374 results on '"Institute Gustave Roussy"'
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2. Trends in self-reported past alcoholic beverage consumption and ethanol intake from 1950 to 1995 observed in eight European countries participating in the European Investigation into Cancer and Nutrition (EPIC)
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J. Linseisen, Françoise Clavel-Chapelon, Calogero Saieva, Heiner Boeing, Magritt Brustad, Aurelio Barricarte, Fabrizio Veglia, Matthias B. Schulze, P. H. M. Peeters, Nadia Slimani, C. Martínez Garcia, Göran Berglund, Ulrich Keil, Elio Riboli, Merethe Kumle, A. Papadimitrou, Kim Overvad, Pagona Lagiou, H. B. Bueno-De-Mesquita, Naomi E. Allen, Lars Weinehall, Kerstin Klipstein-Grobusch, Anne Tjønneland, Pietro Ferrari, Angela A. Mulligan, Vittorio Krogh, Anne C. M. Thiébaut, [Klipstein-Grobusch,K, Boeing,H, Schulze,MB] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany. [Slimani,N, Ferrari,P, Riboli,E] Unit of Nutrition and Cancer, International Agency for Cancer Research, Lyon, France. [Krogh,V] Epidemiology Unit, National Cancer Institute, Milan, Italy. [Keil,U] Department of Epidemiology and Social Medicine, University of Münster, German. [Overvad,K] Department of Epidemiology, University of Aarhus, Denmark. [Tjønneland,A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Clavel-Chapelon,F, Thiébaut,A] INSERM, E3N–EPIC Group, Institute Gustave Roussy, Villejuif, France. [Linseisen,J] Department of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Papadimitrou,A] Department of Hygiene and Epidemiology, School of Medicine, University of Athens, Greece. [Saieva,C] Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy. [Veglia,F] Institute for Scientific Interchange Foundation, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Chronic Disease Epidemiology, National Institute for Public Health and Environmental Protection, Bilthoven, The Netherlands. [Peeters,PHM] Julius Center for General Practice and Patient Oriented Research, University of Utrecht, The Netherland. [Kumle,M, Brustad,M] Institute of Community Medicine, University of Tromsø, Norway. [Martínez García,C] Andalusian School of Public Health, Granada, Spain. [Barricarte,A] Department of Epidemiology, Institute of Public Health of Navarra, Spain. [Berglund,G] Department of Medicine, Lund University, Malmö, Sweden. [Weinehal,G] Epidemiology, Public Health and Clinical Medicine, Umea University, Sweden. [Mulligan,A] Department of Public Health and Primary Care, University of Cambridge, UK. [Allen,N] Cancer Research UK, Cancer Epidemiology Unit, University of Oxford, UK., The work described in this paper was carried out with financial support of the ‘Europe Against Cancer’ Programme of the European Commission (SANCO), Ligue contre le Cancer (France), Société 3M (France), Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), Institute Gustave Roussy, German Cancer Aid, German Cancer Research Centre, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, the Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health,Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane, Sweden, Norwegian Cancer Society, and Norwegian Research Council. Partial support for the publication of this supplement was provided by the Centre de Recherche et d’Information Nutritionnelles (CERIN).
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Male ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings] ,Medicine (miscellaneous) ,Wine ,Distribución por Edad ,Estudios Retrospectivos ,EPIC ,Consumo de Bebidas Alcohólicas ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Recuerdo Mental ,Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Beer [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Population Surveillance [Medical Subject Headings] ,Medicine ,Masculino ,24-Hour dietary recall ,Nutrition and Dietetics ,Adulto ,Femenino ,Vino ,Beer ,Geographicals::Geographic Locations::Europe [Medical Subject Headings] ,Time trends ,European Prospective Investigation into Cancer and Nutrition ,Humanos ,Europe ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings] ,Disciplines and Occupations::Social Sciences::Demography::Sex Distribution [Medical Subject Headings] ,Population Surveillance ,Cerveza ,Female ,Distribución por Sexo ,Adult ,Alcohol Drinking ,Estudios Transversales ,Check Tags::Male [Medical Subject Headings] ,Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Memory::Mental Recall [Medical Subject Headings] ,Spirits ,Age Distribution ,Environmental health ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,Humans ,Europa (Continente) ,ddc:610 ,Disciplines and Occupations::Social Sciences::Demography::Age Distribution [Medical Subject Headings] ,Sex Distribution ,Retrospective Studies ,Consumption (economics) ,Ethanol ,business.industry ,Public Health, Environmental and Occupational Health ,Alcoholic beverage consumption ,Vigilancia de la Población ,Technology, Industry, Agriculture::Food and Beverages::Beverages::Alcoholic Beverages::Wine [Medical Subject Headings] ,EPIC study ,Cross-Sectional Studies ,Check Tags::Female [Medical Subject Headings] ,Mental Recall ,Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings] ,Alcoholic beverages ,Ethanol intake ,business ,Cross-sectional analyses - Abstract
Objective:To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC).Design:Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950–1975 (at age 20), 1960–1985 (at age 30) and 1970–1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time.Setting:The EPIC project.Subjects:In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries.Results:Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950–1975, 1960–1985 and 1970–1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption.Conclusion:The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.
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- 2002
3. COVID-19 in breast cancer patients: a subanalysis of the OnCovid registry
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Laia Garrigós, Cristina Saura, Clara Martinez-Vila, Alberto Zambelli, Mark Bower, Barbara Pistilli, Matteo Lambertini, Diego Ottaviani, Nikolaos Diamantis, Ailsa Lumsden, Sonia Pernas, Daniele Generali, Elia Seguí, Gemma Viñas, Eudald Felip, Ana Sanchez, Gianpiero Rizzo, Armando Santoro, Alessio Cortellini, Ylenia Perone, John Chester, Maria Iglesias, Marta Betti, Bruno Vincenzi, Michela Libertini, Francesca Mazzoni, Federica Zoratto, Rossana Berardi, Annalisa Guida, Rachel Wuerstlein, Angela Loizidou, Rachel Sharkey, Juan Aguilar Company, Marta Matas, Chiara Saggia, Lorenzo Chiudinelli, Emeline Colomba-Blameble, Myria Galazi, Uma Mukherjee, Mieke Van Hemelrijck, Mar Marin, Carla Strina, Aleix Prat, Helena Pla, Eva Maria Ciruelos, Alexia Bertuzzi, Lucia del Mastro, Giampiero Porzio, Thomas Newsom-Davis, Isabel Ruiz, Maria Belen Delany, Marco Krengli, Vittoria Fotia, Alessandro Viansone, Neha Chopra, Margarita Romeo, Ramon Salazar, Ignacio Perez, Francesca d’Avanzo, Michela Franchi, Manuela Milani, Fanny Pommeret, Marco Tucci, Paolo Pedrazzoli, Nadia Harbeck, Daniela Ferrante, David J. Pinato, Alessandra Gennari, Garrigos, L., Saura, C., Martinez-Vila, C., Zambelli, A., Bower, M., Pistilli, B., Lambertini, M., Ottaviani, D., Diamantis, N., Lumsden, A., Pernas, S., Generali, D., Segui, E., Vinas, G., Felip, E., Sanchez, A., Rizzo, G., Santoro, A., Cortellini, A., Perone, Y., Chester, J., Iglesias, M., Betti, M., Vincenzi, B., Libertini, M., Mazzoni, F., Zoratto, F., Berardi, R., Guida, A., Wuerstlein, R., Loizidou, A., Sharkey, R., Aguilar Company, J., Matas, M., Saggia, C., Chiudinelli, L., Colomba-Blameble, E., Galazi, M., Mukherjee, U., Van Hemelrijck, M., Marin, M., Strina, C., Prat, A., Pla, H., Ciruelos, E. M., Bertuzzi, A., del Mastro, L., Porzio, G., Newsom-Davis, T., Ruiz, I., Delany, M. B., Krengli, M., Fotia, V., Viansone, A., Chopra, N., Romeo, M., Salazar, R., Perez, I., D'Avanzo, F., Franchi, M., Milani, M., Pommeret, F., Tucci, M., Pedrazzoli, P., Harbeck, N., Ferrante, D., Pinato, D. J., Gennari, A., Institut Català de la Salut, [Garrigós L] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Saura C] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Head Breast Cancer Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Martinez-Vila C] Department of Oncology, Hospital Althaia Manresa, Barcelona, Spain. [Zambelli A] Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. [Bower M] Department of Oncology and National Centre for HIV Malignancy, Chelsea and Westminster Hospital, London, UK. [Pistilli B] Department of Medical Oncology, Institute Gustave-Roussy, Villejuif, France. [Aguilar Company J] Servei d’Oncologia Mèdica i Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Ruiz I] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pla H] Departament d'Oncologia Institut Català d'Oncologia, Hospital Universitari de Girona Doctor Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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medicine.medical_specialty ,Outcome assessment (Medical care) ,breast cancer ,COVID-19 ,COVID-19 outcomes ,OnCovid ,SARS-CoV-2 ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Population ,Context (language use) ,COVID-19 (Malaltia) - Mortalitat ,Disease ,técnicas de investigación::métodos epidemiológicos::recopilación de datos::estadísticas vitales::mortalidad [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Càncer de mama ,Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores] ,Breast cancer ,Mama - Càncer ,Internal medicine ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Medicine ,education ,COVID-19 outcome ,RC254-282 ,COVID-19 (Malaltia) - Complicacions ,Original Research ,education.field_of_study ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,business.industry ,Mortality rate ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,medicine.disease ,Comorbidity ,Oncology ,Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Avaluació de resultats (Assistència mèdica) ,business ,Complication ,Other subheadings::Other subheadings::/complications [Other subheadings] - Abstract
COVID-19; SARS-CoV-2; Cáncer de mama COVID-19; SARS-CoV-2; Càncer de mama COVID-19; SARS-CoV-2; Breast cancer Background: Cancer patients are at higher risk of COVID-19 complications and mortality than the rest of the population. Breast cancer patients seem to have better prognosis when infected by SARS-CoV-2 than other cancer patients. Methods: We report a subanalysis of the OnCovid study providing more detailed information in the breast cancer population. Results: We included 495 breast cancer patients with a SARS-CoV-2 infection. Mean age was 62.6 years; 31.5% presented more than one comorbidity. The most frequent breast cancer subtype was luminal-like (n = 245, 49.5%) and 177 (35.8%) had metastatic disease. A total of 332 (67.1%) patients were receiving active treatment, with radical intent in 232 (47.6%) of them. Hospitalization rate was 58.2% and all-cause mortality rate was 20.3%. One hundred twenty-nine (26.1%) patients developed one COVID-19 complication, being acute respiratory failure the most common (n = 74, 15.0%). In the multivariable analysis, age older than 70 years, presence of COVID-19 complications, and metastatic disease were factors correlated with worse outcomes, while ongoing anticancer therapy at time of COVID-19 diagnosis appeared to be a protective factor. No particular oncological treatment was related to higher risk of complications. In the context of SARS-CoV-2 infection, 73 (18.3%) patients had some kind of modification on their oncologic treatment. At the first oncological reassessment (median time: 46.9 days ± 36.7), 255 (51.6%) patients reported to be fully recovered from the infection. There were 39 patients (7.9%) with long-term SARS-CoV-2-related complications. Conclusion: In the context of COVID-19, our data confirm that breast cancer patients appear to have lower complications and mortality rate than expected in other cancer populations. Most breast cancer patients can be safely treated for their neoplasm during SARS-CoV-2 pandemic. Oncological treatment has no impact on the risk of SARS-CoV-2 complications, and, especially in the curative setting, the treatment should be modified as little as possible. D.J. Pinato is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416) and acknowledges grant support from the Cancer Treatment and Research Trust (CTRT), infrastructural and grant support by the Cancer Research UK Imperial Centre and the NIHR Imperial Biomedical Research Centre. A. Gennari is supported by the AIRC IG Grant, No. 14230, Associazione Italiana per la Ricerca sul Cancro Foundation, Milan, Italy and acknowledge also support from the UPO Aging Project.
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- 2021
4. The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk
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Berger, Eloïse, Maitre, Noële, Romana Mancini, Francesca, Baglietto, Laura, Perduca, Vittorio, Colineaux, Hélène, Sieri, S., Panico, Salvatore, Sacerdote, Carlotta, Tumino, Rosario, Vineis, Paolo, Boutron-Ruault, Marie Christine, Severi, Gianluca, Castagné, Raphaële, Delpierre, Cyrille, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pisa - Università di Pisa, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], IRCCS Istituto Nazionale dei Tumori [Milano], University of Naples Federico II, Città della Salute e della Scienza University-Hospital, Ragusa Cancer Registry, Imperial College London, Italian Institute for Genomic Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Ligue Contre le Cancer SHSESP 2017–130, This work was supported by La Ligue nationale contre le cancer [Equipe Labellisée LIGUE 2017/CD]). This study has been conducted by using data from the E3N cohort that is managed by Inserm and that has been created and is maintained thanks to the support of the MGEN, the Institute Gustave Roussy and « La Ligue contre le Cancer »., This work was supported by the French National Institute of Cancer [SHSESP 2017–130 to CD]. The funder had no role in the study design, analysis and interpretation of data and in writing the manuscript., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
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Adult ,Lifecourse socio-economic position ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Middle Aged ,Breast cancer ,Socioeconomic Factors ,Risk Factors ,Social mobility ,Humans ,Prospective cohorts ,Aged ,Female ,Research Article - Abstract
Background Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators. Methods We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data. Results In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy. Conclusions These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-020-07648-w.
