22 results on '"Elias Pintus"'
Search Results
2. Non-Small Cell Lung Cancer (NSCLC) in Young Adults, Agelt; 50, Is Associated with Late Stage at Presentation and a Very Poor Prognosis in Patients That Do Not Have a Targeted Therapy Option: A Real-World Study
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Daniel Johnathan Hughes, Matthaios Kapiris, Andreja Podvez Nevajda, Harriet McGrath, Chara Stavraka, Shahreen Ahmad, Benjamin Taylor, Gary J. R. Cook, Sharmistha Ghosh, Debra Josephs, Elias Pintus, Spyridon Gennatas, Andrea Bille, Kimuli Ryanna, George Santis, Ana Montes, Mieke Van Hemelrijck, Eleni Karapanagiotou, Daniel Smith, James Spicer, and Alexandros Georgiou
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Cancer Research ,Oncology ,non-small cell lung cancer ,young adults ,molecular targeted therapies ,precision medicine ,genetic predictive testing - Abstract
(1) Background: Non-small cell lung cancer (NSCLC) in young patients is uncommon. Real-world evidence on the outcomes of these patients is limited. (2) Methods: We conducted a retrospective cohort study of young NSCLC patients, age < 50 years at diagnosis, who were treated between 2011–2020 in South-East-London cancer centres. Clinicopathological characteristics, treatment and outcomes were analysed. (3) Results: Of 248 NSCLC patients, median age was 46 years, 50% (n = 125) female, 58% (n = 145) white, 18% (n = 45) black and 4% (n = 10) Asian ethnicity. Amongst patients with a documented smoking history, 30% (n = 64) were never-smokers. Most patients had adenocarcinoma (77%, n = 191) and presented with metastatic disease (67%, n = 166). Only 31% (n = 76) had treatment with curative intent. In patients who presented or developed metastatic non-squamous NSCLC (n = 179), EGFR mutation status was known in 88% (n = 157) and mutation present in 19% (n = 34), ALK was known in 66% (n = 118) with a translocation in 10% (n = 18), ROS1 status was known in 57% (n = 102) with a translocation in 4% (n = 8), and KRAS status was known in 66% (n = 119) with a mutation in 12% (n = 22). Overall, 76% (n = 152) patients with metastatic NSCLC received first-line systemic anti-cancer therapy. Median overall survival in metastatic NSCLC was 9.0 months (95% CI 6.5–11.6 months), with superior median overall survival in those with a targeted therapy option (28.7 months) compared to those without (6.6 months; p < 0.001). (4) Conclusion: Young patients contribute a significant proportion of those presenting with lung cancer. They present with advanced stage at diagnosis and have a poor prognosis. Identification of a targeted therapy option is associated with improved survival. However, most patients do not have a known genomic driver, which is in part due to limited testing, particularly in the early years of this study period. These findings highlight the particular importance of rapid-turnaround comprehensive genomic profiling in this age group and the need to identify strategies to facilitate earlier diagnosis in young NSCLC patients.
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- 2022
3. Treatment Outcomes for Small Cell Carcinoma of the Bladder: Results From a UK Patient Retrospective Cohort Study
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Frcr John McGrane, Hilary Glen, Frcr Chinnamani Eswar, Frcr Mark Beresford, Frcr Mohini Varughese, Serena Hilman, Deborah Enting, Frcr Maria Vilarino-Varela, Anand Sharma, Ananya Choudhury, Vincent Khoo, Frcr Caroline Manetta, Naveen S. Vasudev, Frcr Daniel R. Henderson, Frcr Darren Mitchell, Alastair Law, Robert Huddart, Frcr Sharon Beesley, Jun Hao Lim, Frcr Sarah Treece, Simon J. Crabb, Shaista Hafeez, Elias Pintus, Frcr Darren Leaning, Caroline Chau, Frcr Yvonne Rimmer, and Frcs Rajagopalan Sriram
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Adult ,Male ,Cancer Research ,Poor prognosis ,medicine.medical_specialty ,medicine.medical_treatment ,Treatment outcome ,Patient characteristics ,Disease ,Small-cell carcinoma ,Disease-Free Survival ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Carcinoma, Small Cell ,Aged ,Neoplasm Staging ,Retrospective Studies ,Chemotherapy ,Radiation ,business.industry ,Hazard ratio ,Retrospective cohort study ,Middle Aged ,medicine.disease ,United Kingdom ,Treatment Outcome ,Urinary Bladder Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,business - Abstract
Purpose: Small cell carcinoma of the bladder (SCCB) is rare, accounting for less than 1% of all bladder carcinomas. It is aggressive, and outcomes are poor as a result of its early metastatic spread. Owing to its rarity, there are limitations on data to propose standardized management pathways. Methods and Materials: We conducted a retrospective analysis of patients presenting with pure or predominant-histology SCCB to 26 institutions in the United Kingdom between 2006 and 2016. The data cutoff date was February 1, 2018. We report patient characteristics, treatment received, and subsequent clinical outcomes. Results: A total of 409 eligible patients were included. Among these, 306 (74.8%) were male, the median age was 71 years (range, 35-96 years), and 189 patients (46.2%) had pure-histology SCCB. At data cutoff, 301 patients (73.6%) had died. The median overall survival (OS) was 15.9 months (95% CI, 13.2-18.7 months). Two hundred patients (48.9%) were confirmed to have bladder-confined disease (N0, M0), with a median OS of 28.3 months (95% CI, 20.9-35.8 months), versus a median OS of 12.7 months (95% CI, 10.9-14.6 months) for the 172 patients (42.1%) with confirmed N1-3 and/or M1 disease (hazard ratio [HR], 2.03; 95% CI, 1.58-2.60; P < .001). A total of 247 patients (61.5%) received primary chemotherapy, with a median OS of 21.6 months (95% CI, 15.5-27.6 months), versus a median OS of 9.1 months (95% CI, 5.4-12.8 months) in patients who did not receive primary chemotherapy (HR, 0.46; 95% CI, 0.37-0.59; P < .001). Choice of chemotherapy agent did not alter outcomes. For those with bladder-confined disease, 61 (30.5%) underwent cystectomy, and 104 (52.0%) received radiation therapy. Survival outcomes were similar for both cystectomy and radiation therapy. Only 6 patients (1.5%) were identified as having brain metastases at any time point. Conclusions: To our knowledge, this is the largest retrospective study of all-stage SCCB to date. Patients have a poor prognosis overall, but survival is improved in those able to receive chemotherapy and with organ-confined disease. Brain metastases are rare.
