المؤلفون: Alan C. Cameron, MBChB, PhD, Kelly McMahon, BSc, Mark Hall, MBChB, Karla B. Neves, PhD, Francisco J. Rios, PhD, Augusto C. Montezano, PhD, Paul Welsh, PhD, Ashita Waterston, MBChB, PhD, Jeff White, MBChB, DM, Patrick B. Mark, MBChB, PhD, Rhian M. Touyz, MBBCh, PhD, Ninian N. Lang, MBChB, PhD

المصدر: JACC. CardioOncology, Vol 2, Iss 3, Pp 443-455 (2020)

مصطلحات موضوعية: germ cell tumors, platinum therapy, testicular cancer, thrombosis, Diseases of the circulatory (Cardiovascular) system, RC666-701, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Cisplatin-based chemotherapy increases the risk of cardiovascular and renal disease. Objectives: We aimed to define the time course, pathophysiology, and approaches to prevent cardiovascular disease associated with cisplatin-based chemotherapy. Methods: Two cohorts of patients with a history of testicular cancer (n = 53) were recruited. Cohort 1 consisted of 27 men undergoing treatment with: 1) surveillance; 2) 1 to 2 cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (low-intensity cisplatin); or 3) 3 to 4 cycles of BEP (high-intensity cisplatin). Endothelial function (percentage flow-mediated dilatation) and cardiovascular biomarkers were assessed at 6 visits over 9 months. Cohort 2 consisted of 26 men previously treated 1 to 7 years ago with surveillance or 3 to 4 cycles BEP. Vasomotor and fibrinolytic responses to bradykinin, acetylcholine, and sodium nitroprusside were evaluated using forearm venous occlusion plethysmography. Results: In cohort 1, the percentage flow-mediated dilatation decreased 24 h after the first cisplatin dose in patients managed with 3 to 4 cycles BEP (10.9 ± 0.9 vs. 16.7 ± 1.6; p < 0.01) but was unchanged from baseline thereafter. Six weeks after starting 3 to 4 cycles BEP, there were increased serum cholesterol levels (7.2 ± 0.5 mmol/l vs. 5.5 ± 0.2 mmol/l; p = 0.01), hemoglobin A1c (41.8 ± 2.0 mmol/l vs. 35.5 ± 1.2 mmol/l; p < 0.001), von Willebrand factor antigen (62.4 ± 5.4 mmol/l vs. 45.2 ± 2.8 mmol/l; p = 0.048) and cystatin C (0.91 ± 0.07 mmol/l vs. 0.65 ± 0.09 mmol/l; p < 0.01). In cohort 2, intra-arterial bradykinin, acetylcholine, and sodium nitroprusside caused dose-dependent vasodilation (p < 0.0001). Vasomotor responses, endogenous fibrinolytic factor release, and cardiovascular biomarkers were not different in patients managed with 3 to 4 cycles of BEP versus surveillance. Conclusions: Cisplatin-based chemotherapy induces acute and transient endothelial dysfunction, dyslipidemia, hyperglycemia, and nephrotoxicity in the early phases of treatment. Cardiovascular and renal protective strategies should target the early perichemotherapy period. (Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer [VECTOR], NCT03557177; Intermediate and Long Term Vascular Effects of Cisplatin in Patients With Testicular Cancer [INTELLECT], NCT03557164)

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666087320301514Test; https://doaj.org/toc/2666-0873Test

الوصول الحر: https://doaj.org/article/0d964defbf61439cbf51ef4f12911b48Test

المؤلفون: Ashita Waterston, Jeff White, Mark A Baxter, Graham MacDonald, Jahangeer Malik, Alistair Law, Åsa Dahle-Smith, Walter Mmeka, Roland Donat, Cj Shukla, John Connor, Colin Houston

المصدر: BMJ Open Quality, Vol 9, Iss 1 (2020)

مصطلحات موضوعية: Medicine (General), R5-920

الوصف: Testicular cancer is the most common malignancy in young adult men. The prognosis is excellent in limited disease and cure is possible even in advanced disease. Quality performance indicators (QPI) are used in many developed countries as a measure of healthcare performance. We report and discuss the development of a national set of QPIs in Scotland for testicular cancer as a method of gathering demographic data and driving improvement in nationwide testicular cancer outcomes.