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- 2020
5. Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study
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Petra H.M. Peeters, Kay-Tee Khaw, Guri Skeie, Ingegerd Johansson, NJ Wareham, Ursula Bachlechner, María José Sánchez, José María Huerta, Jasmine Neamat-Allah, Pietro Ferrari, Antonia Trichopoulou, Androniki Naska, Emily Sonested, Veronique Chajes, Elisabete Weiderpass, Marc J. Gunter, Carine Biessy, Anna Winkvist, Eva Ardanaz, Philippos Orfanos, Antonio Agudo, Franҫoise Clavel-Chapelon, Isabelle Romieu, Timothy J. Key, Paolo Vineis, Guy Fagherazzi, Miren Dorronsoro, Augustin Scalbert, Heinz Freisling, Nadia Slimani, Amalia Mattiello, Marianne Uhre Jakobsen, Verana Katzke, José Ramón Quirós, Valeria Pala, Dora Romaguera, Bas Bueno de Mesquita, Giovanna Masala, Heiner Boeing, Marie-Christine Boutron-Ruault, Inge Huybrechts, Camilla Plambeck Hansen, [Chajès,V, Biessy,C, Ferrari,P, Romieu,I, Freisling,H, Huybrechts,I, Scalbert,A, Sliman,N] Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France. [Bueno de Mesquita,B, Romaguera,D, Gunter,MJ, Vineis,P, Peeters,PHM] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. [Bueno de Mesquita,B] Department For Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Plambeck Hansen,C, Uhre Jakobsen,M] Department of Public Health, Section of Epidemiology, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Fagherazz,G, Boutron-Ruaul,M] INSERM, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. [Clavel- Chapelon,F, Boutron-Ruaul,M] University Paris Sud, UMRS 1018, Villejuif, France. [Clavel-Chapelon,F, Boutron-Ruaul,M] Institute Gustave Roussy, Villejuif, France. [Katzke,V, Neamat-Allah,J] The German Cancer Research Center (DKFZ), Heildelberg, Germany. [Boeing,H, Bachlechner,U] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Naska,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Pala,V] Epidemiology and Prevention Unit, IRCCS Foundation, National Cancer Institute, Milan, Italy. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Skeie,G, Weiderpass,E] Department of Community Medicine, University of Tromsø-The Arctic University of Norway, Norway. [Romaguera,D] Instituto de Investigacion Sanitaria de Palma (IdISPa) and CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Spain. [Agudo,A] Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Huerta,JM, Ardanaz,E, Sánchez,MJ] CIBER Epidemiology and Public Health CIBERESP, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Sánchez,MJ Andalusian School of Public Health, Granada, Spain. [Dorronsoro,M] Public health Direction and Biodonostia- CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Johansson,I] Department of odontology, Umeå University, Sweden. [Winkvis,A] Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Sweden. [Sonested,E] Department of Clinical Sciences in Malmö, Nutrition Epidemiology, Lund University, Malmö, Sweden. [Key,T] The Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. [Khaw,K] Clinical Gerontology Unit, Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom. [Peeters,PHM] Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands., Funding: The EPIC- PANACEA ((European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) project received funding from the Public Health Programme of the European Union (2005328). EPIC was financially supported by the European Commission: Public Health and Consumer Protection Directorate 1993–2004, and Research Directorate-General 2005. Ligue contre le Cancer, Société 3M, Mutuelle
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Male ,riesgo ,ácidos grasos trans ,humanos ,RATIONALE ,lcsh:Medicine ,Àcids grassos ,Oleic Acids ,Ácidos Oléicos ,estudios de seguimiento ,Biochemistry ,chemistry.chemical_compound ,Biomarkers ,Fatty acids ,Isomers ,Phospholipids ,Weight gain ,Fats ,Alcohol consumption ,Weight loss ,Surveys and Questionnaires ,estudios prospectivos ,Medicine and Health Sciences ,PARTICIPANTS ,Public Health Surveillance ,Prospective Studies ,Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings] ,Food science ,lcsh:Science ,Estado Nutricional ,Prospective cohort study ,Ácidos grasos ,ASSOCIATIONS ,Medicine(all) ,2. Zero hunger ,Nutrition and Dietetics ,Multidisciplinary ,Agricultural and Biological Sciences(all) ,NUTRITION TRANSITION ,Marcadores biológicos ,Biochemical markers ,Chemicals and Drugs::Lipids::Fatty Acids [Medical Subject Headings] ,Trans Fatty Acids ,Diseases::Neoplasms [Medical Subject Headings] ,CANCER ,Elaidic acid ,Neoplasias ,3. Good health ,European Prospective Investigation into Cancer and Nutrition ,Multidisciplinary Sciences ,Europe ,Näringslära ,ácido oleico ,ADIPOSE-TISSUE ,BODY-WEIGHT ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic Acids [Medical Subject Headings] ,Marcadors bioquímics ,Science & Technology - Other Topics ,Obesitat ,Biomarker (medicine) ,Female ,Dieta ,medicine.symptom ,Research Article ,Risk ,General Science & Technology ,ácidos oleicos ,PROCESSED FOODS ,Endocrinology and Diabetes ,Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings] ,DIET ,MD Multidisciplinary ,Chemicals and Drugs::Biological Factors::Biological Markers [Medical Subject Headings] ,medicine ,Humans ,VDP::Medisinske Fag: 700 ,vigilancia en salud pública ,Obesity ,obesidad ,Science & Technology ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,lcsh:R ,Body Weight ,peso corporal ,Weight change ,Peso corporal ,VDP::Medical disciplines: 700 ,Oleic acid ,chemistry ,Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight [Medical Subject Headings] ,lcsh:Q ,business ,Genetics and Molecular Biology(all) ,Follow-Up Studies ,Oleic Acid ,Estudios epidemiológicos ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies [Medical Subject Headings] - Abstract
Background Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition ( EPIC) cohort. Methods Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow- up, age, energy, alcohol, smoking status, physical activity, and region. Results In women, doubling elaidic acid was associated with a decreased risk of weight loss ( odds ratio ( OR) = 0.69, 95% confidence interval ( CI) = 0.55- 0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5- year follow- up ( OR = 1.23, 95% CI = 0.97- 1.56, p = 0.082) ( p- trend, The EPIC-PANACEA ((European Prospective Investigation into Cancer-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating out of home And obesity) project received funding from the Public Health Programme of the European Union (2005328). EPIC was financially supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004; Research Directorate-General 2005. Ligue contre le Cancer, Societe 3M, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Institute Carlos III (RTICC Rd06/0020/0091 and Rd12/0036/0018) from the Spanish Ministry of Health, the participating regional governments and institutions (Spain); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (United Kingdom); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer, National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC (Italy); Dutch Ministry of Public Health, Welfare and Sports, Dutch Ministry of Health, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane (Sweden); Norwegian Cancer Society (Norway). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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- 2015
6. Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries
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Nadia Slimani, Dimitrios Karalis, Anette Hjartåker, Dagrun Engeset, C. Martínez Garcia, Domenico Palli, Connie Stripp, Carmen Navarro, Kim Overvad, Androniki Naska, Elizabeth A Spencer, Christina Bamia, Anja Kroke, Paolo Vineis, Antonio Agudo, Corinne Casagrande, Peter Wallström, Anthony B. Miller, Marga C. Ocké, Elio Riboli, J X Zhang, Ailsa A Welch, H. B. Bueno-De-Mesquita, Petra H.M. Peeters, Françoise Clavel-Chapelon, [Agudo,A] Department of Epidemiology, Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Barcelona, Spain. [Slimani,N, Casagrande,C, Riboli,E] International Agency for Research on Cancer, Lyon, France. [Ocke,MC, Bueno-de- Mesquita,HB] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. [Naska,A, Bamia,C, and Karalis,D] School of Medicine, University of Athens, Greece. [Miller,AB] German Cancer Research Centre, Heidelberg, Germany. [Kroke,A] German Institute of Human Nutrition, Postdam-Rehbrücke, Germany. [Vineis,P] Cancer Epidemiology Unit, University of Turin, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, CSPO, Scientific Institute of Tuscany, Florence, Italy. [Peeters,PHM] Julius Center for General Practice and Patient Oriented Research, University of Utrecht, The Netherlands. [Engeset,D] Institute of Community Medicine, University of Tromsø, Norway. [Hjartaker,A] Institute for Basic Medical Sciences, Oslo, Norway. [Navarro,C] Department of Epidemiology, Health Council of Murcia, Spain. [MartÍnez Garcia,C] Andalusian School of Public Health, Granada, Spain. [Wallström,P] Department of Medicine, Lund University, Malmö University Hospital, Sweden. [Zhang,JX] Nutritional Research, Department of Public Health and Clinical Medicine, University of Umea, Sweden. [Welch,AA] Institute of Public Health, School of Clinical Medicine, University of Cambridge, UK. [Spencer,E] Cancer Research UK, Epidemiology Unit, University of Oxford, UK. [Stripp,C] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Overvad,K] Institute of Epidemiology and Social Medicine, University of Aarhus, Denmark. [Clavel-Chapelon,F] INSERM, Institute Gustave Roussy, Villejuif, France.
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Male ,Cross-sectional study ,Names of the days of the week ,Anatomy::Plant Structures::Plant Components, Aerial::Fruit [Medical Subject Headings] ,Medicine (miscellaneous) ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Recuerdo Mental ,Mediana Edad ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Population Surveillance [Medical Subject Headings] ,Vegetables ,Medicine ,Prospective Studies ,Prospective cohort study ,Masculino ,24-Hour dietary recall ,Nutrition and Dietetics ,Adulto ,Femenino ,Geographicals::Geographic Locations::Europe [Medical Subject Headings] ,11 Medical And Health Sciences ,Estudios Prospectivos ,Middle Aged ,European Prospective Investigation into Cancer and Nutrition ,Humanos ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings] ,Europe ,Verduras ,Population Surveillance ,Cohort ,Cohort studies ,Dieta ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Nutrition Surveys::Diet Surveys [Medical Subject Headings] ,Female ,Cohort study ,Adult ,Frutas ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings] ,Anciano ,Estudios Transversales ,Check Tags::Male [Medical Subject Headings] ,Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::Memory::Mental Recall [Medical Subject Headings] ,Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings] ,Diet Surveys ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,Humans ,Europa (Continente) ,Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings] ,Aged ,Nutrition & Dietetics ,business.industry ,Public Health, Environmental and Occupational Health ,Vigilancia de la Población ,Organisms::Eukaryota::Plants::Plants, Edible::Vegetables [Medical Subject Headings] ,Encuestas sobre Dietas ,Diet ,EPIC study ,Cross-Sectional Studies ,Check Tags::Female [Medical Subject Headings] ,Fruit ,Mental Recall ,Cross-sectional analysis ,business ,Body mass index ,Demography - Abstract
Objective:To describe and compare the consumption of the main groups and sub-groups of vegetables and fruits (V&F) in men and women from the centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).Design:Cross-sectional analysis. Dietary intake was assessed by means of a 24-hour dietary recall using computerised interview software and standardised procedures. Crude and adjusted means were computed for the main groups and sub-groups of V&F by centre, separately for men and women. Adjusted means by season, day of the week and age were estimated using weights and covariance analysis.Setting:Twenty-seven centres in 10 European countries participating in the EPIC project.Subjects:In total, 35 955 subjects (13 031 men and 22 924 women), aged 35–74 years, randomly selected from each EPIC cohort.Results:The centres from southern countries had the highest consumption of V&F, while the lowest intake was seen in The Netherlands and Scandinavia for both genders. These differences were more evident for fruits, particularly citrus. However, slightly different patterns arose for some sub-groups of vegetables, such as root vegetables and cabbage. Adjustment for body mass index, physical activity, smoking habits and education did not substantially modify the mean intakes of vegetables and fruits.Conclusions:Total vegetable and fruit intake follows a south–north gradient in both genders, whereas for several sub-groups of vegetables a different geographic distribution exists. Differences in mean intake of V&F by centre were not explained by lifestyle factors associated with V&F intake.
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- 2003
7. Apoptosis and TRAF-1 cleavage in Epstein-Barr virus-positive nasopharyngeal carcinoma cells treated with doxorubicin combined with a farnesyl-transferase inhibitor
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Hector Ardila-Osorio, Abdelmajid Khabir, Rachid Jlidi, Marie C. Brezak, Philip G. Kasprzyk, Tadamassa Ooka, Isabelle Viossat, Jean Michel Vicat, Gregoire Prevost, Paule Opolon, Philippe Busson, Dolly P. Huang, Interactions moléculaires et cancer, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et de Cytologie Pathologique, Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Institut Henri Beaufour, Biomeasure, Milford, Interactions moléculaires et cancer (IMC (UMR 8126)), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Virologie et pathogenèse virale (VPV), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, and This work was supported by the association contre le cancer (grant 5238) , the institute Gustave Roussy (grant 2000.13) and by a joint grant from the INSERM (France) and the DGRST (Tunisia). Jean Michel Vicat was the recipient of the fellowship from the centre nationale de la recherche scientifique and from the ligue nationale contre le cancer (région centre). We thanks to Nouafal Zamzami for helpful discussion. Yann Lecluze and Elizabeth Connault for technical assistance.
