1,568 results on '"Department of Oncology and Radiotherapy"'
Search Results
2. Continuous 7-Days-A-Week External Beam Irradiation in Locally Advanced Cervical Cancer: Final Results of the Phase I/II Study
- Author
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Jassem, Jacek [Department of Oncology and Radiotherapy, Medical University of Gdansk (Poland)]
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- 2012
- Full Text
- View/download PDF
3. Magnetic Resonance Imaging in Postprostatectomy Radiotherapy Planning
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Nejedla, Anna [Department of Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove (Czech Republic)]
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- 2012
- Full Text
- View/download PDF
4. ESMO Management and treatment adapted recommendations in the COVID-19 era: Breast Cancer
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Azambuja, Evandro de, Trapani, Dario, Loibl, Sibylle, Delaloge, Suzette, Senkus, Elzbieta, Criscitiello, Carmen, Poortman, Philip, Gnant, Michael, Di Cosimo, Serena, Cortés, Javier, Cardoso, Fatima, Paluch-Shimon, Shani, Curigliano, Giuseppe, Universitat Autònoma de Barcelona. Departament de Medicina, Institut Català de la Salut, [de Azambuja E] Institut Jules Bordet and l’Université Libre de Bruxelles (U.LB), Brussels, Belgium. [Trapani D] European Institute of Oncology (IEO) IRCCS, Milan, Italy. [Loibl S] GBG Forschungs GmbH, Neu-Isenburg, Germany. [Delaloge S] Oncology, Gustave Roussy and Paris-Saclay University, Villejuif, Île-de-France, France. [Senkus E] Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland. [Criscitiello C] European Institute of Oncology IRCCS, Milan, Italy. [Cortes J] IOB, Institute of Oncology, Quiron Group (Madrid & Barcelona). Vall d'Hebron institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Cancer Research ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Psychological intervention ,Review ,COVID-19 (Malaltia) ,Radiation Oncology -- methods ,Health care ,Pandemic ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Otros calificadores::/terapia [Otros calificadores] ,media_common ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Surgical Oncology -- methods ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Telemedicine ,Surgical Oncology ,Oncology ,Preparedness ,ESMO adapted recommendations ,Female ,Public Health ,Coronavirus Infections ,Autonomy ,medicine.medical_specialty ,media_common.quotation_subject ,Pneumonia, Viral ,Telemedicine -- methods ,Context (language use) ,Breast Neoplasms ,lcsh:RC254-282 ,Betacoronavirus ,breast cancer ,Nursing ,Breast Neoplasms -- diagnosis -- therapy ,medicine ,Humans ,Quality (business) ,Pandemics ,business.industry ,SARS-CoV-2 ,Health Priorities ,Public health ,COVID-19 ,Généralités ,Other subheadings::/therapy [Other subheadings] ,Pneumonia, Viral -- epidemiology -- virology ,Coronavirus ,Mama - Càncer - Tractament ,Radiation Oncology ,Business ,Human medicine ,Coronavirus Infections -- epidemiology -- virology - Abstract
The global preparedness and response to the rapid escalation to severe acute respiratory syndrome coronavirus (SARS-CoV)-2-related disease (COVID-19) to a pandemic proportion has demanded the formulation of a reliable, useful and evidence-based mechanism for health services prioritisation, to achieve the highest quality standards of care to all patients. The prioritisation of high value cancer interventions must be embedded in the agenda for the pandemic response, ensuring that no inconsistency or discrepancy emerge in the health planning processes. The aim of this work is to organise health interventions for breast cancer management and research in a tiered framework (high, medium, low value), formulating a scheme of prioritisation per clinical cogency and intrinsic value or magnitude of benefit. The public health tools and schemes for priority setting in oncology have been used as models, aspiring to capture clinical urgency, value in healthcare, community goals and fairness, while respecting the principles of benevolence, non-maleficence, autonomy and justice. We discuss the priority health interventions across the cancer continuum, giving a perspective on the role and meaning to maintain some services (undeferrable) while temporarily abrogate some others (deferrable). Considerations for implementation and the essential link to pre-existing health services, especially primary healthcare, are addressed, outlining a framework for the development of effective and functional services, such as telemedicine. The discussion covers the theme of health systems strategising, and why oncology care, in particular breast cancer care, should be maintained in parallel to pandemic control measures, providing a pragmatic clinical model within the broader context of public healthcare schemes., SCOPUS: re.j, info:eu-repo/semantics/published
- Published
- 2020
5. An observational, multicentre study of cabazitaxel in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (CAPRISTANA)
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Irina Koroleva, Joan Carles, Fadi El Karak, Denise Bury, Hana Korunkova, Joseph Makdessi, Marwan Ghosn, Simon Hitier, Jana Katolicka, Antoaneta Tomova, Angelika Pichler, Ayse Özatilgan, Gisoo Barnes, Institut Català de la Salut, [Carles J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Pichler A] Department of Hematology and Oncology, Landeskrankenhaus Hochsteiermark, Leoben, Austria. [Korunkova H] Department of Oncology and Radiotherapy, University Hospital, Plzen, Czech Republic. [Tomova A] Department of Oncology, Complex Oncology Center, Plovdiv, Bulgaria. [Ghosn M, El Karak F] Department of Hematology and Oncology, Hotel Dieu de France University Hospital, Saint Joseph University, Beirut, Lebanon, Vall d'Hebron Barcelona Hospital Campus, and Hospital Universitari Vall d'Hebron
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Male ,Neutrophils ,Urological Oncology ,#PCSM ,Phases of clinical research ,Docetaxel ,Prostate cancer ,0302 clinical medicine ,Quality of life ,Antineoplastic Combined Chemotherapy Protocols ,030212 general & internal medicine ,Aged, 80 and over ,health‐related quality of life ,metastatic castration‐resistant prostate cancer ,Middle Aged ,mCRPC ,real‐world ,Diagnosis::Prognosis::Treatment Outcome::Progression-Free Survival [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Progression-Free Survival ,Survival Rate ,Prostatic Neoplasms, Castration-Resistant ,#ProstateCancer ,Cabazitaxel ,030220 oncology & carcinogenesis ,Taxoids ,Cohort study ,medicine.drug ,Adult ,medicine.medical_specialty ,diagnóstico::pronóstico::resultado del tratamiento::supervivencia libre de progresión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Urology ,HRQoL ,terapéutica::farmacoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Therapeutics::Drug Therapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,03 medical and health sciences ,Metàstasi ,Internal medicine ,medicine ,Humans ,Adverse effect ,Aged ,business.industry ,cabazitaxel ,Pròstata - Càncer - Tractament ,medicine.disease ,Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms::Prostatic Neoplasms, Castration-Resistant [DISEASES] ,Comorbidity ,neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales masculinos::neoplasias de la próstata::neoplasias prostáticas resistentes a la castración [ENFERMEDADES] ,Quality of Life ,business ,Follow-Up Studies - Abstract
Càncer de pròstata resistent a la castració metastàsica; Cabazitaxel; Qualitat de vida relacionada amb la salut Cáncer de próstata metastásico resistente a la castración; Cabazitaxel; Calidad de vida relacionada con la salud Metastatic castration-resistant prostate cancer; Cabazitaxel; Health-related quality of life Objectives To obtain routine clinical practice data on cabazitaxel usage patterns for patients with metastatic castration‐resistant prostate cancer (mCRPC) and to describe physician‐assessed cabazitaxel effectiveness, health‐related quality of life (HRQoL) and safety. Patients and Methods CAPRISTANA was an international, observational cohort study examining cabazitaxel use for the treatment of patients with mCRPC. Effectiveness was assessed by overall survival (OS), progression‐free survival (PFS), time to treatment failure (TTF) and disease control rate. HRQoL was assessed using the Functional Assessment of Cancer Therapy‐Prostate questionnaire (FACT‐P) and the three‐level European Quality of Life questionnaire (EQ‐5D‐3L). Safety was assessed by adverse event (AE) reporting. Results A total of 189 patients were treated across 54 centres between April 2012 and June 2016. At baseline, 58.7% had ≥1 comorbidity, 93.7% had an Eastern Cooperative Oncology Group performance status ≤1, and 60.1% had a Gleason score at diagnosis of ≥8. Patients received a median of 6 cabazitaxel cycles; 84.7% received cabazitaxel as second‐line therapy. The median OS, PFS and TTF were 13.2, 5.6 and 4.4 months, respectively. Cabazitaxel led to disease control in 52.9% of patients. HRQoL was maintained (40.3%) or improved (32.2%) in 72.5% of patients based on total FACT‐P scores. Interestingly, 53.6% of patients reported pain improvement and a further 21.2% maintained pain control based on FACT‐P prostate cancer‐specific pain scores. The most common treatment‐related grade ≥3 AEs were neutropenia (7.9%) and anaemia (2.1%). Conclusion Patients in CAPRISTANA treated with cabazitaxel had similar disease outcomes and safety profiles compared with large phase III clinical trials. Most patients had maintained or improved HRQoL scores; >70% of patients had maintained or improved pain control. Research and analysis was supported by Sanofi. The authors were responsible for all content and editorial decisions, and received no honoraria for development of this manuscript. Editorial support was provided by Amber Wood and Anna Longjaloux of MediTech Media, funded by Sanofi. The authors would also like to thank Teri Michelini of Sanofi for support in preparing this manuscript.
