fitzpatrick, John, Flamand, Vincent, Goebell, Peter J., Gravis, Gwendael, Houédé, Nadine, Jacqmin, Didier, Kaplan, Richard, Malavaud, Bernard, Massard, Christophe, Melichar, Bohuslav, Mourey, Loïc, Nathan, Paul, Pasquier, David, Porta, Camillo, Pouessel, Damien, Quinn, David, Ravaud, Alain, Rolland, Frédéric, Schmidinger, Manuela, Tombal, Bertrand, Tosi, Diego, Vauleon, Elodie, Volpe, Alessandro, Wolter, Pascal, Kramar, A., Negrier, S., Sylvester, R., Joniau, S., Mulders, P., Powles, T., Bex, A., Bonnetain, F., Bossi, A., Bracarda, S., Bukowski, R., Catto, J., Choueiri, T.K., Crabb, S., Eisen, T., El Demery, M., Fitzpatrick, J., Flamand, V., Goebell, P.J., Gravis, G., Houédé, N., Jacqmin, D., Kaplan, R., Malavaud, B., Massard, C., Melichar, B., Mourey, L., Nathan, P., Pasquier, D., Porta, C., Pouessel, D., Quinn, D., Ravaud, A., Rolland, F., Schmidinger, M., Tombal, B., Tosi, D., Vauleon, E., Volpe, A., Wolter, P., Escudier, B., and Filleron, T.

Published
2015
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35. Genome-Wide Meta-Analysis Identifies Variants in DSCAM and PDLIM3 That Correlate with Efficacy Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib

Author

Diekstra, Meta HM, Swen, Jesse J, Van Der Zanden, Loes FM, Vermeulen, Sita H, Boven, Epie, Mathijssen, Ron HJ, Fukunaga, Koya, Mushiroda, Taisei, Hongo, Fumiya, Oosterwijk, Egbert, Cambon-Thomsen, Anne, Castellano, Daniel, Fritsch, Achim, Donas, Jesus Garcia, Rodriguez-Antona, Cristina, Ruijtenbeek, Rob, Radu, Marius T, Eisen, Tim, Junker, Kerstin, Roessler, Max, Jaehde, Ulrich, Miki, Tsuneharu, Böhringer, Stefan, Kubo, Michiaki, Kiemeney, Lambertus ALM, Guchelaar, Henk-Jan, Medical Oncology, Internal medicine, Diekstra, Meta HM [0000-0002-9368-3650], Swen, Jesse J [0000-0002-3965-5552], van der Zanden, Loes FM [0000-0003-3914-7491], Mathijssen, Ron HJ [0000-0001-5667-5697], Cambon-Thomsen, Anne [0000-0001-8793-3644], Eisen, Tim [0000-0001-9663-4873], Guchelaar, Henk-Jan [0000-0002-7085-1383], and Apollo - University of Cambridge Repository

Subjects
Cancer Research, sunitinib, clear cell renal cell carcinoma, urologic and male genital diseases, metastatic renal cell carcinoma, genome wide association study, pharmacogenetics, single nucleotide polymorphism, Oncology, SDG 3 - Good Health and Well-being, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Renal disorders Radboud Institute for Health Sciences [Radboudumc 11]
Abstract

Contains fulltext : 251723.pdf (Publisher’s version ) (Open Access) Individual response to sunitinib in metastatic renal cell carcinoma (mRCC) patients is highly variable. Earlier, sunitinib outcome was related to single nucleotide polymorphisms (SNPs) in CYP3A5 and ABCB1. Our aim is to provide novel insights into biological mechanisms underlying sunitinib action. We included mRCC patients from the European EuroTARGET consortium (n = 550) and the RIKEN cohort in Japan (n = 204) which were analysed separately and in a meta-analysis of genome-wide association studies (GWAS). SNPs were tested for association with progression-free survival (PFS) and overall survival (OS) using Cox regression. Summary statistics were combined using a fixed effect meta-analysis. SNP rs28520013 in PDLIM3 and the correlated SNPs rs2205096 and rs111356738 both in DSCAM, showed genome-wide significance (p < 5 × 10(-8)) with PFS and OS in the meta-analysis. The variant T-allele of rs28520013 associated with an inferior PFS of 5.1 months compared to 12.5 months in non-carriers (p = 4.02 × 10(-10), HR = 7.26). T-allele carriers of rs28520013 showed an inferior OS of 6.9 months versus 30.2 months in non-carriers (p = 1.62 × 10(-8), HR = 5.96). In this GWAS we identified novel genetic variants in PDLIM3 and DSCAM that impact PFS and OS in mRCC patients receiving sunitinib. The underlying link between the identified genes and the molecular mechanisms of sunitinib action needs to be elucidated.