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Herpesvirus 4, Human ,Doxorubicin/*pharmacology ,Apoptosis ,medicine.disease_cause ,Biochemistry ,Nitriles/*pharmacology ,Proteins/*metabolism ,0302 clinical medicine ,Heterocyclic Compounds ,Tumor Cells, Cultured ,Cytotoxic T cell ,Enzyme Inhibitors ,Non-U.S. Gov't ,OCIS 000.1430 ,0303 health sciences ,Cultured ,Alkyl and Aryl Transferases/antagonists & inhibitors ,3. Good health ,Tumor Cells ,Drug Combinations ,030220 oncology & carcinogenesis ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Tumor necrosis factor alpha ,Female ,Heterocyclic Compounds, 3-Ring ,Cell Division ,medicine.drug ,Programmed cell death ,Cell Division/drug effects ,3-Ring/*pharmacology ,Biology ,Research Support ,03 medical and health sciences ,Nitriles ,medicine ,otorhinolaryngologic diseases ,Farnesyltranstransferase ,Humans ,Doxorubicin ,030304 developmental biology ,Pharmacology ,Alkyl and Aryl Transferases ,Enzyme Inhibitors/*pharmacology ,Human/isolation & purification ,Herpesvirus 4 ,Proteins ,Nasopharyngeal Neoplasms ,medicine.disease ,Epstein–Barr virus ,TNF Receptor-Associated Factor 1 ,Nasopharyngeal Neoplasms/metabolism/*pathology/virology ,stomatognathic diseases ,Nasopharyngeal carcinoma ,Cell culture ,Cancer research - Abstract
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinomas (NPC) are much more sensitive to chemotherapy than other head and neck carcinomas. Spectacular regressions are frequently observed after induction chemotherapy. However, these favorable responses are difficult to predict and often of short duration. So far there have been only few experiments to investigate the mechanisms which underline the cytotoxic effects of anti-neoplastic drugs against NPC cells. In addition, these studies were performed almost entirely on EBV-negative cell lines therefore not truly representative of NPC cells. For the first time, we have used two EBV-positive NPC tumor lines derived from a North African (C15) and a Chinese (C666-1) patient as in vitro targets for a panel of anti-neoplastic agents. Doxorubicin, taxol and in a lesser extent cis-platinum efficiently inhibited NPC cell proliferation at clinically relevant concentrations, but all three agents failed to induce apoptosis. However, massive apoptosis of C15 cells was achieved when doxorubicin (1 microM) was combined with a farnesyl-transferase inhibitor, BIM 2001 (5 microM). Moreover, this apoptotic process was associated with a caspase-dependent early cleavage of the TNF-receptor associated factor 1 (TRAF-1) molecule, a signaling adaptor which is specifically expressed in latently EBV-infected cells. TRAF-1 cleavage might become a useful indicator of chemo-induced apoptosis in EBV-associated NPCs.
8. Women's experiences of risk-stratified breast cancer screening in the MyPeBS trial: a qualitative comparative study across two European countries.
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McWilliams L, Roux A, Hawkes R, Cholerton R, Delattre H, Bernoux A, Forzy ML, Evans DG, Balleyguier C, Keatley D, Vissac-Sabatier C, Delaloge S, de Montgolfier S, and French DP
- Abstract
Objective: Risk-stratification should improve the benefits-to-harms ratio for breast screening, whereby higher-risk women receive additional screening and low-risk women are screened less. This study investigated the effects of healthcare context by comparing how women in England and France experienced risk-based breast screening., Methods and Measures: Fifty-two women were purposively sampled from participants who underwent risk-based screening in the MyPeBS trial. Women received objectively-derived 5-year breast cancer risk estimates (low = < 1%, average = 1-1.66%, high = ≥ 1.67 to <6%, very-high-risk = ≥ 6%). This determined future trial-related screening schedules and prevention options. Semi-structured interviews were transcribed for thematic framework analysis., Results: Two overarching themes were produced: the importance of supported risk communication and accessibility of risk management . Overall, risk-based breast screening was viewed positively. However, trial procedures, especially in risk estimate provision, differed across sites. Women at increased risk were more reassured when appointments were with specialist healthcare professionals (HCP). When absent, this resulted in reduced satisfaction with risk communication and greater uncertainty about its personal relevance. Low-risk women's views on extended mammogram schedules seemed linked to how health services are organised differently., Conclusions: Context is an important consideration regarding acceptability of healthcare innovations such as risk-stratified screening: it should not be assumed that findings from one country apply universally.
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- 2024
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9. Systematic nutritional screening and assessment in older patients: Rationale for its integration into oncology practice.
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Bauer JM, Pattwell M, Barazzoni R, Battisti NML, Soto-Perez-de-Celis E, Hamaker ME, Scotté F, Soubeyran P, and Aapro M
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- Humans, Aged, Medical Oncology methods, Aged, 80 and over, Risk Factors, Nutrition Assessment, Geriatric Assessment methods, Neoplasms therapy, Neoplasms diagnosis, Neoplasms complications, Nutritional Status, Malnutrition diagnosis, Malnutrition therapy
- Abstract
As the global population ages, so does the number of older people being diagnosed, treated and surviving cancer. Challenges to providing appropriate healthcare management stem from the heterogeneity common in this population. Although malnutrition is highly prevalent in older people with cancer, ranging between 30 % and 80 % according to some analyses, is associated with frailty, and has been shown to be a major risk factor for poor treatment response and worse overall survival, addressing nutrition status is not always a priority among oncology healthcare providers. Evaluation of nutritional status is a two-step process: screening identifies risk factors for reduced nutritional intake and deficits that require more in-depth assessment. Screening activities can be as simple as taking weight and BMI measurements or using short nutritional questionnaires and asking the patient about unintentional weight loss to identify potential nutritional risk. Using geriatric assessment, deficits in the nutritional domain as well as in others reveal potentially reversible geriatric and medical problems to guide specific therapeutic interventions. The authors of this paper are experts in the fields of geriatric medicine, oncology, and nutrition science and believe that there is not only substantial evidence to support regularly performing screening and assessment of nutritional status in older patients with cancer, but that these measures lead to the planning and implementation of patient-centered approaches to nutrition management and thus enhanced geriatric-oncology care. This paper presents rationale for systematic nutrition screening and assessment in older adults with cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.B. - Advisor to the following companies: Nutricia DANONE; Nestlé ; Fresenius; Pfizer; Novartis; Rejuvenate Biomed. Lecturer for: Nutricia DANONE; Nestlé ; Fresenius; Pfizer; Novartis. All income from the above activities goes to the institution he is working for. M.P. - Boards & Committees: BDA Prehab Sub-Group Committee. Travel grants: BDA GET Fund, RMH Charity, SIOG. Speaker fees: Fresenius Kabi, SPCC & SIOG. Research grants: Nutricia. R.B. – has participated to Advisory Boards for Nutricia Research, Eli Lilly, Novo Nordisk, Pfizer. N.M.L.B. – Advisory board: Pfizer, Abbott, Sanofi, Astellas; Travel grants: Exact Sciences, Pfizer, Lilly, Novartis; Speaker fees: Pfizer, AbbVie, Roche, Sanofi, Novartis, Servier, Gilead, AstraZeneca, Lilly. E.S-P-D-C. – Speaker fees: Amgen, Synapsis. F.S. – BMS, Sanofi, Roche, MSD, Prostrakan, Leo pharma, Janssen, Pfizer, Amgen, Pierre Fabre Oncologie, Pharmanovia, Vifor Pharma, GSK, Viatris, Helsinn. P.S. – BMS: Member of Advisory Board on cancer in the elderly (2018–2019), GSK: Conference with honoraria (2020), EISAI: Member of Advisory Board on Management of older patients with thyroid cancer (2021), AbbVie: Member of Advisory Board on Geriatric oncology in hematological malignancies (2023). The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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10. Patterns of practice of image guided particle therapy for cranio-spinal irradiation: A site specific multi-institutional survey of European Particle Therapy Network.
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Trnková P, Dasu A, Placidi L, Stock M, Toma-Dasu I, Brouwer CL, Gosling A, Jouglar E, Kristensen I, Martin V, Moinuddin S, Pasquie I, Peters S, Pica A, Plaude S, Righetto R, Rombi B, Thariat J, van der Weide H, Hoffmann A, and Bolsi A
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- Humans, Europe, Craniospinal Irradiation methods, Surveys and Questionnaires, Radiotherapy Planning, Computer-Assisted methods, Tomography, X-Ray Computed, Delphi Technique, Magnetic Resonance Imaging, Radiotherapy, Image-Guided methods
- Abstract
Purpose: To investigate the current practice patterns in image-guided particle therapy (IGPT) for cranio-spinal irradiation (CSI)., Methods: A multi-institutional survey was distributed to European particle therapy centres to analyse all aspects of IGPT. Based on the survey results, a Delphi consensus analysis was developed to define minimum requirements and optimal workflow for clinical practice. The centres participating in the institutional survey were invited to join the Delphi process., Results: Eleven centres participated in the survey. Imaging for treatment planning was rather similar among the centres with Computed Tomography (CT) being the main modality. For positioning verification, 2D IGPT was more commonly used than 3D IGPT. Two centres performed routinely imaging for plan adaptation, by the rest ad hoc. Eight centres participated in the Delphi consensus analysis. The full consensus was reached on the use of CT imaging without contrast for treatment planning and the role of magnetic resonance imaging (MRI) in target and organs-at-risk delineation. There was an agreement on the necessity to perform patient position verification and correction before each isocentre. The most important outcome was the clear need for standardization and harmonization of the workflow., Conclusion: There were differences in CSI IGPT clinical practice among the European particle therapy centres. Moreover, the optimal workflow as identified by experts was not yet reached. There is a strong need for consensus guidelines. The state-of-the-art imaging technology and protocols need to be implemented into clinical practice to improve the quality of IGPT for CSI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)
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- 2024
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11. Patient care and access to clinical trials in gynaecological oncology: global implications of the early phase of the COVID-19 pandemic.
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Nasser S, Fotopoulou C, Gültekin M, Dimitrova D, Bilir E, Inci G, Morice P, Mirza MR, Martin AG, Berek J, and Sehouli J
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- Humans, Female, SARS-CoV-2, Prospective Studies, Health Services Accessibility statistics & numerical data, Surveys and Questionnaires, Medical Oncology, Gynecology statistics & numerical data, Patient Care, Pandemics, COVID-19 epidemiology, Genital Neoplasms, Female therapy, Genital Neoplasms, Female surgery, Clinical Trials as Topic
- Abstract
Purpose: Our prospective international survey evaluated the impact of the early phase of the COVID-19 pandemic on the management gynaecological malignancies from the multidisciplinary physicians' perspective with particular focus on clinical infrastructures and trial participation., Methods: Our survey consisted of 53 COVID-related questions. It was sent to healthcare professionals in gynaecological oncology centres across Europe and Pan-Arabian region via the study groups and gynaecological societies from April 2020 to October 2020. All healthcare professionals treating gynaecological cancers were able to participate in our survey., Results: A total of 255 answers were collected from 30 countries. The majority (73%) of participants were gynaecological oncologists from university hospitals (71%) with at least an Intensive Care Unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years (range 0-12 weeks). Most cases that were prioritised for surgical intervention across all gynaecological tumours were early-stage disease (74%), primary situation (61%) and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumour types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. Almost half of the participants stated the pandemic negatively impacted the financial structure and support for clinical trials. Approximately 20% of clinicians did not feel well-informed regarding clinical algorithm for COVID-19 patients throughout the pandemic. Thirty percent stated that they are currently having trouble in providing adequate medical care due to staff shortage., Conclusion: Despite well-established guidelines, pandemic clearly affected clinical research and patientcare. Our survey underlines the necessity for building robust emergency algorithms tailored to gynaecological oncology to minimise negative impact in crises and to preserve access to clinical trials., (© 2024. The Author(s).)
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- 2024
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12. Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents.
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Williams MD, Liu Z, Rossi ED, Agarwal S, Ryška A, Ghuzlan AA, Bychkov A, Baloch Z, Chernock R, Chiosea SL, Cipriani NA, Erkilic S, Fridman M, Hang JF, Harahap AS, Jung CK, Kakudo K, Khalil M, Khanafshar E, Kumarasinghe P, Lloyd R, Nguyen TP, Ocal IT, Prasad ML, Pusztaszeri M, Rana C, Sadow P, Sajed DP, Seethala R, Tallini G, Vuong HG, Yegen G, LiVolsi VA, and Nikiforov YE
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Context: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported., Objective: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions., Methods: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey., Results: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania., Conclusion: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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13. Mitochondrial sites of contact with the nucleus.
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Campanella M and Kannan B
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- Animals, Humans, Mitochondrial Membranes metabolism, Eukaryotic Cells cytology, Cell Nucleus metabolism, Cell Nucleus genetics, Mitochondria metabolism, Mitochondria genetics
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Membrane contact sites (MCS) between mitochondria and the nucleus have been recently described. Termed nucleus associated mitochondria (NAM), they prime the expression of genes required for cellular resistance to stressors, thus offering a tethering mechanism for homeostatic communication. Here, we discuss the composition of NAM and their physiological and pathological significance., (© 2024 Campanella and Kannan.)
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- 2024
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14. Cost-effectiveness of avelumab first-line maintenance therapy for adult patients with locally advanced or metastatic urothelial carcinoma in France.