- Published
- 2018
6. 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)†
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Cardoso, F, Senkus, E., Costa, A, Papadopoulos, E, Aapro, M, André, F, Harbeck, N, Aguilar Lopez, B, Barrios, CH, Bergh, J, Prat, A, Boers-Doets, CB, Cardoso, MJ, Carey, LA, Cortés, J, Curigliano, G, Diéras, V, Saghir NS, EL, Eniu, A, Fallowfield, L, Francis, PA, Gelmon, K, Johnston, SRD, Kaufman, B, Koppikar, S, Krop, IE, Mayer, M, Nakigudde, G, Offersen, BV, Ohno, S, Pagani, O, Paluch-Shimon, S, Penault-Llorca, F, Prat, A., Rugo, HS, Sledge, GW, Spence, D, Thomssen, C, Vorobiof, DA, Xu, B., Norton, L, Winer, EP, Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland, Medical University of Gdansk, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
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0301 basic medicine ,Consensus Development Conferences as Topic ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Medical Oncology ,03 medical and health sciences ,0302 clinical medicine ,Biomarkers, Tumor ,Humans ,Breast ,Mastectomy ,Societies, Medical ,ComputingMilieux_MISCELLANEOUS ,Neoplasm Staging ,Clinical Trials as Topic ,Integrative Medicine ,Evidence-Based Medicine ,Hematology ,Chemoradiotherapy, Adjuvant ,Neoadjuvant Therapy ,3. Good health ,Europe ,030104 developmental biology ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Special article ,Female ,Biopsy, Large-Core Needle - Abstract
International audience
- Published
- 2018
7. Corrigendum to '3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3)' [Breast 31 (February 2017) 244-259]
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Cardoso, F., Costa, A., Senkus, E., Aapro, M., Andre, F., Barrios, C.H., Bergh, J., Bhattacharyya, G., Biganzoli, L., Cardoso, M.J., Carey, L., Corneliussen-James, D, Curigliano, G, Dieras, V, El Saghir, N, Eniu, E, Fallowfield, L., Fenech, E, Francis, D, Gelmon, B, Gennari, D, Hudis, B, Kaufman, B., Krop, B, Meijer, D, Mertz, B, Ohno, B, Pagani, B, Papadopoulos, E., Peccatori, E, Penault-Llorca, L, Piccart, L, Pierga, D, Rugo, B, Shockney, L., Sledge, A, Swain, L, Thomssen, E, Tutt, L, Vorobiof, D., Xu, B., Norton, L., Winer, E., Eniu, A., Fenech, D., Francis, P., Gelmon, K., Gennari, A., Harbeck, N., Hudis, C., Krop, I., Mayer, M., Meijer, H., Mertz, S., Ohno, S., Pagani, O., Peccatori, F., Penault-Llorca, F., Piccart, M.J., Pierga, J.Y., Rugo, H., Sledge, G., Swain, S., Thomssen, C., Tutt, A., European School of Oncology & Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal, Champalimaud Clinical Center, European Institute of Oncology [Milan] (ESMO), Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland, Medical University of Gdansk, Breast Center, Genolier Cancer Center, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Department of Medicine, PUCRS School of Medicine, Department of Oncology–Pathology, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Medical Oncology, Fortis Hospital, 'Sandro Pitigliani' Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Breast Unit, Department of Hematology and Oncology, Lineberger Comprehensive Cancer Center (UNC Lineberger), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), METAvivor Research and Support, MetaVivor Research and Support, Division of Experimental Therapeutics, Department of Medical Oncology, Institut Curie, Paris 75248, France, Brustzentrum der Universitat München, Universität München, Advanced BC.org, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Advanced breast ,Cancer ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,General Medicine ,medicine.disease ,3. Good health ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Surgery ,business ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2017
8. NCT01110291: induction of CYP3A activity and lowered exposure to docetaxel in patients with primary breast cancer
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Seppo Pyrhönen, Kari Laine, Liisa Sailas, Sirkku Jyrkkiö, Johanna Hilli, Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Unit of Clinical Pharmacology, Turku University Hospital (TYKS), Department of Oncology, Vaasa Central Hospital, Department of Oncology and Radiotherapy, and medbase Oy Ltd
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Oncology ,Cancer Research ,Administration, Oral ,Docetaxel ,urologic and male genital diseases ,Toxicology ,030226 pharmacology & pharmacy ,Dexamethasone ,Induction ,0302 clinical medicine ,Cytochrome P-450 CYP3A ,Pharmacology (medical) ,ComputingMilieux_MISCELLANEOUS ,Middle Aged ,Peroral midazolam ,3. Good health ,Area Under Curve ,030220 oncology & carcinogenesis ,Corticosteroid ,Female ,Taxoids ,Breast disease ,therapeutics ,medicine.drug ,Adult ,medicine.medical_specialty ,medicine.drug_class ,Midazolam ,Antineoplastic Agents ,Breast Neoplasms ,CYP3A activity ,03 medical and health sciences ,Breast cancer ,Internal medicine ,medicine ,Humans ,Adverse effect ,Glucocorticoids ,neoplasms ,Pharmacology ,business.industry ,organic chemicals ,Cancer ,medicine.disease ,Survival Analysis ,Endocrinology ,business - Abstract
To study the CYP3A activity before and after docetaxel administration. Furthermore, it was investigated whether peroral midazolam could predict docetaxel exposure and adverse events.Twenty patients with primary high risk breast cancer were given docetaxel as a 1-h infusion 80 mg/m(2) in a 21-day cycle in 3 cycles followed by 3 cycles of cyclophosphamide, epirubicin and fluorouracil. CYP3A activity was assessed a day before and a day after docetaxel by 7.5 mg oral midazolam. All patients were given peroral dexamethasone a total dose of 45 mg, of which 15 mg was given before docetaxel infusion and 30 mg before the latter assessment of CYP3A activity. All except one patient were given 11-19 mg of intravenous dexamethasone before docetaxel infusion.CYP3A activity was clearly induced when assessed a day after docetaxel administration as shown by lower midazolam AUC (P0.0001) and higher AUC ratio (1-OH-midazolam/midazolam, P = 0.018). The mean docetaxel AUC was about a half of that previously reported in the literature. Incidence of febrile neutropenia was smaller (15%) than reported in literature with comparable docetaxel doses and seemed to associate with slower metabolism. No correlation between pharmacokinetics of midazolam and docetaxel was found at baseline.We show here a markedly reduced docetaxel exposure followed by CYP3A induction by, most likely, dexamethasone. Peroral midazolam seemed not to predict docetaxel exposure. Slow CYP3A-mediated metabolism might predispose patients to adverse events of docetaxel.
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- 2010
9. High-resolution CT by diffraction-enhanced x-ray imaging: mapping of breast tissue samples and comparison with their histo-pathology
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Petri Sipilä, Pekka Virkkunen, Manuel Fernández, Mikko Tenhunen, Marja-Liisa Karjalainen-Lindsberg, Christian Nemoz, Stefan Fiedler, Marjut Leidenius, Jani Keyriläinen, Pekka Suortti, Karl von Smitten, Alberto Bravin, European Synchrotron Radiation Facility (ESRF), Department of Oncology and Radiotherapy, Turku University Central Hospital, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Molecular Biology Laboratory [Hamburg] (EMBL), Department of Pathology, Helsinki University Central Hospital, Department of Physics, Helsinki University Central Hospital-HUCH Cancer Center, Helsinki Medical Imaging Center, Breast surgery unit, Radiation Metrology Laboratory, Radiation and Nuclear Safety Authority, Department of Physical Sciences [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, INCA, Serduc, Raphael, University of Helsinki, Bravin, A, Keyrilainen, J, Fernandez, M, Fiedler, S, Nemoz, C, Karjalainen-Lindsberg, M, Tenhunen, M, Virkkunen, P, Leidenius, M, von Smitten, K, Sipila, P, and Suortti, P
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Diffraction ,Materials science ,Image quality ,Radiography ,media_common.quotation_subject ,MESH: Mammography ,FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA) ,Synchrotron radiation ,Breast Neoplasms ,MESH: Algorithms ,[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,High-resolution CT, diffraction-enhanced x-ray imaging ,Sensitivity and Specificity ,[SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,X-Ray Diffraction ,MESH: Radiographic Image Interpretation, Computer-Assisted ,Humans ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,media_common ,MESH: Humans ,[PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph] ,Radiological and Ultrasound Technology ,business.industry ,MESH: X-Ray Diffraction ,X-ray ,Reproducibility of Results ,Refraction ,MESH: Sensitivity and Specificity ,3. Good health ,Radiographic Image Enhancement ,MESH: Reproducibility of Results ,MESH: Radiographic Image Enhancement ,030220 oncology & carcinogenesis ,[PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph] ,Radiographic Image Interpretation, Computer-Assisted ,Female ,Monochromatic color ,Tomography, X-Ray Computed ,MESH: Tomography, X-Ray Computed ,Nuclear medicine ,business ,MESH: Female ,Algorithms ,MESH: Breast Neoplasms ,Mammography - Abstract
International audience; The aim of this study was to introduce high-resolution computed tomography (CT) of breast tumours using the diffraction-enhanced x-ray imaging (DEI) technique and to compare results with radiological and histo-pathological examinations. X-ray CT images of tumour-bearing breast tissue samples were acquired by monochromatic synchrotron radiation (SR). Due to the narrow beam and a large sample-to-detector distance scattering is rejected in the absorption contrast images (SR-CT). Large contrast enhancement is achieved by the use of the DEI-CT method, where the effects of refraction and scatter rejection are analysed by crystal optics. Clinical mammograms and CT images were recorded as reference material for a radiological examination. Three malignant and benign samples were studied in detail. Their radiographs were compared with optical images of stained histological sections. The DEI-CT images map accurately the morphology of the samples, including collagen strands and micro-calcifications of dimensions less than 0.1 mm. Histo-pathological examination and reading of the radiographs were done independently, and the conclusions were in general agreement. High-resolution DEI-CT images show strong contrast and permit visualization of details invisible in clinical radiographs. The radiation dose may be reduced by an order of magnitude without compromising image quality, which would make possible clinical in vivo DEI-CT with future compact SR sources.
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- 2007
10. Toward high-contrast breast CT at low radiation dose
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Petri Sipilä, Pekka Virkkunen, Karl von Smitten, Marja-Liisa Karjalainen-Lindsberg, Alberto Bravin, Jani Keyriläinen, Pekka Suortti, Manuel Fernández, Heikki Suhonen, Stefan Fiedler, Marjut Leidenius, Department of Oncology and Radiotherapy, Turku University Central Hospital, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Helsinki University Central Hospital, Helsinki Medical Imaging Center, Breast surgery unit, Radiation Metrology Laboratory, Radiation and Nuclear Safety Authority, European Molecular Biology Laboratory [Hamburg] (EMBL), Department of Physical Sciences [Helsinki], University of Helsinki, Biomedical Beamline (ID17), European Synchrotron Radiation Facility (ESRF), Collaboration, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Serduc, Raphael, Keyrilainen, J, Fernandez, M, Karjalainen-Lindsberg, M, Virkkunen, P, Leidenius, M, von Smitten, K, Sipila, P, Fiedler, S, Suhonen, H, Suortti, P, and Bravin, A
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low radiation dose ,Spectrum analyzer ,medicine.medical_specialty ,MESH: Radiation Dosage ,Radiobiology ,media_common.quotation_subject ,Radiography ,MESH: Mammography ,FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA) ,Radiation Dosage ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Contrast (vision) ,Dosimetry ,Radiology, Nuclear Medicine and imaging ,media_common ,MESH: Humans ,business.industry ,Soft tissue ,breast CT ,[SDV.ETH] Life Sciences [q-bio]/Ethics ,3. Good health ,[SDV.ETH]Life Sciences [q-bio]/Ethics ,030220 oncology & carcinogenesis ,Female ,Radiology ,Tomography ,Tomography, X-Ray Computed ,Nuclear medicine ,business ,Diagnostic Mammography ,MESH: Tomography, X-Ray Computed ,MESH: Female ,Mammography - Abstract
International audience; This study was approved by the local research ethics committee, and patient informed consent was obtained. The purpose of this study was to demonstrate that high-spatial-resolution low-dose analyzer-based x-ray computed tomography (CT) can substantially improve the radiographic contrast of breast tissue in vitro when compared with that attained by using diagnostic mammography and CT. An excised human breast tumor was examined by using analyzer-based x-ray imaging with synchrotron radiation. The correspondence between analyzer-based x-ray images and diagnostic mammograms, CT images, and histopathologic findings was determined. Calcifications and fine details of soft tissue, which are at the contrast detection limit on diagnostic mammograms, are clearly visible on planar analyzer-based x-ray images. Analyzer-based x-ray CT yields high contrast from smoothly varying internal structures, such as tumorous mass lesions, corresponding to information on actual structures seen at histopathologic analysis. The mean glandular dose of 1.9 mGy in analyzer-based x-ray CT is approximately equivalent to the dose administered during single-view screening mammography. The improved visibility of mammographically indistinguishable lesions in vitro suggests that analyzer-based x-ray CT may be a valuable method in radiographic evaluation of the breast, thereby justifying further investigations.
