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1. A modified Delphi study to develop a practical guide for selecting patients with prostate cancer for active surveillance

Author

Samuel W. D. Merriel, Daniel Moon, Phil Dundee, Niall Corcoran, Peter Carroll, Alan Partin, Joseph A. Smith, Freddie Hamdy, Caroline Moore, Piet Ost, and Tony Costello

Subjects
Prostate cancer, Cancer treatment protocols, Patient selection, Active surveillance, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Active surveillance (AS) is a management option for men diagnosed with lower risk prostate cancer. There is wide variation in all aspects of AS internationally, from patient selection to investigations and follow-up intervals, and a lack of clear evidence on the optimal approach to AS. This study aimed to provide guidance for clinicians from an international panel of prostate cancer experts. Methods A modified Delphi approach was undertaken, utilising two rounds of online questionnaires followed by a face-to-face workshop. Participants indicated their level of agreement with statements relating to patient selection for AS via online questionnaires on a 7-point Likert scale. Factors not achieving agreement were iteratively developed between the two rounds of questionnaires. Draft statements were presented at the face-to-face workshop for discussion and consensus building. Results 12 prostate cancer experts (9 urologists, 2 academics, 1 radiation oncologist) participated in this study from a range of geographical regions (4 USA, 4 Europe, 4 Australia). Complete agreement on statements presented to the participants was 29.4% after Round One and 69.0% after Round Two. Following robust discussions at the face-to-face workshop, agreement was reached on the remaining statements. PSA, PSA density, Multiparametric MRI, and systematic biopsy (with or without targeted biopsy) were identified as minimum diagnostic tests required upon which to select patients to recommend AS as a treatment option for prostate cancer. Patient factors and clinical parameters that identified patients appropriate to potentially receive AS were agreed. Genetic and genomic testing was not recommended for use in clinical decision-making regarding AS. Conclusions The lack of consistency in the practice of AS for men with lower risk prostate cancer between and within countries was reflected in this modified Delphi study. There are, however, areas of common practice and agreement from which clinicians practicing in the current environment can use to inform their clinical practice to achieve the best outcomes for patients.

Published
2021
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2. Placebo comparator group selection and use in surgical trials: the ASPIRE project including expert workshop

Author

David J Beard, Marion K Campbell, Jane M Blazeby, Andrew J Carr, Charles Weijer, Brian H Cuthbertson, Rachelle Buchbinder, Thomas Pinkney, Felicity L Bishop, Jonathan Pugh, Sian Cousins, Ian Harris, L Stefan Lohmander, Natalie Blencowe, Katie Gillies, Pascal Probst, Carol Brennan, Andrew Cook, Dair Farrar-Hockley, Julian Savulescu, Richard Huxtable, Amar Rangan, Irene Tracey, Peter Brocklehurst, Manuela L Ferreira, Jon Nicholl, Barnaby C Reeves, Freddie Hamdy, Samuel CS Rowley, Naomi Lee, and Jonathan A Cook

Subjects
placebo control, rct, surgery, invasive, procedure, ethics, Medical technology, R855-855.5
Abstract

Background: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. Objectives: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. Design: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. Setting: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. Results: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. Conclusions: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. Limitations: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. Future work: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. Funding: Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council–National Institute for Health Research Methodology Research programme.

Published
2021
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3. Strategies adopted by men to deal with uncertainty and anxiety when following an active surveillance/monitoring protocol for localised prostate cancer and implications for care: a longitudinal qualitative study embedded within the ProtecT trial

Author

Julia Wade, Vincent J Gnanapragasam, David Neal, Athene Lane, Edward Rowe, Freddie Hamdy, James Catto, Emma Turner, David Gillatt, Eleanor Walsh, Derek Rosario, Roger Kockelbergh, Alan Paul, Peter Holding, Howard Kynaston, Owen Hughes, Prasad Bollina, Alan Doherty, and Edgar Paez

Subjects
Medicine
Published
2020
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4. Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data.

Author

Niedzica Camacho, Peter Van Loo, Sandra Edwards, Jonathan D Kay, Lucy Matthews, Kerstin Haase, Jeremy Clark, Nening Dennis, Sarah Thomas, Barbara Kremeyer, Jorge Zamora, Adam P Butler, Gunes Gundem, Sue Merson, Hayley Luxton, Steve Hawkins, Mohammed Ghori, Luke Marsden, Adam Lambert, Katalin Karaszi, Gill Pelvender, Charlie E Massie, Zsofia Kote-Jarai, Keiran Raine, David Jones, William J Howat, Steven Hazell, Naomi Livni, Cyril Fisher, Christopher Ogden, Pardeep Kumar, Alan Thompson, David Nicol, Erik Mayer, Tim Dudderidge, Yongwei Yu, Hongwei Zhang, Nimish C Shah, Vincent J Gnanapragasam, CRUK-ICGC Prostate Group, William Isaacs, Tapio Visakorpi, Freddie Hamdy, Dan Berney, Clare Verrill, Anne Y Warren, David C Wedge, Andrew G Lynch, Christopher S Foster, Yong Jie Lu, G Steven Bova, Hayley C Whitaker, Ultan McDermott, David E Neal, Rosalind Eeles, Colin S Cooper, and Daniel S Brewer

Subjects
Genetics, QH426-470
Abstract

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.

Published
2017
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5. Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells.

Author

Siamak Redhai, Josephine E E U Hellberg, Mark Wainwright, Sumeth W Perera, Felix Castellanos, Benjamin Kroeger, Carina Gandy, Aaron Leiblich, Laura Corrigan, Thomas Hilton, Benjamin Patel, Shih-Jung Fan, Freddie Hamdy, Deborah C I Goberdhan, and Clive Wilson

Subjects
Genetics, QH426-470
Abstract

Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic β-cells, BMP signalling is also implicated in the control of secretion.

Published
2016
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6. Associations between an obesity related genetic variant (FTO rs9939609) and prostate cancer risk.

Author

Sarah J Lewis, Ali Murad, Lina Chen, George Davey Smith, Jenny Donovan, Tom Palmer, Freddie Hamdy, David Neal, J Athene Lane, Michael Davis, Angela Cox, and Richard M Martin

Subjects
Medicine, Science
Abstract

Observational studies suggest that obese men have a lower risk of incident prostate cancer, but an increased risk of advanced and fatal cancers. These observations could be due to confounding, detection bias, or a biological effect of obesity. Genetic studies are less susceptible to confounding than observational epidemiology and can suggest how associations between phenotypes (such as obesity) and diseases arise. To determine whether the associations between obesity and prostate cancer are causal, we conducted a genetic association study of the relationship between a single nucleotide polymorphism known to be associated with obesity (FTO rs9939609) and prostate cancer. Data are from a population-based sample of 1550 screen-detected prostate cancers, 1815 age- and general practice matched controls with unrestricted prostate specific antigen (PSA) values and 1175 low-PSA controls (PSA

Published
2010
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8. Organochlorine pesticide exposure and risk of prostate cancer development and progression: a systematic review [version 1; peer review: 2 approved with reservations]

Author

Laurent Brureau, Luc Multigner, Freddie Hamdy, Pascal Blanchet, and Richard Bryant

Subjects
Systematic Review, Articles, Organochlorine pesticides, prostate cancer, biochemical recurrence, advanced disease
Abstract

Background: There is an increasing body of evidence linking the exposure of an individual to pesticides such as organochlorine pesticides (OPCs) and an increased risk of developing diseases such as cancer. Exposure to OPCs has been suggested to increase the risk of developing hormone-dependant cancers such as prostate cancer (PCa). However, there is a relative paucity of information about the influence of exposure to these pesticides on the evolution of PCa, including risk of tumour development, progression to metastasis, and disease recurrence following therapy. Methods: We used several databases such as PubMed MEDLINE Database, Web of Science, and Scopus, in order to conduct a systematic review of the available epidemiological data implicating an association between exposure to OCPs and biochemical recurrence (BCR) of PCa. We searched all peer-reviewed articles published up to July 31 st 2020. Pre-defined eligibility criteria for the inclusion of studies were that they be original studies, reviews, previous meta-analyses, or case–control or cohort studies. Results: Agent Orange is the most widely-studied OCP in the context of any possible causal role in the recurrence of PCa following radical prostatectomy, or in the progression to advanced disease. Only two studies didn’t demonstrate a significant association between exposure to OCPs and subsequent BCR following radical prostatectomy. Another study identified a significant association between exposure to Oxychlordane and PCB44 and progression to advanced PCa. Conclusion: This review confirmed a relative lack of high-quality evidence regarding this topic. However, the available evidence to date suggests the presence of a potential causal relationship between exposure to OPCs and PCa development and progression.

Published
2021
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9. AA9int: SNP interaction pattern search using non-hierarchical additive model set.