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- 2021
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4. Safe provision of systemic anti-cancer treatment for urological cancer patients during COVID-19: a tertiary centre experience in the first wave of COVID-19
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Alfred Chung Pui So, Christina Karampera, Muhammad Khan, Beth Russell, Charlotte Moss, Maria J. Monroy-Iglesias, Kiruthikah Thillai, Debra Hannah Josephs, Elias Pintus, Sarah Rudman, Mieke Van Hemelrijck, Saoirse Dolly, and Deborah Enting
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Male ,Urologic Neoplasms ,Reproductive Medicine ,Urology ,COVID-19 ,Humans ,Female ,Immunotherapy ,General Medicine ,Pandemics ,Retrospective Studies - Abstract
BackgroundSafe provision of systemic anti-cancer treatment (SACT) during the COVID-19 pandemic remains an ongoing concern amongst clinicians.MethodsRetrospective analysis on uro-oncology patients who continued or started SACT between 1st March and 31st May 2020 during the pandemic (with 2019 as a comparator).Results441 patients received SACT in 2020 (292 prostate, 101 renal, 38 urothelial, 10 testicular) compared to 518 patients in 2019 (340 prostate, 121 renal, 42 urothelial, 15 testicular). In 2020, there were 75.00% fewer patients with stage 3 cancers receiving SACT (p p = 0.00194). The number of patients started on a new line of SACT was similar between both years (118 in 2019 vs 102 in 2020;p = 0.898) but with 53.45% fewer patients started on chemotherapy in 2020 (p p = 0.649) whereas 6-month mortality was lower (9.32% in 2019 vs 1.96% in 2020;p = 0.0209) in 2020.ConclusionThis study suggests that delivery of SACT to uro-oncology patients during COVID-19 pandemic may be safe in high-incidence areas with appropriate risk-reduction strategies.
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- 2022
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5. Rucaparib for metastatic castration-resistant prostate cancer (mCRPC): TRITON3 interim overall survival and efficacy of rucaparib vs docetaxel or second-generation androgen pathway inhibitor therapy
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Alan Haruo Bryce, Josep M. Piulats, M. Neil Reaume, Peter James Ostler, Raymond S. McDermott, Joel Roger Gingerich, Elias Pintus, Srikala S. Sridhar, Wassim Abida, Gedske Daugaard, Axel Heidenreich, Laurence E. M. Krieger, Brieuc Sautois, Andrea Loehr, Darrin Despain, Jowell Go, Simon Paul Watkins, Simon Chowdhury, Charles J. Ryan, and Karim Fizazi
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Cancer Research ,Oncology - Abstract
18 Background: TRITON3 (NCT02975934) is a randomized, multicenter, open-label, phase 3 study of rucaparib vs physician’s choice (docetaxel [DTX], abiraterone [ABI] or enzalutamide [ENZ]) in patients (pts) with chemotherapy-naïve mCRPC with BRCA1/2 (BRCA) or ATM alterations. It was previously reported that rucaparib significantly improved the primary endpoint of radiographic progression-free survival (rPFS) vs physician’s choice in pts with BRCA or ATM alterations. We report here the interim overall survival (OS) and also report on efficacy of rucaparib compared individually with either DTX or ABI/ENZ. Methods: Pts had disease progression after 1 prior second-generation androgen pathway inhibitor therapy in any setting and were randomized 2:1 to rucaparib 600 mg BID or physician’s choice of DTX, ABI or ENZ. An ordered step-down multiple comparisons procedure was used to control the overall error rate. OS was a key secondary endpoint with rPFS as the primary endpoint tested first in the BRCA subgroup, then the intent-to-treat (ITT) population. Subgroup analyses based on physician’s choice were exploratory. Results: As of August 25, 2022, 302 pts with BRCA and 103 pts with ATM alterations were randomized. OS maturity was 54% in the BRCA subgroup and 59% in the ITT population. rPFS and OS are shown. The most frequent treatment-emergent adverse event (TEAE) in the rucaparib, DTX and ABI/ENZ groups was asthenia/fatigue (61.1%, 67.6% and 57.6%, respectively). The most frequent grade ≥3 TEAE in the rucaparib, DTX and ABI/ENZ groups was anemia (23.7%), neutropenia (14.1%), and hypertension (10.2%), respectively. Conclusions: Rucaparib significantly improved rPFS vs either DTX or ABI/ENZ; safety was consistent with prior reports. Interim OS results suggest a trend towards improvement for rucaparib vs DTX or ABI/ENZ in pts with mCRPC and BRCA alterations. Clinical trial information: NCT02975934 . [Table: see text]
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- 2023
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6. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma
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Sanjay Popat, Lewis Au, Jan Attig, Catherine Horsfield, Hayley Bridger, Kitty Chan, Haixi Yan, David Moore, Lara-Rose Iredale, Salma Kadiri, Sebastian Brandner, Rebecca C. Fitzgerald, Bruce Tanchel, Maise Al-Bakir, Katey S. S. Enfield, Merche Jimenez-Linan, Andrew P. Robinson, Kim Edmonds, Stuart Horswell, Elena Provenzano, Andrew V. Biankin, Benny Chain, Scott Shepherd, Antonia Toncheva, Carlos Caldas, Gerald Langman, Fabio Gomes, I Puccio, Amy Kerr, Sharmistha Ghosh, Caroline Dive, James Larkin, Siow Ming Lee, Nicholas McGranahan, Peter Ellery, Charlotte Spencer, Dionysis Papadatos-Pastos, Charles Swanton, Maryam Razaq, Richard J. Gilbertson, Rachael Thompson, William Drake, Lyra Del Rosario, Debra Enting, Lisa Pickering, Crispin T. Hiley, David A Moore, Christian H. Ottensmeier, Ehsan Ghorani, Simon Chowdhury, Simon Tavaré, Sophie Ward, Gordon Stamp, Peter J. Parker, Sam M. Janes, Giorgia Trevisan, Mary Falzon, Ultan McDermott, Christopher Abbosh, Fiona Byrne, Kroopa Joshi, Kim Dhillon, George Kassiotis, James L. Reading, Heather Shaw, Tariq Enver, Dean A. Fennell, Jonathan Ledermann, Annika Fendler, Emma Beddowes, Peter Cockcroft, Mary Mangwende, Desiree Schnidrig, Ian Tomlinson, Mark Linch, Ben Challacombe, Vasiliki Michalarea, Yvonne Summers, Fiona H Blackhall, Robert Mason, Emma Nye, Robert E. Hynds, Debra H. Josephs, Mariana Werner Sunderland, Adrian Tookman, Emilia L. Lim, Paddy Stone, Cristina Naceur-Lombardelli, Bernard Olisemeke, Teresa Marafioti, Mat Carter, Grant D. Stewart, Sanjay Jogai, Richard Marais, Imran Uddin, Kevin Litchfield, Daniel Hochhauser, Alexander