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Porte F, Granghaud A, Chang J, Kearney M, Morel A, Plessala I, Cawston H, Roiz J, Xiao Y, Solbes MN, Lambert P, Ravaud A, Loriot Y, Thiery-Vuillemin A, and Lévy P
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- Humans, France, Male, Female, Urinary Bladder Neoplasms drug therapy, Urinary Bladder Neoplasms economics, Urinary Bladder Neoplasms pathology, Quality-Adjusted Life Years, Aged, Middle Aged, Adult, Carcinoma, Transitional Cell drug therapy, Carcinoma, Transitional Cell economics, Carcinoma, Transitional Cell mortality, Carcinoma, Transitional Cell pathology, Neoplasm Metastasis, Urologic Neoplasms drug therapy, Urologic Neoplasms mortality, Urologic Neoplasms economics, Urologic Neoplasms pathology, Maintenance Chemotherapy economics, Antibodies, Monoclonal, Humanized economics, Antibodies, Monoclonal, Humanized therapeutic use, Cost-Benefit Analysis
- Abstract
Background: This study evaluated the cost-effectiveness of avelumab first-line (1L) maintenance therapy plus best supportive care (BSC) versus BSC alone for adults with locally advanced or metastatic urothelial carcinoma (la/mUC) that had not progressed following platinum-based chemotherapy in France., Methods: A three-state partitioned survival model was developed to assess the lifetime costs and effects of avelumab plus BSC versus BSC alone. Data from the phase 3 JAVELIN Bladder 100 trial (NCT02603432) were used to inform estimates of clinical and utility values considering a 10-year time horizon and a weekly cycle length. Cost data were estimated from a collective perspective and included treatment acquisition, administration, follow-up, adverse event-related hospitalization, transport, post-progression, and end-of-life costs. Health outcomes were measured in quality-adjusted life-years (QALYs) and life-years gained. Costs and clinical outcomes were discounted at 2.5% per annum. Incremental cost-effectiveness ratios (ICERs) were used to compare cost-effectiveness and willingness to pay in France. Uncertainty was assessed using a range of sensitivity analyses., Results: Avelumab plus BSC was associated with a gain of 2.49 QALYs and total discounted costs of €136,917; BSC alone was associated with 1.82 QALYs and €39,751. Although avelumab plus BSC was associated with increased acquisition costs compared with BSC alone, offsets of -€20,424 and -€351 were observed for post-progression and end-of-life costs, respectively. The base case analysis ICER was €145,626/QALY. Sensitivity analyses were consistent with the reference case and showed that efficacy parameters (overall survival, time to treatment discontinuation), post-progression time on immunotherapy, and post-progression costs had the largest impact on the ICER., Conclusions: This analysis demonstrated that avelumab plus BSC is associated with a favorable cost-effectiveness profile for patients with la/mUC who are eligible for 1L maintenance therapy in France., Competing Interests: F. Porte is an employee of Merck Santé S.A.S., Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany at the time of the project. A. Granghaud was an employee of Pfizer S.A.S., Paris, France at the time of the study. J. Chang is an employee of Pfizer and holds stock and other ownership interest with Bayer, Bristol Myers Squibb, and Pfizer. M. Kearney is an employee of Merck KGaA, Darmstadt, Germany, and holds stock in Merck KGaA, Darmstadt, Germany, Novartis and UCB. A. Morel is an employee of Pfizer S.A.S., Paris, France. I. Plessala was an employee of Amaris Consulting, Paris, France at the time of the study. H. Cawston is an employee of Amaris Consulting, Paris, France. J. Roiz is an employee of and reposts stocks and other ownership interest with Evidera. Y. Xiao is an employee of Evidera. M.-N. Solbes is an employee of Merck Santé S.A.S., Lyon, France, an affiliate of Merck KGaA, Darmstadt, Germany. P. Lambert is an employee of Pfizer S.A.S., Paris, France. A. Ravaud has received grants or contracts from Merck KGaA, Darmstadt, Germany, and Pfizer; has received travel and accommodation expenses from Ipsen Merck KGaA, Darmstadt, Germany, Merck & Co., Kenilworth, NJ, and Pfizer; and has participated in advisory boards for Esai, Ipsen, Merck KGaA, Darmstadt, Germany, and Pfizer. Y. Loriot has served in consulting or advisory roles for Astellas Pharma, Bristol Myers Squibb, Immunomedics, Janssen, Loxo/Lilly, Merck KGaA, Darmstadt, Germany, Merck & Co., Kenilworth, NJ, Pfizer, Roche, Seattle Genetics, and Taiho Pharmaceutical; has received travel and accommodations expenses from Astellas Pharma, Janssen Oncology, Merck & Co., Kenilworth, NJ, Roche, and Seattle Genetics; and has received institutional research funding from Astellas Pharma, Basilea, Bristol Myers Squibb, Exelixis, Gilead Sciences, Incyte, Janssen Oncology, Merck KGaA, Darmstadt, Germany, Merck & Co., Kenilworth, NJ, Nektar, Pfizer, Roche, Sanofi, Seattle Genetics, and Taiho Pharmaceutical. A. Thiery-Vuillemin has participated in advisory boards for Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen, Merck & Co., Kenilworth, NJ, Novartis, Pfizer, Roche/Genentech and Sanofi; reports employment by Bristol Myers Squibb; has served on steering committees for AstraZeneca, Bristol-Myers Squibb and Novartis; has received institutional research funding from Bayer, Ipsen and Pfizer; has served as principal investigator for Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Excelixis, Incyte, Ipsen, Johnson & Johnson, Merck & Co., Kenilworth, NJ, Novartis, Pfizer, Roche, Sanofi, and UNICANCER/GETUG; has received travel and accommodation expenses from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Johnson & Johnson, Merck & Co., Kenilworth, NJ, Pfizer and Roche; and is a member of ASCO and GETUG. P. Lévy has served in consulting or advisory role and had received honoraria from Merck KGaA, Darmstadt, Germany. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2024 Porte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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15. Hyperthermic intraperitoneal chemotherapy in colorectal cancer.
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Fisher OM, Brown C, Esquivel J, Larsen SG, Liauw W, Alzahrani NA, Morris DL, Kepenekian V, Sourrouille I, Dumont F, Tuech JJ, Ceribelli C, Doussot B, Sgarbura O, Alhosni M, Quenet F, Glehen O, and Cashin PH
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Propensity Score, Disease-Free Survival, Treatment Outcome, Proportional Hazards Models, Colorectal Neoplasms therapy, Colorectal Neoplasms pathology, Colorectal Neoplasms mortality, Hyperthermic Intraperitoneal Chemotherapy, Peritoneal Neoplasms secondary, Peritoneal Neoplasms therapy, Peritoneal Neoplasms mortality, Mitomycin administration & dosage, Mitomycin therapeutic use, Oxaliplatin administration & dosage, Oxaliplatin therapeutic use, Cytoreduction Surgical Procedures
- Abstract
Background: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients., Patients and Methods: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed., Results: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period., Conclusions: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)
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- 2024
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16. Recurrent Laryngeal Nerve Intraoperative Neuromonitoring Indications in Non-Thyroid and Non-Parathyroid Surgery.
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Brunet A, Rovira A, Quer M, Sanabria A, Guntinas-Lichius O, Zafereo M, Hartl DM, Coca-Pelaz A, Shaha AR, Marie JP, Vander Poorten V, Piazza C, Kowalski LP, Randolph GW, Shah JP, Rinaldo A, and Simo R
- Abstract
Introperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) is a well-established technique to aid in thyroid/parathyroid surgery. However, there is little evidence to support its use in non-thyroid or non-parathyroid surgery. The aim of this paper was to review the current evidence regarding the use of IONM in non-thyroid/non-parathyroid surgery in the head and neck and thorax. A literature search was performed from their inception up to January 2024, including the term "recurrent laryngeal nerve monitoring". IONM in non-thyroid/non-parathyroid surgery has mainly been previously described in oesophageal surgery and in tracheal resections. However, there is little published evidence on the role of IONM with other resections in the vicinity of the RLN. Current evidence is low-level for the use of RLN IONM in non-thyroid/non-parathyroid surgery. However, clinicians should consider its use in surgery for pathologies where the RLN is exposed and could be injured.
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- 2024
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17. Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer.
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Rigon M, Mutti L, and Campanella M
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- Humans, Mesothelioma genetics, Mesothelioma diagnosis, Mesothelioma, Malignant, Pleural Neoplasms genetics, Asbestos, Lung Neoplasms pathology
- Abstract
Mesothelioma is a type of late-onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it mainly targets the lining of the lungs, making pleural mesothelioma (PMe) the most common and widely studied mesothelioma type. PMe is caused by exposure to fibres of asbestos, which when inhaled leads to inflammation and scarring of the pleura. Despite the ban on asbestos by most Western countries, the incidence of PMe is on the rise, also facilitated by a lack of specific symptomatology and diagnostic methods. Therapeutic options are also limited to mainly palliative care, making this disease untreatable. Here we present an overview of biological aspects underlying PMe by listing genetic and molecular mechanisms behind its onset, aggressive nature, and fast-paced progression. To this end, we report on the role of deubiquitinase BRCA1-associated protein-1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf ofFederation of European Biochemical Societies.)
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- 2024
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18. Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.
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Jahangir CA, Page DB, Broeckx G, Gonzalez CA, Burke C, Murphy C, Reis-Filho JS, Ly A, Harms PW, Gupta RR, Vieth M, Hida AI, Kahila M, Kos Z, van Diest PJ, Verbandt S, Thagaard J, Khiroya R, Abduljabbar K, Acosta Haab G, Acs B, Adams S, Almeida JS, Alvarado-Cabrero I, Azmoudeh-Ardalan F, Badve S, Baharun NB, Bellolio ER, Bheemaraju V, Blenman KR, Botinelly Mendonça Fujimoto L, Burgues O, Chardas A, Cheang MCU, Ciompi F, Cooper LA, Coosemans A, Corredor G, Dantas Portela FL, Deman F, Demaria S, Dudgeon SN, Elghazawy M, Fernandez-Martín C, Fineberg S, Fox SB, Giltnane JM, Gnjatic S, Gonzalez-Ericsson PI, Grigoriadis A, Halama N, Hanna MG, Harbhajanka A, Hart SN, Hartman J, Hewitt S, Horlings HM, Husain Z, Irshad S, Janssen EA, Kataoka TR, Kawaguchi K, Khramtsov AI, Kiraz U, Kirtani P, Kodach LL, Korski K, Akturk G, Scott E, Kovács A, Laenkholm AV, Lang-Schwarz C, Larsimont D, Lennerz JK, Lerousseau M, Li X, Madabhushi A, Maley SK, Manur Narasimhamurthy V, Marks DK, McDonald ES, Mehrotra R, Michiels S, Kharidehal D, Minhas FUAA, Mittal S, Moore DA, Mushtaq S, Nighat H, Papathomas T, Penault-Llorca F, Perera RD, Pinard CJ, Pinto-Cardenas JC, Pruneri G, Pusztai L, Rajpoot NM, Rapoport BL, Rau TT, Ribeiro JM, Rimm D, Vincent-Salomon A, Saltz J, Sayed S, Hytopoulos E, Mahon S, Siziopikou KP, Sotiriou C, Stenzinger A, Sughayer MA, Sur D, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson EA, Tramm T, Tran WT, van der Laak J, Verghese GE, Viale G, Wahab N, Walter T, Waumans Y, Wen HY, Yang W, Yuan Y, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Specht Stovgaard E, Salgado R, Gallagher WM, and Rahman A
- Subjects
- Humans, Female, Biomarkers, Tumor genetics, Prognosis, Phenotype, United Kingdom, Tumor Microenvironment, Breast Neoplasms
- Abstract
Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
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- 2024
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19. Outcomes of patients with resected stage III/IV acral or mucosal melanoma, treated with adjuvant anti-PD-1 based therapy.