Author

Hui-Yi Lin, Po-Yu Huang, Dung-Tsa Chen, Heng-Yuan Tung, Thomas A. Sellers, Julio M. Pow-Sang, Rosalind A. Eeles, Doug Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G. Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A. Haiman, Johanna Schleutker, Børge G. Nordestgaard, Ruth C. Travis, Freddie Hamdy, David E. Neal, Nora Pashayan, Kay-Tee Khaw, Janet L. Stanford, William J. Blot, Stephen N. Thibodeau, Christiane Maier, Adam S. Kibel, Cezary Cybulski, Lisa A. Cannon-Albright, Hermann Brenner, Radka Kaneva, Jyotsna Batra, Manuel R. Teixeira, Hardev Pandha, Yong-Jie Lu, The PRACTICAL Consortium, and Jong Y. Park

Published
2018
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10. SNP interaction pattern identifier (SIPI): an intensive search for SNP-SNP interaction patterns.

Author

Hui-Yi Lin, Dung-Tsa Chen, Po-Yu Huang, Yung-Hsin Liu, Augusto Ochoa, Jovanny Zabaleta, Donald Mercante, Zhide Fang, Thomas A. Sellers, Julio M. Pow-Sang, Chia-Ho Cheng, Rosalind A. Eeles, Doug Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G. Giles, Fredrik Wiklund, Henrik Gronberg, Christopher A. Haiman, Johanna Schleutker, Børge G. Nordestgaard, Ruth C. Travis, Freddie Hamdy, Nora Pashayan, Kay-Tee Khaw, Janet L. Stanford, William J. Blot, Stephen N. Thibodeau, Christiane Maier, Adam S. Kibel, Cezary Cybulski, Lisa A. Cannon-Albright, Hermann Brenner, Radka Kaneva, Jyotsna Batra, Manuel R. Teixeira, Hardev Pandha, Yong-Jie Lu, The PRACTICAL Consortium, and Jong Y. Park

Published
2017
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12. Data from LYRIC/AEG-1 Is Targeted to Different Subcellular Compartments by Ubiquitinylation and Intrinsic Nuclear Localization Signals

Author

David E. Neal, Hayley C. Whitaker, Freddie Hamdy, Hing Leung, Kanagasabai Sahadevan, Ian G. Mills, Anne Y. Warren, Joanne Girling, and Hayley J. Thirkettle

Abstract

Purpose: LYRIC/AEG-1 has been reported to influence breast cancer survival and metastases, and its altered expression has been found in a number of cancers. The cellular function of LYRIC/AEG-1 has previously been related to its subcellular distribution in cell lines. LYRIC/AEG-1 contains three uncharacterized nuclear localization signals (NLS), which may regulate its distribution and, ultimately, function in cells.Experimental Design: Immunohistochemistry of a human prostate tissue microarray composed of 179 prostate cancer and 24 benign samples was used to assess LYRIC/AEG-1 distribution. Green fluorescent protein-NLS fusion proteins and deletion constructs were used to show the ability of LYRIC/AEG-1 NLS to target green fluorescent protein from the cytoplasm to the nucleus. Immunoprecipitation and Western blotting were used to show posttranslational modification of LYRIC/AEG-1 NLS regions.Results: Using a prostate tissue microarray, significant changes in the distribution of LYRIC/AEG-1 were observed in prostate cancer as an increased cytoplasmic distribution in tumors compared with benign tissue. These differences were most marked in high grade and aggressive prostate cancers and were associated with decreased survival. The COOH-terminal extended NLS-3 (amino acids 546-582) is the predominant regulator of nuclear localization, whereas extended NLS-1 (amino acids 78-130) regulates its nucleolar localization. Within the extended NLS-2 region (amino acids 415-486), LYRIC/AEG-1 can be modified by ubiquitin almost exclusively within the cytoplasm.Conclusions: Changes in LYRIC/AEG-1 subcellular distribution can predict Gleason grade and survival. Two lysine-rich regions (NLS-1 and NLS-3) can target LYRIC/AEG-1 to subcellular compartments whereas NLS-2 is modified by ubiquitin in the cytoplasm.

Published
2023

14. Supplementary Figure 3 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Norman J. Maitland, Claire E. Lewis, Magnus Essand, Peter Hoskin, Lindsay Georgopoulos, Nicola J. Brown, Freddie Hamdy, Roshna Mistry, Bernard Burke, Neil Cross, Julian Burton, Craig Murdoch, Fiona J. Morrow, Seth B. Coffelt, Hsin-Yu Fang, Simon D. Scott, Athina Giannoudis, and Munitta Muthana

Abstract

Supplementary Figure 3 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Published
2023

15. Supplementary Figure 1 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Norman J. Maitland, Claire E. Lewis, Magnus Essand, Peter Hoskin, Lindsay Georgopoulos, Nicola J. Brown, Freddie Hamdy, Roshna Mistry, Bernard Burke, Neil Cross, Julian Burton, Craig Murdoch, Fiona J. Morrow, Seth B. Coffelt, Hsin-Yu Fang, Simon D. Scott, Athina Giannoudis, and Munitta Muthana

Abstract

Supplementary Figure 1 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Published
2023

17. Data from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Norman J. Maitland, Claire E. Lewis, Magnus Essand, Peter Hoskin, Lindsay Georgopoulos, Nicola J. Brown, Freddie Hamdy, Roshna Mistry, Bernard Burke, Neil Cross, Julian Burton, Craig Murdoch, Fiona J. Morrow, Seth B. Coffelt, Hsin-Yu Fang, Simon D. Scott, Athina Giannoudis, and Munitta Muthana

Abstract

New therapies are required to target hypoxic areas of tumors as these sites are highly resistant to conventional cancer therapies. Monocytes continuously extravasate from the bloodstream into tumors where they differentiate into macrophages and accumulate in hypoxic areas, thereby opening up the possibility of using these cells as vehicles to deliver gene therapy to these otherwise inaccessible sites. We describe a new cell-based method that selectively targets an oncolytic adenovirus to hypoxic areas of prostate tumors. In this approach, macrophages were cotransduced with a hypoxia-regulated E1A/B construct and an E1A-dependent oncolytic adenovirus, whose proliferation is restricted to prostate tumor cells using prostate-specific promoter elements from the TARP, PSA, and PMSA genes. When such cotransduced cells reach an area of extreme hypoxia, the E1A/B proteins are expressed, thereby activating replication of the adenovirus. The virus is subsequently released by the host macrophage and infects neighboring tumor cells. Following systemic injection into mice bearing subcutaneous or orthotopic prostate tumors, cotransduced macrophages migrated into hypoxic tumor areas, upregulated E1A protein, and released multiple copies of adenovirus. The virus then infected neighboring cells but only proliferated and was cytotoxic in prostate tumor cells, resulting in the marked inhibition of tumor growth and reduction of pulmonary metastases. This novel delivery system employs 3 levels of tumor specificity: the natural “homing” of macrophages to hypoxic tumor areas, hypoxia-induced proliferation of the therapeutic adenovirus in host macrophages, and targeted replication of oncolytic virus in prostate tumor cells. Cancer Res; 71(5); 1805–15. ©2011 AACR.

Published
2023

19. Supplementary Figure 5 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Norman J. Maitland, Claire E. Lewis, Magnus Essand, Peter Hoskin, Lindsay Georgopoulos, Nicola J. Brown, Freddie Hamdy, Roshna Mistry, Bernard Burke, Neil Cross, Julian Burton, Craig Murdoch, Fiona J. Morrow, Seth B. Coffelt, Hsin-Yu Fang, Simon D. Scott, Athina Giannoudis, and Munitta Muthana

Abstract

Supplementary Figure 5 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Published
2023

21. Supplementary Figure 2 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Norman J. Maitland, Claire E. Lewis, Magnus Essand, Peter Hoskin, Lindsay Georgopoulos, Nicola J. Brown, Freddie Hamdy, Roshna Mistry, Bernard Burke, Neil Cross, Julian Burton, Craig Murdoch, Fiona J. Morrow, Seth B. Coffelt, Hsin-Yu Fang, Simon D. Scott, Athina Giannoudis, and Munitta Muthana

Abstract

Supplementary Figure 2 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Published
2023

22. Supplementary Figure 4 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Author

Norman J. Maitland, Claire E. Lewis, Magnus Essand, Peter Hoskin, Lindsay Georgopoulos, Nicola J. Brown, Freddie Hamdy, Roshna Mistry, Bernard Burke, Neil Cross, Julian Burton, Craig Murdoch, Fiona J. Morrow, Seth B. Coffelt, Hsin-Yu Fang, Simon D. Scott, Athina Giannoudis, and Munitta Muthana

Abstract

Supplementary Figure 4 from Use of Macrophages to Target Therapeutic Adenovirus to Human Prostate Tumors

Published
2023

23. Cost-effectiveness analysis of prostate cancer screening in the UK:A decision model analysis based on the CAP trial

Author

Edna Keeney, Sabina Sanghera, Richard M. Martin, Roman Gulati, Fredrik Wiklund, Eleanor I. Walsh, Jenny L. Donovan, Freddie Hamdy, David E. Neal, J. Athene Lane, Emma L. Turner, Howard Thom, and Mark S. Clements

Subjects
Male, Adult, Pharmacology, Cost-Benefit Analysis, Health Policy, Public Health, Environmental and Occupational Health, Prostatic Neoplasms, Middle Aged, Prostate-Specific Antigen, State Medicine, United Kingdom, Humans, Mass Screening, Quality-Adjusted Life Years, ICEP, Early Detection of Cancer
Abstract

Background and ObjectiveMost guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK.MethodsWe used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective.ResultsAll screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies.ConclusionsOf the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.