Polson, William Yang, Hang Xu, Peter Hill, Jonathon Olsburgh, Gordon Beattie, Justine Korteweg, Nnenna Kanu, Martin Forster, Andrew Tutt, Ben Shum, Elias Pintus, Alison Cluroe, Matt Krebs, Patricia Roxburgh, Caroline Stirling, Selvaraju Veeriah, Olivia Curtis, Marc Robert de Massy, Emine Hatipoglu, Tom Lund, Kai-Keen Shiu, Tina Mackay, Pablo D. Becker, Faye Gishen, Massimo Loda, Aida Murra, Karin A. Oien, Joanne Webb, Jose Lopez, Sarah Sarker, Adrienne M. Flanagan, Ula Mahadeva, Ian Proctor, Ruby Stewart, John Le Quesne, Elaine Borg, Archana Fernando, Babu Naidu, Andrew Rowan, Abby Sharp, Mairead McKenzie, Ayse Akarca, Anthony J. Chalmers, James Spicer, Gary Middleton, Hollie Bancroft, Jo Dransfield, Nicos Fotiadis, Charlotte Ferris, Ron Sinclair, Mary Varia, Peter Van Loo, Lavinia Spain, Lena Karapagniotou, Nikki Hunter, Roberto Salgado, Sarah Vaughan, Chi-wah Lok, Karen Harrison-Phipps, Hema Verma, Jacqui Shaw, Rodelaine Wilson, Zoe Rhodes, Anna Green, Reena Khiroya, Miriam Mitchison, Ashish Chandra, Colin Watts, Peter Colloby, Uzma Asghar, Laura Farrelly, Tim O'Brien, Stephan Beck, Steve Hazell, Tanya Ahmad, Martin Collard, John Bridgewater, James D. Brenton, Sarah Rudman, Eleanor Carlyle, Andrew C. Kidd, Lizi Manzano, Sergio A. Quezada, Sioban Fraser, Allan Hackshaw, Nadia Yousaf, Samra Turajlic, Henning Walczak, David Nicol, Mariam Jamal-Hanjani, Sarah Howlett, Andrew Furness, Simranpreet Summan, Kevin G. Blyth, S. Baijal, Gert Attard, Marcos Duran Vasquez, Mita Afroza Akther, Karla Lingard, Ben Deakin, Ariana Huebner, and David G. Harrison
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Cancer Research ,Receptors, Antigen, T-Cell ,Biology ,CD8-Positive T-Lymphocytes ,Clinical Trials, Phase II as Topic ,Antigen ,Immunity ,Exome Sequencing ,medicine ,Tumor Microenvironment ,Humans ,Prospective Studies ,Spotlight ,Mode of action ,Receptor ,Carcinoma, Renal Cell ,Immune Checkpoint Inhibitors ,Sequence Analysis, RNA ,Gene Expression Profiling ,T-cell receptor ,Endogenous Retroviruses ,Genomics ,medicine.disease ,Kidney Neoplasms ,Clear cell renal cell carcinoma ,Nivolumab ,Oncology ,Drug Resistance, Neoplasm ,Cancer research ,Tumor Escape ,Single-Cell Analysis ,CD8 - Abstract
ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.
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- 2021
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7. The presenting dental status of solid tumours with bone metastases requiring bone-targeting agents - part 3: prostate cancer
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Vinod Patel, Megan Burns, Sheelen Patel, Sanford Grossman, Rana Wali, Isabel Sassoon, Elias Pintus, and Marianne Henien
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General Dentistry - Abstract
Introduction Metastatic prostate cancer (MPC) patients due to receive bone-targeting agents (BTAs) are expected to undertake a dental assessment before commencing. The aim of this study was to determine the dental status of this tumour group and understand the challenges the dental practitioner faces in attempting to achieve 'dental fitness'.Materials and methods Data were retrospectively collected from a dedicated pre-BTA dental assessment clinic and analysed for MPC. Statistical analysis and observational data were used to compare patient and tumour demographics.Results A total of 111 patients were included in this cohort, with the majority of patients presenting with only bone metastases (BM) and no additional metastatic sites. On average, MPC patients presented with 19.3 teeth and were below the threshold for functional dentition. The 75-84-year-old age group had the worst horizontal bone loss score and subsequently lose six teeth over a decade (p = 0.001). In addition, all MPC tumour sub-categories showed favourable survival rates.Conclusion MPC patients have a high dental burden on presentation, likely associated with their age. Favourable survival prospects and the cumulation of BTAs and dental disease would suggest a heightened risk of medication-related osteonecrosis of the jaw in this group compared to many other tumour sites.
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- 2020
8. Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue
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Richard Marais, Andrew Furness, Thomas B.K. Watkins, Maise Al-Bakir, Dionysis Papadatos-Pastos, Maryam Razaq, Mairead McKenzie, Lisa Pickering, Peter Ellery, Jonathan Ledermann, Andrew V. Biankin, Richard J. Gilbertson, Peter Cockcroft, Mary Mangwende, Sophie Ward, Mary Falzon, Cristina Naceur-Lombardelli, Carlos Caldas, Karla Pearce, Jacqui Shaw, Salma Kadiri, Lars Dyrskjøt, Mark Linch, Daniel Burgess, Nelson Alexander, Christian H. Ottensmeier, Kevin G. Blyth, Lisa L. Gallegos, Rodelaine Wilson, Hayley Bridger, Fiona H Blackhall, Peter J. Parker, Charles Swanton, Allan Hackshaw, Gert Attard, Gordon Stamp, Dean A. Fennell, Debra H. Josephs, Andrew P. Robinson, Kim Edmonds, Tina Mackay, Mita Afroza Akther, Miriam Mitchison, Sam M. Janes, Giorgia Trevisan, Adrienne M. Flanagan, Alison Cluroe, Henning Walczak, Stuart Horswell, Lena Karapagniotou, Simon Tavaré, Sarah Sarker, Teresa Marafioti, Matt Krebs, Anna Green, Philippe Lamy, Reena Khiroya, Samantha M. Hill, Andrew Tutt, Ashish Chandra, Selvaraju Veeriah, Faye Gishen, Lisa Thompson, Sarah Vaughan, Stacey Stanislaw, Kevin Litchfield, Colin Watts, Caroline Dive, Zayd Tippu, Ron Sinclair, Merche Jimenez-Linan, Lavinia Spain, Lizi Manzano, Zoe Rhodes, Caroline Stirling, Elena Provenzano, Andrew Rowan, Katey S. S. Enfield, Vasiliki Michalarea, Nahid Sheikh, Antonia Toncheva, Charlotte Ferris, James Spicer, Kai-Keen Shiu, Aida Murra, Gerald Langman, Scott Thomas Colville Shepherd, Nicholas McGranahan, Fabio Gomes, Daniel Hochhauser, Hang Xu, Sergio A. Quezada, James Larkin, Siow Ming Lee, Chi-wah Lok, Massimo Loda, Gary Middleton, Hollie Bancroft, Jo Dransfield, David Moore, Jennifer Thomas, Rebecca C. Fitzgerald, Peter Colloby, Annika Fendler, Emma Beddowes, Ultan McDermott, Christopher Abbosh, Uzma Asghar, Martin Forster, John Le Quesne, Katherine F. Leith, Paddy Stone, Bernard Olisemeke, Bruce Tanchel, Laura Farrelly, Grant D. Stewart, Justine Korteweg, Sanjay Jogai, Nnenna Kanu, Desiree Schnidrig, Heidi Rosenbaum, Elaine Borg, Mat Carter, Anthony J. Chalmers, Andrew C. Kidd, Alexandre Harlé, Ula Mahadeva, Crispin