وصف الملف: electronic resource

العلاقة: https://bmjopenquality.bmj.com/content/9/1/e000726.fullTest; https://doaj.org/toc/2399-6641Test

الوصول الحر: https://doaj.org/article/69a95f666a3d4ac5b1edff8b1dfe317aTest

المؤلفون: Timothy Iveson, Kathleen A Boyd, Rachel S Kerr, Jose Robles-Zurita, Mark P Saunders, Andrew H Briggs, Jim Cassidy, Niels Henrik Hollander, Josep Tabernero, Andrew Haydon, Bengt Glimelius, Andrea Harkin, Karen Allan, John McQueen, Sarah Pearson, Ashita Waterston, Louise Medley, Charles Wilson, Richard Ellis, Sharadah Essapen, Amandeep S Dhadda, Mark Harrison, Stephen Falk, Sherif Raouf, Charlotte Rees, Rene K Olesen, David Propper, John Bridgewater, Ashraf Azzabi, David Farrugia, Andrew Webb, David Cunningham, Tamas Hickish, Andrew Weaver, Simon Gollins, Harpreet Wasan, James Paul

المصدر: Health Technology Assessment, Vol 23, Iss 64 (2019)

مصطلحات موضوعية: oxaliplatin, capecitabine, disease-free survival, chemotherapy, adjuvant, quality-adjusted life-years, colorectal neoplasms, fluorouracil, randomised controlled trial, Medical technology, R855-855.5

الوصف: Background: Oxaliplatin and fluoropyrimidine chemotherapy administered over 6 months is the standard adjuvant regimen for patients with high-risk stage II or III colorectal cancer. However, the regimen is associated with cumulative toxicity, characterised by chronic and often irreversible neuropathy. Objectives: To assess the efficacy of 3-month versus 6-month adjuvant chemotherapy for colorectal cancer and to compare the toxicity, health-related quality of life and cost-effectiveness of the durations. Design: An international, randomised, open-label, non-inferiority, Phase III, parallel-group trial. Setting: A total of 244 oncology clinics from six countries: UK (England, Scotland, Wales and Northern Ireland), Denmark, Spain, Sweden, Australia and New Zealand. Participants: Adults aged ≥ 18 years who had undergone curative resection for high-risk stage II or III adenocarcinoma of the colon or rectum. Interventions: The adjuvant treatment regimen was either oxaliplatin and 5-fluorouracil or oxaliplatin and capecitabine, randomised to be administered over 3 or 6 months. Main outcome measures: The primary outcome was disease-free survival. Overall survival, adverse events, neuropathy and health-related quality of life were also assessed. The main cost categories were chemotherapy treatment and hospitalisation. Cost-effectiveness was assessed through incremental cost comparisons and quality-adjusted life-year gains between the options and was reported as net monetary benefit using a willingness-to-pay threshold of £30,000 per quality-adjusted life-year per patient. Results: Recruitment is closed. In total, 6088 patients were randomised (3044 per group) between 27 March 2008 and 29 November 2013, with 6065 included in the intention-to-treat analyses (3-month analysis, n = 3035; 6-month analysis, n = 3030). Follow-up for the primary analysis is complete. The 3-year disease-free survival rate in the 3-month treatment group was 76.7% (standard error 0.8%) and in the 6-month treatment group was 77.1% (standard error 0.8%), equating to a hazard ratio of 1.006 (95% confidence interval 0.909 to 1.114; p-value for non-inferiority = 0.012), confirming non-inferiority for 3-month adjuvant chemotherapy. Frequent adverse events (alopecia, anaemia, anorexia, diarrhoea, fatigue, hand–foot syndrome, mucositis, sensory neuropathy, neutropenia, pain, rash, altered taste, thrombocytopenia and watery eye) showed a significant increase in grade with 6-month duration; the greatest difference was for sensory neuropathy (grade ≥ 3 was 4% for 3-month vs.16% for 6-month duration), for which a higher rate of neuropathy was seen for the 6-month treatment group from month 4 to ≥ 5 years (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1366-5278Test; https://doaj.org/toc/2046-4924Test