Published
2022

24. PD03-12 COVID-19 DISRUPTION TO PROSTATE CANCER MANAGEMENT IN A UK TERTIARY REFERRAL CENTRE

Author

Matthew Byrne, Nithesh Ranasinha, Claudia Mercader, Mutie Raslan, Caroline Gordon, Kate Hutton, Sarah Head, Ruth MacPherson, Charlotte Minett, Louise Flaxman, Jessica Smyth, Natasha Young, Fergus Gleeson, Clare Verrill, Richard Colling, Francisco Lopez, Richard Bell, Tom Leslie, Richard Bryant, Freddie Hamdy, and Alastair D. Lamb

Subjects
Urology
Published
2022

25. MP51-13 FLUORINE-18 (18F) PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) POSITRON EMISSION TOMOGRAPHY (PET) AND THE DIAGNOSIS AND STAGING OF PRIMARY PROSTATE CANCER (PCA)

Author

Matthew Byrne, Nithesh Ranasinha, Claudia Mercader, Mutie Raslan, Francesca Lewis, Stefanos Gorgoraptis, Ganesh Sathanapally, Ana Catarina Lopes Vieira, Golebka Jedrzej, Bryony Peiris, Mark Tuthill, Andrew Protheroe, Philip Camilleri, Phil Turner, Gerard Andrade, Saiful Miah, Tom Leslie, Richard Bryant, Freddie Hamdy, Ruth MacPherson, Fergus Gleeson, and Alastair D. Lamb

Subjects
Urology
Published
2022

27. Precision surgery: the role of intra-operative real-time image guidance - outcomes from a multidisciplinary European consensus conference

Author

Paolo, Dell'Oglio, Elio, Mazzone, Tessa, Buckle, Tobias, Maurer, Nassir, Navab, Matthias N, van Oosterom, Clare, Schilling, Max Jh, Witjes, Alexander L, Vahrmeijer, Joachim, Klode, Boris, Vojnovic, Alexandre, Mottrie, Henk G, van der Poel, Freddie, Hamdy, and Fijs Wb, van Leeuwen

Subjects
Meeting Report
Abstract

Developments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of image-guided surgery is to improve surgical outcome, the specific motives and goals that drive can differ between the different expert groups. To establish the current and future role of intra-operative image guidance within the field of image-guided surgery a Delphi consensus survey was conducted during the 2(nd) European Congress on Image-guided surgery. This multidisciplinary survey included questions on the conceptual potential and clinical value of image-guided surgery and was aimed at defining specific areas of research and development in the field in order to stimulate further advances towards precision surgery. Obtained results based on questionnaires filled in by 56 panel experts (clinicians: N=30, researchers: N=20 and industry: N=6) were discussed during a dedicated expert discussion session during the conference. The outcome of this Delphi consensus is indicative of the potential improvements offered by image-guided surgery and of the need for further research in this emerging field, that can be enriched by the identification of reliable molecular targets.

Published
2021

28. Abstract 2171: The spatial landscape of clonal somatic mutations in benign and malignant tissue

Author

Andrew Erickson, Emelie Berglund, Mengxiao He, Maja Marklund, Reza Mirzazadeh, Niklas Schultz, Linda Kvastad, Alma Andersson, Ludvig Bergenstråhle, Joseph Bergenstråhle, Ludvig Larsson, Alia Shamikh, Elisa Basmaci, Teresita Diaz De Ståhl, Timothy Rajakumar, Kim Thrane, Andrew L. Ji, Paul A. Khavari, Firaz Tarish, Anna Tanoglidi, Jonas Maaskola, Richard Colling, Tuomas Mirtti, Freddie Hamdy, Dan J. Woodcock, Thomas Helleday, Ian G. Mills, Alastair D. Lamb, and Joakim Lundenberg

Subjects
Cancer Research, Oncology
Abstract

Introduction: Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. In order to obtain spatial information of clonal genetic events, prior studies have used methods such as laser capture microdissection, which results in assessment of small regions or even single cells. These studies have an inherent bias as a limited number of regions per tissue section can be retrieved and examined. Furthermore, because investigators have selected such regions based on morphology, previous studies have limited their analyses to histologically defined tumour areas while excluding regions populated by benign cells. The possibility to perform unsupervised genome and tissue-wide analysis would therefore provide an important contribution to delineate clonal events. We sought study spatial genome integrity in situ to gain molecular insight into clonal relationships. Materials and Methods: We employed spatially resolved transcriptomics (Visium, 10x Genomics) to infer spatial copy number variations in >120 000 spatial regions across multiple organs, including three whole axial prostates and additional tissues from skin, breast and brain tumors. We used this information to deduce clonal relationships between regions harboring 5-20 cells. Results: We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. We perform an in-depth spatial analysis of cancers that includes an unprecedented interrogation of up to 50,000 tissue domains in a single patient, and 120,000 tissue domains across 10 patients. In a prostate section, we observed that many CNVs occurred in histologically benign luminal epithelial cells, most notably in chromosomes 8 and 10. This clone constituted a region of exclusively benign acinar cells branching off a duct lined by largely copy neutral cells. The changes in these cells were shared with the nearby intermediate risk prostate cancer cells in the same tissue section. We observed similar findings in another patient’s cutaneous squamous cell carcinoma (cSCC), wherein benign squamous epithelial had alterations in chromosomes 1 and 12 that were shared with nearby cSCC. Our results suggest a model for how genomic instability arises in histo-pathologically benign tissue that may represent early events in cancer evolution. Furthermore the spatial information allowed us to identify small clonal units not evident from morphology and hence would be overlooked by pathologists. Conclusions: We present the first large-scale, comprehensive atlas of genomic evolution at high spatial resolution in prostate cancer. Our study adds an important new approach to the armamentarium of cancer molecular pathology. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for focal therapy in prostate cancer. Citation Format: Andrew Erickson, Emelie Berglund, Mengxiao He, Maja Marklund, Reza Mirzazadeh, Niklas Schultz, Linda Kvastad, Alma Andersson, Ludvig Bergenstråhle, Joseph Bergenstråhle, Ludvig Larsson, Alia Shamikh, Elisa Basmaci, Teresita Diaz De Ståhl, Timothy Rajakumar, Kim Thrane, Andrew L. Ji, Paul A. Khavari, Firaz Tarish, Anna Tanoglidi, Jonas Maaskola, Richard Colling, Tuomas Mirtti, Freddie Hamdy, Dan J. Woodcock, Thomas Helleday, Ian G. Mills, Alastair D. Lamb, Joakim Lundenberg. The spatial landscape of clonal somatic mutations in benign and malignant tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2171.

Published
2022

29. Author Correction: Large-scale transcriptome-wide association study identifies new prostate cancer risk regions

Author

Manuela Gago, Stella Koutros, Børge Nordestgaard, Nora Pashayan, Nicholas Mancuso, Peter Kraft, Paul Townsend, Rosalind Eeles, Frank Claessens, Davor Lessel, Hermann Brenner, Freddie Hamdy, Johanna Schleutker, Jyotsna Batra, and Fredrick Schumacher

Subjects
History, Science, General Physics and Astronomy, 02 engineering and technology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Author Correction, Association (psychology), lcsh:Science, 030304 developmental biology, Prostate cancer risk, 0303 health sciences, Multidisciplinary, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Published Erratum, General Chemistry, 021001 nanoscience & nanotechnology, Genealogy, Spelling, 3. Good health, Scale (social sciences), ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, lcsh:Q, 0210 nano-technology
Abstract

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, In the original HTML version of this Article, the order of authors within the author list was incorrect. The consortium PRACTICAL consortium was incorrectly listed after Bogdan Pasaniuc and should have been listed after Kathryn L. Penney. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.