T. Hiley, Fiona Byrne, Heather Shaw, Mariam Jamal-Hanjani, Karin A. Oien, Ian Proctor, Joanne Webb, Sioban Fraser, Sarah Howlett, Ruby Stewart, Peter Van Loo, Nadia Yousaf, Tanya Ahmad, Martin Collard, Sanjay Popat, James D. Brenton, Sarah Rudman, Lewis Au, David G. Harrison, Elias Pintus, Patricia Roxburgh, Olivia Curtis, Ben Deakin, Ariana Huebner, Debra Enting, Simranpreet Summan, S. Baijal, Iver Nordentoft, Carol Jones, Haixi Yan, Sebastian Brandner, Tariq Enver, Lara-Rose Iredale, Yvonne Summers, Babu Naidu, Abby Sharp, Stephen Hazell, Aoune Barhoumi, Emma Nye, Robert E. Hynds, Sharmistha Ghosh, Emilia L. Lim, Ben Shum, Nikki Hunter, John Bridgewater, Eleanor Carlyle, Stephan Beck, Nicolai Juul Birkbak, Steve Hazell, Samra Turajlic, Amy Kerr, Ian Tomlinson, Adrian Tookman, Litchfield, Kevin [0000-0002-3725-0914], Birkbak, Nicolai J [0000-0003-1613-9587], Nordentoft, Iver [0000-0003-4856-4086], Dyrskjøt, Lars [0000-0001-7061-9851], Apollo - University of Cambridge Repository, Division of genetics and epidemiology, The institute of cancer research [London], The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Royal Marsden, University of Arizona, University of Western Ontario, Physic and Astronomy Department, University of Western Ontario (UWO), Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Aarhus University Hospital, Cancer Research UK Lung Cancer Centre of Excellence [Londres, Royaume-Uni], University College of London [London] (UCL), Comprehensive Cancer Center, UCL Cancer Institute [University College London], The Wellcome Trust Sanger Institute [Cambridge], Research Department of Pathology, Innovation North - Faculty of Information and Technology, Leeds Metropolitan University, Department of histopathology, University College Hospital, Mammalian Genetics Laboratory, Centre for Research on Adaptive Nanostructures and Nanodevices, Trinity College Dublin, Cancer Research UK London Research Institute, Guy's and St Thomas' Hospital [London], Breakthrough Breast Cancer Centre, London Institute of Cancer, Cancer Research UK Cambridge Research Institute and Department of Oncology, University of Cambridge, University of Cambridge [UK] (CAM), Cancer Division [Sydney, Australia] (The Kinghorn Cancer Centre), Garvan Institute of Medical Research [Sydney, Australia], Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, University of Leicester, Experimental Cancer Medicine Centre, University of Southampton-Faculty of Medicine, Moses, Wittemyer, Harrison and Woodruff, P.C., University of Oxford, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), and Garvan Institute of medical research
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0301 basic medicine ,tumor sequencing ,medicine.medical_specialty ,Sampling protocol ,tumor mutational burden ,tumor sampling ,Lung Neoplasms ,molecular profiling ,Biopsy ,homogenization ,Tissue sample ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Biomarkers, Tumor ,Humans ,Solid tumor ,lcsh:QH301-705.5 ,Representative sampling ,medicine.diagnostic_test ,Manchester Cancer Research Centre ,ResearchInstitutes_Networks_Beacons/mcrc ,Clonal structure ,biomarkers ,High-Throughput Nucleotide Sequencing ,Tumor tissue ,tumor hetereogeneity ,Tumor Burden ,030104 developmental biology ,lcsh:Biology (General) ,representative sampling ,Urinary Bladder Neoplasms ,Mutation ,Radiology ,030217 neurology & neurosurgery - Abstract
International audience; Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias isinherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mmbiopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB butlow clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure.
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- 2020
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9. Polyclonal BRCA2 mutations following carboplatin treatment confer resistance to the PARP inhibitor rucaparib in a patient with mCRPC: a case report
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Andrew Simmons, Elias Pintus, and Minh Nguyen
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Male ,0301 basic medicine ,Cancer Research ,Indoles ,endocrine system diseases ,medicine.medical_treatment ,Genes, BRCA2 ,BRCA ,Reversion ,Case Report ,Poly(ADP-ribose) Polymerase Inhibitors ,lcsh:RC254-282 ,Germline ,Carboplatin ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Surgical oncology ,Genetics ,medicine ,Humans ,Poly (ADP-ribose) polymerase ,Rucaparib ,Germ-Line Mutation ,BRCA2 Protein ,Chemotherapy ,business.industry ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Prostatic Neoplasms, Castration-Resistant ,Treatment Outcome ,PARP inhibitor ,030104 developmental biology ,Oncology ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,business - Abstract
Background Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for the treatment of breast cancer susceptibility genes 1 and 2 (BRCA1/2) mutant ovarian and breast cancers, and are now being evaluated in metastatic castration-resistant prostate cancer (mCRPC). Reversion mutations that restore BRCA1/2 function have been shown to be responsible for resistance to platinum-based chemotherapy and PARP inhibitors, however there is no information on the sequential use of these agents in prostate cancer. Case presentation A patient with mCRPC associated with a germline BRCA2 mutation was sequentially treated with carboplatin and the PARP inhibitor rucaparib. Genomic profiling of the available baseline tumor and progression blood samples using next-generation sequencing panel tests identified polyclonal BRCA2 reversion mutations post carboplatin treatment but prior to rucaparib treatment. A total of 12 somatic reversion mutations were detected and ranged from small indels to larger deletions of up to 387 amino acids. These alterations are all predicted to restore the BRCA2 open reading frame and potentially protein function. The patient received limited benefit while on rucaparib, likely due to these reversion mutations observed prior to treatment. Conclusions Here we report a case of a patient with prostate cancer who received a platinum agent and PARP inhibitor sequentially and in whom polyclonal BRCA2 reversion mutations were identified as the likely mechanism of acquired resistance to carboplatin and primary resistance to PARP inhibition. These findings suggest caution is warranted in sequencing these agents.