الوصول الحر: https://doaj.org/article/4215111445164519a465163178fd46e0Test

المؤلفون: Colin R. Lindsay, Pavlina Spiliopoulou, Ashita Waterston

المصدر: Therapeutic Advances in Medical Oncology, Vol 7 (2015)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Until recently, treatment for metastatic melanoma was characterised by a limited availability of treatment options that offer objective survival benefit. Cytotoxic agents fundamentally lack the ability to achieve disease control and cytokine therapy with interleukin-2 has an unacceptably high – for the use across all patient cohorts – rate of toxicities. The validation of braf as an oncogene driving melanoma tumorigenesis, as well as the discovery of the role of CTLA-4 receptor in the evasion of anticancer immune response by melanoma, has revolutionised our treatment options against a disease with dismal prognosis. Quick implementation of translational discoveries brought about BRAF/MEK inhibition in clinic, while at the same time, wider experience with CTLA-4 blockade enabled clinicians to manage previously fatal immune-related toxicities with greater confidence. The suitability for clinical use of other oncogenic drivers such as NRAS and c-kit is currently being tested whilst the PD-1/PD-L1/PD-L2 axis has emerged as a new immunotherapy target with exciting early phase results. The recent exponential progress in treatment of melanoma has set an example of translational medicine and the current review aims to explain why, as well as suggesting new goals for the future.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1758-8340Test; https://doaj.org/toc/1758-8359Test

الوصول الحر: https://doaj.org/article/0ad40af4f5794602b70b9c21e4973ad8Test

المؤلفون: Clyde, Great Western Road, Glasgow G Yn, Uk, Karen Mactier, C. Barrie, A. Law, Graham MacDonald, Navya Bezawada, Jeff White, Arthur Norton, Walter Mmeka, Allan Drummond, Jahangeer Malik, Ashita Waterston, Colin Muir

المصدر: Journal of the Royal College of Physicians of Edinburgh. 51:53-57

مصطلحات موضوعية: medicine.medical_specialty, business.industry, Advanced stage, General Medicine, Disease, Malignancy, medicine.disease, Multidisciplinary team, Education, medicine.anatomical_structure, medicine, Routine clinical practice, Intensive care medicine, business, Germ cell, Testicular cancer

الوصف: Testicular cancer is the most common malignancy in young men. We discuss four cases of germ cell tumours (GCTs) presenting to general practitioners and physicians where there were notable preventable delays in the diagnosis and management. This diagnostic delay is associated with a more advanced stage of disease, and subsequent increased treatment-related morbidity and decreased survival. Our series highlights the variety of ways in which GCTs may present and we discuss the importance of prompt diagnosis through a thorough history and examination, early measurement of serum tumour markers and appropriate multidisciplinary team discussion. GCTs are highly curable cancers in the majority of patients and delays in management can, therefore, have devastating consequences.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::55a65118b89baef0e2372d5c78136343Test
https://doi.org/10.4997/jrcpe.2021.113Test

المؤلفون: Vikas Chadha, Paul Cauchi, Wilma Kincaid, Ashita Waterston, Stefano Schipani, Sachin Salvi, Oliver Cram, Diana Ritchie

المصدر: Eye (London, England).