Published
2019

31. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin Jaiswal, Michael Curran, Tina C. Albershardt, Anshika Bajaj, Jacob F. Archer, Rebecca S. Reeves, Lisa Y. Ngo, Peter Berglund, Jan ter Meulen, Caroline Denis, Hormas Ghadially, Thomas Arnoux, Fabien Chanuc, Nicolas Fuseri, Robert W. Wilkinson, Nicolai Wagtmann, Yannis Morel, Pascale Andre, Michael B. Atkins, Matteo S. Carlino, Antoni Ribas, John A. Thompson, Toni K. Choueiri, F. Stephen Hodi, Wen-Jen Hwu, David F. McDermott, Victoria Atkinson, Jonathan S. Cebon, Bernie Fitzharris, Michael B. Jameson, Catriona McNeil, Andrew G. Hill, Eric Mangin, Malidi Ahamadi, Marianne van Vugt, Mariëlle van Zutphen, Nageatte Ibrahim, Georgina V. Long, Robyn Gartrell, Zoe Blake, Ines Simoes, Yichun Fu, Takuro Saito, Yingzhi Qian, Yan Lu, Yvonne M. Saenger, Sadna Budhu, Olivier De Henau, Roberta Zappasodi, Kyle Schlunegger, Bruce Freimark, Jeff Hutchins, Christopher A. Barker, Jedd D. Wolchok, Taha Merghoub, Elena Burova, Omaira Allbritton, Peter Hong, Jie Dai, Jerry Pei, Matt Liu, Joel Kantrowitz, Venus Lai, William Poueymirou, Douglas MacDonald, Ella Ioffe, Markus Mohrs, William Olson, Gavin Thurston, Cristian Capasso, Federica Frascaro, Sara Carpi, Siri Tähtinen, Sara Feola, Manlio Fusciello, Karita Peltonen, Beatriz Martins, Madeleine Sjöberg, Sari Pesonen, Tuuli Ranki, Lukasz Kyruk, Erkko Ylösmäki, Vincenzo Cerullo, Fabio Cerignoli, Biao Xi, Garret Guenther, Naichen Yu, Lincoln Muir, Leyna Zhao, Yama Abassi, Víctor Cervera-Carrascón, Mikko Siurala, João Santos, Riikka Havunen, Suvi Parviainen, Akseli Hemminki, Angus Dalgleish, Satvinder Mudan, Mark DeBenedette, Ana Plachco, Alicia Gamble, Elizabeth W. Grogan, John Krisko, Irina Tcherepanova, Charles Nicolette, Pooja Dhupkar, Ling Yu, Eugenie S. Kleinerman, Nancy Gordon, Italia Grenga, Lauren Lepone, Sofia Gameiro, Karin M. Knudson, Massimo Fantini, Kwong Tsang, James Hodge, Renee Donahue, Jeffrey Schlom, Elizabeth Evans, Holm Bussler, Crystal Mallow, Christine Reilly, Sebold Torno, Maria Scrivens, Cathie Foster, Alan Howell, Leslie Balch, Alyssa Knapp, John E. Leonard, Mark Paris, Terry Fisher, Siwen Hu-Lieskovan, Ernest Smith, Maurice Zauderer, William Fogler, Marilyn Franklin, Matt Thayer, Dan Saims, John L. Magnani, Jian Gong, Michael Gray, George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose, Taylor H. Schreiber, Sofia R. Gameiro, Paul E. Clavijo, Clint T. Allen, James W. Hodge, Kwong Y. Tsang, Jane Grogan, Nicholas Manieri, Eugene Chiang, Patrick Caplazi, Mahesh Yadav, Patrick Hagner, Hsiling Chiu, Michelle Waldman, Anke Klippel, Anjan Thakurta, Michael Pourdehnad, Anita Gandhi, Ian Henrich, Laura Quick, Rob Young, Margaret Chou, Andrew Hotson, Stephen Willingham, Po Ho, Carmen Choy, Ginna Laport, Ian McCaffery, Richard Miller, Kimberly A. Tipton, Kenneth R. Wong, Victoria Singson, Chihunt Wong, Chanty Chan, Yuanhiu Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, James West, Bryan A. Irving, Ritika Jaini, Matthew Loya, Charis Eng, Melissa L. Johnson, Alex A. Adjei, Mateusz Opyrchal, Suresh Ramalingam, Pasi A. Janne, George Dominguez, Dmitry Gabrilovich, Laura de Leon, Jeannette Hasapidis, Scott J. Diede, Peter Ordentlich, Scott Cruickshank, Michael L. Meyers, Matthew D. Hellmann, Pawel Kalinski, Amer Zureikat, Robert Edwards, Ravi Muthuswamy, Nataša Obermajer, Julie Urban, Lisa H. Butterfield, William Gooding, Herbert Zeh, David Bartlett, Olga Zubkova, Larissa Agapova, Marina Kapralova, Liudmila Krasovskaia, Armen Ovsepyan, Maxim Lykov, Artem Eremeev, Vladimir Bokovanov, Olga Grigoryeva, Andrey Karpov, Sergey Ruchko, Alexandr Shuster, Danny N. Khalil, Luis Felipe Campesato, Yanyun Li, Adam S. Lazorchak, Troy D. Patterson, Yueyun Ding, Pottayil Sasikumar, Naremaddepalli Sudarshan, Nagaraj Gowda, Raghuveer Ramachandra, Dodheri Samiulla, Sanjeev Giri, Rajesh Eswarappa, Murali Ramachandra, David Tuck, Timothy Wyant, Jasmin Leshem, Xiu-fen Liu, Tapan Bera, Masaki Terabe, Birgit Bossenmaier, Gerhard Niederfellner, Yoram Reiter, Ira Pastan, Leiming Xia, Yang Xia, Yangyang Hu, Yi Wang, Yangyi Bao, Fu Dai, Shiang Huang, Elaine Hurt, Robert E. Hollingsworth, Lawrence G. Lum, Alfred E. Chang, Max S. Wicha, Qiao Li, Thomas Mace, Neil Makhijani, Erin Talbert, Gregory Young, Denis Guttridge, Darwin Conwell, Gregory B. Lesinski, Rodney JM Macedo Gonzales, Austin P. Huffman, Ximi K. Wang, Ran Reshef, Andy MacKinnon, Jason Chen, Matt Gross, Gisele Marguier, Peter Shwonek, Natalija Sotirovska, Susanne Steggerda, Francesco Parlati, Amani Makkouk, Mark K. Bennett, Ethan Emberley, Tony Huang, Weiqun Li, Silinda Neou, Alison Pan, Jing Zhang, Winter Zhang, Netonia Marshall, Thomas U. Marron, Judith Agudo, Brian Brown, Joshua Brody, Christopher McQuinn, Matthew Farren, Hannah Komar, Reena Shakya, Thomas Ludwug, Y. Maurice Morillon, Scott A. Hammond, John W. Greiner, Pulak R. Nath, Anthony L. Schwartz, Dragan Maric, David D. Roberts, Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Deborah J. Wong, Manish Patel, Gerald Falchook, Shubham Pant, Patrick A. Ott, Melinda Whiteside, Amita Patnaik, John Mumm, Filip Janku, Ivan Chan, Todd Bauer, Rivka Colen, Peter VanVlasselaer, Gail L. Brown, Nizar M. Tannir, Martin Oft, Jeffrey Infante, Evan Lipson, Ajay Gopal, Sattva S. Neelapu, Philippe Armand, Stephen Spurgeon, John P. Leonard, Rachel E. Sanborn, Ignacio Melero, Thomas F. Gajewski, Matthew Maurer, Serena Perna, Andres A. Gutierrez, Raphael Clynes, Priyam Mitra, Satyendra Suryawanshi, Douglas Gladstone, Margaret K. Callahan, James Crooks, Sheila Brown, Audrey Gauthier, Marc Hillairet de Boisferon, Andrew MacDonald, Laura Rosa Brunet, William T. Rothwell, Peter Bell, James M. Wilson, Fumi Sato-Kaneko, Shiyin Yao, Shannon S. Zhang, Dennis A. Carson, Cristina Guiducci, Robert L. Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Tomoko Hayashi, Ezra E. W. Cohen, David Schaer, Yanxia Li, Julie Dobkin, Michael Amatulli, Gerald Hall, Thompson Doman, Jason Manro, Frank Charles Dorsey, Lillian Sams, Rikke Holmgaard, Krishnadatt Persaud, Dale Ludwig, David Surguladze, John S. Kauh, Ruslan Novosiadly, Michael Kalos, Kyla Driscoll, Hardev Pandha, Christy Ralph, Kevin Harrington, Brendan Curti, Wallace Akerley, Sumati Gupta, Alan Melcher, David Mansfield, David R. Kaufman, Emmett Schmidt, Mark Grose, Bronwyn Davies, Roberta Karpathy, Darren Shafren, Katerina Shamalov, Cyrille Cohen, Naveen Sharma, James Allison, Tala Shekarian, Sandrine Valsesia-Wittmann, Christophe Caux, Aurelien Marabelle, Brian M. Slomovitz, Kathleen M. Moore, Hagop Youssoufian, Marshall Posner, Poonam Tewary, Alan D. Brooks, Ya-Ming Xu, Kithsiri Wijeratne, Leslie A. A. Gunatilaka, Thomas J. Sayers, John P. Vasilakos, Tesha Alston, Simon Dovedi, James Elvecrog, Iwen Grigsby, Ronald Herbst, Karen Johnson, Craig Moeckly, Stefanie Mullins, Kristen Siebenaler, Julius SternJohn, Ashenafi Tilahun, Mark A. Tomai, Katharina Vogel, Eveline E. Vietsch, Anton Wellstein, Martin Wythes, Stefano Crosignani, Joseph Tumang, Shilpa Alekar, Patrick Bingham, Sandra Cauwenberghs, Jenny Chaplin, Deepak Dalvie, Sofie Denies, Coraline De Maeseneire, JunLi Feng, Kim Frederix, Samantha Greasley, Jie Guo, James Hardwick, Stephen Kaiser, Katti Jessen, Erick Kindt, Marie-Claire Letellier, Wenlin Li, Karen Maegley, Reece Marillier, Nichol Miller, Brion Murray, Romain Pirson, Julie Preillon, Virginie Rabolli, Chad Ray, Kevin Ryan, Stephanie Scales, Jay Srirangam, Jim Solowiej, Al Stewart, Nicole Streiner, Vince Torti, Konstantinos Tsaparikos, Xianxian Zheng, Gregory Driessens, Bruno Gomes, Manfred Kraus, Chunxiao Xu, Yanping Zhang, Giorgio Kradjian, Guozhong Qin, Jin Qi, Xiaomei Xu, Bo Marelli, Huakui Yu, Wilson Guzman, Rober Tighe, Rachel Salazar, Kin-Ming Lo, Jessie English, Laszlo Radvanyi, Yan Lan, Michael Postow, Yasin Senbabaoglu, Billel Gasmi, Hong Zhong, Cailian Liu, Daniel Hirschhorhn-Cymerman, Yuanyuan Zha, Gregory Malnassy, Noreen Fulton, Jae-Hyun Park, Wendy Stock, Yusuke Nakamura, Hongtao Liu, Xiaoming Ju, Rachelle Kosoff, Kimberly Ramos, Brandon Coder, Robert Petit, Michael Princiotta, Kyle Perry, Jun Zou, Ainhoa Arina, Christian Fernandez, Wenxin Zheng, Michael A. 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Connolly, Jason Baird, Marka Crittenden, David Friedman, Hong Xiao, Rom Leidner, Bryan Bell, Kristina Young, Michael Gough, Zhen Bian, Koby Kidder, Yuan Liu, Emily Curran, Xiufen Chen, Leticia P. Corrales, Justin Kline, Ethan G. Aguilar, Jennifer Guerriero, Alaba Sotayo, Holly Ponichtera, Alexandra Pourzia, Sara Schad, Ruben Carrasco, Suzan Lazo, Roderick Bronson, Anthony Letai, Richard S. Kornbluth, Sachin Gupta, James Termini, Elizabeth Guirado, Geoffrey W. Stone, Christina Meyer, Laura Helming, Nicholas Wilson, Robert Hofmeister, Natalie J. Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A. Fuertes Marraco, Daniel E. Speiser, Tara S. Abraham, Bo Xiang, Michael S. Magee, Scott A. Waldman, Adam E. Snook, Wojciech Blogowski, Ewa Zuba-Surma, Marta Budkowska, Daria Salata, Barbara Dolegowska, Teresa Starzynska, Leo Chan, Srinivas Somanchi, Kelsey McCulley, Dean Lee, Nico Buettner, Feng Shi, Paisley T. 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Sefrin, Lars Hillringhaus, Valeria Lifke, Alexander Lifke, Anna Skaletskaya, Jose Ponte, Thomas Chittenden, Yulius Setiady, Eva Sivado, Vincent Thomas, Meddy El Alaoui, Sébastien Papot, Charles Dumontet, Mike Dyson, John McCafferty, Said El Alaoui, Praveen K. Bommareddy, Andrew Zloza, Frederick Kohlhapp, Ann W. Silk, Sachin Jhawar, Tomas Paneque, Jenna Newman, Pedro Beltran, Felicia Cao, Bang-Xing Hong, Tania Rodriguez-Cruz, Xiao-Tong Song, Stephen Gottschalk, Hugo Calderon, Sam Illingworth, Alice Brown, Kerry Fisher, Len Seymour, Brian Champion, Emma Eriksson, Jessica Wenthe, Ann-Charlotte Hellström, Gabriella Paul-Wetterberg, Angelica Loskog, Ioanna Milenova, Magnus Ståhle, Justyna Jarblad-Leja, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Sharad Goyal, Ann Silk, Janice Mehnert, Nashat Gabrail, Jennifer Bryan, Daniel Medina, Leah Mitchell, Kader Yagiz, Fernando Lopez, Daniel Mendoza, Anthony Munday, Harry Gruber, Douglas Jolly, Steven Fuhrmann, Sasa Radoja, Wei Tan, Aldo Pourchet, Alan Frey, Ian Mohr, Matthew Mulvey, Robert H. I. Andtbacka, Merrick Ross, Sanjiv Agarwala, Kenneth Grossmann, Matthew Taylor, John Vetto, Rogerio Neves, Adil Daud, Hung Khong, Stephanie M. Meek, Richard Ungerleider, Scott Welden, Maki Tanaka, Matthew Williams, Sigrun Hallmeyer, Bernard Fox, Zipei Feng, Christopher Paustian, Carlo Bifulco, Sadia Zafar, Otto Hemminki, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Tameem Ansari, Srividya Sundararaman, Diana Roen, Paul Lehmann, Anja C. Bloom, Lewis H. Bender, Ian B. Walters, Jay A. Berzofsky, Fanny Chapelin, Eric T. Ahrens, Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Alexander Scholz, Danhui Zhang, Gilson Baia, Yann Chong Tan, Jeremy Sokolove, Dongkyoon Kim, Kevin Williamson, Xiaomu Chen, Jillian Colrain, Gregg Espiritu Santo, Ngan Nguyen, Wayne Volkmuth, Norman Greenberg, William Robinson, Daniel Emerling, Charles G. Drake, Daniel P. Petrylak, Emmanuel S. Antonarakis, Adam S. Kibel, Nancy N. Chang, Tuyen Vu, Dwayne Campogan, Heather Haynes, James B. Trager, Nadeem A. Sheikh, David I. Quinn, Peter Kirk, Murali Addepalli, Thomas Chang, Ping Zhang, Marina Konakova, Katsunobu Hagihara, Steven Pai, Laurie VanderVeen, Palakshi Obalapur, Peiwen Kuo, Phi Quach, Lawrence Fong, Deborah H. Charych, Jonathan Zalevsky, John L. Langowski, Yolanda Kirksey, Ravi Nutakki, Shalini Kolarkar, Rhoneil Pena, Ute Hoch, Stephen K. Doberstein, John Cha, Zach Mallon, Myra Perez, Amanda McDaniel, Snjezana Anand, Darrin Uecker, Richard Nuccitelli, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, Ariana N. Renrick, Menaka Thounaojam, Portia Thomas, Samuel Pellom, Anil Shanker, Duafalia Dudimah, Alan Brooks, Yu-Lin Su, Tomasz Adamus, Qifang Zhang, Sergey Nechaev, Marcin Kortylewski, Spencer Wei, Clark Anderson, Chad Tang, Jonathan Schoenhals, Efrosini Tsouko, John Heymach, Patricia de Groot, Joe Chang, Kenneth R. Hess, Adi Diab, Padmanee Sharma, David Hong, James Welsh, Andrea J. Parsons, Jardin Leleux, Stephane Ascarateil, Marie Eve Koziol, Dina Bai, Peihong Dai, Weiyi Wang, Ning Yang, Stewart Shuman, Liang Deng, Patrick Dillon, Gina Petroni, David Brenin, Kim Bullock, Walter Olson, Mark E. Smolkin, Kelly Smith, Carmel Nail, Craig L. Slingluff, Meenu Sharma, Faisal Fa’ak, Louise Janssen, Hiep Khong, Zhilan Xiao, Yared Hailemichael, Manisha Singh, Christina Vianden, Willem W. Overwijk, Andrea Facciabene, Pierini Stefano, Fang Chongyung, Stavros Rafail, Michael Nielsen, Peter Vanderslice, Darren G. Woodside, Robert V. Market, Ronald J. Biediger, Upendra K. Marathi, Kevin Hollevoet, Nick Geukens, Paul Declerck, Nathalie Joly, Laura McIntosh, Eustache Paramithiotis, Magnus Rizell, Malin Sternby, Bengt Andersson, Alex Karlsson-Parra, Rui Kuai, Lukasz Ochyl, Anna Schwendeman, James Moon, Weiwen Deng, Thomas E. Hudson, Bill Hanson, Chris S. Rae, Joel Burrill, Justin Skoble, George Katibah, Michele deVries, Peter Lauer, Thomas W. Dubensky, Xin Chen, Li Zhou, Xiubao Ren, Charu Aggarwal, Drishty Mangrolia, Roger Cohen, Gregory Weinstein, Matthew Morrow, Joshua Bauml, Kim Kraynyak, Jean Boyer, Jian Yan, Jessica Lee, Laurent Humeau, Sandra