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- 2020
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10. Clinical predictors of long-term efficacy of first-line pembrolizumab monotherapy in non-small cell lung cancer (NSCLC): an interim analysis of real-world data
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Helen-Cara Younan, Shuai Zhang, Maria Monroy, Manar Almusarhed, Max Julve, Debashree Roy, Sopozme Toghey, Zartaj Ahmed, Stephanie Slater, Shaymaa Altharwane, Alex Giorgiou, Sharmistha Ghosh, Spyridon Gennatas, Eleni Karapanagiotou, Ana Montes, Elias Pintus, James Spicer, Riyaz Shah, Samreen Ahmed, Tom Newsom-Davis, Waleed Mohammed, Danielle Power, Joanne Evans, Olivia Hatcher, Amish Lakhani, Amit Samani, and Debra Josephs
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2022
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11. 1868P Real-world safety of the 6-weekly pembrolizumab regimen in cancer patients treated in South East London
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A. Georgiou, M. Kapiris, C. Nikolaou, Debra H. Josephs, Sarah Rudman, S. Ghosh, Sophie Papa, Ana Montes, L. Karapanagiotou, Muhammad Shamim Khan, Mark Harries, Deborah Enting, Elias Pintus, James Spicer, C. Aversa, K. Zaki, and L. Cain
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medicine.medical_specialty ,business.industry ,Context (language use) ,Hematology ,Pembrolizumab ,Discontinuation ,Clinical trial ,Regimen ,Oncology ,Tolerability ,Internal medicine ,Toxicity ,Medicine ,business ,Adverse effect - Abstract
Background: Pembrolizumab (pembro) is a PD-1 inhibitor indicated for the treatment (tx) of a several malignancies. Most clinical trials used a 3-weekly tx (Q3W) but a 6-weekly 400mg regimen (Q6W) is now approved, based on pharmacokinetic data, also supported by the KEYNOTE-555 trial. The real world tolerability of the Q6W remains unknown. The COVID-19 pandemic led to rapid adoption of the Q6W tx, usually in patients (pts) previously receiving Q3W tx, as it facilitates less hospital visits. We report the toxicity profile of pts treated with Q6W pembro and the comparison of the preceding Q3W tx. Methods: We retrospectively analysed adverse events for non-small cell lung cancer (NSCLC), urothelial cancer (UC) and melanoma pts, who received at least 1 cycle of Q6W pembro. Pts that received pembro in combination tx were excluded. Previous Q3W monotherapy was permitted. Toxicity was graded as per CTCAE v5.0. Results: We included 94 pts (melanoma=39, NSCLC=38, UC=17). Median number of Q6W cycles received was 3 (range 1-6). 71% received the Q3W regimen (median 7 cycles, range 1-32) prior to switching to Q6W. New toxicity of any severity was recorded in 52% (49/94) during Q6W versus 70% (47/67) during Q3W tx. G 3/4 toxicities occurred in 15% (15) during Q6W versus 0% during previous Q3W tx. Of the 27 who started de novo with Q6W, 4 (15%) developed G 3/4 toxicities. G 3/4 toxicities were: GI (4% [colitis = 2, gastritis =1, oral lichen planus = 1]), nephritis (3%), arthralgia (2%), skin (2%), myositis/CK rise (2%), anaemia (1%), myocarditis (1%). Steroids for management of toxicity were initiated in 22% (21) pts, including 8 with G2 toxicity. Three (3%) pts switched back to Q3W administration. None of them received Q6W again. In total 9% of pts in Q6W discontinued tx due to toxicity. Conclusions: In our cohort of pts, the majority were previously treated with the Q3W regimen without significant toxicity. Switch to Q6W or de novo Q6W pembro led to a 15% rate of G 3/4 toxicity and 9% discontinuation rate. In pts pre-treated with Q3W, we cannot distinguish whether this was due to cumulative toxicity or due to switch to Q6W. More studies are required to ascertain the safety of the Q6W schedule. In the COVID-19 context, any Q6W toxicity concern should be weighed against the advantages of fewer hospital visits. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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- 2021
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12. Impact of Abiraterone Acetate plus Prednisone or Enzalutamide on Patient-reported Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer: Final 12-mo Analysis from the Observational AQUARiUS Study
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Antoine Thiery-Vuillemin, Mads Hvid Poulsen, Edouard Lagneau, M Lukac, Dominique Beal-Ardisson, A. Birtle, Louis Marie Dourthe, Alison Reid, Guillaume Ploussard, Geneviève Pissart, Elias Pintus, Suzy Van Sanden, Florence Lefresne, Redas Trepiakas, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Odense University Hospital (OUH), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Clinique La Croix du Sud, Royal Preston Hospital [Preston, UK] (RPH), Clinique Sainte Anne [Strasbourg], Hôpital privé Jean Mermoz [Lyon], Frimley Health NHS Foundation Trust [Slough], Zealand University Hospital [Naestved, Denmark], Janssen Pharmaceutica N.V. [Beerse, Belgium], Parexel International Czech Republic s.r.o, The Royal Marsden NHS Foundation Trust [Sutton, UK], AQUARiUS Investigators, CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
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Quality of life ,Oncology ,Male ,medicine.medical_specialty ,Time Factors ,[SDV]Life Sciences [q-bio] ,Urology ,AQUARiUS ,030232 urology & nephrology ,Abiraterone Acetate ,Antineoplastic Agents ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Prednisone ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Nitriles ,Phenylthiohydantoin ,Enzalutamide ,medicine ,Humans ,Patient Reported Outcome Measures ,Prospective Studies ,Neoplasm Metastasis ,Abiraterone ,Aged ,Aged, 80 and over ,Patient-reported outcomes ,business.industry ,Abiraterone acetate ,Repeated measures design ,Cancer ,medicine.disease ,Metastatic castration-resistant prostate cancer ,3. Good health ,[SDV] Life Sciences [q-bio] ,Prostatic Neoplasms, Castration-Resistant ,chemistry ,030220 oncology & carcinogenesis ,Benzamides ,Observational study ,business ,medicine.drug - Abstract
International audience; Background: Few studies have examined patient-reported outcomes (PROs) with abiraterone acetate plus prednisone (abiraterone) versus enzalutamide in metastatic castration-resistant prostate cancer (mCRPC).Objective: To determine the impact of abiraterone and enzalutamide on PROs.Design, setting, and participants: AQUARiUS (NCT02813408) was a prospective, 12-mo, observational study in patients with mCRPC from Denmark, France, and the UK.Intervention: Abiraterone or enzalutamide treatment according to routine practise.Outcome measurements and statistical analysis: PROs were collected over 12 mo using Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Brief Fatigue Inventory-Short Form (BFI-SF), Brief Pain Inventory-Short Form, and European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (QLQ-C30) at baseline and routine visits. Outcomes included mean change in PROs, patients with clinically meaningful worsening (CMW) in PROs, and safety. Data were analysed using repeated measures linear and logistic models adjusted for baseline characteristics.Results and limitations: Abiraterone-treated (N = 105) and enzalutamide-treated (N = 106) patients were included. Key PRO items (cognitive impairments and fatigue) were significantly (p < 0.05) in favour of abiraterone versus enzalutamide during the study. "Perceived cognitive impairment" and "comments from others" (FACT-Cog); "fatigue right now", "usual level of fatigue", and "worst level of fatigue" (BFI-SF); and "cognitive functioning" and "fatigue" (QLQ-C30) were significantly in favour of abiraterone over enzalutamide for three or more consecutive periods up to month 12. From study initiation, significantly fewer patients receiving abiraterone experienced one or more CMW episode in cognition and fatigue. Fatigue and asthenia (adverse events) were lower with abiraterone than with enzalutamide (5% vs 15% and 10% vs 11%, respectively). There were no treatment-related deaths. Limitations included lack of randomisation.Conclusions: In a real-world setting, this 12-mo analysis suggests an advantage of abiraterone acetate plus prednisone over enzalutamide on fatigue and cognitive function; this finding occurred early after treatment initiation. This difference should be considered when choosing treatment.Patient summary: This study looked at the effect of two treatments (abiraterone acetate plus prednisone and enzalutamide) for metastatic castration-resistant prostate cancer on patient quality of life over 12 mo. Using established questionnaires, patients reported that they experienced less fatigue and cognitive impairments (including memory loss and reduced thinking abilities) with abiraterone acetate plus prednisone than with enzalutamide.