- Published
- 2008
11. Refraction and scattering of X-rays in analyzer-based imaging
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Heikki Suhonen, Jani Keyriläinen, Pekka Suortti, Manuel Fernandez, Alberto Bravin, Department of Physical Sciences [Helsinki], University of Helsinki, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Polytech, Université Montpellier 2 - Sciences et Techniques (UM2), MENTA, Menta, European Synchrotron Radiation Facility (ESRF), Department of Oncology and Radiotherapy, Turku University Central Hospital, Collaboration, Suhonen, H, Fernandez, M, Bravin, A, Keyriläinen, J, Suortti, P, Serduc, Raphael, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and Polytech'Montpellier
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Paper ,Nuclear and High Energy Physics ,Voigtian function ,FIS/07 - FISICA APPLICATA (A BENI CULTURALI, AMBIENTALI, BIOLOGIA E MEDICINA) ,Second moment of area ,02 engineering and technology ,Collimated light ,030218 nuclear medicine & medical imaging ,MESH: X-Rays ,03 medical and health sciences ,0302 clinical medicine ,Optics ,Perfect crystal ,analyzer-based imaging ,Polymethyl Methacrylate ,Scattering, Radiation ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Scattering, Radiation ,MESH: Polymethyl Methacrylate ,Instrumentation ,Voigt profile ,Physics ,Radiation ,Geometrical optics ,business.industry ,Scattering ,Phantoms, Imaging ,X-Rays ,Fatty Acids ,X-ray scattering ,021001 nanoscience & nanotechnology ,Refraction ,MESH: Fatty Acids ,diffraction enhanced imaging ,MESH: Phantoms, Imaging ,MESH: Paper ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Biological small-angle scattering ,0210 nano-technology ,business - Abstract
International audience; A new algorithm is introduced for separation of the scattered and non-scattered parts of a monochromatic and well collimated synchrotron radiation beam transmitted through a sample and analyzed by reflection from a perfect crystal in the non-dispersive setting. The observed rocking curve is described by the Voigt function, which is a convolution of Lorentzian and Gaussian functions. For the actual fitting, pseudo-Voigtians are used. The fit yields the scaled integrated intensity (the effect of absorption), the center of the rocking curve (the effect of refraction), and the intensity of the transmitted beam is divided into the scattered and non-scattered parts. The algorithm is tested using samples that exhibit various degrees of refraction and scattering. Very close fits are achieved in an angular range that is 15 times the full width at half-maximum of the intrinsic rocking curve of the analyzer. The scattering part has long tails of Lorentzian shape owing to the ;long-slit geometry' of the set-up. Quantitative images of absorption, refraction and scattering are constructed and compared with results of earlier treatments. The portion of scattering and the second moment of the observed rocking curve both increase linearly with the sample thickness and yield identical maps of the effects of scattering. The effects of refraction are calculated using the geometrical optics approximation, and a good agreement with experiment is found. The fits with reduced number of data points (minimum number is five) yield closely the same results as fits to the full data set.
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- 2007
12. Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action.
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Meyer ML, Peters S, Mok TS, Lam S, Yang PC, Aggarwal C, Brahmer J, Dziadziuszko R, Felip E, Ferris A, Forde PM, Gray J, Gros L, Halmos B, Herbst R, Jänne PA, Johnson BE, Kelly K, Leighl NB, Liu S, Lowy I, Marron TU, Paz-Ares L, Rizvi N, Rudin CM, Shum E, Stahel R, Trunova N, Ujhazy P, Bunn PA Jr, and Hirsch FR
- Abstract
Background: Lung cancer remains a critical public health issue, presenting multifaceted challenges in prevention, diagnosis, and treatment. This article aims to review the current landscape of lung cancer research and management, delineate the persistent challenges, and outline pragmatic solutions., Materials and Methods: Global experts from academia, regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the National Cancer Institute (NCI), professional societies, the pharmaceutical and biotech industries, and patient advocacy groups were gathered by the New York Lung Cancer Foundation to review the state of the art in lung cancer and to formulate calls to action., Results: Improving lung cancer management and research involves promoting tobacco cessation, identifying individuals at risk who could benefit from early detection programs, and addressing treatment-related toxicities. Efforts should focus on conducting well-designed trials to determine the optimal treatment sequence. Research into innovative biomarkers and therapies is crucial for more personalized treatment. Ensuring access to appropriate care for all patients, whether enrolled in clinical trials or not, must remain a priority., Conclusions: Lung cancer is a major health burden worldwide, and its treatment has become increasingly complex over the past two decades. Improvement in lung cancer management and research requires unified messaging and global collaboration, expanded education, and greater access to screening, biomarker testing, treatment, as well as increased representativeness, participation, and diversity in clinical trials., (Copyright © 2024 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)
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- 2024
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13. Management of Patients with Advanced Prostate Cancer. Report from the 2024 Advanced Prostate Cancer Consensus Conference (APCCC).
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Gillessen S, Turco F, Davis ID, Efstathiou JA, Fizazi K, James ND, Shore N, Small E, Smith M, Sweeney CJ, Tombal B, Zilli T, Agarwal N, Antonarakis ES, Aparicio A, Armstrong AJ, Bastos DA, Attard G, Axcrona K, Ayadi M, Beltran H, Bjartell A, Blanchard P, Bourlon MT, Briganti A, Bulbul M, Buttigliero C, Caffo O, Castellano D, Castro E, Cheng HH, Chi KN, Clarke CS, Clarke N, de Bono JS, De Santis M, Duran I, Efstathiou E, Ekeke ON, El Nahas TIH, Emmett L, Fanti S, Fatiregun OA, Feng FY, Fong PCC, Fonteyne V, Fossati N, George DJ, Gleave ME, Gravis G, Halabi S, Heinrich D, Herrmann K, Hofman MS, Hope TA, Horvath LG, Hussain MHA, Jereczek-Fossa BA, Jones RJ, Joshua AM, Kanesvaran R, Keizman D, Khauli RB, Kramer G, Loeb S, Mahal BA, Maluf FC, Mateo J, Matheson D, Matikainen MP, McDermott R, McKay RR, Mehra N, Merseburger AS, Morgans AK, Morris MJ, Mrabti H, Mukherji D, Murphy DG, Murthy V, Mutambirwa SBA, Nguyen PL, Oh WK, Ost P, O'Sullivan JM, Padhani AR, Parker C, Poon DMC, Pritchard CC, Rabah DM, Rathkopf D, Reiter RE, Renard-Penna R, Ryan CJ, Saad F, Sade JP, Sandhu S, Sartor OA, Schaeffer E, Scher HI, Sharifi N, Skoneczna IA, Soule HR, Spratt DE, Srinivas S, Sternberg CN, Suzuki H, Taplin ME, Thellenberg-Karlsson C, Tilki D, Türkeri LN, Uemura H, Ürün Y, Vale CL, Vapiwala N, Walz J, Yamoah K, Ye D, Yu EY, Zapatero A, and Omlin A
- Abstract
Background and Objective: Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts on key questions in clinical management in order to supplement evidence-based guidelines. Here we present voting results for questions from APCCC 2024., Methods: Before the conference, a panel of 120 international PC experts used a modified Delphi process to develop 183 multiple-choice consensus questions on eight different topics. Before the conference, these questions were administered via a web-based survey to the voting panel members ("panellists")., Key Findings and Limitations: Consensus was a priori defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. The voting results show varying degrees of consensus, as discussed in this article and detailed in the Supplementary material. These findings do not include a formal literature review or meta-analysis., Conclusions and Clinical Implications: The voting results can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Diagnostic and treatment decisions should always be individualised on the basis of patient and cancer characteristics, and should incorporate current and emerging clinical evidence, guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2024 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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14. Impact of Splenectomy on Long-term Outcomes after Gastrectomy for Gastric Cancer - a Population-based Study.
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Junttila A, Helminen O, Helmiö M, Huhta H, Jalkanen A, Kallio R, Koivukangas V, Kokkola A, Laine S, Lietzen E, Louhimo J, Meriläinen S, Pohjanen VM, Rantanen T, Ristimäki A, Räsänen JV, Saarnio J, Sihvo E, Toikkanen V, Tyrväinen T, Valtola A, and Kauppila JH
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Background: No national studies comparing long-term survival after total or partial gastrectomy with splenectomy due to injury or due to oncological reasons or spleen preservation exist. The aim of the study was to examine the overall 5-year survival of gastric adenocarcinoma patients undergoing total or partial gastrectomy with splenectomy due to injury or oncological reasons or spleen preservation in a population-based nationwide setting., Methods: This study included all patients undergoing total or partial gastrectomy with splenectomy or spleen preservation for gastric adenocarcinoma in Finland in 2005-2016, with follow-up until December 31, 2019. A total of 2,196 patients with gastric cancer diagnosis and total or partial gastrectomy were identified in the registries. Of these, 2,118 patients were applicable for this study. Cox proportional hazard models provided hazard ratios (HR) with 95% confidence intervals (CI) of overall 5-year survival. Results were adjusted for age, sex, year of operation, comorbidities, tumor location, pathological stage, and neoadjuvant therapy., Results: The observed overall 5-year survival was 38.7% in patients with no or minor spleen injury, 39.7% in patients with splenectomy due to injury and 30.8% in patients with splenectomy due to oncological reasons (p=0.032). R0 gastrectomy with splenectomy due to oncological reasons was associated with higher 5-year mortality (the adjusted model HR 1.26, 95% CI 1.01-1.56) compared to patients with spleen preservation., Conclusion: The overall survival is worst in gastrectomy patients with splenectomy due to oncological reasons highlighting the poor prognosis in patients with advanced gastric cancer. Splenectomy due to injury does not compromise prognosis., Competing Interests: Declarations of interest None Declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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15. Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase III IMpower133 study and the Phase III IMbrella A extension study.