Oyola, Susan Duff, David Weiner, Zane Yang, Mark Bagarazzi, Douglas G. McNeel, Jens Eickhoff, Robert Jeraj, Mary Jane Staab, Jane Straus, Brian Rekoske, Glenn Liu, Marit Melssen, William Grosh, Nikole Varhegyi, Nadejda Galeassi, Donna H. Deacon, Elizabeth Gaughan, Maurizio Ghisoli, Minal Barve, Robert Mennel, Gladice Wallraven, Luisa Manning, Neil Senzer, John Nemunaitis, Masahiro Ogasawara, Shuichi Ota, Kaitlin M. Peace, Diane F. Hale, Timothy J. Vreeland, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Guy T. Clifton, Mark O. Hardin, Anne Toms, Na Qiao, Jennifer Litton, George E. Peoples, Elizabeth A. Mittendorf, Lila Ghamsari, Emilio Flano, Judy Jacques, Biao Liu, Jonathan Havel, Vladimir Makarov, Timothy A. Chan, Jessica B. Flechtner, John Facciponte, Stefano Ugel, Francesco De Sanctis, George Coukos, Sébastien Paris, Agnes Pottier, Laurent Levy, Bo Lu, Federica Cappuccini, Emily Pollock, Richard Bryant, Freddie Hamdy, Adrian Hill, Irina Redchenko, Hussein Sultan, Takumi Kumai, Valentyna Fesenkova, Esteban Celis, Ingrid Fernando, Claudia Palena, Justin M. David, Elizabeth Gabitzsch, Frank Jones, James L. Gulley, Mireia Uribe Herranz, Hiroshi Wada, Atsushi Shimizu, Toshihiro Osada, Satoshi Fukaya, Eiji Sasaki, Milad Abolhalaj, David Askmyr, Kristina Lundberg, Ann-Sofie Albrekt, Lennart Greiff, Malin Lindstedt, Dallas B. Flies, Tomoe Higuchi, Wojciech Ornatowski, Jaryse Harris, Sarah F. Adams, Todd Aguilera, Marjan Rafat, Laura Castellini, Hussein Shehade, Mihalis Kariolis, Dadi Jang, Rie vonEbyen, Edward Graves, Lesley Ellies, Erinn Rankin, Albert Koong, Amato Giaccia, Reham Ajina, Shangzi Wang, Jill Smith, Mariaelena Pierobon, Sandra Jablonski, Emanuel Petricoin, Louis M. Weiner, Lorcan Sherry, John Waller, Mark Anderson, Alison Bigley, Chantale Bernatchez, Cara Haymaker, Harriet Kluger, Michael Tetzlaff, Natalie Jackson, Ivan Gergel, Mary Tagliaferri, Patrick Hwu, Mario Snzol, Michael Hurwitz, Theresa Barberi, Allison Martin, Rahul Suresh, David Barakat, Sarah Harris-Bookman, Charles Drake, Alan Friedman, Sara Berkey, Stephanie Downs-Canner, Robert P. Edwards, Tyler Curiel, Kunle Odunsi, Tullia C. Bruno, Brandon Moore, Olivia Squalls, Peggy Ebner, Katherine Waugh, John Mitchell, Wilbur Franklin, Daniel Merrick, Martin McCarter, Brent Palmer, Jeffrey Kern, Dario Vignali, Jill Slansky, Anissa S. H. Chan, Xiaohong Qiu, Kathryn Fraser, Adria Jonas, Nadine Ottoson, Keith Gordon, Takashi O. Kangas, Steven Leonardo, Kathleen Ertelt, Richard Walsh, Mark Uhlik, Jeremy Graff, Nandita Bose, Ravi Gupta, Nitin Mandloi, Kiran Paul, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan, Amitabha Chaudhuri, Yu Chen, Jing Lin, Yun-bin Ye, Chun-wei Xu, Gang Chen, Zeng-qing Guo, Andrey Komarov, Alex Chenchik, Michael Makhanov, Costa Frangou, Yi Zheng, Carla Coltharp, Darryn Unfricht, Ryan Dilworth, Leticia Fridman, Linying Liu, Milind Rajopadhye, Peter Miller, Fernando Concha-Benavente, Julie Bauman, Sumita Trivedi, Raghvendra Srivastava, James Ohr, Dwight Heron, Uma Duvvuri, Seungwon Kim, Heather Torrey, Toshi Mera, Yoshiaki Okubo, Eva Vanamee, Rosemary Foster, Denise Faustman, Edward Stack, Daisuke Izaki, Kristen Beck, Dan Tong Jia, Paul Armenta, Ashley White-Stern, Douglas Marks, Bret Taback, Basil Horst, Laura Hix Glickman, David B. Kanne, Kelsey S. Gauthier, Anthony L. Desbien, Brian Francica, Justin L. Leong, Leonard Sung, Ken Metchette, Shailaja Kasibhatla, Anne Marie Pferdekamper, Lianxing Zheng, Charles Cho, Yan Feng, Jeffery M. McKenna, John Tallarico, Steven Bender, Chudi Ndubaku, Sarah M. McWhirter, Elena Gonzalez Gugel, Charles J. M. Bell, Adiel Munk, Luciana Muniz, Nina Bhardwaj, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nathalie Scholler, Catherine Yin, Pien Van der Meijs, Andrew M. Prantner, Cecile M. Krejsa, Leia Smith, Brian Johnson, Daniel Branstetter, Paul L. Stein, Juan C. Jaen, Joanne BL Tan, Ada Chen, Timothy Park, Jay P. Powers, Holly Sexton, Guifen Xu, Steve W. Young, Ulrike Schindler, Wentao Deng, David John Klinke, Hannah M. Komar, Gregory Serpa, Omar Elnaggar, Philip Hart, Carl Schmidt, Mary Dillhoff, Ming Jin, Michael C. Ostrowski, Madhuri Koti, Katrina Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Charles Graham, Andrew Craig, Julie-Ann Francis, Beatrix Kotlan, Timea Balatoni, Emil Farkas, Laszlo Toth, Mihaly Ujhelyi, Akos Savolt, Zoltan Doleschall, Szabolcs Horvath, Klara Eles, Judit Olasz, Orsolya Csuka, Miklos Kasler, Gabriella Liszkay, Eytan Barnea, Collin Blakely, Patrick Flynn, Reid Goodman, Raphael Bueno, David Sugarbaker, David Jablons, V. Courtney Broaddus, Brian West, Paul R. Kunk, Joseph M. Obeid, Kevin Winters, Patcharin Pramoonjago, Edward B. Stelow, Todd W. Bauer, Osama E. Rahma, Adam Lamble, Yoko Kosaka, Fei Huang, Kate A. Saser, Homer Adams, Christina E. Tognon, Ted Laderas, Shannon McWeeney, Marc Loriaux, Jeffery W. Tyner, Brian J. Druker, Evan F. Lind, Zhuqing Liu, Shanhong Lu, Lawrence P. Kane, Gulidanna Shayan, Julia Femel, Ryan Lane, Jamie Booth, Amanda W. Lund, Anthony Rodriguez, Victor H. Engelhard, Alessandra Metelli, Bill X. Wu, Caroline W. Fugle, Rachidi Saleh, Shaoli Sun, Jennifer Wu, Bei Liu, Zihai Li, Zachary S. Morris, Emily I. Guy, Clinton Heinze, Jasdeep Kler, Monica M. Gressett, Lauryn R. Werner, Stephen D. Gillies, Alan J. Korman, Hans Loibner, Jacquelyn A. Hank, Alexander L. Rakhmilevich, Paul M. Harari, Paul M. Sondel, Erica Huelsmann, Joseph Broucek, Dorothee Brech, Tobias Straub, Martin Irmler, Johannes Beckers, Florian Buettner, Elke Schaeffeler, Matthias Schwab, Elfriede Noessner, Alison Wolfreys, Andre Da Costa, John Silva, Andrea Crosby, Ludovicus Staelens, Graham Craggs, Annick Cauvin, Sean Mason, Alison M. Paterson, Andrew C. Lake, Caroline M. Armet, Rachel W. O’Connor, Jonathan A. Hill, Emmanuel Normant, Ammar Adam, Detlev M. Biniszkiewicz, Scott C. Chappel, Vito J. Palombella, Pamela M. Holland, Annette Becker, Manmohan R. Leleti, Eric Newcomb, Joanne B. L. Tan, Suthee Rapisuwon, Arash Radfar, Kellie Gardner, Geoffrey Gibney, Michael Atkins, Keith R. Rennier, Robert Crowder, Ping Wang, Russell K. Pachynski, Rosa M. Santana Carrero, Sarai Rivas, Figen Beceren-Braun, Scott Anthony, Kimberly S. Schluns, Deepali Sawant, Maria Chikina, Hiroshi Yano, Creg Workman, Elise Salerno, Ileana Mauldin, Donna Deacon, Sofia Shea, Joel Pinczewski, Thomas Gajewski, Stefani Spranger, Brendan Horton, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Raj K. Puri, Randy F. Sweis, Riyue Bao, Jason Luke, Marie-Nicole Theodoraki, Frances-Mary Mogundo, Haejung Won, Dayson Moreira, Chan Gao, Xingli Zhao, Priyanka Duttagupta, Jeremy Jones, Massimo D’Apuzzo, and Sumanta Pal