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Jacques SK, McKeown J, Grover P, Johnson DB, Zaremba A, Dimitriou F, Weiser R, Farid M, Namikawa K, Sullivan RJ, Rutkowski P, Lebbe C, Hamid O, Zager JS, Michielin O, Neyns B, Nakamura Y, Robert C, Mehnert J, Ascierto PA, Bhave P, Park B, Zimmer L, Mangana J, Mooradian M, Placzke J, Allayous C, Glitza Oliva IC, Mehmi I, Depalo D, Wicky A, Schwarze JK, Roy S, Boatwright C, Vanella V, Long GV, Menzies AM, Lo SN, and Carlino MS
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- Humans, Retrospective Studies, Neoplasm Recurrence, Local, Combined Modality Therapy, Melanoma drug therapy, Melanoma surgery, Skin Neoplasms drug therapy, Skin Neoplasms surgery
- Abstract
Importance: Acral (AM) and mucosal melanomas (MM) are rare subtypes with a poor prognosis. In those with advanced disease, anti-PD-1 (PD1) therapy has reduced activity compared to that seen in non-acral cutaneous melanoma., Objective: To determine the efficacy of adjuvant PD1 in resected AM or MM., Design: An international, retrospective cohort study SETTING: Data up to November 2021 collected from 20 centres across 10 countries., Participants: One hundred and ninety four patients with resected stage III or IV
1 AM or MM who received adjuvant PD1 were included and compared to matched patients from the Melanoma Institute Australia (MIA) database using a propensity score matching analysis., Main Outcomes and Measures: Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) were investigated., Results: Forty five of 139 (32%) AM and 9 of 55 (16%) MM patients completed adjuvant therapy. The main reason for early treatment cessation in both groups was disease recurrence: 51 (37%) and 30 (55%) in the AM and MM groups, respectively. In the AM group adjuvant PD1 was associated with a longer RFS [HR-0.69 (0.52-0.92, p = 0.0127)], DMFS [HR0.58 (0.38-0.89, p = 0.0134)] and OS [HR of 0.59 (0.38-0.92, p-value 0.0196)] when compared to the historical cohort. In the MM group there was no statistical difference in RFS [HR1.36 (0.69-2.68,p-value 0.3799], DMFS or OS., Conclusion and Relevance: After adjuvant PD1, both AM and MM have a high risk of recurrence. Our data suggests a benefit to using adjuvant PD1 therapy in resected AM but not in resected MM. Additional studies to investigate the efficacy of adjuvant PD1 for MM are needed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MSC: consultant advisor for Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche, Merck and Sanofi, and received honoraria from BMS, MSD, Sanofi and Novartis. DBJ: advisory boards or as a consultant for BMS, Catalyst Biopharma, Iovance, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko, and has received research funding from BMS and Incyte. RJS: Advisory boards/consulting for BMS, Merck, Novartis, Marengo, Pfizer, and Replimune and received research funding from Merck. FD: receives/received honoraria and travel support from Pierre Fabre, Merck Sharp & Dohme, Bristol Myers Squibb and Sun Pharma.CL : consultant advisor for BMS, MSD, Novartis, Pierre-Fabre, Merck and Sanofi YN: advisory boards/consulting for MSD and Novartis and received honoraria from Alexion Pharma, BMS, Maruho, MSD, Novartis, Ono Pharma, Sanofi, SunPharma, and Tanabe-Mitsubishi Pharma AMM: consultant advisor for BMS, MSD, Novartis, Roche, Pierre-Fabre, QBioticsKN: advisory board for Novartis and MSD, honoraria from Ono pharmaceutical, Novartis, Bristol-Myers Squibb, and MSD.LZ: served as consultant and has received honoraria from BMS, MSD, Novartis, Pierre Fabre, Sanofi, and Sunpharma and travel support from MSD, BMS, Pierre Fabre, Sanofi, Sunpharma and Novartis, outside the submitted work.JS: Honoraria: Novartis; Travel, Accommodations, Expenses: Amgen, Merck Sharp & DohmePB: conference sponsorship BMS, MSD, Novartis; speaker fees: Novartis, MSD.JP: Received travel support from Pierre Fabre, MSD, BMS, Novartis outside the scope of this study. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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20. Design Considerations in the PSMAfore Trial.
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Sartor O, Fizazi K, Herrmann K, and Morris MJ
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- 2024
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21. 2023 MASCC/ESMO consensus antiemetic guidelines related to integrative and non-pharmacological therapies.
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Molassiotis A, Affronti ML, Fleury M, Olver I, Giusti R, and Scotte F
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- Adult, Humans, Consensus, Nausea therapy, Nausea drug therapy, Vomiting drug therapy, Practice Guidelines as Topic, Acupuncture Therapy, Antiemetics therapeutic use
- Abstract
Purpose: Review the literature to propose suggestions or recommendations for controlling nausea and vomiting through integrative and non-pharmacological treatments for the MASCC/ESMO 2023 update of its antiemetic guidelines., Methods: The authors identified available systematic reviews and/or meta-analyses for 12 integrative therapies, including acupressure, acupuncture, auricular therapy, electrical stimulation of point PC6, ginger use (i.e., Zingiber officinale), guided imagery, hypnosis, inhalation aromatherapy, music therapy, food-based interventions, progressive muscle relaxation, and reflexology. Reviews were assessed for quality through the AMSTAR2 tool. A consensus committee reviewed recommendations as per MASCC/ESMO established processes., Results: Thirty-nine systematic reviews and/or meta-analyses were used. There were major methodological flaws for many of the trials used as the bases for the reviews. No recommendation for ingested ginger could be made because of conflicting evidence. Recommendations were possible for acupuncture/electroacupuncture treatments, food-based interventions, and progressive muscle relaxation training alone or combined with guided imagery. No recommendations could be reached for a number of food-based approaches, inhalation aromatherapy, hypnosis in adults, music therapy, and reflexology., Conclusion: While a limited number of suggestions are provided, there is a need for significantly higher quality trials in many of the therapeutic approaches assessed, before stronger recommendations and a wider range of approaches are made., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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22. Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.
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El Zarif T, Nassar AH, Pond GR, Zhuang TZ, Master V, Nazha B, Niglio S, Simon N, Hahn AW, Pettaway CA, Tu SM, Abdel-Wahab N, Velev M, Flippot R, Buti S, Maruzzo M, Mittra A, Gheeya J, Yang Y, Rodriguez PA, Castellano D, de Velasco G, Roviello G, Antonuzzo L, McKay RR, Vincenzi B, Cortellini A, Hui G, Drakaki A, Glover M, Khaki AR, El-Am E, Adra N, Mouhieddine TH, Patel V, Piedra A, Gernone A, Davis NB, Matthews H, Harrison MR, Kanesvaran R, Giudice GC, Barata P, Farolfi A, Lee JL, Milowsky MI, Stahlfeld C, Appleman L, Kim JW, Freeman D, Choueiri TK, Spiess PE, Necchi A, Apolo AB, and Sonpavde GP
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- Male, Humans, Middle Aged, Aged, Nivolumab adverse effects, Immune Checkpoint Inhibitors adverse effects, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Penile Neoplasms drug therapy, Penile Neoplasms etiology, Penile Neoplasms pathology, Antineoplastic Agents, Immunological adverse effects, Carcinoma, Squamous Cell drug therapy
- Abstract
Background: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors., Methods: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons., Results: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher., Conclusions: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2023
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23. Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels: A Meta-Analysis.
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Mahal BA, Kwak L, Xie W, Eastham JA, James ND, Sandler HM, Feng FY, Brihoum M, Fizazi K, Sweeney C, Ravi P, and D'Amico AV
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- Male, Humans, Middle Aged, Docetaxel therapeutic use, Prostate, Prostatectomy, Randomized Controlled Trials as Topic, Prostate-Specific Antigen, Prostatic Neoplasms drug therapy
- Abstract
Importance: Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm., Objective: To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM)., Data Sources: PubMed search from 2000 to 2022., Study Selection: Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel., Data Extraction and Synthesis: Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022., Main Outcomes and Measures: Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months)., Results: From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86])., Conclusions and Relevance: Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.
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- 2023
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24. RAD51 as a biomarker for homologous recombination deficiency in high-grade serous ovarian carcinoma: robustness and interobserver variability of the RAD51 test.
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Kramer CJ, Llop-Guevara A, Yaniz-Galende E, Pellegrino B, Ter Haar NT, Herencia-Ropero A, Campanini N, Musolino A, Bosse T, Leary A, Serra V, and Vreeswijk MP
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- Female, Humans, Observer Variation, Reproducibility of Results, Homologous Recombination, Biomarkers, Tumor genetics, Rad51 Recombinase genetics, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology
- Abstract
The RAD51 test is emerging as a promising biomarker for the assessment of functional homologous recombination deficiency (HRD). Yet, the robustness and reproducibility of the immunofluorescence-based RAD51 test, in different academic laboratories, have not been systematically investigated. Therefore, we tested the performance of the RAD51 assay in formalin-fixed paraffin-embedded (FFPE) high-grade serous ovarian carcinoma (HGSOC) samples in four European laboratories. Here, we confirm that subtle differences in staining procedures result in low variability of RAD51 and γH2AX scores. However, substantial variability in RAD51 scoring was observed in some samples, likely due to complicating technical and biological features, such as high RAD51 signal-to-noise ratio and RAD51 heterogeneity. These results support the need to identify and perform additional quality control steps and/or automating image analysis. Altogether, resolving technical issues should be a priority, as identifying tumours with functional HRD is urgently needed to guide the individual treatment of HGSOC patients. Follow-up studies are needed to define the key tissue quality requirements to assess HRD by RAD51 in FFPE tumour samples, as this test could help in guiding the individual treatment of HGSOC patients., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)
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- 2023
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25. In Vitro Imaging and Molecular Characterization of Ca 2+ Flux Modulation by Nanosecond Pulsed Electric Fields.
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Camera F, Colantoni E, Garcia-Sanchez T, Benassi B, Consales C, Muscat A, Vallet L, Mir LM, Andre F, and Merla C
- Subjects
- Humans, Apoptosis, Genes, fos, Signal Transduction, Calcium, Dietary, Calcium, Neuroblastoma therapy
- Abstract
In recent years, the application of pulsed electric fields with very short durations (nanoseconds) and extremely high amplitudes (MV/m) has been investigated for novel medical purposes. Various electric protocols have been explored for different objectives, including the utilization of fractionated pulse doses to enhance cell electrosensitization to the uptake of different markers or an increase in apoptosis. This study focused on the use of fluorescence imaging to examine molecular calcium fluxes induced by different fractionated protocols of short electric pulses in neuroblastoma (SH-SY5Y) and mesenchymal stem cells (HaMSCs) that were electroporated using nanosecond pulsed electric fields. In our experimental setup, we did not observe cell electrosensitization in terms of an increase in calcium flux following the administration of fractionated doses of nanosecond pulsed electric fields with respect to the non-fractionated dose. However, we observed the targeted activation of calcium-dependent genes ( c-FOS , c-JUN , EGR1 , NURR-1 , β3-TUBULIN ) based on the duration of calcium flux, independent of the instantaneous levels achieved but solely dependent on the final plateau reached. This level of control may have potential applications in various medical and biological treatments that rely on calcium and the delivery of nanosecond pulsed electric fields.
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- 2023
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26. Molecular Theranostics in Radioiodine-Refractory Differentiated Thyroid Cancer.
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Petranović Ovčariček P, Campenni A, de Keizer B, Deandreis D, Kreissl MC, Vrachimis A, Tuncel M, and Giovanella L
- Abstract
Differentiated thyroid cancer (DTC) is the most common subtype of thyroid cancer and has an excellent overall prognosis. However, metastatic DTC in certain cases may have a poor prognosis as it becomes radioiodine-refractory. Molecular imaging is essential for disease evaluation and further management. The most commonly used tracers are [
18 F]FDG and isotopes of radioiodine. Several other radiopharmaceuticals may be used as well, with different diagnostic performances. This review article aims to summarize radiopharmaceuticals used in patients with radioiodine-refractory DTC (RAI-R DTC), focusing on their different molecular pathways. Additionally, it will demonstrate possible applications of the theranostics approach to this subgroup of metastatic DTC.- Published
- 2023
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27. Brachytherapy for Organ and Function Preservation in Soft-Tissue Sarcomas in Adult and Paediatric Patients.
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Laskar S, Manjali JJ, Chargari C, and Chard J
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- Humans, Adult, Child, Aged, Radiotherapy Dosage, Radiotherapy, Adjuvant, Brachytherapy methods, Sarcoma pathology, Soft Tissue Neoplasms radiotherapy, Soft Tissue Neoplasms surgery
- Abstract
Adjuvant radiotherapy is an integral component in the management of soft-tissue sarcomas. Brachytherapy is a very convenient and conformal way of delivering adjuvant radiotherapy in such tumours, which spares the surrounding normal tissue. Randomised studies have established the efficacy of brachytherapy in the adjuvant setting, with a 5-year local control of 80-85%. High dose rate, low dose rate and pulsed dose rate have shown equivalent local control, but high dose rate has gained popularity owing to patient convenience, radiation safety and flexibility in dose optimisation. Freehand insertion perioperative brachytherapy (intraoperative placement and postoperative treatment) is the most commonly used technique in soft-tissue sarcomas, with intraoperative radiotherapy and radioactive seed placement being the less commonly used techniques. Brachytherapy can be used as monotherapy or in combination with external beam radiotherapy, such as in cases of close/positive margins for safe dose escalation. Although the quantum of side-effects with external beam radiotherapy has considerably reduced with the evolution of technology and the introduction of intensity modulation (intensity-modulated radiotherapy), brachytherapy still scores better in terms of dose conformality, especially in recurrent tumours (previously irradiated) and when used to treat paediatric and geriatric patients., (Copyright © 2023. Published by Elsevier Ltd.)
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- 2023
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28. Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic, multicenter cross-sectional cohort study.
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Hol MLF, Indelicato DJ, Slater O, Kolb F, Hewitt RJ, Ong J, Becking AG, Gains J, Bradley J, Sandler E, Gaze MN, Pieters B, Mandeville H, Fajardo RD, Schoot R, Merks JHM, Hammond P, Smeele LE, and Suttie M
- Subjects
- Child, Humans, Infant, Cross-Sectional Studies, Cohort Studies, Combined Modality Therapy, Head and Neck Neoplasms radiotherapy, Rhabdomyosarcoma, Embryonal, Rhabdomyosarcoma radiotherapy, Rhabdomyosarcoma pathology
- Abstract
Background: The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities., Methods: Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age-sex-ethnicity-matched controls. Additionally, we computed individual facial asymmetry., Findings: A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p < .001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p = .002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p = .080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤ .001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p = .046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p = .009) and Paris-method (p = .007)., Interpretation: When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians' bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
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- 2023
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29. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer.
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Tarantino P, Viale G, Press MF, Hu X, Penault-Llorca F, Bardia A, Batistatou A, Burstein HJ, Carey LA, Cortes J, Denkert C, Diéras V, Jacot W, Koutras AK, Lebeau A, Loibl S, Modi S, Mosele MF, Provenzano E, Pruneri G, Reis-Filho JS, Rojo F, Salgado R, Schmid P, Schnitt SJ, Tolaney SM, Trapani D, Vincent-Salomon A, Wolff AC, Pentheroudakis G, André F, and Curigliano G
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- Humans, Female, Consensus, Medical Oncology, Breast Neoplasms diagnosis, Breast Neoplasms drug therapy
- Abstract
Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement., (Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)
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- 2023
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30. Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.