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Reck M, Dziadziuszko R, Sugawara S, Kao S, Hochmair M, Huemer F, de Castro G Jr, Havel L, Bernabé Caro R, Losonczy G, Lee JS, Kowalski DM, Andric Z, Califano R, Veatch A, Gerstner G, Batus M, Morris S, Kaul M, Cuchelkar V, Li H, Danner BJ, Nabet BY, and Liu SV
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- Humans, Male, Female, Middle Aged, Aged, Neoplasm Staging, Etoposide administration & dosage, Etoposide therapeutic use, Follow-Up Studies, Survival Rate, Adult, Aged, 80 and over, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Small Cell Lung Carcinoma drug therapy, Small Cell Lung Carcinoma mortality, Small Cell Lung Carcinoma pathology, Lung Neoplasms drug therapy, Lung Neoplasms mortality, Lung Neoplasms pathology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carboplatin administration & dosage, Carboplatin therapeutic use
- Abstract
Objectives: IMbrella A is a Phase III extension study that allowed rollover from Roche/Genentech-sponsored atezolizumab trials, including IMpower133, a Phase I/III trial of first-line atezolizumab or placebo plus carboplatin/etoposide in extensive-stage small cell lung cancer. We report outcomes from an exploratory analysis of IMpower133 with extended time-to-event data for patients who rolled over to IMbrella A., Materials and Methods: IMpower133 patients could roll over to IMbrella A to receive atezolizumab 1200 mg intravenously every three weeks if they continued to receive atezolizumab at IMpower133 closure or were in survival follow-up after atezolizumab discontinuation. Overall survival and safety were assessed; only serious adverse events and AEs of special interest were collected in IMbrella A., Results: Eighteen of 26 eligible patients rolled over to IMbrella A. At clinical cutoff (March 16, 2023), median follow-up in the atezolizumab plus carboplatin/etoposide arm (IMpower133 and IMbrella A) was 59.4 months. The three-, four-, and five-year overall survival (95 % CI) estimates were 16 % (11 %-21 %), 13 % (8 %-18 %), and 12 % (7 %-17 %), respectively. In IMbrella A, serious adverse events occurred in three patients (16.7 %), and one adverse event of special interest was reported (grade two hypothyroidism)., Conclusion: This long-term analysis of patients from IMbrella A previously enrolled in IMpower133 provides the first report of five-year overall survival outcomes in patients with extensive-stage small cell lung cancer treated with first-line cancer immunotherapy and chemotherapy. While limited by small patient numbers and lack of long-term data for the IMpower133 control arm, exploratory overall survival analyses in patients treated with atezolizumab plus carboplatin/etoposide compared favorably with historical data with chemotherapy alone. NCT03148418., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors report editorial support funded by the Sponsor. Martin Reck reports receiving consulting fees, honoraria and travel support from Amgen, AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Mirati, Merck, MSD, Lily, Novartis, Pfizer, Sanofi, Roche, and Regeneron; and participation on a data safety monitoring or advisory board for Sanofi and Daiichi Sankyo. Rafal Dziadziuszko reports receiving honoraria from Roche, AstraZeneca, Amgen, Novartis, MSD, Bristol Myers Squibb, Takeda, and Pfizer; and materials from Novartis. Shunichi Sugawara reports receiving grants (to institution) from AstraZeneca, Chugai Pharma, MSD, Bristol Myers Squibb, and Ono Pharmaceutical; and honoraria from AstraZeneca, Chugai Pharma, MSD, Bristol Myers Squibb, and Ono Pharmaceutical. Steven Kao reports receiving grants (to institution) from AstraZeneca; honoraria from AstaZeneca, Pfizer, MSD, Bristol Myers Squibb, Roche, Amgen, Beigene, and Boehringer Ingelheim; and travel support from MSD. Maximilian Hochmair reports receiving honoraria from MSD, Roche, Lilly, AstraZeneca, Takeda, Bristol Myers Squibb, and Amgen. Florian Huemer declares no conflict of interest. Gilberto de Castro, Jr reports receiving consulting fees from Daiichi-Sankyo; honoraria from AstraZeneca, Bristol Myers Squibb, Jannsen, Lilly, MSD, Novartis, Roche, Amgen, and Daiichi-Sankyo; travel support from Roche, Amgen, Daiichi-Sankyo, MSD, AstraZeneca, and Bristol Myers Squibb; and participation on a data safety monitoring or advisory board for GlaxoSmithKline, AstraZeneca, MSD, and Novartis. Libor Havel declares no conflict of interest. Reyes Bernabé Caro reports receiving an investigational grant from Roche; honoraria from Roche, Bristol Myers Squibb, Pfizer, MSD, Amgen, Takeda, and AstraZeneca; and participation in a data safety monitoring or advisory board for Takeda, Roche, Bristol Myers Squibb, and AstraZeneca. György Losonczy and Jong-Seok Lee declare no conflict of interest. Dariusz M. Kowalski reports participation on an advisory board and consultancy for Roche, Boehringer Ingelheim, Novartis, Bristol Myers Squibb, MSD, Sanofi-Aventis, Takeda, Pfizer, and Johnson & Johnson. Zoran Andric declares no conflict of interest. Raffaele Califano reports receiving grants (to institution) from Roche and MSD; consulting fees from Roche, MSD, Bristol Myers Squibb, and AstraZeneca; and honoraria from Roche, MSD, and AstraZeneca; membership in the EORTC lung cancer group and ESMO educational publication working group; and stock or stock options in The Christie Private Care and Supportive Care UK. Andrea Veatch, Gregory Gerstner, and Marta Batus declare no conflicts of interest. Stefanie Morris reports employment with and stock or stock options in Roche. Monika Kaul, Vaikunth Cuchelkar, Huafei Li, Bradford J. Danner, and Barzin Y. Nabet report employment with Roche. Stephen V. Liu reports receiving grants from AbbVie, Alkermes, Elevation Oncology, Ellipses, Genentech, Gilead, Merck, Merus, Nuvalent, RAPT, and Turning Point Therapeutics; and consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Mirati, Novartis, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics; and participation on a data safety monitoring for Candel Therapeutics., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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16. Stereotactic body radiotherapy plus neoadjuvant chemoimmunotherapy in operable non-small-cell lung cancer.
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Dziadziuszko R and Tomasik B
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Competing Interests: RD has participated on data safety and monitoring boards or advisory boards for AstraZeneca, Roche, Bristol Myers Squibb, MSD, Pfizer, Novartis, GlaxoSmithKline, and Janssen Cilag; received consulting fees from Celon Pharma; received support for attending meetings or travel from GlaxoSmithKline; and received drug samples from Novartis and Pfizer. BT has received grants or contracts from Roche and payment for lectures from Pfizer.
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- 2024
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17. Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update.
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Loibl S, Jassem J, Sonnenblick A, Parlier D, Winer E, Bergh J, Gelber RD, Restuccia E, Im YH, Huang CS, Dalenc F, Calvo I, Procter M, Caballero C, Clark E, Raimbault A, McConnell R, Monturus E, de Azambuja E, Gomez HL, Bliss J, Viale G, Bines J, and Piccart M
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The APHINITY trial (ClinicalTrials.gov identifier: NCT01358877) previously demonstrated that pertuzumab added to adjuvant trastuzumab and chemotherapy improved invasive disease-free survival (iDFS) for patients with early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC). Here, we report the preplanned third interim analysis of overall survival (OS) and a descriptive updated iDFS analysis with 8.4 years of median follow-up of 4,804 patients in the intent-to-treat population. The 8-year OS was 92.7% in the pertuzumab versus 92.0% in the placebo group (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .078, above the 0.006 significance threshold). The HR was 0.80 [95% CI 0.63 to 1.00] in the node-positive cohort and 0.99 [95% CI, 0.64 to 1.55] in the node-negative cohort. Updated results of 8-year iDFS in the node-positive cohort showed an absolute improvement of 4.9% favoring pertuzumab (86.1% v 81.2%; HR, 0.72 [95% CI, 0.60 to 0.87]). The node-negative cohort did well without adding pertuzumab (8-year iDFS and OS in the placebo group were 93.3% and 96.4%, respectively). The iDFS benefit was seen in the hormone receptor-negative (HR, 0.82 [95% CI, 0.64 to 1.06]) and HR+ cohorts (HR of 0.75 [95% CI, 0.61 to 0.92]). Despite improvement in overall iDFS, the addition of pertuzumab did not improve OS at this third interim analysis.
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- 2024
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18. Extracorporeal photophoresis in treatment of corticosteroid refractory colitis induced by combined immunotherapy for metastatic melanoma.
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Pásek M, Kopecký J, Tretera V, Arenberger P, and Arenbergerová M
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- 2024
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19. Liquid Biopsy in Progressing Prostate Cancer Patients Starting Docetaxel with or Without Enzalutamide: A Biomarker Study of the PRESIDE Phase 3b Trial.
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Ruiz-Vico M, Wetterskog D, Orlando F, Thakali S, Wingate A, Jayaram A, Cremaschi P, Vainauskas O, Brighi N, Castellano-Gauna D, Åström L, Matveev VB, Bracarda S, Esen A, Feyerabend S, Senkus E, López-Brea Piqueras M, Gupta S, Wenstrup R, Boysen G, Martins K, Iwata K, Chowdhury S, Gourgioti G, Serikoff A, Gonzalez-Billalabeitia E, Merseburger AS, Demichelis F, and Attard G
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Background and Objective: The PRESIDE (NCT02288247) randomized trial demonstrated prolonged progression-free survival (PFS) with continuing enzalutamide beyond progression in metastatic castration-resistant prostate cancer (mCRPC) patients starting docetaxel. This study aims to test the associations of PFS and circulating tumor DNA (ctDNA) prior to and after one cycle (cycle 2 day 1 [C2D1]) of docetaxel and with a liquid biopsy resistance biomarker (LBRB; plasma androgen receptor [AR] gain and/or circulating tumor cells [CTCs] expressing AR splice variant 7 [CTC-AR-V7]) prior to continuation of enzalutamide/placebo., Methods: Patients consenting to the biomarker substudy and donating blood before starting docetaxel with enzalutamide/placebo (N = 157) were included. Sequential plasma DNA samples were characterized with a prostate-cancer bespoke next-generation-sequencing capture panel (PCF_SELECT), and CTCs were assessed for AR-V7 (Epic Sciences, San Diego, CA, USA). Cox models, Kaplan-Meier, and restricted mean survival time (RMST) at 18 mo were calculated., Key Findings and Limitations: There was a significant association of worse PFS with pre-docetaxel ctDNA detection (N = 86 (55%), 8.1 vs 10.8 mo hazard ratio [HR] = 1.78, p = 0.004) or persistence/rise of ctDNA at C2D1 (N = 35/134, 5.5 vs 10.9 mo, HR = 1.95, 95% confidence interval [CI] = 1.15-3.30, p = 0.019). LBRB-positive patients (N = 62) had no benefit from continuing enzalutamide with docetaxel (HR = 0.78, 95% CI = 0.41-1.48, p = 0.44; RMST: 7.9 vs 7.1 mo, p = 0.50). Conversely, resistance biomarker-negative patients (N = 87) had significantly prolonged PFS (HR = 0.49, 95% CI = 0.29-0.82, p = 0.006; RMST: 11.5 vs 8.9 mo, p = 0.005). Eight patients were unevaluable. An exploratory analysis identified increased copy-number gains (CDK6/CDK4) at progression on docetaxel. Limitations included relatively low detection of CTC-AR-V7. Validation of impact on overall survival is required., Conclusions and Clinical Implications: Liquid biopsy gives an early indication of docetaxel futility, could guide patient selection for continuing enzalutamide, and identifies cell cycle gene alterations as a potential cause of docetaxel resistance in mCRPC., Patient Summary: In the PRESIDE biomarker study, we found that detecting circulating tumor DNA in plasma after starting treatment with docetaxel (chemotherapy) for metastatic prostate cancer resistant to androgen deprivation therapy can predict early how long patients will take to respond to treatment. Patients negative for a liquid biopsy resistance biomarker (based on the status of androgen receptor (AR) gene and AR splice variant 7 in circulating tumor cells) benefit from continuing enzalutamide in combination with docetaxel, while patients positive for the resistance biomarker did not. Additionally, we identified alterations in the cell cycle genes CDK6 and CDK4 as a potential genetic cause of resistance to docetaxel, which may support testing of specific drugs targeting these alterations., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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20. At the Crossroads of Local and Systemic Treatment of Operable Non-Small Cell Lung Cancer.