Subjects
0301 basic medicine, Pharmacology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Cancer, Immunotherapy, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, Molecular Medicine, Immunology and Allergy, Medicine, business
Abstract

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Published
2016

32. Artificial intelligence in predicting bladder cancer outcome: a comparison of neuro-fuzzy modeling and artificial neural networks

Author

Catto, J. W. F., Linkens, D. A., Abbod, M. F., Chen, M., Burton, J. L., Feeley, K. M., and Freddie Hamdy

Abstract

PURPOSE: New techniques for the prediction of tumor behavior are needed, because statistical analysis has a poor accuracy and is not applicable to the individual. Artificial intelligence (AI) may provide these suitable methods. Whereas artificial neural networks (ANN), the best-studied form of AI, have been used successfully, its hidden networks remain an obstacle to its acceptance. Neuro-fuzzy modeling (NFM), another AI method, has a transparent functional layer and is without many of the drawbacks of ANN. We have compared the predictive accuracies of NFM, ANN, and traditional statistical methods, for the behavior of bladder cancer. EXPERIMENTAL DESIGN: Experimental molecular biomarkers, including p53 and the mismatch repair proteins, and conventional clinicopathological data were studied in a cohort of 109 patients with bladder cancer. For all three of the methods, models were produced to predict the presence and timing of a tumor relapse. RESULTS: Both methods of AI predicted relapse with an accuracy ranging from 88% to 95%. This was superior to statistical methods (71-77%; P < 0.0006). NFM appeared better than ANN at predicting the timing of relapse (P = 0.073). CONCLUSIONS: The use of AI can accurately predict cancer behavior. NFM has a similar or superior predictive accuracy to ANN. However, unlike the impenetrable "black-box" of a neural network, the rules of NFM are transparent, enabling validation from clinical knowledge and the manipulation of input variables to allow exploratory predictions. This technique could be used widely in a variety of areas of medicine.

Published
2016

33. Welcome

Author

Freddie Hamdy

Subjects
Urology
Published
2016

34. PROSPECTIV-a pilot trial of a nurse-led psychoeducational intervention delivered in primary care to prostate cancer survivors: study protocol for a randomised controlled trial

Author

Eila, Watson, Peter, Rose, Emma, Frith, Freddie, Hamdy, David, Neal, Christof, Kastner, Simon, Russell, Fiona M, Walter, Sara, Faithfull, Jane, Wolstenholme, Rafael, Perera, David, Weller, Christine, Campbell, Clare, Wilkinson, Richard, Neal, Prasanna, Sooriakumaran, Hugh, Butcher, and Mike, Matthews

Subjects
Male, Primary Health Care, Prostatic Neoplasms, Pilot Projects, Patient-Centred Medicine, Rehabilitation Medicine, Patient Education as Topic, Adaptation, Psychological, Quality of Life, Protocol, Humans, Survivors, Sexuality, Primary Care, Aged, Follow-Up Studies
Abstract

Background Prostate cancer survivors can experience physical, sexual, psychological and emotional problems, and there is evidence that current follow-up practices fail to meet these men's needs. Studies show that secondary and primary care physicians see a greater role for primary care in delivering follow-up, and that primary care-led follow-up is acceptable to men with prostate cancer. Methods and analysis A two-phase study with target population being men who are 9–24 months from diagnosis. Phase 1 questionnaire aims to recruit 300 men and measure prostate-related quality of life and unmet needs. Men experiencing problems with urinary, bowel, sexual or hormonal function will be eligible for phase 2, a pilot trial of a primary care nurse-led psychoeducational intervention. Consenting eligible participants will be randomised either to intervention plus usual care, or usual care alone (40 men in each arm). The intervention, based on a self-management approach, underpinned by Bandura's Social Cognitive Theory, will provide advice and support tailored to these men's needs and address any problems they are experiencing. Telephone follow-up will take place at 6 months. Study outcomes will be measured by a questionnaire at 7 months. Phase 1 will allow us to estimate the prevalence of urinary, sexual, bowel and hormone-related problems in prostate cancer survivors and the level of unmet needs. ‘Usual care’ will also be documented. Phase 2 will provide information on recruitment and retention, acceptability of the intervention/outcome measures, effect sizes of the intervention and cost-effectiveness data, which is required to inform development of a larger, phase 3 randomised controlled trial. The main outcome of interest is change in prostate-cancer-related quality of life. Methodological issues will also be addressed. Ethics and dissemination Ethics approval has been gained (Oxford REC A 12/SC/0500). Findings will be disseminated in peer-reviewed journals, at conferences, through user networks and relevant clinical groups. Trial registration number ISRCTN 97242511.

Published
2014

35. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187

Author

Kimberley J, Reeves, Jack E, Hurrell, Marco, Cecchini, Gabri, van der Pluijm, Jenny M, Down, Colby L, Eaton, Freddie, Hamdy, Philippe, Clement-Lacroix, and Nicola J, Brown

Subjects
Male, Integrins, Neovascularization, Pathologic, Cell Survival, Prostatic Neoplasms, Antineoplastic Agents, Bone Neoplasms, Xenograft Model Antitumor Assays, Disease Models, Animal, Mice, Cell Movement, Cell Line, Tumor, Animals, Humans, Cell Proliferation
Abstract

Micrometastasis is a barrier to the development of effective cancer therapies for prostate cancer metastasis to bone. The mechanisms remain incompletely characterised, primarily due to an inability to adequately monitor the initial metastatic events in vivo. This study aimed to establish a new model, allowing the tracking of prostate cancer cells homing to bone, and furthermore, to evaluate the response of this approach to therapeutic modulation, using the integrin antagonist GLPG0187. A single murine metatarsal was engrafted into a dorsal skinfold chamber implanted on a SCID mouse. Fluorescently-labeled human prostate (PC3-GFP) or oral (SCC4-GFP) cancer cells were administered via intracardiac (i.c) injection, with simultaneous daily GLPG0187 or vehicle-control treatment (i.p. 100 mg/kg/day) for the experimental duration. Metatarsal recordings were taken every 48 h for up to 4 weeks. Tissue was harvested and processed for microCT, multiphoton analysis, histology and immunohistochemistry. Cell viability, proliferation and migration in vitro were also quantified following treatment with GLPG0187. Metatarsals rapidly revascularised by inosculation with the host vasculature (day 5-7). PC3-GFP cells adhered to the microvascular endothelium and/or metatarsal matrix 3 days after administration, with adhesion maintained for the experimental duration. GLPG0187 treatment significantly (p 0.05) reduced PC3 cell number within the metatarsal in vivo and reduced migration (p 0.05) and proliferation (p 0.05) but not cell viability in vitro. This new model allows evaluation of the early events of tumour-cell homing and localisation to the bone microenvironment, in addition to determining responses to therapeutic interventions.

Published
2013

36. Estimating age and ethnic variation in the histological prevalence of prostate cancer to inform the impact of screening policies

Author

Jose, Leal, Freddie, Hamdy, and Jane, Wolstenholme

Subjects
Adult, Aged, 80 and over, Male, Age Factors, Prostate, Prostatic Neoplasms, Bayes Theorem, Middle Aged, Young Adult, Asymptomatic Diseases, Prevalence, Humans, Mass Screening, Aged
Abstract

To estimate histological prevalence of prostate cancer by age and ethnic group.A literature review identified autopsy studies of men without clinical diagnosis of prostate cancer during their lifetime. A total of 25 studies fulfilled the inclusion criteria, and a Bayesian logistic meta-regression was carried out to examine the association between histological prevalence, age by decade and ethnic group (white, African American and Chinese/Japanese).Histological cancer was estimated to increase with age from 2% (95% confidence interval 1-3%) between 20-29 years-of-age to 69% (95% confidence interval 51-83%) by 90-99 years-of-age in the white ethnic group. The African American group was associated with the highest prevalence of cancer, albeit non-significantly (odds ratio 1.2, 95% confidence interval 0.9-1.5), whereas the Chinese/Japanese group was significantly associated with the lowest prevalence relative to the white group (odds ratio 0.6, 95% confidence interval 0.4-0.9).The present study provides an updated and improved analysis of the histological prevalence of prostate cancer. The results confirm ethnicity as a potential predictor of prevalence, but highlight the need for further research in the area. The findings are valuable for understanding the epidemiology and natural history of prostate cancer across ethnicities, and increasing the body of evidence aimed at estimating benefits and risks associated with prostate cancer screening programs.