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- 2019
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13. The impact of COVID-19 on delivery of systemic anti-cancer treatment in urological cancer patients: A comparison with 2019 data from Guy’s Cancer Center
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Charlotte Moss, Saoirse Dolly, Maria J. Monroy-Iglesias, Mieke Van Hemelrijck, Elias Pintus, Kiruthikah Thillai, Debra H. Josephs, Deborah Enting, Sarah Rudman, Muhammad Shamim Khan, Beth Russell, and Christina Karampera
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Cancer Research ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Outbreak ,Cancer ,medicine.disease ,Cancer treatment ,Oncology ,Internal medicine ,Cancer centre ,medicine ,Urological cancer ,business - Abstract
e17057 Background: The provision of cancer services has been strongly impacted by the outbreak of SARS-CoV-2. Our Cancer Centre in South-East London treats approximately 8,800 patients annually and is one of the largest Comprehensive Cancer Centres in the UK. When dealing with the second wave of COVID-19, it is important to further evaluate the safety of cancer treatments whilst balancing the risks of COVID-19 infection and complications. Here, we report on the patient/tumour characteristics of those patients undergoing SACT for a urological cancer diagnosis during the first wave, so as to help establish clinical guidelines for the management of these patients in a SARS-CoV-2 epidemic. Methods: All urological cancer patients receiving at least one SACT between 1st March- 31st May 2020 (COVID-19 period) were compared to the same timeframe in 2019. SARS-CoV2 infection was defined as a positive RT-PCR test; patients with symptoms or radiological changes alone were excluded. As part of Guy’s Cancer Cohort, we collected information on demographics, and cancer type, stage, and treatment. Results: A total of 455 patients (305 prostate, 102 renal, 38 bladder, and 10 testicular) received SACT in 2020 as compared to 535 (353 prostate, 129 renal, 37 bladder, and 15 testicular) in 2019 (15% overall decline). Patient characteristics in terms of demographics were fairly comparable, with 10% female patients in 2019 and 9% in 2020; 49% aged 70+ vs 45%; and 77% in the low socio-economic category vs 78%. There was an increase in patients with stage 4 (89% vs 95% in 2020) and a slight change in distribution of SACT types (2019 vs 2020): chemotherapy (18% vs 14%), immunotherapy (7% vs 10%), biological or targeted (63% vs 66%), combination of biological/targeted (6% vs 5%), other combinations (5% vs 5%). The proportion of SACT delivered as part of radical treatment declined from 3% to 0.2% in 2020. A total of 5 patients (1%) developed COVID-19 (2 prostate, 2 renal, and 1 bladder). All were male and aged 60+; three had 2+ comorbidities. One patient was on immunotherapy and four on biological or targeted treatment. Four patients had severe pneumonia and one died of their COVID-19 (bladder cancer). Conclusions: Whilst there was a decline of number of patients receiving SACT during COVID-19, we were still able to provide a safe high-quality urological cancer SACT pathway during the peak of the COVID-19 pandemic, with very few COVID-19 positive patients. In a next step we will evaluate oncological outcomes at 6 months follow-up
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- 2021
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14. Abstract S09-03: Real world data analysis of patients with genitourinary cancers receiving systemic anticancer treatment during the COVID-19 pandemic at Guy's Cancer Centre: A single centre retrospective study in the UK
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Deborah Enting, Christina Karampera, Kieran Palmer, Charlotte Moss, Kamarul Zaki, Elias Pintus, Debra H. Josephs, Saoirse Dolly, Rushan Sylva, Mieke Van Hemelrijck, Beth Russell, and Sarah Rudman
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Cancer Research ,medicine.medical_specialty ,Bladder cancer ,business.industry ,medicine.medical_treatment ,Mortality rate ,Cancer ,Retrospective cohort study ,medicine.disease ,Targeted therapy ,Prostate cancer ,Oncology ,Internal medicine ,Medicine ,Gastrointestinal cancer ,business ,Testicular cancer - Abstract
Background: To understand the impact of the COVID-19 pandemic on National Health Services (NHS) cancer service delivery, care and patients, we examined the impact of changes in cancer service delivery, treatment intensity and delay by evaluating oncological outcomes of genitourinary (GU) cancer patients receiving systemic anticancer treatment (SACT) during 1st March and 8th July 2020. Methods: We used data from patients with GU cancers (i.e. prostate, urothelial, kidney and testicular) treated with SACT at Guy’s Cancer Centre during the first wave of the COVID-19 pandemic in the UK: demographics (sex, age, ethnicity, ECOG performance status (PS), comorbidities, smoking history, socio-economic status (SES)) and disease characteristics (stage, treatment type and setting, lines of treatment), as well as results from SARS-CoV-2 PCR testing. Classification of COVID-19 severity was based on the World Health Organisation (WHO) guidelines. Results: A total of 457 GU cancer patients received SACT during the study period: 68% prostate cancer, 23% renal cancer, 7% urothelial cancer, 2% testicular cancer. Mean age was 69 years (SD: 11.2). 