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Dziadziuszko R and Rzyman W
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- Humans, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung surgery, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms surgery, Lung Neoplasms pathology
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- 2024
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21. Tumor RNA sequencing identifies a group of Mycosis Fungoides patients with failure of skin-directed therapies.
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Häyrinen M, Teppo HR, Väkevä L, Ranki A, Barton HJ, Porvari K, Kiiskilä J, Kuusisto MEL, Kuitunen H, Lemma S, Sahi H, Haapasaari KM, and Kuittinen O
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- 2024
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22. Circulating tumor DNA measurement: a new pillar of medical oncology?
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Melichar B
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- Humans, Medical Oncology methods, Biomarkers, Tumor blood, Circulating Tumor DNA blood, Circulating Tumor DNA analysis, Neoplasms blood, Neoplasms diagnosis, Neoplasms genetics
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- 2024
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23. CDK5-cyclin B1 regulates mitotic fidelity.
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Zheng XF, Sarkar A, Lotana H, Syed A, Nguyen H, Ivey RG, Kennedy JJ, Whiteaker JR, Tomasik B, Huang K, Li F, D'Andrea AD, Paulovich AG, Shah K, Spektor A, and Chowdhury D
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- Humans, Coenzymes metabolism, HeLa Cells, Models, Molecular, Mutation, Phosphoproteins metabolism, Protein Binding, Proteome metabolism, Reproducibility of Results, Cyclin B1 metabolism, Cyclin-Dependent Kinase 5 antagonists & inhibitors, Cyclin-Dependent Kinase 5 deficiency, Cyclin-Dependent Kinase 5 genetics, Cyclin-Dependent Kinase 5 metabolism, Mitosis, Multiprotein Complexes metabolism
- Abstract
CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression
1 . Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p392 . Here, using independent chemical genetic approaches, we specifically abrogated CDK5 activity during mitosis, and observed mitotic defects, nuclear atypia and substantial alterations in the mitotic phosphoproteome. Notably, cyclin B1 is a mitotic co-factor of CDK5. Computational modelling, comparison with experimentally derived structures of CDK-cyclin complexes and validation with mutational analysis indicate that CDK5-cyclin B1 can form a functional complex. Disruption of the CDK5-cyclin B1 complex phenocopies CDK5 abrogation in mitosis. Together, our results demonstrate that cyclin B1 partners with both CDK5 and CDK1, and CDK5-cyclin B1 functions as a canonical CDK-cyclin complex to ensure mitotic fidelity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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24. Stereotactic Body Radiotherapy for Centrally Located Inoperable Early-Stage NSCLC: EORTC 22113-08113 LungTech Phase II Trial Results.
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Levy A, Adebahr S, Hurkmans C, Ahmed M, Ahmad S, Guckenberger M, Geets X, Lievens Y, Lambrecht M, Pourel N, Lewitzki V, Konopa K, Franks K, Dziadziuszko R, McDonald F, Fortpied C, Clementel E, Fournier B, Rizzo S, Fink C, Riesterer O, Peulen H, Andratschke N, McWilliam A, Gkika E, Schimek-Jasch T, Grosu AL, Le Pechoux C, Faivre-Finn C, and Nestle U
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- Humans, Male, Female, Aged, Middle Aged, Aged, 80 and over, Prospective Studies, Neoplasm Staging, Radiosurgery methods, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung radiotherapy, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms pathology, Lung Neoplasms radiotherapy, Lung Neoplasms surgery
- Abstract
Introduction: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC., Methods: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT., Results: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively., Conclusions: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial., Competing Interests: Disclosure Dr. Levy reports academic funding from Roche, Beigene, AstraZeneca, and Pharmamar. Dr. Adebahr was supported by the German Cancer Consortium (DKTK) and is now supported by a grant from the Federal Ministry of Education and Research (BMBF). The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)
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- 2024
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25. Clinical features and prognostic biomarkers in patients with SMARCA4 -mutated non-small cell lung cancer.
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Long J, Chen Y, Luo X, Rao R, Wang C, Guo Y, Xu J, Lin P, Song Y, Qu L, Liu Q, Lu J, Zhou C, Song Z, Lin X, Adachi H, Jassem J, Hamaji M, and Yu Z
- Abstract
Background: Patients with non-small cell lung cancer (NSCLC) carrying SMARCA4 mutations ( SMARCA4 -Mut) tend to have more advanced disease and a poor prognosis. However, due to the rarity of this mutation and the lack of related studies, the characteristics of SMARCA4 -Mut NSCLC patients remains poorly determined. To clarify the clinical characteristics and prognostic factors of SMARCA4 -Mut NSCLC, we initiated the present study to provide a clinical reference., Methods: We used data from two cohorts of NSCLC- SMARCA4 -mutated samples: The Cancer Genome Atlas (TCGA) database and our center's clinical data. The TCGA database was used to obtain 481 NSCLC- SMARCA4 -Mut samples for clinical characterization. The center collected data on 224 consecutive NSCLC patients treated between December 2020 to July 2022. Among them, 26 harbored SMARCA4 mutations, and 20 were eligible for inclusion in the study. Clinical, pathological, and molecular features, as well as prognostic role of SMARCA4 mutations were analyzed. Additionally, we analyzed the prognostic impact of Napsin A expression in SMARCA4 -Mut patients., Results: The TCGA database included 480 patients with SMARCA4 -Mut NSCLC, 311 males (64.8%) and 169 females (35.2%), with a median age of 67 years. Among the 20 SMARCA4 -Mut patients in our center series, 12 (60%) were males and 8 (40%) females, with a median age of 63. The intergroup prognostic correlation analysis showed that SMARCA4 -Mut patients had significantly worse prognosis than those the wild-type SMARCA4 ( SMARCA4 -WT) (P=0.04). Within the SMARCA4 -Mut group, patients with Napsin A expression had longer overall survival (OS) (P=0.03) than those without expression. Median survival in the Napsin A-positive and negative groups was 32 and 15 months, respectively. According to time-dependent receiver operating curve analysis, patients with Napsin A expression had significantly longer first-line treatment progression-free survival (PFS1) [area under the curve (AUC) =0.748] and OS (AUC =0.586). No prognostic value of Napsin A was found in patients SMARCA4 -WT patients., Conclusions: SMARCA4 -Mut is an adverse prognostic feature in NSCLC patients. Napsin A expression in SMARCA4 -Mut patients is associated with prolonged OS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-381/coif). J.J. serves as an unpaid editorial board member of Translational Lung Cancer Research from October 2023 to September 2025. The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)
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- 2024
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26. A Comparative Review of Autonomous Artificial Intelligence vs Artificial Intelligence-Assisted Human Optical Diagnosis of Colorectal Polyps.
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Cao T and Zhong C
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- 2024
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27. Mutational signatures and their association with cancer survival and gene expression in multiple cancer types.
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Karihtala P, Kilpivaara O, and Porvari K
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Different endogenous and exogenous mutational processes cause specific patterns of somatic mutations and mutational signatures. Although their biological research has been intensive, there are only rare studies assessing the possible prognostic role of mutational signatures. We used data from The Cancer Genome Atlas to study the associations between the activity of the mutational signatures and four survival endpoints in 18 types of malignancies. We further explored the prognostic differences according to, for example, the HPV status in head and neck squamous cell carcinomas and smoking status in lung cancers. The predictive power of the signatures over time was evaluated with a dynamic area under the curve model, and the links between mutational signature activities and differences in gene expression patterns were analyzed. In 12 of 18 studied cancer types, we identified at least one mutational signature whose activity predicted survival outcomes after adjusting for the established prognostic factors. For example, overall survival was associated with the activity of mutational signatures in nine cancer types and disease-specific survival in seven cancer types. The clock-like signatures SBS5 and SBS40 were most commonly associated with survival endpoints. The genes of the myosin binding protein and melanoma antigen families were among the most substantially dysregulated genes between the signatures of low and high activity. The differences in gene expression also revealed various enriched pathways. Based on these data, specific mutational signatures associate with the gene expression and have the potential to serve as strong prognostic factors in several cancer types., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
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- 2024
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28. The Role of Artificial Intelligence on Tumor Boards: Perspectives from Surgeons, Medical Oncologists and Radiation Oncologists.
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Nardone V, Marmorino F, Germani MM, Cichowska-Cwalińska N, Menditti VS, Gallo P, Studiale V, Taravella A, Landi M, Reginelli A, Cappabianca S, Girnyi S, Cwalinski T, Boccardi V, Goyal A, Skokowski J, Oviedo RJ, Abou-Mrad A, and Marano L
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- Humans, Neoplasms therapy, Surgeons, Medical Oncology methods, Radiation Oncology methods, Artificial Intelligence, Oncologists, Radiation Oncologists
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The integration of multidisciplinary tumor boards (MTBs) is fundamental in delivering state-of-the-art cancer treatment, facilitating collaborative diagnosis and management by a diverse team of specialists. Despite the clear benefits in personalized patient care and improved outcomes, the increasing burden on MTBs due to rising cancer incidence and financial constraints necessitates innovative solutions. The advent of artificial intelligence (AI) in the medical field offers a promising avenue to support clinical decision-making. This review explores the perspectives of clinicians dedicated to the care of cancer patients-surgeons, medical oncologists, and radiation oncologists-on the application of AI within MTBs. Additionally, it examines the role of AI across various clinical specialties involved in cancer diagnosis and treatment. By analyzing both the potential and the challenges, this study underscores how AI can enhance multidisciplinary discussions and optimize treatment plans. The findings highlight the transformative role that AI may play in refining oncology care and sustaining the efficacy of MTBs amidst growing clinical demands.