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Page DB, Broeckx G, Jahangir CA, Verbandt S, Gupta RR, Thagaard J, Khiroya R, Kos Z, Abduljabbar K, Acosta Haab G, Acs B, Akturk G, Almeida JS, Alvarado-Cabrero I, Azmoudeh-Ardalan F, Badve S, Baharun NB, Bellolio ER, Bheemaraju V, Blenman KR, Botinelly Mendonça Fujimoto L, Bouchmaa N, Burgues O, Cheang MCU, Ciompi F, Cooper LA, Coosemans A, Corredor G, Dantas Portela FL, Deman F, Demaria S, Dudgeon SN, Elghazawy M, Ely S, Fernandez-Martín C, Fineberg S, Fox SB, Gallagher WM, Giltnane JM, Gnjatic S, Gonzalez-Ericsson PI, Grigoriadis A, Halama N, Hanna MG, Harbhajanka A, Hardas A, Hart SN, Hartman J, Hewitt S, Hida AI, Horlings HM, Husain Z, Hytopoulos E, Irshad S, Janssen EA, Kahila M, Kataoka TR, Kawaguchi K, Kharidehal D, Khramtsov AI, Kiraz U, Kirtani P, Kodach LL, Korski K, Kovács A, Laenkholm AV, Lang-Schwarz C, Larsimont D, Lennerz JK, Lerousseau M, Li X, Ly A, Madabhushi A, Maley SK, Manur Narasimhamurthy V, Marks DK, McDonald ES, Mehrotra R, Michiels S, Minhas FUAA, Mittal S, Moore DA, Mushtaq S, Nighat H, Papathomas T, Penault-Llorca F, Perera RD, Pinard CJ, Pinto-Cardenas JC, Pruneri G, Pusztai L, Rahman A, Rajpoot NM, Rapoport BL, Rau TT, Reis-Filho JS, Ribeiro JM, Rimm D, Vincent-Salomon A, Salto-Tellez M, Saltz J, Sayed S, Siziopikou KP, Sotiriou C, Stenzinger A, Sughayer MA, Sur D, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson EA, Tramm T, Tran WT, van der Laak J, van Diest PJ, Verghese GE, Viale G, Vieth M, Wahab N, Walter T, Waumans Y, Wen HY, Yang W, Yuan Y, Adams S, Bartlett JMS, Loibl S, Denkert C, Savas P, Loi S, Salgado R, and Specht Stovgaard E
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- Humans, Biomarkers, Benchmarking, Lymphocytes, Tumor-Infiltrating, Spatial Analysis, Tumor Microenvironment, Colonic Neoplasms
- Abstract
Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical biomarkers, the breast cancer stromal tumor infiltrating lymphocytes score and the colon cancer Immunoscore, and describe investigative opportunities to improve clinical utility of these spatial biomarkers. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)
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- 2023
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31. MicroRNAs Regulate Ca 2+ Homeostasis in Murine Embryonic Stem Cells.
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Reid KM, Sanchez-Nieto JM, Terrasse S, Faccenda D, Pernaute B, Campanella M, Rodriguez TA, and Cobb BS
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- Animals, Mice, Thapsigargin pharmacology, Cell Differentiation genetics, Embryonic Stem Cells, Homeostasis, MicroRNAs metabolism
- Abstract
MicroRNAs (miRNAs) are important regulators of embryonic stem cell (ESC) biology, and their study has identified key regulatory mechanisms. To find novel pathways regulated by miRNAs in ESCs, we undertook a bioinformatics analysis of gene pathways differently expressed in the absence of miRNAs due to the deletion of Dicer , which encodes an RNase that is essential for the synthesis of miRNAs. One pathway that stood out was Ca
2+ signaling. Interestingly, we found that Dicer-/- ESCs had no difference in basal cytoplasmic Ca2+ levels but were hyperresponsive when Ca2+ import into the endoplasmic reticulum (ER) was blocked by thapsigargin. Remarkably, the increased Ca2+ response to thapsigargin in ESCs resulted in almost no increase in apoptosis and no differences in stress response pathways, despite the importance of miRNAs in the stress response of other cell types. The increased Ca2+ response in Dicer- / - ESCs was also observed during purinergic receptor activation, demonstrating a physiological role for the miRNA regulation of Ca2+ signaling pathways. In examining the mechanism of increased Ca2+ responsiveness to thapsigargin, neither store-operated Ca2+ entry nor Ca2+ clearance mechanisms from the cytoplasm appeared to be involved. Rather, it appeared to involve an increase in the expression of one isoform of the IP3 receptors ( Itpr2 ). miRNA regulation of Itpr2 expression primarily appeared to be indirect, with transcriptional regulation playing a major role. Therefore, the miRNA regulation of Itpr2 expression offers a unique mechanism to regulate Ca2+ signaling pathways in the physiology of pluripotent stem cells.- Published
- 2023
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32. Effects of food-based interventions in the management of chemoradiotherapy-induced nausea and vomiting: a systematic review.
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Molassiotis A, Zhao IY, Crichton M, Olver I, Fleury M, Giusti R, Scotte F, and Affronti ML
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- Child, Adult, Humans, Vomiting chemically induced, Vomiting prevention & control, Nausea chemically induced, Nausea prevention & control, Chemoradiotherapy adverse effects, Antiemetics therapeutic use, Neoplasms drug therapy, Neoplasms radiotherapy
- Abstract
Background: Cancer treatment-related nausea and vomiting continue to be common and distressing symptoms for patients, despite improvements in antiemetics. Dietary modifications could potentially improve this symptom experience. Clinicians frequently provide dietary advice to patients, although the evidence base of such suggestions or recommendations is not clear., Purpose: This systematic review aimed to examine the current literature on food interventions associated with improvements in cancer treatment-related nausea and vomiting., Methods: Eight electronic databases were searched with a specific search term strategy covering trials without time or language limitations. Eligible studies focused on a food substance, defined as any nutritious substance that people eat or drink to maintain life and well-being. Trials in children and adults during chemotherapy or radiotherapy were included. Cochrane risk of bias tool was used to assess trial quality and GRADE was used to assess the certainty in the effect of each outcome., Results: Seventeen trials were included, 3 focusing on children and 14 on adults. Two trials included patients receiving radiation. Ten out of 17 trials (59%) had a high risk of bias. Strongest evidence with highest certainty was found for dietary counseling to meet macronutrient requirements in reducing incidence of radiotherapy-related nausea and vomiting in adults (n=2 studies; n=124 participants; GRADE level: moderate). There was also moderate certainty in the beneficial effect of protein supplementation on nausea and vomiting incidence in adults during radiotherapy (n=2 studies; n=124 participants; GRADE level: moderate). A significant positive effect on CINV incidence and/or severity in adults was also found for dietary counseling to meet macronutrient requirements during chemotherapy, a peppermint drink, scaly wood mushroom, chamomile, protein with ginger, and a colorless odorless diet (GRADE level: low to very low)., Conclusions: The review identified food-based approaches that could improve the nausea and vomiting experience in patients with cancer and provide guidance to clinicians. However, confidence in these findings was low and studies were heterogeneous and mostly of low quality, requiring further investigation before stronger recommendations can be made. Future research is needed to confirm efficacy and safety., Trial Registration: PROSPERO CRD42022341154., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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33. 17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.
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Michot JM, Guerra M, Quivoron C, Mahjoubi L, Alouani E, Ouali K, Parisi C, Danlos F, Goldschmidt V, Hénon C, Baldini C, Ponce S, and Ribrag V
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- Humans, Switzerland, Congresses as Topic, Lymphoma therapy
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- 2023
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34. Efficacy of ipilimumab 3 mg/kg following progression on low-dose ipilimumab in metastatic melanoma.
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Lai-Kwon J, Jacques S, Carlino M, Benannoune N, Robert C, Allayous C, Baroudjian B, Lebbe C, Zimmer L, Eroglu Z, Topcu TO, Dimitriou F, Haydon A, Lo SN, Menzies AM, and Long GV
- Subjects
- Humans, Middle Aged, Ipilimumab adverse effects, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Nivolumab adverse effects, Melanoma pathology, Neoplasms, Second Primary drug therapy
- Abstract
Background: Differing doses of ipilimumab (IPI) are used in combination with an anti-PD1 antibody in advanced melanoma. There is no data on the outcomes of patients who progress following low-dose IPI (< 3 mg/kg) and are subsequently treated with IPI 3 mg/kg (IPI3). We conducted a multicentre retrospective survey to assess the efficacy of this strategy., Methods: Patients with resected stage III, unresectable stage III or IV melanoma who received low dose IPI (< 3 mg/kg) with an anti-PD1 antibody with recurrence (neo/adjuvant) or progressive disease (metastatic), who then received IPI3± anti-PD1 antibody were eligible. Best investigator-determined Response Evaluation Criteria in Solid Tumours response, progression-free survival (PFS) and overall survival (OS) were analysed., Results: Total 36 patients received low-dose IPI with an anti-PD1 antibody, 18 (50%) in the neo/adjuvant and 18 (50%) in the metastatic setting. Of which, 20 (56%) had primary resistance and 16 (44%) had acquired resistance. All patients received IPI3 for unresectable stage III or IV melanoma; median age 60 (29-78), 18 (50%) M1d disease, 32 (89%) Eastern Cooperative Oncology Group performance status 0-1. Around 35 (97%) received IPI3 with nivolumab and 1 received IPI3 alone. The response rate to IPI3 was 9/36 (25%). In patients with primary resistance, the response rate was 6/20 (30%). After a median follow-up of 22 months (95% CI: 15-27 months), the median PFS and OS were not reached in patients who responded; 1-year PFS and OS were 73% and 100%, respectively., Conclusions: IPI3 following recurrence/progression on low dose IPI has clinical activity, including in primary resistance. IPI dosing is therefore critical in a subset of patients., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MC: consultant advisor: Amgen, Bristol-Myers Squibb, Eisai, Ideaya, Merck Sharp and Dohme, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche; honoraria: Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis. CR: consultant for Roche, Novartis, Pierre Fabre, MSD, BMS, Sanofi, Pfizer, AstraZeneca. CA: travel, accommodation and expenses from Roche/Amgen/BMS. BB: lectures, boards, travel accommodation from BMS, Pierre Fabre, MSD, Novartis, Sanofi. CL: consultant advisor to BMS, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; honoraria: Roche, BMS, Novartis, Amgen, MSD, Pierre Fabre, Pfizer and Incyte; research funding: Roche, BMS; and speaker’s bureau: Roche, BMS, Novaris, Amgen and MSD. LZ: consultant and/or honoraria: Roche, Bristol-Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Novartis, Pierre Fabre, Sanofi, and Sunpharma; travel support: MSD, BMS, Amgen, Pierre Fabre, Sunpharma, Sanofi and Novartis. ZE: advisory boards for Pfizer, Genentech, Regeneron, Eisai, OncoSec, Natera; research funding: Pfizer, Novartis, Boehringer-Ingelheim. FD: honoraria and travel support: Merck Sharp & Dohme, Bristol Myers Squibb and Sun Pharma. AMM: consultant advisor to BMS, MSD, Novartis, Roche, Pierre-Fabre and QBiotics. GVL: consultant advisor to Agenus, Amgen, Array Biopharma, Boehringer Ingelheim International, Bristol Myers Squibb, Evaxion, Hexal, Highlight Therapeutics S.L., Merck Sharpe & Dohme, Novartis Pharma, OncoSec, Pierre Fabre, Provectus, Qbiotics, Regeneron. All other authors have no disclosures., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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35. Severe colitis in patients with melanoma treated with BRAF/MEK inhibitors.
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Carbonnel F, Routier E, Lazure T, Mussini C, Bellanger C, Merklen C, Bejou B, Buisson A, Amiot A, Meyer A, Dong C, and Robert C
- Subjects
- Female, Humans, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Mitogen-Activated Protein Kinase Kinases therapeutic use, Mutation, Neoplasm Recurrence, Local drug therapy, Protein Kinase Inhibitors adverse effects, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf therapeutic use, Melanoma drug therapy, Melanoma genetics, Skin Neoplasms drug therapy, Skin Neoplasms etiology, Skin Neoplasms pathology
- Abstract
Background and Aims: Dual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors., Methods: We studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally., Results: Between January 2021 and March 2022, nine women and one man, aged 50-90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis., Conclusion: BRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon., (© 2022 John Wiley & Sons Ltd.)
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- 2023
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36. Vaginal changes, sexual functioning and distress of women with locally advanced cervical cancer treated in the EMBRACE vaginal morbidity substudy.