91% were males, 82% were classified as low SES and out of the 291 patients we had ethnicity data on 199 (68%) were White British. The majority of patients had a PS of 1 and 95% of all patients had stage IV disease and hence received palliative SACT, with 58% being in the second line setting. Half of the patients received hormone therapy, 17% received chemotherapy, 20% received targeted therapy, 13% received immunotherapy (IO) and 1% received combination IO and targeted treatment. Only 5 (1%) patients tested SARS-CoV-2 positive: 2 had prostate cancer, 2 renal and 1 bladder cancer. Mean age was 66 years (SD: 5.6). They were all male, 2 White British, 1 Black African and 2 of unknown ethnicity and were all classified as low SES. Average PS was 2. Of these 5 patients 3 had at least two comorbidities (i.ehypertension, diabetes mellitus, renal impairment, frailty) and were receiving multiple medications. All had stage IV disease and received palliative SACT. 3 were on hormone therapy alone and 2 on chemotherapy. 2 of the patients presented symptoms within less than 7 days from PCR diagnosis, 1 within 7 to 14 days and 1 after 14 days. All 5 COVID-19 positive patients required hospitalization, 4 suffered severe pneumonia, 1 died from COVID-19 and 2 died from cancer related causes. In comparison, the mortality rate for the COVID-19 negative patients was 3.3%. Conclusion: Despite the impact of COVID-19 in health provision, a large number of our GU patients at Guy’s Cancer Centre safely received SACT. Our results suggest that the continuation of SACT during the COVID-19 pandemic did not increase the risk of COVID-19 in our patient cohort (SARS-CoV-2 infection rate: 1%). Of note, the infection rate was lower than observed in a similar study in our centre for gastrointestinal cancer patients (SARS-CoV-2 infection rate: 3.4%). In light of the above, decisions against SACT or SACT intensity should carefully be evaluated. Citation Format: Christina Karampera, Beth Russell, Charlotte Moss, Rushan Sylva, Kieran Palmer, Elias Pintus, Sarah Rudman, Debra Josephs, Kamarul Zaki, Mieke Van Hemelrijck, Saoirse Dolly, Deborah Enting. Real world data analysis of patients with genitourinary cancers receiving systemic anticancer treatment during the COVID-19 pandemic at Guy's Cancer Centre: A single centre retrospective study in the UK [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S09-03.
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- 2021
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15. Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and cognition in patients with metastatic castration-resistant prostate cancer: initial results from the observational AQUARiUS study
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Louis Marie Dourthe, Guillaume Ploussard, M Lukac, Suzy Van Sanden, Dominique Beal-Ardisson, Geneviève Pissart, Redas Trepiakas, Laurent Antoni, Elias Pintus, Alison Reid, Antoine Thiery-Vuillemin, Mads Hvid Poulsen, Edouard Lagneau, and A. Birtle
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,03 medical and health sciences ,Prostate cancer ,chemistry.chemical_compound ,0302 clinical medicine ,Quality of life ,Prednisone ,Internal medicine ,medicine ,Enzalutamide ,Original Research ,enzalutamide ,business.industry ,Abiraterone acetate ,Cancer ,Cognition ,medicine.disease ,030104 developmental biology ,Oncology ,chemistry ,abiraterone acetate ,metastatic castration-resistant prostate cancer ,patient-reported outcomes ,030220 oncology & carcinogenesis ,Observational study ,business ,medicine.drug - Abstract
Introduction Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are commonly prescribed for metastatic castration-resistant prostate cancer (mCRPC). Data comparing their effects on patient-reported outcomes (PROs) from routine clinical practice are limited. Methods AQUARiUS (NCT02813408) is an ongoing, two-cohort, prospective, observational, non-randomised, multicentre, phase IV European study assessing the effects of AAP and ENZ on PROs in 211 patients with mCRPC over 12 months. Patients receive AAP or ENZ per routine clinical practice. Data on cognition, fatigue, pain and health-related quality of life are measured using the Functional Assessment of Cancer Therapy-Cognitive Function, Brief Fatigue Inventory-Short Form, Brief Pain Inventory-Short Form and European Organization for Research and Treatment of Cancer Quality of Life-C30 questionnaires, respectively. Results This 3-month analysis was conducted in 105 patients; 46 received AAP and 59 received ENZ. There were statistically significant differences in mean change from baseline favouring AAP over ENZ at months 1, 2 and 3 for perceived cognitive impairments and cognitive functioning. At each time-point, ENZ-treated patients had a significantly higher risk of experiencing clinically meaningful worsening in perceived cognitive impairments versus those receiving AAP. Statistically significant differences in mean change from baseline favouring AAP over ENZ were seen for usual level of fatigue and fatigue interference at months 2 and 3 and for current fatigue and worse level of fatigue at month 3. Differences favouring AAP versus ENZ were seen for the fatigue scale of the QLQ-C30 questionnaire (months 1 and 3). There was a significantly higher risk of clinically meaningful worsening in usual level of fatigue with ENZ versus AAP at month 3. No significant differences between cohorts were observed for pain (BPI-SF) at any time-point. Conclusion This analysis suggests more favourable outcomes with AAP versus ENZ for cognition and fatigue in the first 3 months of treatment initiation for mCRPC. These findings require confirmation from future analyses of data from AQUARiUS from a larger number of patients with a longer follow-up period.