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- 2024
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29. Comparison of the effectiveness of neoadjuvant chemotherapy and adjuvant chemotherapy for improving prognosis in triple-negative breast cancer patients.
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Li W, Chang Y, Bai X, and Cao H
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Objective: To compare the effectiveness of surgery combined with neoadjuvant chemotherapy and radiotherapy (SNCR) versus surgery combined with adjuvant chemotherapy and radiotherapy (SACR) in improving the prognosis of triple-negative breast cancer (TNBC) patients., Methods: Clinical data from 112 TNBC patients treated between January 2014 and February 2019 were retrospectively collected. Data included clinical characteristics and 5-year disease-free survival (DFS). Kaplan-Meier (K-M) survival curves were used to analyze the associations of various factors with DFS. Lasso-Cox regression was used to screen significant variables identified by K-M survival analysis. Multivariate Cox regression was used to determine independent prognostic factors affecting DFS., Results: K-M survival analysis showed that treatment regimen (P=0.012), TNM (tumor, node, metastasis) staging (P=0.049), N staging (P=0.015), P53 (P=0.015), KI-67 (P=0.002), neutrophil-to-lymphocyte ratio (NLR) (P<0.001), platelet-to-lymphocyte ratio (PLR) (P<0.001), and cancer antigen 153 (CA153) (P<0.001) were associated with DFS in TNBC patients. Lasso-Cox regression analysis identified treatment regimen, TNM stage, P53, KI-67, NLR, PLR, and CA153 as features related to DFS when λ=0.053741 (1se). Multivariate Cox regression analysis revealed that treatment regimen (P<0.001, 95% CI: 2.309-14.396, HR=5.765), P53 (P=0.010, 95% CI: 1.315-7.864, HR=3.216), and NLR (P=0.001, 95% CI: 2.098-14.553, HR=5.525) were independent prognostic factors affecting DFS. A nomogram model was constructed, and time-dependent receiver operating characteristic (ROC) curve analysis showed that the model's areas under the curve (AUC) for predicting 1-, 3-, and 5-year DFS were 0.928, 0.816, and 0.665, respectively., Conclusion: The SNCR regimen significantly improves DFS in patients with stage IIb to IIIa TNBC compared to the traditional SACR regimen., Competing Interests: None., (AJTR Copyright © 2024.)
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- 2024
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30. Phase II study shows potential benefit of adenoviral vascular endothelial growth factor C (VEGF-C) and lymph node transfer in lymphedema.
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Rannikko EH, Pajula S, Suominen SH, Kiiski J, Mani MR, Halle M, Kaartinen IS, Lahdenperä O, Arnardottir TH, Kauhanen SM, Kavola H, Majava M, Niemi TS, Brück NM, Mäki MT, Seppänen MP, Saarikko AM, and Hartiala P
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Background: Breast cancer-related lymphedema (BCRL) is a common complication lacking medical treatment. Lymfactin® is an adenovirus type 5-based gene therapy and prolymphangiogenic growth factor vector that induces vascular endothelial growth factor C (VEGF-C) expression. Our aim was to evaluate the therapeutic effect of Lymfactin® with vascularized lymph node transfer (VLNT)., Methods: This Phase II, double-blind, placebo-controlled, randomized multicenter study evaluated the efficacy and safety of Lymfactin® in combination with VLNT. The primary endpoints were edema volume, quality of life (LyQoLI), and lymphoscintigraphy. All adverse events were recorded. A mixed model of repeated measures analysis of covariance was performed. This study was a continuation of a previous Phase I Lymfactin® study., Results: Thirty-nine patients with BCRL were recruited between June 2018 and December 2019 and randomized to receive either Lymfactin® (n = 20) or placebo (n = 19). The primary endpoints showed a positive effect of VLNT in both groups compared to the baseline, but without statistical differences between groups at 12 months. Additionally, greater improvements were observed in the tissue dielectric constant ratios measuring skin interstitial fluid levels in the Lymfactin® group compared to the placebo group (p = 0.020). No differences in adverse events were detected between the groups., Conclusions: This study was one of the few studies to objectively show a positive effect of VLNT in a prospective clinical multicenter setting. It was also the first-ever randomized prospective clinical study showing a quantitatively positive effect of a medical therapy on the edema of lymphedema although failing to show differences between groups in primary outcome measures., Competing Interests: Statement of Financial Disclosures, Conflicts of Interest, and Products: SS, JK, IK, AS, and PH have received honoraria for participating in advisory boards of Herantis Pharma Plc. (Espoo, Finland), which was responsible for trial management and has reviewed this manuscript. Authors do not have financial disclosures to report., (Copyright © 2024 by the American Society of Plastic Surgeons.)
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- 2024
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31. Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer: A Secondary Analysis of the SOLD Randomized Clinical Trial.
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Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, Villman KK, Halonen P, Granstam-Björneklett H, Tanner M, Sailas L, Turpeenniemi-Hujanen T, Yachnin J, Huttunen T, Neven P, Canney P, Harvey VJ, Kellokumpu-Lehtinen PL, and Lindman H
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- Humans, Female, Middle Aged, Chemotherapy, Adjuvant methods, Adult, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Docetaxel therapeutic use, Epirubicin therapeutic use, Epirubicin administration & dosage, Antineoplastic Agents, Immunological therapeutic use, Aged, Drug Administration Schedule, Treatment Outcome, Disease-Free Survival, Fluorouracil therapeutic use, Fluorouracil administration & dosage, Trastuzumab therapeutic use, Trastuzumab administration & dosage, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Receptor, ErbB-2 metabolism
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Importance: The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival., Objective: To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy., Design, Setting, and Participants: This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included women aged 18 years or older with early ERBB2-positive, axillary node-negative or axillary node-positive breast cancer who were enrolled from January 3, 2008, to December 16, 2014, at 65 centers in 7 European countries. The current exploratory analysis was conducted after achieving the maximum attainable follow-up data when the last patient enrolled had completed the last scheduled visit in December 2022., Intervention: Chemotherapy consisted of 3 cycles of docetaxel administered at 3-week intervals followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide at 3-week intervals. Trastuzumab was administered in both groups for 9 weeks concomitantly with docetaxel. In the 9-week group, no further trastuzumab was administered after chemotherapy, whereas in the 1-year group, trastuzumab was continued after chemotherapy to complete 1 year of administration., Main Outcomes and Measures: The primary objective was disease-free survival (DFS). Distant DFS and OS were secondary objectives. Survival between groups was compared using the Kaplan-Meier method and log-rank test or univariable Cox proportional hazards regression., Results: Among the 2174 women analyzed, median age was 56 years (IQR, 48-64 years). The median follow-up time was 8.1 years (IQR, 8.0-8.9 years); 357 DFS events and 176 deaths occurred. Trastuzumab for 9 weeks was associated with shorter DFS compared with trastuzumab for 1 year (hazard ratio [HR], 1.36; 90% CI, 1.14-1.62); 10-year DFS was 80.3% in the 1-year group vs 78.6% in the 9-week group. The 5-year and 10-year OS rates were comparable between the 9-week and 1-year groups (95.0% vs 95.9% and 89.1% vs 88.2%, respectively; HR for all time points, 1.20; 90% CI, 0.94-1.54). In multivariable analyses, 9-week treatment was associated with shorter DFS compared with 1-year treatment (HR for recurrence or death, 1.36; 95% CI, 1.10-1.68; P = .005), but there was no between-group difference in OS (HR, 1.22; 95% CI, 0.90-1.64; P = .20). Only 4 patients (0.2%) died of a cardiac cause., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, 1-year vs 9-week adjuvant trastuzumab was associated with improved DFS among patients with ERRB2-positive breast cancer receiving chemotherapy, but there was no significant difference in OS between the groups., Trial Registration: ClinicalTrials.gov Identifier: NCT00593697.
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- 2024
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32. 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).