- Author
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Suvaal I, Kirchheiner K, Nout RA, Sturdza AE, Van Limbergen E, Lindegaard JC, Putter H, Jürgenliemk-Schulz IM, Chargari C, Tanderup K, Pötter R, Creutzberg CL, and Ter Kuile MM
- Subjects
- Humans, Female, Prospective Studies, Vagina pathology, Sexual Behavior, Morbidity, Uterine Cervical Neoplasms pathology, Brachytherapy
- Abstract
Objective: The EMBRACE-vaginal morbidity substudy prospectively evaluated physician-assessed vaginal changes and patient-reported-outcomes (PRO) on vaginal and sexual functioning problems and distress in the first 2-years after image-guided radio(chemo)therapy and brachytherapy for locally advanced cervical cancer., Methods: Eligible patients had stage IB1-IIIB cervical cancer with ≤5 mm vaginal involvement. Assessment of vaginal changes was graded using CTCAE. PRO were assessed using validated Quality-of-Life and sexual questionnaires. Statistical analysis included Generalized-Linear-Mixed-Models and Spearman's rho-correlation coefficients., Results: 113 eligible patients were included. Mostly mild (grade 1) vaginal changes were reported over time in about 20% (range 11-37%). At 2-years, 47% was not sexually active. Approximately 50% of the sexually active women reported any vaginal and sexual functioning problems and distress over time; more substantial vaginal and sexual problems and distress were reported by up to 14%, 20% and 8%, respectively. Physician-assessed vaginal changes and PRO sexual satisfaction differed significantly (p ≤ .05) between baseline and first follow-up, without further significant changes over time. No or only small associations between physician-assessed vaginal changes and PRO vaginal functioning problems and sexual distress were found., Conclusions: Mild vaginal changes were reported after image-guided radio(chemo)therapy and brachytherapy, potentially due to the combination of tumors with limited vaginal involvement, EMBRACE-specific treatment optimization and rehabilitation recommendations. Although vaginal and sexual functioning problems and sexual distress were frequently reported, the rate of substantial problems and distress was low. The lack of association between vaginal changes, vaginal functioning problems and sexual distress shows that sexual functioning is more complex than vaginal morbidity alone., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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37. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.
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Krämer A, Bochtler T, Pauli C, Baciarello G, Delorme S, Hemminki K, Mileshkin L, Moch H, Oien K, Olivier T, Patrikidou A, Wasan H, Zarkavelis G, Pentheroudakis G, and Fizazi K
- Subjects
- Humans, Follow-Up Studies, Neoplasm Staging, Neoplasms, Unknown Primary pathology
- Abstract
Competing Interests: Disclosure AK reports personal fees as an invited speaker from Roche; fees paid to his institution for advisory board membership from Roche; institutional funding from Bristol Myers Squibb (BMS); non-remunerated role as a principal investigator for Roche. TB reports fees paid to his institution as a study oncologist, for expert testimony and study-related travel expenses from Roche. CP reports fees paid to her institution as an invited speaker from Roche; institutional funding as a coordinating principal investigator from Roche. GB reports personal fees for advisory board membership from Gensenta; institutional funding as a Steering Committee member from Bayer; non-remunerated roles as a principal investigator for Eli Lilly, Merck Sharp & Dohme (MSD) and Roche; member of the American Society of Clinical Oncology (ASCO). SD reports personal fees as an invited speaker from Bracco Germany; non-remunerated leadership role as President (2010-2012) and Vice-President (2012-2014) of DEGUM (German Ultrasound Society); non-remunerated role as member and chairman of the ‘Radiation Protection in Medicine’ (2017-2020) working group for the Radiation Protection Commission (SSK) at the German Federal Ministry of Environmental Protection. KH has reported no potential conflicts of interest. LM reports a non-remunerated role as co-chair of the Steering Committee for the CUPISCO trial from Roche. HM reports personal fees as an invited speaker from Amgen and Roche; personal fees for advisory board membership from AstraZeneca, Janssen and Merck; institutional funding from Roche. KO reports institutional funding from BioClavis, BioTheranostics and Leica; non-remunerated advisory role as member of Steering Group for Early Detection and Diagnosis of Cancer Roadmap for Cancer Research UK and as member of Innovation Expert Advisory Group (EAG) for NHS England Cancer Innovation Programme; co-author of the RCPath dataset on CUP and malignancy of unknown origin for the Royal College of Pathologists; Cancer Research UK affiliate at the Beatson Institute; member of the National Cancer Research Institute (UK). AP reports personal fees for a congress subscription from Amgen; personal fees for advisory board membership in urothelial cancer from Basilea; personal fees for congress expenses from Janssen. HW reports personal fees as an invited speaker and for advisory board membership from Array BioPharma, Bayer, BMS, Celgene, Erytech, Incyte, Merck KGaA, Pierre Fabre, Servier Sirtex Medical and Roche/Genentech; personal fees for consultancy from OnoSil; personal fees for an advisory role and as a Trial Steering Committee member from Zymeworks; personal fees and institutional funding for an advisory role, as a coordinating principal investigator and member of Trial Steering Committee from Sirtex Medical; non-remunerated advisory roles with Bayer, Pfizer and Pierre Fabre. GZ reports personal fees as an invited speaker from Amgen, Ipsen, Leo Pharma and Merck. GP is the Chief Medical Officer for ESMO and member of ASCO and the Hellenic Cooperative Oncology Group and the Hellenic Society of Medical Oncology (HeCOG). KF reports personal fees for advisory board membership from Curevac and Orion; fees paid to his institution as an invited speaker from Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis, Pfizer and Sanofi; fees paid to his institution for advisory board membership from AAA, Astellas, AstraZeneca, Bayer, Janssen, MSD, Novartis/AAA and Pfizer; institutional funding as trial chair from AstraZeneca, Bayer, BMS, Janssen, MSD, Orion and Pfizer; non-remunerated role as principal investigator and trial chair for Bayer, BMS, Merck, Novartis/AAA and Orion. TO has declared no conflicts of interest.
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- 2023
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38. Personalized Medicine in Infant Population with Cancer: Pharmacogenetic Pilot Study of Polymorphisms Related to Toxicity and Response to Chemotherapy.
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Urtasun A, Olivera GG, Sendra L, Aliño SF, Berlanga P, Gargallo P, Hervás D, Balaguer J, Juan-Ribelles A, Andrés MDM, Cañete A, and Herrero MJ
- Abstract
Background: Pharmacogenetics is a personalized medicine tool that aims to optimize treatments by adapting them to each individual's genetics, maximizing their efficacy while minimizing their toxicity. Infants with cancer are especially vulnerable, and their co-morbidities have vital repercussions. The study of their pharmacogenetics is new in this clinical field., Methods: A unicentric, ambispective study of a cohort of infants receiving chemotherapy (from January 2007 to August 2019). The genotypes of 64 patients under 18 months of age were correlated with severe drug toxicities and survival. A pharmacogenetics panel was configured based on PharmGKB, drug labels, and international experts' consortiums., Results: Associations between SNPs and hematological toxicity were found. Most meaningful were: MTHFR rs1801131 GT increasing the anemia risk (OR 1.73); rs1517114 GC, XPC rs2228001 GT, increasing neutropenia risk (OR 1.50 and 4.63); ABCB1 rs1045642 AG, TNFRSF11B rs2073618 GG, CYP2B6 rs4802101 TC and SOD2 rs4880 GG increasing thrombocytopenia risk (OR 1.70, 1.77, 1.70, 1.73, respectively). Regarding survival, MTHFR rs1801133 GG, TNFRSF11B rs2073618 GG, XPC rs2228001 GT, CYP3A4 rs2740574 CT, CDA rs3215400 del.del, and SLC01B1 rs4149015 GA were associated with lower overall survival probabilities (HR 3.12, 1.84, 1.68, 2.92, 1.90, and 3.96, respectively). Lastly, for event-free survival, SLC19A1 rs1051266 TT and CDA rs3215400 del.del increased the relapse probability (HR 1.61 and 2.19, respectively)., Conclusions: This pharmacogenetic study is a pioneer in dealing with infants under 18 months of age. Further studies are needed to confirm the utility of the findings in this work to be used as predictive genetic biomarkers of toxicity and therapeutic efficacy in the infant population. If confirmed, their use in therapeutic decisions could improve the quality of life and prognosis of these patients.
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- 2023
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39. Recurrence-Free Survival in Early and Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung after Complete Tumor Resection.
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Altieri B, La Salvia A, Modica R, Marciello F, Mercier O, Filosso PL, de Latour BR, Giuffrida D, Campione S, Guggino G, Fadel E, Papotti M, Colao A, Scoazec JY, Baudin E, and Faggiano A
- Abstract
Background: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers., Methods: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed., Results: 39 patients (M:F = 26:13), with a median age of 64 years (44-83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4-169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46-12.07, p = 0.008 and HR = 13.56, 95%CI 2.45-74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23-38.83, p = 0.002 and HR = 11.88, 95%CI 2.28-61.84, p = 0.003, respectively)., Conclusion: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy.
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- 2023
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40. Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status.
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Carril-Ajuria L, Colomba E, Romero-Ferreiro C, Cerbone L, Ratta R, Barthelemy P, Vindry C, Fléchon A, Cherifi F, Boughalem E, Linassier C, Fornarini G, Rebuzzi SE, Gross-Goupil M, Saldana C, Martin-Soberón M, de Velasco G, Manneh R, Pernaut C, Sanchez de Torre A, Flippot R, Escudier B, and Albiges L
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- Humans, Male, Female, Immune Checkpoint Inhibitors adverse effects, Retrospective Studies, Prospective Studies, Carcinoma, Renal Cell pathology, Kidney Neoplasms drug therapy, Kidney Neoplasms pathology
- Abstract
Background: Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown., Methods: We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated., Results: We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS., Conclusion: We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results., Competing Interests: Conflict of interest statement LCA: BMS Belgium Travel, Accommodation and Expenses. EC: Consulting or Advisory Role – BMS; Ipsen; Sanofi; GSK; Eisai; Merck; Janssen; Pfizer; Travel, Accommodations, Expenses – BMS Brazil; Pfizer; IPSEN. BE: Honoraria – Bristol-Myers Squibb; EUSA Pharma; Ipsen; Novartis; Oncorena; Pfizer; Roche/Genentech Consulting or Advisory Role – AVEO; Bristol-Myers Squibb; EUSA Pharma; Ipsen; Novartis; Pfizer; Roche/Genentech Research Funding – BMS France (Inst) Travel, Accommodations, Expenses – Bristol-Myers Squibb; Ipsen; MSD; Pfizer; Roche/Genentech. LA: Consulting fees compensated to the institution for Pfizer, Novartis, Bristol Myer Squibb, Ipsen, Roche, MSD, AstraZeneca, Merck, Amgen, Astellas, Exelixis, Corvus Pharmaceuticals, Peloton Therapeutics, outside the submitted work. RM: Honoraria for advisory role and speaker: BMS, MSD, Pfizer, Ipsen, AstraZeneca, Roche, Janssen, Astellas, Tecnofarma. AF: Honoraria: BMS, Ipsen, MSD, Pfizer. Travel, Accommodations, Expenses – BMS; Ipsen; MSD; Pfizer. Rest of authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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41. Patient-reported outcomes in childhood head and neck rhabdomyosarcoma survivors and their relation to physician-graded adverse events-A multicenter study using the FACE-Q Craniofacial module.
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Morfouace M, Hol MLF, Schoot RA, Slater O, Indelicato DJ, Kolb F, Smeele LE, Merks JHM, Rae C, Maurice-Stam H, Klassen AF, and Grootenhuis MA
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- Child, Humans, Adolescent, Young Adult, Adult, Cross-Sectional Studies, Quality of Life, Survivors, Patient Reported Outcome Measures, Rhabdomyosarcoma, Embryonal, Rhabdomyosarcoma therapy, Physicians
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Introduction: Adverse events (AE) of treatment are prevalent and diverse in head and neck rhabdomyosarcoma (HNRMS) survivors. These AEs are often reported by physicians; however, patients' perceptions of specific AE are not well known. In this study, we explored patient-reported outcomes measuring appearance, health-related quality of life (HRQOL), and facial function in HNRMS survivors. Second, we assess the relationship between physician grading of AE and patient reporting., Materials and Methods: Survivors of pediatric HNRMS, diagnosed between 1993 and 2017, who were at least 2 years after completing treatment were invited to an outpatient clinic as part of a multicenter cross-sectional cohort study. At the outpatient clinics, survivors aged ≥8 years filled out the FACE-Q Craniofacial module; a patient-reported outcome instrument measuring issues specific to patients with facial differences. AE were systematically assessed by a multidisciplinary team based on the Common Terminology Criteria of Adverse Events system., Results: Seventy-seven survivors with a median age of 16 years (range 8-43) and median follow-up of 10 years (range 2-42) completed the questionnaire and were screened for AEs. Patient-reported outcomes varied widely between survivors. Many survivors reported negative consequences: 82% on appearance items, 81% on HRQOL items, and 38% on facial function items. There was a weak correlation between physician-scored AEs and the majority of patient-reported outcomes specific for those AEs., Conclusions: Physician-graded AEs are not sufficient to provide tailored care for HNMRS survivors. Findings from this study highlight the importance of incorporating patient-reported outcome measures in survivorship follow-up., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2023
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42. Response to first line platinum-based chemotherapy in mismatch repair deficient (MMRd)/ microsatellite instability high (MSI-high) endometrial carcinoma.