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- 2018
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16. Genomic profiling of patients with metastatic castration-resistant prostate cancer (mCRPC) for the evaluation of rucaparib: Next-generation sequencing (NGS) of tumour tissue and cell-free DNA (cfDNA)
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Peter Ostler, D. Spaeth, Charles J. Ryan, I. Mejlholm, M.N. Reaume, Simon Chowdhury, E.R. Goldfischer, Raymond S. McDermott, A. Loehr, I. Byard, B. Laguerre, Elias Pintus, J.M. Piulats, Wassim Abida, David Campbell, E. Voog, A. Benjelloun, Arif Hussain, A. Reid, J. Burke, T. Golsorkhi, Simon Paul Watkins, Jeremy Shapiro, and D. Morris
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Genomic profiling ,business.industry ,Urology ,Castration resistant ,medicine.disease ,DNA sequencing ,Tumour tissue ,chemistry.chemical_compound ,Prostate cancer ,Cell-free fetal DNA ,chemistry ,Cancer research ,Medicine ,business ,Rucaparib - Published
- 2019
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17. No longer any role for routine follow-up chest x-rays in men with stage I germ cell cancer
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Anand Sharma, E Bataillard, Andrew Protheroe, C Glicksman, Mark Tuthill, Zoe Traill, Johnson Joseph, Marcia Hall, Clare Verrill, Andrew Gogbashian, J Redgwell, Manil Subesinghe, Mark Sullivan, N Dallas, Elias Pintus, and H De La Pena
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Male ,Cancer Research ,Lung Neoplasms ,Databases, Factual ,Cost-Benefit Analysis ,0302 clinical medicine ,030212 general & internal medicine ,Orchiectomy ,Young adult ,Child ,Aged, 80 and over ,Health Care Costs ,Middle Aged ,Neoplasms, Germ Cell and Embryonal ,Radiation Exposure ,Cost savings ,Multicenter Study ,medicine.anatomical_structure ,Treatment Outcome ,Oncology ,England ,030220 oncology & carcinogenesis ,Predictive value of tests ,Radiography, Thoracic ,Radiology ,Adult ,medicine.medical_specialty ,Adolescent ,Unnecessary Procedures ,Radiation Dosage ,03 medical and health sciences ,Young Adult ,Testicular Neoplasms ,Cost Savings ,Predictive Value of Tests ,medicine ,Biomarkers, Tumor ,Journal Article ,Humans ,Testicular cancer ,Aged ,Neoplasm Staging ,Lung ,business.industry ,Cancer ,medicine.disease ,Surgery ,business ,Tomography, X-Ray Computed ,Stage I Testicular Cancer - Abstract
Following radical orchidectomy for testicular cancer, most patients undergo protocolled surveillance to detect tumour recurrences rather than receive adjuvant chemotherapy. Current United Kingdom national and most international guidelines recommend that patients require a chest x-ray (CXR) and serum tumour markers at each follow-up visit as well as regular CT scans; there is however, variation among cancer centres with follow-up protocols. Seminomas often do not cause tumour marker elevation; therefore, CT scans are the main diagnostic tool for detecting relapse. For non-seminomatous tumours, serum beta-HCG (HCG) and AFP levels are a very sensitive harbinger of relapse, but this only occurs in 50% of patients [1], and therefore, imaging remains as important. CXRs are meant to aid in the detection of lung recurrences and before the introduction of modern cross-sectional imaging in the early 1980s, CXRs would have been the only method of identifying lung metastasis. We examined the Thames Valley and Mount Vernon Cancer Centre databases to evaluate the role of CXRs in the 21st century for the follow-up of men with stage I testicular cancer between 2003 and 2015 to assess its value in diagnosing relapsed germ cell tumours. From a total of 1447 patients, we identified 159 relapses. All relapses were detected either by rising tumour markers or planned follow-up CT scans. Not a single relapse was identified on CXR. We conclude that with timely and appropriate modern cross-sectional imaging and tumour marker assays, the CXR no longer has any value in the routine surveillance of stage I testicular cancer and should be removed from follow-up guidelines and clinical practice. Omitting routine CXR from follow-up schedules will reduce anxiety as well as time that patients spend at hospitals and result in significant cost savings.
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- 2017
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18. Initial results from AQUARiUS, a prospective, observational, multi-centre phase IV study assessing patient-reported outcomes (PROs) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with abiraterone acetate plus prednisone (AAP) or enzalutamide (ENZ)
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Guillaume Ploussard, Redas Trepiakas, A. Reid, Dominique Beal-Ardisson, Louis-Marie Dourthe, L. Dearden, Antoine Thiery-Vuillemin, Elias Pintus, Mads Hvid Poulsen, Edouard Lagneau, S. Van Sanden, A. Birtle, and M Lukac
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Oncology ,medicine.medical_specialty ,business.industry ,Abiraterone acetate ,Hematology ,Castration resistant ,medicine.disease ,Surgery ,chemistry.chemical_compound ,Prostate cancer ,chemistry ,Prednisone ,Internal medicine ,medicine ,Enzalutamide ,Observational study ,Multi centre ,business ,medicine.drug - Published
- 2017
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19. Genomic profiling of circulating tumour DNA (ctDNA) and tumour tissue for the evaluation of rucaparib in metastatic castration-resistant prostate cancer (mCRPC)
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I. Mejlholm, Wassim Abida, Albert Font, Arif Hussain, Andrew Simmons, Peter Ostler, Simon Paul Watkins, Gurkamal Chatta, Simon Chowdhury, E.R. Goldfischer, I. Dumbadze, A. Benjelloun, Raymond S. McDermott, A. Loehr, Elias Pintus, Sheela Tejwani, Mitchell E. Gross, David L. Morris, Jeremy Shapiro, and Josep M. Piulats
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Genomic profiling ,business.industry ,Hematology ,Castration resistant ,medicine.disease ,03 medical and health sciences ,Tumour tissue ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,030212 general & internal medicine ,Rucaparib ,business ,DNA - Published
- 2018
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20. Six-month patient-reported outcome (PRO) results from AQUARiUS, a prospective, observational, multicenter phase 4 study in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone acetate + prednisone (AAP) or enzalutamide (ENZ)
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Antoine Thiery Vuillemin, Paul Robinson, Guillaume Ploussard, Dominique Beal-Ardisson, Mads Hvid Poulsen, Hervé Besson, Edouard Lagneau, Redas Trepiakas, A. Reid, Alison Birtle, Elias Pintus, M Lukac, and Louis-Marie Dourthe
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,030232 urology & nephrology ,Abiraterone acetate ,Castration resistant ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,0302 clinical medicine ,chemistry ,Prednisone ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Enzalutamide ,Observational study ,In patient ,Patient-reported outcome ,business ,medicine.drug - Abstract
5058Background: AQUARiUS is an ongoing study of PROs and medical resource use in chemotherapy-naive pts with mCRPC newly initiated on AAP or ENZ in a real-world setting. Initial 3-month (mo) subset...
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- 2018
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21. 129 Treating non small cell lung cancer with erlotinib: the Nurse Led clinic experience
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Elias Pintus, James Spicer, S. Eestila, Rohit Lal, Ana Montes, R. Thomas, P. Tindale-Paul, Vasiliki Michalarea, S. Compton, and M. Colvin
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Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.disease ,Nurse-led clinic ,Internal medicine ,Medicine ,Erlotinib ,Non small cell ,business ,Intensive care medicine ,Lung cancer ,medicine.drug - Published
- 2013
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22. Characteristics and survival of advanced non-small cell lung cancer (NSCLC) in young Black patients: a Guy’s Cancer Centre real-world study
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Daniel Johnathan Hughes, Matthaios Kapiris, Andreja Podvez Nevajda, Chara Stavraka, Gary Cook, Debra Josephs, Sharmistha Ghosh, Elias Pintus, Spyridon Gennatas, Shahreen Ahmed, George Santis, Kimuli Ryanna, Ana Montes, Daniel Smith, Eleni Karapanagiotou, Mieke Van Hemelrijck, James Spicer, and Alexandros Georgiou
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