مصطلحات موضوعية: Ophthalmology

الوصف: Ophthalmic treatments are successful in managing uveal melanomas achieving good local control. However, a large number still metastasise, primarily to the liver, resulting in mortality. There is no consensus across the world on the mode, frequency, duration or utility of regular liver surveillance for metastasis and there are no published protocols. The Scottish Ocular Oncology Service (SOOS) constituted a Scottish Consensus Statement Group (SCSG) which included ocular oncologists, medical oncologists, radiologists and a uveal melanoma patient as a lay member. This group carried out an extensive review of literature followed by discussions to arrive at a consensus regarding surveillance planning for posterior uveal melanoma patients in Scotland. The Consensus Statement would provide a framework to guide each patient's surveillance plan and provide all patients with clarity and transparency on the issue. The SCSG was unable to find adequate evidence on which to base the strategy. The consensus statement recommends a risk-stratified approach to surveillance for these patients dividing them into low to medium-risk and high-risk groups defining the mode and duration of surveillance for each. It supplements the UK-wide Uveal Melanoma National Guidelines and allows a more uniform consensus-based approach to surveillance in Scotland. It has been adopted nationally by all health care providers in Scotland as a guideline and is available to patients on a publicly accessible website.摘要: 眼科能成功治疗葡萄膜黑色素瘤, 并有效控制葡萄膜黑色素瘤的发展转移。尽管如此, 仍有大量患者发生转移, 葡萄膜黑色素瘤主要转移到肝脏并导致死亡。目前世界上关于葡萄膜黑色素瘤肝脏转移定期监测的模式、频率、持续时间及实用程度并没有共识, 且没有已发表的方案。苏格兰眼肿瘤协会(SOOS)建立了苏格兰共识声明小组(SCSG), 小组成员包括眼肿瘤医生、肿瘤科医生、放射科医生以及一位作为非专业人员的葡萄膜黑色素瘤患者。该小组对文献进行了广泛回顾和讨论, 并且对苏格兰后葡萄膜黑色素瘤患者的监测达成共识。该共识声明小组将提出框架以指导每位患者的病情监测, 并且在病情上对所有患者保持公开透明。SCSG并未找到充足证据作为该策略的基础。该临床共识建议将所有患者根据风险分级分为低、中、高风险组, 定义每个组的监测模式及持续时间。该共识补充说明了全英国葡萄膜黑色素瘤国家指南, 并促使在苏格兰采用更统一的并基于共识的监测方法。它已在全苏格兰内被所有医生作为指南, 并向患者提供一个公众开放的网站。.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d16d8a06dea63cee09fed8c0c5d6f7d3Test
https://pubmed.ncbi.nlm.nih.gov/35945341Test

المؤلفون: Paul Welsh, Ashita Waterston, Augusto C. Montezano, Francisco J. Rios, Jeff White, Karla B Neves, Rhian M. Touyz, Patrick B. Mark, Kelly R. McMahon, Alan C. Cameron, Mark Hall, Ninian N. Lang

المصدر: Jacc. Cardiooncology
JACC. CardioOncology, Vol 2, Iss 3, Pp 443-455 (2020)
JACC: CardioOncology

مصطلحات موضوعية: Oncology, lcsh:Diseases of the circulatory (Cardiovascular) system, medicine.medical_specialty, medicine.medical_treatment, cisplatin, BEP, bleomycin, etoposide and cisplatin, vWF, von Willebrand factor, atherosclerosis, cancer, chemotherapy, Bleomycin, lcsh:RC254-282, endothelial dysfunction, Nephrotoxicity, ICAM, intracellular adhesion molecule, chemistry.chemical_compound, Internal medicine, platinum therapy, medicine, 0FMD, flow-mediated dilatation, Endothelial dysfunction, germ cell tumors, t-PA, tissue plasminogen activator, Testicular cancer, Etoposide, thrombosis, Original Research, Cisplatin, Chemotherapy, business.industry, ACh, acetylcholine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, testicular cancer, chemistry, lcsh:RC666-701, Cohort, SNP, sodium nitroprusside, PAI, plasminogen activator inhibitor, vasoreactivity, FBF, forearm blood flow, Cardiology and Cardiovascular Medicine, business, BK, bradykinin, Editorial Comment, medicine.drug