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Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, Matos L, Gelmon K, Aapro MS, Bajpai J, Barrios CH, Bergh J, Bergsten-Nordström E, Biganzoli L, Cardoso MJ, Carey LA, Chavez-MacGregor M, Chidebe R, Cortés J, Curigliano G, Dent RA, El Saghir NS, Eniu A, Fallowfield L, Francis PA, Franco Millan SX, Gilchrist J, Gligorov J, Gradishar WJ, Haidinger R, Harbeck N, Hu X, Kaur R, Kiely B, Kim SB, Koppikar S, Kuper-Hommel MJJ, Lecouvet FE, Mason G, Mertz SA, Mueller V, Myerson C, Neciosup S, Offersen BV, Ohno S, Pagani O, Partridge AH, Penault-Llorca F, Prat A, Rugo HS, Senkus E, Sledge GW, Swain SM, Thomssen C, Vorobiof DA, Vuylsteke P, Wiseman T, Xu B, Costa A, Norton L, and Winer EP
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- Humans, Female, Consensus, Practice Guidelines as Topic, Breast Neoplasms therapy, Breast Neoplasms pathology, Palliative Care standards
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This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking. Each guideline is accompanied by the level of evidence (LoE), grade of recommendation (GoR) and percentage of consensus reached at the consensus conferences. Updated diagnostic and treatment algorithms are also provided. The guidelines represent the best management options for patients living with ABC globally, assuming accessibility to all available therapies. Their adaptation (i.e. resource-stratified guidelines) is often needed in settings where access to care is limited., Competing Interests: Declaration of competing interest Matti S. Aapro: Consultant for Accord Pharmaceuticals, Amgen, BMS, Celgene, Clinigen Group, Daiichi Sankyo, Eisai Co.Ltd, Eli Lilly, Genomic Health (Exact Sciences), G1 Therapeutics, Inc., GlaxoSmithKline (GSK), Helsinn Healthcare SA, Hospira (Pfizer), Johnson & Johnson, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro (GSK), Teva Pharmaceuticals Industries Ltd., Vifor Pharma. Received honoraria for lectures at symposia of Accord Pharmaceuticals, Amgen, Astellas, Bayer HealthCare Pharmaceuticals (Schering), Biocon, Boeringer Ingelheim, Cephalon, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Dr Reddy's Laboratories, Genomic Health (Exact Sciences), Glenmark Pharmaceuticals Limited, GSK, Helsinn Healthcare SA, Hospira (Pfizer), Ipsen, Janssen Biotech, Kyowa Kirin Group, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro (GSK), Taiho Pharmaceutical, Teva Pharmaceutical Industries Ltd., Vifor Pharma. Grant/Research supports: Amgen, Eisai, Genomic Health (Exact Sciences), Helsinn, Hospira, Novartis, Merck, Mundipharma, Pfizer, Roche, Sandoz, Tesaro, Teva, Vifor. Jyoti Bajpai: Institutional financial interests for conducting research: Eli Lilly, MSD, Novartis, Roche, Paxman Coolers Ltd, Samsung Bioepis co. Ltd, Sun Pharma. Carlos H. Barrios: Receipt of grants/research supports: (to the institution) Nektar, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, GSK, Janssen, OBI Pharma, Lilly, Seagen, Roche, BMS, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda, TRIO, PharmaMar, Celgene, PPD, Syneos Health, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, Worldwide, Gilead Sciences, Bayer, Servier. Receipt of honoraria or consultation fees: Advisory Boards and Consulting: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, Daiichi. Stock shareholder: Ownership or stocks: Tummi, MEDSir. Jonas Bergh: Receipt of grants/research supports: Research grants from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche & Sanofi-Aventis to Karolinska Institutet and/or University Hospital. No personal payments. Other support: Payment for a chapter in UpToDate on breast cancer prediction to Asklepios Medicin HB. Laura Biganzoli: Personal financial interests (Honoraria, consultancy or advisory role): Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Menarini, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, SeaGen. Institutional financial interests: Celgene, Genomic Health, Novartis. Travel grants: AstraZeneca, Daiichi-Sankyo. Fatima Cardoso: Receipt of honoraria or consultation fees: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, Touchime. Maria-Joao Cardoso: Receipt of honoraria or consultation fees: AstraZeneca, Merck-Sharp, Novartis and Roche. Lisa A. Carey: Other support: Research funding (institution): NanoString Technologies, Seagen, Veracyte, AstraZeneca. Uncompensated relationships: Lilly, Seagen, Novartis, Genentech/Roche, GlaxoSmithKline. Mariana Chavez-MacGregor: Receipt of grants/research supports: BCRF, Susan G Komen. Receipt of honoraria or consultation fees: Astra Zeneca, Pfizer, Lilly, Roche, Merck. Javier Cortés: Receipt of grants/research supports: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies. Receipt of honoraria or consultation fees: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo, Astrazeneca. Stock shareholder: MedSIR, Nektar Pharmaceuticals, Leuko (relative). Other support: Research funding to the Institution: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London. Travel, accommodation, expenses: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca, Gilead. Patents: Pharmaceutical Combinations of a Pi3k Inhibitor and A Microtubule Destabilizing Agent. Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde. WO 2014/199294 A. ISSUED. Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/0338368 A1. LICENSED. Giuseppe Curigliano: Receipt of grants/research supports: Merck. Receipt of honoraria or consultation fees: Merck, Lilly, Pfizer, Daichi Sankyo, Seagen, Novartis, Roche, Astra Zeneca, Ellipsis. Participation in a sponsored speakers' bureau: Seagen, Novartis, Lilly, Pfizer, Daichii Sankyo. Rebecca A. Dent: Receipt of grants/research supports: AstraZeneca, Roche. Receipt of honoraria or consultation fees: AstraZeneca, DKSH, Eisai, Merck, Novartis, Pfizer, Roche. Nagi S. El Saghir: Receipt of honoraria or consultation fees: Roche, Novartis, Lilly. Alexandru Eniu: Receipt of honoraria or consultation fees: Astra Zeneca, Daiichi Sankyo, Gilead, Janssen, MSD, Novartis, SeaGen. Receipt of grants/research supports: AstraZeneca. Full or part-time employment: European School of Oncology (ESO). Lesley Fallowfield: Receipt of grants/research supports: Novartis, Bristol-Myers Squibb, Lilly. Receipt of honoraria or consultation fees: Voluntis, Genomic Health, NanoString Technologies, Novartis, Pfizer, MSD, Novartis, Abbvie, Clovis Oncology, Puma Biotechnology, AstraZeneca, Takeda, Genomic Health/Exact Sciences, Lilly, Seagen, Roche. Sandra X. Franco Millan: Receipt of honoraria or consultation fees: Novartis, Pfizer, Eli Lilly. Participation in a sponsored speakers' bureau: Novartis, Pfizer, Eli Lilly. Karen Gelmon: Receipt of grants/research supports: Pfizer, AstraZeneca. Receipt of honoraria or consultation fees: Pfizer, Lilly, Novartis, AstraZeneca, Merck, Gilead, Seagen. Jenny Gilchrist: Receipt of honoraria or consultation fees: Eli-Lilly, AstraZeneca, Novartis, Pfizer, MSD, Gilead, Juniper Biologics. Joseph Gligorov: Receipt of grants/research supports: Eisai, Exact Science, Guardant, Roche Genentech. Receipt of honoraria or consultation fees: Astra Zeneca, Daiichi, Eisai, Evapharma, Exact Science, Gilead, Guardant Lilly, Merck, Novartis, Onxeo, Pfizer, Roche Genentech, Seattle Genetics. Participation in a sponsored speakers' bureau: Eisai, Eva Pharm, Novartis, Roche Genentech, Seattle Genetics. Other support (please specify): Institutional: Institut Universitaire de Cancérologie AP-HP Sorbonne Université; French breast cancer guidelines St Paul. Nadia Harbeck: Receipt of grants/research supports: all to institution. Receipt of honoraria or consultation fees: AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, PierreFabre, Pfizer, Roche, Sandoz, Seagen, Viatris, Zuelligpharma. Participation on a sponsored speakers' bureau: EPG Communication, MEDSCAPE, Springer. Stock shareholder: WSG minority ownership. Spouse/Partner: Consulting for WSG. Ranjit Kaur: Receipt of grants/research supports: Novartis, Roche, Pfizer, Astrazeneca. Receipt of honoraria or consultation fees: Novartis, Roche, Pfizer, Astrazeneca. Participation in a sponsored speakers' bureau: Novartis, Roche, Pfizer, Astrazeneca. Belinda Kiely: Receipt of honoraria or consultation fees: Speakers fees: Novartis, Eisai. Advisory boards: Roche, Gilead, Novartis. Other support (please specify): meeting registrations fees: Novartis, Pfizer, MSD. Sung-Bae Kim: Receipt of grants/research supports: Novartis, Sanofi-Aventis, and DongKook Pharm Co. Receipt of honoraria or consultation fees: Novartis, AstraZeneca, Lilly, Dae Hwa Pharmaceutical Co. Ltd, ISU Abxis, OBI pharma, Beigene and Daiichi-Sankyo. Stock shareholder: Genopeaks. Smruti Koppikar: Receipt of honoraria or consultation fees: Eli Lilly, Novartis, Cipla, Roche. Participation in a sponsored speakers' bureau: Eli Lilly, Novartis, Cipla, Roche. Marion Kuper-Hommel: Receipt of honoraria or consulting fees: Astra Zeneca. Ginny Mason: Participation in a sponsored speakers' bureau: Novartis. Volkmar Mueller: Receipt of grants/research supports: Institutional research support from Novartis, Roche, Seagen, Genentech, Astra Zeneca. Receipt of honoraria or consultation fees: Speaker honoraria: Astra Zeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre. Consultancy honoraria from Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, DaiichiSankyo, Eisai, Lilly, Sanofi, Seagen, Gilead, Stemline, ClinSol. Other support (please specify): Travel grants: Roche, Pfizer, Daiichi Sankyo, Gilead. Claire Myerson: Receipt of honoraria or consultation fees: Novartis Pharma. Silvia Neciosup: Receipt of grants/research supports: Roche, Pfizer. Participation in a sponsored speakers' bureau: Tecnofarma, AZ, Roche, Pfizer. Larry Norton: Receipt of honoraria or consultation fees: Blackrock QLS Advisors, Cold Spring Harbor Laboratory, UNC Breast Spore EAB Meeting, Codagenix Scientific Advisory Board Meeting, Martell Diagnostic Laboratories, Inc., Celgene, Agenus, Immix Biopharma, Inc. Shinji Ohno: Participation in a sponsored speakers' bureau: Chugai, Lilly, MSD, Nippon Kayaku. Shani Paluch-Shimon: Receipt of grants/research supports: Pfizer. Receipt of honoraria or consultation fees: Pfizer, Lily, Novartis, Astra Zeneca, Roche, MSD, Gilead, Rhenium/Exact Sciences, Stemline, Daichi Sankyo. Participation in a sponsored speakers' bureau: Pfizer, Lily, Novartis, Astra Zeneca, Roche, MSD, Gilead. Ann H. Partridge: Uptodate Royalties. Aleix Prat: Receipt of grants/research supports: Boehringer, Novartis, Roche, Nanostring, Sysmex Europa GmbH, Medica Scientia inno. Research, SL, Celgene, Astellas and Pzifer. Receipt of honoraria or consultation fees: Roche, Pfizer, Novartis, Amgen, BMS, Puma, Oncolytics Biotech, MSD, Guardan Health, Peptomyc and Lilly, Nanostring Technologies and Daiichi Sankyo. Other support: Clinical trials: Boehringer, Lilly, Roche, Novartis, Amgen and Daiichi Sankyo. Hope S. Rugo: Receipt of grants/research supports: Astellas Pharma Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Gilead Sciences, Inc.; GlaxoSmithKline; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals Inc.; Taiho Oncology, Inc. and Veru Inc. Receipt of honoraria or consultation fees: Puma, NAPO, Blueprint, and Scorpion Therapeutics Daichi Sankyo. Elzbieta Senkus: Receipt of honoraria or consultation fees: AstraZeneca, Curio Science, Egis, Eli Lilly, Gilead, high5md, MSD, Novartis, Pfizer, Roche, Swixx. Other support: travel support: AstraZeneca, Egis, Gilead, Novartis, Roche. Contracted research: Amgen, AstraZeneca, Eli Lilly, Gilead, Novartis, OBI Pharma, Roche, Samsung, Seagen. Medical writing: AstraZeneca, Eli Lilly. Royalties: Springer. Sandra M. Swain: Receipt of grants/research supports: Kailos Genetics, Genentech/Roche. Receipt of honoraria or consultation fees: Athenex, AstraZeneca, Biotheranostics, Natera, Exact Sciences, Lilly, Merck, Genentech/Roche, Sanofi, Daiichi Sankyo, Molecular Templates, Napo Pharmaceuticals. Stock shareholder: SEAGEN. Other support: CO- PI of INAVO 122 Genentech/Roche with in-kind travel to investigator meetings, Travel related expenses in kind Sanofi and Daiichi Sankyo. Peter Vuylsteke: Receipt of grants/research supports: UICC grant. Receipt of honoraria or consultation fees: Roche, Novartis and MSD. Theresa Wiseman: Receipt of grants/research supports: Receiver of SPCC Pfizer grant. Binghe Xu: Receipt of grants/research supports: sponsored research to my institution from Roche, AstraZeneca and Pfizer. Receipt of honoraria or consultation fees: advisory or consultancy fees from Novartis and Roche. Participation in a sponsored speakers' bureau: speakers’ bureau fees from AstraZeneca, Pfizer, Roche, Eisai. Elizabeth Bergsten-Nordström, Alberto Costa, Runcie C. W. Chidebe, Prudence A. Francis, Xichun Hu, Renate Haidinger, Leonor Matos, Shirley A. Mertz, Birgitte V. Offersen, Olivia Pagani, Eva Schumacher-Wulf, Daniel A. Vorobiof, Frédéric E. Lecouvet, and Eric P. Winer reported no significant relationships. William J. Gradishar, George W. Sledge and Christoph Thomssen have not submitted a disclosure of interests’ form., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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33. Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management.