Published
2022
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36. Logical Imputation to Optimize Prognostic Risk Classification in Metastatic Renal Cell Cancer

Author

Maurits, Jake S.F., primary, van der Zanden, Loes F.M., additional, Diekstra, Meta H.M., additional, Ambert, Valentin, additional, Castellano, Daniel, additional, Garcia-Donas, Jesus, additional, Troyas, Rosa Guarch, additional, Guchelaar, Henk-Jan, additional, Jaehde, Ulrich, additional, Junker, Kerstin, additional, Martinez-Cardus, Anna, additional, Radu, Marius T., additional, Rodriguez-Antona, Cristina, additional, Roessler, Max, additional, Warren, Anne, additional, Eisen, Tim, additional, Oosterwijk, Egbert, additional, Kiemeney, Lambertus A.L.M., additional, and Vermeulen, Sita H., additional

Published
2022
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37. Neoadjuvant and Adjuvant Therapy for Renal Cell Carcinoma

Author

Haas, Naomi B., primary, Shevach, Jeffrey, additional, Davis, Ian D., additional, Eisen, Tim, additional, Gross-Gupil, Marine, additional, Kapoor, Anil, additional, Master, Viraj A., additional, Ryan, Christopher W., additional, and Schimdinger, Manuela, additional

Published
2022
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42. Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study

Author

Ursprung, Stephan, Woitek, Ramona, McLean, Mary, Priest, Andrew N, Crispin-Ortuzar, Mireia, Brodie, Cara R, Gill, Andrew, Gehrung, Marcel, Beer, Lucian, Riddick, Antony CP, Field-Rayner, Johanna, Grist, James T, Deen, Surrin S, Riemer, Frank, Kaggie, Joshua, Zaccagna, Fulvio, Duarte, Joao AG, Locke, Matthew J, Frary, Amy, Aho, Tevita F, Armitage, James N, Casey, Ruth, Mendichovszky, Iosif A, Welsh, Sarah, Barrett, Tristan, Graves, Martin, Eisen, Tim, Mitchell, Thomas J, Warren, Anne, Brindle, Kevin, Sala, Evis, Stewart, Grant, Gallagher, Ferdia, Ursprung, Stephan [0000-0003-2476-178X], McLean, Mary [0000-0002-3752-0179], Priest, Andrew N [0000-0002-9771-4290], Gill, Andrew [0000-0002-9287-9563], Beer, Lucian [0000-0003-4388-7580], Deen, Surrin S [0000-0002-6206-7337], Riemer, Frank [0000-0002-3805-5221], Kaggie, Joshua [0000-0001-6706-3442], Zaccagna, Fulvio [0000-0001-6838-9532], Frary, Amy [0000-0002-4373-3517], Welsh, Sarah [0000-0001-5690-2677], Barrett, Tristan [0000-0002-1180-1474], Graves, Martin [0000-0003-4327-3052], Eisen, Tim [0000-0001-9663-4873], Warren, Anne [0000-0002-1170-7867], Brindle, Kevin [0000-0003-3883-6287], Sala, Evis [0000-0002-5518-9360], Stewart, Grant [0000-0003-3188-9140], Gallagher, Ferdia [0000-0003-4784-5230], Apollo - University of Cambridge Repository, Ursprung S., Woitek R., McLean M.A., Priest A.N., Crispin-Ortuzar M., Brodie C.R., Gill A.B., Gehrung M., Beer L., Riddick A.C.P., Field-Rayner J., Grist J.T., Deen S.S., Riemer F., Kaggie J.D., Zaccagna F., Duarte J.A.G., Locke M.J., Frary A., Aho T.F., Armitage J.N., Casey R., Mendichovszky I.A., Welsh S.J., Barrett T., Graves M.J., Eisen T., Mitchell T.J., Warren A.Y., Brindle K.M., Sala E., Stewart G.D., Gallagher F.A., Gill, Andrew B [0000-0002-9287-9563], Kaggie, Joshua D [0000-0001-6706-3442], Welsh, Sarah J [0000-0001-5690-2677], Brindle, Kevin M [0000-0003-3883-6287], Stewart, Grant D [0000-0003-3188-9140], and Gallagher, Ferdia A [0000-0003-4784-5230]