الوصف: Background Cisplatin-based chemotherapy increases the risk of cardiovascular and renal disease. Objectives We aimed to define the time course, pathophysiology, and approaches to prevent cardiovascular disease associated with cisplatin-based chemotherapy. Methods Two cohorts of patients with a history of testicular cancer (n = 53) were recruited. Cohort 1 consisted of 27 men undergoing treatment with: 1) surveillance; 2) 1 to 2 cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (low-intensity cisplatin); or 3) 3 to 4 cycles of BEP (high-intensity cisplatin). Endothelial function (percentage flow-mediated dilatation) and cardiovascular biomarkers were assessed at 6 visits over 9 months. Cohort 2 consisted of 26 men previously treated 1 to 7 years ago with surveillance or 3 to 4 cycles BEP. Vasomotor and fibrinolytic responses to bradykinin, acetylcholine, and sodium nitroprusside were evaluated using forearm venous occlusion plethysmography. Results In cohort 1, the percentage flow-mediated dilatation decreased 24 h after the first cisplatin dose in patients managed with 3 to 4 cycles BEP (10.9 ± 0.9 vs. 16.7 ± 1.6; p < 0.01) but was unchanged from baseline thereafter. Six weeks after starting 3 to 4 cycles BEP, there were increased serum cholesterol levels (7.2 ± 0.5 mmol/l vs. 5.5 ± 0.2 mmol/l; p = 0.01), hemoglobin A1c (41.8 ± 2.0 mmol/l vs. 35.5 ± 1.2 mmol/l; p < 0.001), von Willebrand factor antigen (62.4 ± 5.4 mmol/l vs. 45.2 ± 2.8 mmol/l; p = 0.048) and cystatin C (0.91 ± 0.07 mmol/l vs. 0.65 ± 0.09 mmol/l; p < 0.01). In cohort 2, intra-arterial bradykinin, acetylcholine, and sodium nitroprusside caused dose-dependent vasodilation (p < 0.0001). Vasomotor responses, endogenous fibrinolytic factor release, and cardiovascular biomarkers were not different in patients managed with 3 to 4 cycles of BEP versus surveillance. Conclusions Cisplatin-based chemotherapy induces acute and transient endothelial dysfunction, dyslipidemia, hyperglycemia, and nephrotoxicity in the early phases of treatment. Cardiovascular and renal protective strategies should target the early perichemotherapy period. (Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer [VECTOR], NCT03557177; Intermediate and Long Term Vascular Effects of Cisplatin in Patients With Testicular Cancer [INTELLECT], NCT03557164)
Central Illustration

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b7b0e33ae5e1978d0b80127f30701a6Test
http://europepmc.org/articles/PMC7539369Test

المؤلفون: Maria Oto, Natasha E. Fullerton, Emanuela Molinari, Ashita Waterston

المصدر: Cerebellum & Ataxias, Vol 6, Iss 1, Pp 1-12 (2019)
Cerebellum & Ataxias

مصطلحات موضوعية: medicine.medical_specialty, Neurology, Rehabilitation, Posterior Fossa syndrome, business.industry, Cerebellar mutism syndrome, medicine.medical_treatment, Modafinil, Cognition, Review, behavioral, lcsh:RC346-429, Mood, Physical medicine and rehabilitation, medicine, Neurology (clinical), Neurosurgery, Disengagement theory, business, Neurorehabilitation, lcsh:Neurology. Diseases of the nervous system, medicine.drug

الوصف: Disorders of the cerebellum may present with motor, cognitive, behavioral and affective symptoms. There is a growing interest in developing neuroanatomical models of symptoms generation that involve the cerebellum and the cerebello-cortical connections. We describe an exciting first case report of successful use of Modafinil in an adult patient with post-operative posterior fossa syndrome. Following resection of a melanoma metastasis in the cerebellum the patient developed striking affective and behavioral symptoms in the form of withdrawn flat mood and disengagement. This neurobehavioral presentation severely impacted on his quality of life, independence, and ability to engage in the neuro-rehabilitative program. Pharmacological treatment with Modafinil ameliorated these emotional and behavioral aspects, and also fatigue. Treatment with Modafinil hence affected recovery and outcome for the patient. To our knowledge, this is the first description of a successful pharmacological intervention in an adult with post-surgical posterior fossa syndrome and negative neurobehavioral presentation. Our findings illustrate the variability of the presentation of post-operative posterior fossa syndrome in adults, and the importance of delivering targeted treatment to maximize the benefits of neurorehabilitation. The manuscript highlights the following points: 1. post-operative consequences currently under the wide umbrella of posterior fossa syndrome, can indeed manifest in adults; 2. a wide spectrum of neurobehavioral symptoms can occur, including a presentation with predominantly negative features; 3. the type of neurobehavioral presentation should guide the treatment choice with particular consideration of drugs that potentially modulate the cerebello-frontal connections; 4. Modafinil can be a candidate for effective treatment in presentations with predominantly negative behavioral symptoms.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bc96db9f893d68629529c0560828c90Test
http://link.springer.com/article/10.1186/s40673-019-0105-6Test