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Colomba E, Alexandre J, Le Teuff G, Genestie C, Coupez D, Coquard IR, Brachet PE, de Percin S, Sajous C, Fabbro M, Delanoy N, Joly F, Frenel JS, Pautier P, and Leary A
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- Female, Humans, Retrospective Studies, Platinum therapeutic use, Microsatellite Instability, DNA Mismatch Repair, Colorectal Neoplasms pathology, Endometrial Neoplasms drug therapy, Endometrial Neoplasms genetics
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Background: Around 15% of metastatic endometrial carcinoma (EC) are MMRd/MSI-H improving response to immune checkpoint inhibitors (ICI). So far, few data existed considering the chemotherapy (CT) sensitivity in MMRd/MSI-H EC, especially response to first-line platinum-based treatment., Patients and Methods: We performed a multicentric retrospective analysis reporting the response to first line platinum CT in MMRd/MSI-H EC patients. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) with first line platinum-based CT., Results: A total of 112 patients MMRd/MSI-H EC from 8 centers were identified. Median overall survival was 58.0 months (95% CI: 45.3-95.1). Among them, 78 patients received first line platinum CT in recurrent/metastatic setting. With a median follow up of 32.6 months (min: 0.03; max: 135.0), ORR and DCR (disease control rate) were 50% (95% CI: 38.5-61.5) and 68% (95% CI: 56.4-78.1), respectively. Median PFS and OS from first line platinum-based CT was 7.8 months (95% CI: 6.0-9.0) and 51.9 months (95% CI: 28.0-NE), respectively. Median PFS with ICI in second line (n = 48) was 10.7 months (95% CI: 3.4-NE) from ICI initiation., Conclusion: ORR in first line metastatic MMRd/MSI-H EC is consistent with efficacy in an all comer metastatic EC population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This research received no specific funding/grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Colomba has received honoraria (self and Institution) from AGSK, Eisai, Tesaro, Clovis Oncology, Tesaro, and IPSEN, Sanofi, BMS, Pfizer. She has served in a consulting or advisory role for IPSEN, MSD, EISAI, Clovis Oncology, Pfizer, and Tesaro; has received institutional research funding from IPSEN, and has been reimbursed for travel, accommodations, or other expenses by IPSEN, EISAI, Pfizer. Dr. Alexandre reports receiving personal fees from AstraZeneca, GlaxoSmithKline/Tesaro, Pharmamar, Novartis, and Roche; and non-financial support from Novartis and Janssen. Pr Ray-Coquard has received Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: Clovis Oncology; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Pharma Mar; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Genmab; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Pfizer. Dr. Fabbro has received Honoria from MSD. Dr. Delanoy declares conflicts of interest with Clovis for honoria (self). Dr. Frenel declares conflicts of interest with Pfizer, Roche, Astra Zeneca (Board member and travel fees). Dr. Pautier has received Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Genentech; Research grant / Funding (institution): PharmaMar. Dr. Leary has received honoraria from AstraZeneca, Clovis Oncology, Tesaro, and PharmaMar; has served in a consulting or advisory role for AstraZeneca, Biocad, Clovis Oncology, GamaMabs Pharma, Gritstone, Pfizer, Seattle Genetics, and Tesaro; has received institutional research funding from AstraZeneca, Clovis Oncology, Genentech, Inivata, Merus, and MSD Oncology; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca. G Le Teuff, Dr. Genestie, Dr. Coupez, Dr. De Percin, Dr. Brachet, Pr Joly, Dr. Sajous has no disclosure to declare., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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43. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.
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Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, Rastogi P, Cui K, Arahmani A, Aktan G, Armstrong AC, Arnedos M, Balmaña J, Bergh J, Bliss J, Delaloge S, Domchek SM, Eisen A, Elsafy F, Fein LE, Fielding A, Ford JM, Friedman S, Gelmon KA, Gianni L, Gnant M, Hollingsworth SJ, Im SA, Jager A, Jóhannsson ÓÞ, Lakhani SR, Janni W, Linderholm B, Liu TW, Loman N, Korde L, Loibl S, Lucas PC, Marmé F, Martinez de Dueñas E, McConnell R, Phillips KA, Piccart M, Rossi G, Schmutzler R, Senkus E, Shao Z, Sharma P, Singer CF, Španić T, Stickeler E, Toi M, Traina TA, Viale G, Zoppoli G, Park YH, Yerushalmi R, Yang H, Pang D, Jung KH, Mailliez A, Fan Z, Tennevet I, Zhang J, Nagy T, Sonke GS, Sun Q, Parton M, Colleoni MA, Schmidt M, Brufsky AM, Razaq W, Kaufman B, Cameron D, Campbell C, and Tutt ANJ
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- Humans, Female, Phthalazines adverse effects, Germ Cells pathology, BRCA1 Protein genetics, Breast Neoplasms drug therapy, Breast Neoplasms genetics
- Abstract
Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety., Patients and Methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015., Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome., Conclusion: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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44. Early Coronary Artery Calcification Progression over Two Years in Breast Cancer Patients Treated with Radiation Therapy: Association with Cardiac Exposure (BACCARAT Study).
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Honaryar MK, Allodji R, Ferrières J, Panh L, Locquet M, Jimenez G, Lapeyre M, Camilleri J, Broggio D, de Vathaire F, and Jacob S
- Abstract
Background: Radiotherapy (RT) for breast cancer (BC) can induce coronary artery disease many years after RT. At an earlier stage, during the first two years after RT, we aimed to evaluate the occurrence of increased coronary artery calcium (CAC) and its association with cardiac exposure. Methods: This prospective study included 101 BC patients treated with RT without chemotherapy. Based on CAC CT scans performed before and two years after RT, the event ‘CAC progression’ was defined by an increase in overall CAC score (CAC RT+ two years—CAC before RT > 0). Dosimetry was evaluated for whole heart, left ventricle (LV), and coronary arteries. Multivariable logistic regression models were used to assess association with doses. Results: Two years after RT, 28 patients presented the event ‘CAC progression’, explained in 93% of cases by a higher CAC score in the left anterior descending coronary (LAD). A dose−response relationship was observed with LV exposure (for Dmean LV: OR = 1.15, p = 0.04). LAD exposure marginally explained increased CAC in the LAD (for D2 LV: OR =1.03, p = 0.07). Conclusion: The risk of early CAC progression may be associated with LV exposure. This progression might primarily be a consequence of CAC increase in the LAD and its exposure.
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- 2022
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45. Transoral Robotic Surgery for Recurrent Tumors of the Upper Aerodigestive Tract (RECUT): An International Cohort Study.
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Hardman JC, Holsinger FC, Brady GC, Beharry A, Bonifer AT, D'Andréa G, Dabas SK, de Almeida JR, Duvvuri U, Floros P, Ghanem TA, Gorphe P, Gross ND, Hamilton D, Kurukulasuriya C, Larsen MHH, Lin DJ, Magnuson JS, Meulemans J, Miles BA, Moore EJ, Pantvaidya G, Roof S, Rubek N, Simon C, Subash A, Topf MC, Van Abel KM, Vander Poorten V, Walgama ES, Greenlay E, Potts L, Balaji A, Starmer HM, Stephen S, Roe J, Harrington K, and Paleri V
- Subjects
- Cohort Studies, Humans, Margins of Excision, Retrospective Studies, Treatment Outcome, Carcinoma, Squamous Cell pathology, Head and Neck Neoplasms surgery, Natural Orifice Endoscopic Surgery, Oropharyngeal Neoplasms, Robotic Surgical Procedures adverse effects
- Abstract
Background: Transoral robotic surgery (TORS) is an emerging minimally invasive surgical treatment for residual, recurrent, and new primary head and neck cancers in previously irradiated fields, with limited evidence for its oncological effectiveness., Methods: A retrospective observational cohort study of consecutive cases performed in 16 high-volume international centers before August 2018 was conducted (registered at clinicaltrials.gov [NCT04673929] as the RECUT study). Overall survival (OS), disease-free survival, disease-specific survivals (DSS), and local control (LC) were calculated using Kaplan-Meier estimates, with subgroups compared using log-rank tests and Cox proportional hazards modeling for multivariable analysis. Maximally selected rank statistics determined the cut point for closest surgical resection margin based on LC., Results: Data for 278 eligible patients were analyzed, with median follow-up of 38.5 months. Two-year and 5-year outcomes were 69.0% and 62.2% for LC, 71.8% and 49.8% for OS, 47.2% and 35.7% for disease-free survival, and 78.7% and 59.1% for disease-specific survivals. The most discriminating margin cut point was 1.0 mm; the 2-year LC was 80.9% above and 54.2% below or equal to 1.0 mm. Increasing age, current smoking, primary tumor classification, and narrow surgical margins (≤1.0 mm) were statistically significantly associated with lower OS. Hemorrhage with return to theater was seen in 8.1% (n = 22 of 272), and 30-day mortality was 1.8% (n = 5 of 272). At 1 year, 10.8% (n = 21 of 195) used tracheostomies, 33.8% (n = 66 of 195) used gastrostomies, and 66.3% (n = 53 of 80) had maintained or improved normalcy of diet scores., Conclusions: Data from international centers show TORS to treat head and neck cancers in previously irradiated fields yields favorable outcomes for LC and survival. Where feasible, TORS should be considered the preferred surgical treatment in the salvage setting., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2022
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46. Caution Regarding Assessment of Toxic Effects and Survival in Treatment De-escalation With Radiotherapy vs Transoral Surgery for Human Papillomavirus-Associated Oropharyngeal Cancer.
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Paleri V, Simon C, and Gorphe P
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- Humans, Papillomaviridae, Alphapapillomavirus, Oropharyngeal Neoplasms radiotherapy, Oropharyngeal Neoplasms surgery, Papillomavirus Infections surgery
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- 2022
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47. "Global Multidisciplinary Team Meetings": Challenging Cases Virtual Forums from the International Multidisciplinary Anal Cancer Conference (IMACC).
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Segelov E, Guren MG, Sebag-Montefiore D, Rao S, Johnsson A, Franco P, Deutsch E, Arnold D, and Spindler KG
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- Anal Canal, Clinical Decision-Making, Humans, Anus Neoplasms diagnosis, Anus Neoplasms therapy, Patient Care Team
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- 2022
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48. Acute Respiratory Distress Syndrome Associated with Multisystem Inflammatory Syndrome in a Child with Covid-19 and Diabetic Ketoacidosis: A Case Report.
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Duong-Quy S, Huynh-Truong-Anh D, Le-Thi-Hong N, Le-Van T, Le-Thi-Kim S, Nguyen-Quang T, Nguyen-Thi-Kim T, Nguyen-Phuong N, Nguyen-Chi T, Nguyen-Van T, Duong-Thi-Thanh V, Nguyen-Tien D, Ngo C, and Craig T
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (Covid-19), has uncontrollable effects on many organs. A great number of previously published scientific reports have revealed that patients with diabetes mellitus face a more severe form of Covid-19 with a higher death rate. Here we present the case of a 13-year-old unvaccinated boy who was admitted to an intensive care unit (ICU) with a history of fever, cough, dyspnea, throat pain, nausea, and confusion that progressed to lethargy after 24 h. On clinical examination, he was in a coma with Kussmaul's breathing, and was anuric. His blood biochemical analysis demonstrated hyperglycemia, severe metabolic acidosis, kidney failure, electrolyte disturbances, and inflammation. Chest x-ray showed pneumonia and a pleural effusion. The results of the SARS-CoV-2 real-time polymerase chain reaction were positive. The patient was diagnosed with Covid-19-induced acute respiratory distress syndrome associated with multisystem inflammatory syndrome in children secondary to his acute respiratory failure, acute kidney injury, and new-onset type 1 diabetes mellitus with diabetic ketoacidosis. He was intubated for invasive mechanical ventilation and received a normal saline infusion and continuous insulin infusion (0.1 IU/kg/h) for the treatment of his diabetic ketoacidosis. He was also treated with methylprednisolone, aspirin, and heparin, and underwent continuous renal replacement therapy for acute renal failure for 9 days. The patient was discharged from ICU on day 16 and was followed up regularly as an outpatient with daily treatment, including subcutaneous insulin injection (30 IU/day) and a calcium channel blocker for hypertension (nifedipine 20 mg/day)., (© 2022. The Author(s).)
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- 2022
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49. Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update Q and A.
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Raab R, Ismaila N, Andre F, Stearns V, and Kalinsky K
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- Biomarkers, Female, Humans, Medical Oncology, Breast Neoplasms drug therapy
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- 2022
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50. Management of Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases: ASCO Guideline Update.
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Ramakrishna N, Anders CK, Lin NU, Morikawa A, Temin S, Chandarlapaty S, Crews JR, Davidson NE, Franzoi MAB, Kirshner JJ, Krop IE, Patt DA, Perlmutter J, and Giordano SH
- Subjects
- Female, Humans, Brain Neoplasms secondary, Brain Neoplasms therapy, Breast Neoplasms drug therapy, Central Nervous System Neoplasms secondary, Central Nervous System Neoplasms therapy, Radiosurgery, Receptor, ErbB-2 genetics
- Abstract
Purpose: To provide updated evidence- and consensus-based guideline recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer up to 2021., Methods: An Expert Panel conducted a targeted systematic literature review (for both systemic therapy for non-CNS metastases and for CNS metastases of HER2+ guideline updates) that identified 545 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events., Results: Of the 545 publications identified and reviewed, six on systemic therapy were identified to form the evidentiary basis for the systemic therapy for CNS metastases guideline recommendations., Recommendations: Patients with brain metastases should receive appropriate local therapy and systemic therapy, if indicated. Local therapies include surgery, whole-brain radiotherapy, and stereotactic radiosurgery. Memantine and hippocampal avoidance should be added to whole-brain radiotherapy when possible. Treatments depend on factors such as patient prognosis, presence of symptoms, resectability, number and size of metastases, prior therapy, and whether metastases are diffuse. Other options include systemic therapy, best supportive care, enrollment onto a clinical trial, and/or palliative care. There are insufficient data to recommend for or against performing routine magnetic resonance imaging to screen for brain metastases; clinicians should have a low threshold for magnetic resonance imaging of the brain because of the high incidence of brain metastases among patients with HER2-positive advanced breast cancer.Additional information is available at www.asco.org/breast-cancer-guidelines.
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- 2022
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