Subjects
Cancer Research, renal cell carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, cancer metabolism, monocarboxylate transporter, Article, Hyperpolarized, hyperpolarized 13C magnetic resonance imaging, Oncology, C magnetic resonance imaging, RC254-282
Abstract

Simple Summary We evaluated renal cancer with varying aggressive appearances on histology, using an emerging form of non-invasive metabolic MRI. This imaging technique assesses the uptake and metabolism of a breakdown product of glucose (pyruvate) labelled with hyperpolarized carbon-13. We show that pyruvate metabolism is dependent on the aggressiveness of an individual tumor and we provide a mechanism for this finding from tissue analysis of molecules influencing pyruvate metabolism, suggesting a role for its membrane transporter. Abstract Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Published
2022

46. External Validation of the 2003 Leibovich Prognostic Score in Patients Randomly Assigned to SORCE, an International Phase III Trial of Adjuvant Sorafenib in Renal Cell Cancer

Author

Oza, Bhavna, primary, Eisen, Tim, additional, Frangou, Eleni, additional, Stewart, Grant D., additional, Bex, Axel, additional, Ritchie, Alastair W.S., additional, Kaplan, Rick, additional, Smith, Benjamin, additional, Davis, Ian D., additional, Stockler, Martin R., additional, Albiges, Laurence, additional, Escudier, Bernard, additional, Larkin, James, additional, Joniau, Steven, additional, Hancock, Barry, additional, Hermann, Gregers G., additional, Bellmunt, Joaquim, additional, Parmar, Mahesh K.B., additional, Royston, Patrick, additional, and Meade, Angela, additional

Published
2022
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47. Genome-Wide Meta-Analysis Identifies Variants in DSCAM and PDLIM3 That Correlate with Efficacy Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib

Author

Diekstra, Meta H.M., Swen, Jesse J., van der Zanden, Loes F.M., Vermeulen, Sita H., Boven, Epie, Mathijssen, Ron H.J., Fukunaga, Koya, Mushiroda, Taisei, Hongo, Fumiya, Oosterwijk, Egbert, Cambon-Thomsen, Anne, Castellano, Daniel, Fritsch, Achim, Donas, Jesus Garcia, Rodriguez-Antona, Cristina, Ruijtenbeek, Rob, Radu, Marius T., Eisen, Tim, Junker, Kerstin, Roessler, Max, Jaehde, Ulrich, Miki, Tsuneharu, Böhringer, Stefan, Kubo, Michiaki, Kiemeney, Lambertus A.L.M., Guchelaar, Henk Jan, Diekstra, Meta H.M., Swen, Jesse J., van der Zanden, Loes F.M., Vermeulen, Sita H., Boven, Epie, Mathijssen, Ron H.J., Fukunaga, Koya, Mushiroda, Taisei, Hongo, Fumiya, Oosterwijk, Egbert, Cambon-Thomsen, Anne, Castellano, Daniel, Fritsch, Achim, Donas, Jesus Garcia, Rodriguez-Antona, Cristina, Ruijtenbeek, Rob, Radu, Marius T., Eisen, Tim, Junker, Kerstin, Roessler, Max, Jaehde, Ulrich, Miki, Tsuneharu, Böhringer, Stefan, Kubo, Michiaki, Kiemeney, Lambertus A.L.M., and Guchelaar, Henk Jan