المؤلفون: Claire Glen, Yun Yi Tan, Ashita Waterston, Thomas R. Jeffry Evans, Robert J. Jones, Mark C. Petrie, Ninian N. Lang

المصدر: JACC. CardioOncology. 4(1)

مصطلحات موضوعية: Oncology, Cardiology and Cardiovascular Medicine

الوصف: Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized melanoma treatment. Approximately half of patients with melanoma harbor a BRAF gene mutation with subsequent dysregulation of the RAF-MEK-ERK signaling pathway. Targeting this pathway with BRAF and MEK blockade results in control of cell proliferation and, in most cases, disease control. These pathways also have cardioprotective effects and are necessary for normal vascular and cardiac physiology. BRAF and MEK inhibitors are associated with adverse cardiovascular effects including hypertension, left ventricular dysfunction, venous thromboembolism, atrial arrhythmia, and electrocardiographic QT interval prolongation. These effects may be underestimated in clinical trials. Baseline cardiovascular assessment and follow-up, including serial imaging and blood pressure assessment, are essential to balance optimal anti-cancer therapy while minimizing cardiovascular side effects. In this review, an overview of BRAF/MEK inhibitor-induced cardiovascular toxicity, the mechanisms underlying these, and strategies for surveillance, prevention, and treatment of these effects are provided.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c4c2007f08f8246d34ad5bac364bdddTest
https://pubmed.ncbi.nlm.nih.gov/35492830Test

المؤلفون: Christoph Hoeller, Marie-Francoise Avril, Pietro Quaglino, François Aubin, Lars Bastholt, Takashi Inozume, Virginia Ferraresi, Michael B. Jameson, Kevin B. Kim, Oliver Bechter, Dirk Schadendorf, Kenji Yokota, Carmen Loquai, Maria-Jose Passos, Inge Marie Svane, Michele Maio, Catherine Barrow, Frank Meiss, Nageatte Ibrahim, Andrzej Mackiewicz, Phillip Parente, Tatsuya Takenouchi, Caroline Dutriaux, Piotr Rutkowski, Alfonsus J M van den Eertwegh, Paola Queirolo, Catriona M. McNeil, Peter Mohr, Felix Kiecker, Susana Puig, Friedegund Meier, Lutz Kretschmer, Alexander C.J. van Akkooi, Alex Menzies, Timothy Crook, Christian U. Blank, Suzana Matkovic, Michael C. Brown, Ragini R. Kudchadkar, Max Levin, Rüdiger Hein, Tanja Skytta, Gerald P. Linette, Clemens Krepler, Adnan Khattak, Ernest Marshall, Joseph Kerger, Oddbjorn Straume, Laurent Mortier, Jochen Utikal, Micaela Hernberg, James Larkin, Yoshio Kiyohara, Mario Mandalà, Henrik Schmidt, Daniil Stroyakovskiy, Pablo Luis Ortiz Romero, Naoya Yamazaki, John Walker, Anna Maria Di Giacomo, Lionel Geoffrois, Jean-Philippe Lacour, Caroline Robert, Vincent Descamps, Shahneen Sandhu, Gil Bar-Sela, Paul C. Nathan, Marcin Dzienis, Ralf Gutzmer, Claus Garbe, Andrey Meshcheryakov, Patrick Combemale, Martin Fehr, Guzel Mukhametshina, Helena Kapiteijn, Geke A. P. Hospers, Jun Aoi, Andrew Haydon, Rutger H. T. Koornstra, Marie-Thérèse Leccia, Sigrun Hallmeyer, Pier Francesco Ferrucci, Jean-Jacques Grob, Leonel Hernandez-Aya, Jan-Christoph Simon, Vanna Chiarion Sileni, Alain Algazi, Lidija Sekulovic, Sandrine Marreaud, Bernard Fitzharris, Jacob Schachter, Xinni Song, Wolf-Henning Boehncke, Rahima Jamal, Paul Lorigan, Maureen J.B. Aarts, Reinhard Dummer, Mike McCrystal, César Martins, Reiner Hofmann-Wellenhof, Alexander M.M. Eggermont, Carola Berking, Elaine Dunwoodie, Bernard Guillot, Michal Kicinski, Philippe Saiag, Céleste Lebbé, Thierry Lesimple, Stefan Suciu, Michal Lotem, Paula Ferreira, Mohammed M. Milhem, Laurent Machet, Patrick Terheyden, Anna Katharina Winge-Main, Peter Hersey, Jean-Francois Baurain, Axel Hauschild, Stéphane Dalle, Jean-Philippe Arnault, Paolo A. Ascierto, Gerard Groenewegen, Florent Grange, Georgina V. Long, Victoria Atkinson, Philippa Corrie, Matteo S. Carlino, Thomas Jouary, Daniel Hendler, Richard Casasola, Ashita Waterston, Jessica C. Hassel