Published
2013

37. Prostate

Author

Freddie Hamdy

Subjects
Urology
Published
1996

39. Evaluation of the frequency of putative prostate cancer stem cells in primary and metastatic prostate cancer

Author

Colby L, Eaton, Marc, Colombel, Gabri, van der Pluijm, Marco, Cecchini, Antoinette, Wetterwald, Jenny, Lippitt, Ishtiaq, Rehman, Freddie, Hamdy, and George, Thalman

Subjects
Male, Integrins, Prostate, Prostatic Neoplasms, Bone Neoplasms, Cell Count, Nerve Tissue Proteins, Adenocarcinoma, Immunohistochemistry, Bone and Bones, Nestin, Intermediate Filament Proteins, Antigens, CD, Biomarkers, Tumor, Neoplastic Stem Cells, Humans
Abstract

Tumour cells with a stem cell-like phenotype have recently been identified in prostate tumors and it has been suggested that this population may be responsible for the diversity of cell types within tumors and also for the initiation of metastases. These cells carry a number of defined markers: they are cd133 and cd44+ve and express high levels of alpha2beta1 integrin. In this study we have, for the first time, assessed matched primary and bone marrow biopsies from prostate cancer patients for the distribution of cells carrying these and a number of other putative stem cell markers.Eleven matched (primary and bone metastasis) specimens from prostate cancer patients were assessed for the presence of cd133, cd44, alpha2beta1 integrin, CXCR4, c-met, alpha6 integrin, and nestin using immunohistochemistry and stain intensity and distribution scored.In the bone metastases, tumor cells staining positively for cd133 were detected at low frequency in approximately 50% of samples. Staining for nestin was confined to endothelium. Positive staining of tumor cells for the other antigens was present at variable frequency in70% of metastases with the exception of CXCR4 which was absent from all but 2 specimens. Where positive staining of tumor cells was present in the metastasis, cells staining for each antigen were present in the matched primary with the exception of cd44 which was absent in all but 2/11 matched primary tissues.In established metastases no single or combination of marker expression profiles identify the established metastatic phenotype, although cd44 expression was shown to be more frequent in metastases that in primary cancers.

Published
2010

40. Re: Outpatient Urological Procedures in Antibiotic-Naïve Patients with Bladder Cancer with Asymptomatic Bacteriuria

Author

Markus Zeitlinger, Freddie Hamdy, and Sarah Howles

Subjects
Male, medicine.medical_specialty, Bladder cancer, Bacteriuria, business.industry, medicine.drug_class, Urology, Antibiotics, Diagnostic Techniques, Urological, medicine.disease, Anti-Bacterial Agents, Therapy naive, Urinary Bladder Neoplasms, Internal medicine, Outpatients, medicine, Humans, Female, business, Asymptomatic bacteriuria
Published
2013

41. Quality improvement report: Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study. Commentary: presenting unbiased information to patients can be difficult

Author

Paul Little, Jenny Donovan, Nicola Mills, Monica Smith, Lucy Brindle, Ann Jacoby, Tim Peters, Stephen Frankel, David Neal, and Freddie Hamdy

Subjects
Research design, Male, medicine.medical_specialty, media_common.quotation_subject, MEDLINE, law.invention, Presentation, Randomized controlled trial, Informed consent, law, Terminology as Topic, medicine, Humans, Intensive care medicine, General Environmental Science, media_common, Randomized Controlled Trials as Topic, Informed Consent, business.industry, Patient Selection, General Engineering, Prostatic Neoplasms, General Medicine, Surgery, Clinical trial, Clinical equipoise, Research Design, General Earth and Planetary Sciences, business, Qualitative research
Abstract

Problem: Recruitment to randomised trials is often difficult, and many important trials are not mounted because recruitment is thought to be “impossible.” Design: Controversial ProtecT (prostate testing for cancer and treatment) trial embedded within qualitative research. Background and setting: Screening for prostate cancer is hotly debated, and evidence from trials about the effectiveness of treatments (surgery, radiotherapy, and monitoring) is lacking. Mounting a treatment trial is controversial because of past failures and concerns that differences in complications of treatment but not survival make randomisation unacceptable to patients and clinicians, particularly for a trial including monitoring. Strategy for change: In-depth interviews explored interpretation of study information. Audiotape recordings of recruitment appointments enabled scrutiny of content and presentation of study information by recruiters. Initial qualitative findings showed that recruiters had difficulty discussing equipoise and presenting treatments equally; they unknowingly used terminology that was misinterpreted by participants. Findings were used to determine changes to content and presentation of information. Effects of change: Changes to the order of presenting treatments encouraged emphasis on equivalence, misinterpreted terms were avoided, the non-radical arm was redefined, and randomisation and clinical equipoise were presented more convincingly. The randomisation rate increased from 40% to 70%, all treatments became acceptable, and the three arm trial became the preferred design. Lessons learnt: Changes to information and presentation resulted in efficient recruitment acceptable to patients and clinicians. Embedding this controversial trial within qualitative research improved recruitment. Such methods probably have wider applicability and may enable even the most difficult evaluative questions to be tackled.

Published
2002

42. Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells

Author

Holen, I., Croucher, P. I., Freddie Hamdy, and Eaton, C. L.

Subjects
musculoskeletal diseases
Abstract

Factors that aid survival of prostate cancer cells in the presence of the various categories of cytotoxic cytokines present in tumors in vivo are largely unknown. Osteoprotegerin (OPG) is a decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that inhibits TRAIL-induced apoptosis. In relation to this activity, we hypothesized that the ability to produce OPG by prostate cancer cells would confer a survival advantage on these cells. In this study we have demonstrated that high levels of OPG are produced by the hormone-insensitive prostate cancer cell lines PC3 and Du145, whereas the hormone-sensitive cell line LNCaP produced 10-20-fold less OPG under the same conditions. A strong negative correlation was observed between levels of endogenously produced OPG in the medium and the capacity of TRAIL to induce apoptosis in cells that produced high levels of OPG. The antiapoptotic effect of OPG was reversed by coadministration of 100-fold molar excess of receptor-activator of nuclear factor-kappaB ligand, another protein that selectively binds OPG. These observations suggest that prostate cancer-derived OPG may be an important survival factor in hormone-resistant prostate cancer cells.

Published
2002

44. Welcome

Author

Freddie Hamdy

Subjects
Urology
Published
2007

50. Artificial intelligence and bladder cancer arrays

Author

Wild, P. J., Catto, J. W., Abbod, M. F., Linkens, D. A., Herr, A., Pilarsky, C., Wissmann, C., Stoehr, R., Denzinger, S., Knuechel, R., Freddie Hamdy, and Hartmann, A.

Subjects
Male, Urinary Bladder Neoplasms, Artificial Intelligence, Disease Progression, Humans, Female, Neoplasm Invasiveness, Neoplasm Metastasis, Carcinoma in Situ, Cell Division, Neoplasm Staging, Oligonucleotide Array Sequence Analysis
Abstract

Non-muscle invasive bladder cancer is a heterogenous disease whose management is dependent upon the risk of progression to muscle invasion. Although the recurrence rate is high, the majority of tumors are indolent and can be managed by endoscopic means alone. The prognosis of muscle invasion is poor and radical treatment is required if cure is to be obtained. Progression risk in non-invasive tumors is hard to determine at tumor diagnosis using current clinicopathological means. To improve the accuracy of progression prediction various biomarkers have been evaluated. To discover novel biomarkers several authors have used gene expression microarrays. Various statistical methods have been described to interpret array data, but to date no biomarkers have entered clinical practice. Here, we describe a new method of microarray analysis using neurofuzzy modeling (NFM), a form of artificial intelligence, and integrate it with artificial neural networks (ANN) to investigate non-muscle invasive bladder cancer array data (n=66 tumors). We develop a predictive panel of 11 genes, from 2800 expressed genes, that can significantly identify tumor progression (average Logrank p = 0.0288) in the analyzed cancers. In comparison, this panel appears superior to those genes chosen using traditional analyses (average Logrank p = 0.3455) and tumor grade (Logrank, p = 0.2475) in this non-muscle invasive cohort. We then analyze panel members in a new non-muscle invasive bladder cancer cohort (n=199) using immunohistochemistry with six commercially available antibodies. The combination of 6 genes (LIG3, TNFRSF6, KRT18, ICAM1, DSG2 and BRCA2) significantly stratifies tumor progression (Logrank p = 0.0096) in the new cohort. We discuss the benefits of the transparent NFM approach with respect to other reported methods.

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