Abstract

Individual response to sunitinib in metastatic renal cell carcinoma (mRCC) patients is highly variable. Earlier, sunitinib outcome was related to single nucleotide polymorphisms (SNPs) in CYP3A5 and ABCB1. Our aim is to provide novel insights into biological mechanisms underlying sunitinib action. We included mRCC patients from the European EuroTARGET consortium (n = 550) and the RIKEN cohort in Japan (n = 204) which were analysed separately and in a meta-analysis of genome-wide association studies (GWAS). SNPs were tested for association with progression-free survival (PFS) and overall survival (OS) using Cox regression. Summary statistics were combined using a fixed effect meta-analysis. SNP rs28520013 in PDLIM3 and the correlated SNPs rs2205096 and rs111356738 both in DSCAM, showed genome-wide significance (p < 5 × 10−8 ) with PFS and OS in the meta-analysis. The variant T-allele of rs28520013 associated with an inferior PFS of 5.1 months compared to 12.5 months in non-carriers (p = 4.02 × 10−10, HR = 7.26). T-allele carriers of rs28520013 showed an inferior OS of 6.9 months versus 30.2 months in non-carriers (p = 1.62 × 10−8, HR = 5.96). In this GWAS we identified novel genetic variants in PDLIM3 and DSCAM that impact PFS and OS in mRCC patients receiving sunitinib. The underlying link between the identified genes and the molecular mechanisms of sunitinib action needs to be elucidated.

Published
2022

49. Description of the EuroTARGET cohort: A European collaborative project on TArgeted therapy in renal cell cancer—GEnetic- and tumor-related biomarkers for response and toxicity

Author

van der Zanden, Loes F.M., Vermeulen, Sita H., Oskarsdottir, Arna, Maurits, Jake S.F., Diekstra, Meta H.M., Ambert, Valentin, Cambon-Thomsen, Anne, Castellano, Daniel, Fritsch, Achim, Garcia Donas, Jesus, Guarch Troyas, Rosa, Guchelaar, Henk-Jan, Hartmann, Arndt, Hulsbergen-van de Kaa, Christina, Jaehde, Ulrich, Junker, Kerstin, Martinez-Cardus, Anna, Masson, Gisli, Oosterwijk-Wakka, Jeannette, Radu, Marius T., Rafnar, Thorunn, Rodriguez-Antona, Cristina, Roessler, Max, Ruijtenbeek, Rob, Stefansson, Kari, Warren, Anne, Wessels, Lodewyk, Eisen, Tim, Kiemeney, Lambertus A.L.M., and Oosterwijk, Egbert

Published
2017
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50. Results from the randomised UKLS trial: Lung cancer mortality reduction by LDCT screening confirmed in an international meta-analysis

Author

Field, John K., Vulkan, Daniel, Davies, Micahel P.A., Baldwin, David R., Brain, Kate E., Devaraj, Anand, Eisen, Tim, Holemans, John A., Kavanagh, Terry, Kerr, Keith M., Ledson, Martin, Lifford, Kate J., McRonald, Fiona E., Nair, Arjun, Page, Richard D., Parmar, Mahesk K.B., Rassi, Doris M., Rintoul, Robert C., Wald, Nicolas J., Weler, David, Whynes, David K., Williamson, Paul R., Yadegarfar, Casham, Gabe, Rhian, and Duffy, Stephen W.

Abstract

Background\ud \ud The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial.\ud Methods\ud \ud From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50–75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence.\ud Findings\ud \ud 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1–7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41–1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76–0.92) from nine eligible trials.\ud Interpretation\ud \ud The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups.\ud Funding\ud \ud NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.\ud Keywords\ud Lung Cancer\ud CT Screening\ud Lung Cancer Mortality\ud Meta-analysis

Published
2021

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