المساهمون: University Medical Center [Utrecht], Azienda Ospedaliera Ospedale Papa Giovanni XXIII [Bergamo, Italy], The University of Sydney, Princess Alexandra Hospital, Brisbane, University of Queensland [Brisbane], Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), N.N. Blokhin National Medical Research Center of Oncology, Edith Cowan University (ECU), Royal Marsden NHS Foundation Trust, Universitat de Barcelona (UB), Instituto de Salud Carlos III [Madrid] (ISC), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Radboud University Medical Center [Nijmegen], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University Hospital of Siena, Amsterdam UMC - Amsterdam University Medical Center, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Merck & Co. Inc, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Institut Gustave Roussy (IGR), Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Internal medicine, CCA - Cancer Treatment and quality of life

المصدر: EORTC Melanoma Group 2021, ' Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial ', The Lancet Oncology, vol. 22, no. 5, pp. 643-654 . https://doi.org/10.1016/S1470-2045Test(21)00065-6
Lancet Oncology, 22, 643-654
Lancet Oncology, 22, 5, pp. 643-654
Lancet Oncology
Lancet Oncology, 2021, 22 (5), pp.643-654. ⟨10.1016/S1470-2045(21)00065-6⟩
The Lancet Oncology, 22(5), 643-654. Lancet Publishing Group

مصطلحات موضوعية: Male, Skin Neoplasms, Medizin, Pembrolizumab, law.invention, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], MESH: Aged, 80 and over, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, 80 and over, MESH: Double-Blind Method, 030212 general & internal medicine, Neoplasm Metastasis, Humanized, Melanoma, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Hazard ratio, MESH: Neoplasm Staging, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Female, Adult, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Humans, Neoplasm Staging, medicine.medical_specialty, MESH: Melanoma, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Antibodies, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Adjuvant therapy, education, Cancer staging, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH: Adult, MESH: Neoplasm Metastasis, MESH: Male, Clinical trial, MESH: Antibodies, Monoclonal, Humanized, business, MESH: Female

الوصف: Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial assessed pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. At 15-month median follow-up, pembrolizumab improved recurrence-free survival (hazard ratio [HR] 0·57 [98·4% CI 0·43–0·74], p1 mm), IIIB, or IIIC (without in-transit metastasis), and with an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Patients were randomly assigned (1:1) via a central interactive voice response system to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for up to 18 doses or until disease recurrence or unacceptable toxicity. Randomisation was stratified according to disease stage and region, using a minimisation technique, and clinical investigators, patients, and those collecting or analysing the data were masked to treatment assignment. The two coprimary endpoints were recurrence-free survival in the intention-to-treat (ITT) population and in patients with PD-L1-positive tumours. The secondary endpoint reported here was distant metastasis-free survival in the ITT and PD-L1-positive populations. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37. Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to receive either pembrolizumab (n=514) or placebo (n=505). At an overall median follow-up of 42·3 months (IQR 40·5–45·9), 3·5-year distant metastasis-free survival was higher in the pembrolizumab group than in the placebo group in the ITT population (65·3% [95% CI 60·9–69·5] in the pembrolizumab group vs 49·4% [44·8–53·8] in the placebo group; HR 0·60 [95% CI 0·49–0·73]; p

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca46af8de45fdf5ffd9d70f717e94208Test
https://research.vumc.nl/en/publications/8aae177c-dfa8-4325-b8c2-e7b1d7339027Test