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Ramirez-Gamero A, Martínez-Cordero H, Beltrán BE, Florindez J, Malpica L, and Castillo JJ
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- Humans, Risk Assessment, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Doxorubicin administration & dosage, Vincristine therapeutic use, Vincristine administration & dosage, Prednisone therapeutic use, Lenalidomide therapeutic use, Lenalidomide administration & dosage, Prognosis, Bortezomib therapeutic use, Bortezomib administration & dosage, Diagnosis, Differential, Disease Management, Middle Aged, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics, Antibodies, Monoclonal, Etoposide, Plasmablastic Lymphoma diagnosis, Plasmablastic Lymphoma therapy, Plasmablastic Lymphoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Disease Overview: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals., Diagnosis: The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others., Risk Stratification: Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival., Management: Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted., (© 2024 Wiley Periodicals LLC.)
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- 2024
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34. Front-line and second-line treatment for mantle cell lymphoma in clinical practice: A multicenter retrospective analysis.
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Harmanen M, Sorigue M, Khan M, Prusila R, Klaavuniemi T, Kari E, Jantunen E, Sunela K, Rajamäki A, Alanne E, Kuitunen H, Jukkola A, Sancho JM, Kuittinen O, and Rönkä A
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- Humans, Male, Aged, Female, Retrospective Studies, Middle Aged, Aged, 80 and over, Adult, Treatment Outcome, Cytarabine therapeutic use, Cytarabine administration & dosage, Bendamustine Hydrochloride administration & dosage, Bendamustine Hydrochloride therapeutic use, Disease Management, Neoplasm Staging, Retreatment, Lymphoma, Mantle-Cell drug therapy, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell diagnosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects
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Background: There are few reports of clinical practice treatment patterns and efficacy in mantle cell lymphoma (MCL)., Materials and Methods: We retrospectively studied a large, multicenter, cohort of patients with MCL diagnosed between 2000 and 2020 in eight institutions., Results: 536 patients were registered (73% male, median of 70 years). Front-line treatment was based on high-dose cytarabine, bendamustine, and anthracyclines in 42%, 12%, and 15%, respectively. The median PFS for all patients was 45 months; 68, 34, and 30 months for those who received high-dose cytarabine-based, bendamustine-based and anthracycline-based therapy. 204 patients received second-line. Bendamustine-based treatment was the most common second-line regimen (36% of patients). The median second-line PFS (sPFS) for the entire cohort was 14 months; 19, 24, and 31 for bendamustine-, platinum-, and high-dose cytarabine-based regimens, with broad confidence intervals for these latter estimates. Patients treated with cytarabine-based therapies in the front-line and those with front-line PFS longer than 24 months had a substantially superior sPFS., Conclusion: Front-line treatment in this cohort of MCL was as expected and with a median PFS of over 3.5 years. Second-line treatment strategies were heterogeneous and the median second-line PFS was little over 1 year., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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35. Non-Small-Cell Lung Cancer Patients Harboring ROS1 Rearrangement: Real World Testing Practices, Characteristics and Treatment Patterns (ROS1REAL Study).
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Janzic U, Maimon Rabinovich N, Shalata W, Kian W, Szymczak K, Dziadziuszko R, Jakopovic M, Mountzios G, Pluzanski A, Araujo A, Charpidou A, Daher S, and Agbarya A
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- Humans, Female, Middle Aged, Male, Aged, Retrospective Studies, Adult, Aged, 80 and over, Crizotinib therapeutic use, Protein Kinase Inhibitors therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Protein-Tyrosine Kinases genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Proto-Oncogene Proteins genetics, Gene Rearrangement
- Abstract
ROS1 rearrangements are considered rare in non-small-cell lung cancer (NSCLC). This retrospective real-world study aimed to evaluate first-line treatment with crizotinib, a tyrosine kinase inhibitor (TKI) standard of care vs. new generation ROS1 anti-cancer agents. Forty-nine ROS1-expressing NSCLC patients, diagnosed with advanced metastatic disease, were included. Molecular profiling using either FISH/CISH or NGS was performed on tissue samples. Twenty-eight patients were treated with crizotinib, while fourteen patients were administered newer drugs (entrectinib, repotrectinib) and seven patients received platinum-doublet chemotherapy in a first-line setting. Overall response rate and disease control rate for the crizotinib and entrectinb/repotrectinib cohort were 68% and 82% vs. 86% and 93%, respectively. Median progression free survival was 1.6 years (95% CI 1.15-2.215) for the crizotinib treatment vs. 2.35 years for the entrectinib/repotrectinib cohort (95% CI 1.19-3.52). Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.
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- 2024
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36. A randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679/ECHO-302).
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Lara PN Jr, Villanueva L, Ibanez C, Erman M, Lee JL, Heinrich D, Lipatov ON, Gedye C, Gokmen E, Acevedo A, Semenov A, Park SH, Gafanov RA, Kose F, Jones M, Du X, Munteanu M, Perini R, Choueiri TK, and Motzer RJ
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- Humans, Male, Female, Middle Aged, Aged, Adult, Aged, 80 and over, Oximes, Carcinoma, Renal Cell drug therapy, Sunitinib therapeutic use, Sunitinib administration & dosage, Sulfonamides administration & dosage, Sulfonamides therapeutic use, Sulfonamides adverse effects, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Pyrimidines therapeutic use, Pyrimidines administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Kidney Neoplasms drug therapy, Kidney Neoplasms pathology, Kidney Neoplasms mortality, Indazoles administration & dosage, Indazoles therapeutic use
- Abstract
Background: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC., Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1., Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2-14.3) and 10.3 months (2.7-13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2-44.1] and sunitinib/pazopanib (29.2% [18.6-41.8]). Grade 3-5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects., Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab., Clinical Trial Registration: ClinicalTrials.gov; NCT03260894 ., (© 2023. The Author(s).)
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- 2024
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37. The Association of Metformin, Other Antidiabetic Medications, and Statins with the Prognosis of Hepatocellular Carcinoma in Patients with Type 2 Diabetes: A Retrospective Cohort Study.
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Tuunanen I, Hautakoski A, Huhtamäki H, Arffman M, Sund R, Puistola U, Karihtala P, Jukkola A, and Urpilainen E
- Abstract
This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74-0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.
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- 2024
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38. Microbial and Metabolic Gut Profiling across Seven Malignancies Identifies Fecal Faecalibacillus intestinalis and Formic Acid as Commonly Altered in Cancer Patients.
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Kulecka M, Czarnowski P, Bałabas A, Turkot M, Kruczkowska-Tarantowicz K, Żeber-Lubecka N, Dąbrowska M, Paszkiewicz-Kozik E, Walewski J, Ługowska I, Koseła-Paterczyk H, Rutkowski P, Kluska A, Piątkowska M, Jagiełło-Gruszfeld A, Tenderenda M, Gawiński C, Wyrwicz L, Borucka M, Krzakowski M, Zając L, Kamiński M, Mikula M, and Ostrowski J
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- Humans, Female, Male, Middle Aged, Aged, Neoplasms metabolism, Neoplasms microbiology, Adult, Dysbiosis microbiology, Metabolomics methods, Metabolome, Gas Chromatography-Mass Spectrometry, Metagenomics methods, Gastrointestinal Microbiome, Feces microbiology, Formates metabolism
- Abstract
The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, and 40 patients with colorectal cancer, stomach cancer, breast cancer, lung cancer, melanoma, lymphoid neoplasms and acute myeloid leukemia (AML), respectively, and compared the data with those from sex- and age-matched healthy controls (HC). α-diversity differed only between the lymphoid neoplasm and AML groups and their respective HC, while β-diversity differed between all groups and their HC. Of 203 unique species, 179 and 24 were under- and over-represented, respectively, in the case groups compared with HC. Of these, Faecalibacillus intestinalis was under-represented in each of the seven groups studied, Anaerostipes hadrus was under-represented in all but the stomach cancer group, and 22 species were under-represented in the remaining five case groups. There was a marked reduction in the gut microbiome cancer index in all case groups except the AML group. Of the short-chain fatty acids and amino acids tested, the relative concentration of formic acid was significantly higher in each of the case groups than in HC, and the abundance of seven species of Faecalibacterium correlated negatively with most amino acids and formic acid, and positively with the levels of acetic, propanoic, and butanoic acid. We found more differences than similarities between the studied malignancy groups, with large variations in diversity, taxonomic/metabolomic profiles, and functional assignments. While the results obtained may demonstrate trends rather than objective differences that correlate with different types of malignancy, the newly developed gut microbiota cancer index did distinguish most of the cancer cases from HC. We believe that these data are a promising step forward in the search for new diagnostic and predictive tests to assess intestinal dysbiosis among cancer patients.
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- 2024
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39. The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes.
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Hosio M, Urpilainen E, Hautakoski A, Arffman M, Sund R, Ahtikoski A, Puistola U, Jukkola A, Läärä E, and Karihtala P
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- Humans, Female, Middle Aged, Aged, Finland epidemiology, Menopause, Proportional Hazards Models, Hormone Replacement Therapy adverse effects, Cardiovascular Diseases mortality, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 mortality, Diabetes Mellitus, Type 2 complications, Breast Neoplasms mortality, Breast Neoplasms drug therapy
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We investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36-0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32-0.74), and (HR 0.51, 95% Cl 0.35-0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D., (© 2024. The Author(s).)
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- 2024
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40. Temozolomide (TMZ) in the Treatment of Glioblastoma Multiforme-A Literature Review and Clinical Outcomes.
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Jezierzański M, Nafalska N, Stopyra M, Furgoł T, Miciak M, Kabut J, and Gisterek-Grocholska I
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- Humans, Brain Neoplasms drug therapy, Treatment Outcome, Glioblastoma drug therapy, Temozolomide therapeutic use, Antineoplastic Agents, Alkylating therapeutic use
- Abstract
Glioblastoma multiforme (GBM) is one of the most aggressive primary tumors of the central nervous system. It is associated with a very poor prognosis, with up to half of patients failing to survive the first year after diagnosis. It develops from glial tissue and belongs to the adult-type diffuse glioma group according to the WHO classification of 2021. Therapy for patients with GBM is currently based on surgical resection, radiation therapy, and chemotherapy, but despite many efforts, there has been minimal progress in tumor management. The most important chemotherapeutic agent in the treatment of this tumor is temozolomide (TMZ), a dacarbazine derivative that presents alkylating activity. It is usually administered to patients concurrently with radiation therapy after surgical resection of the tumor, which is defined as the Stupp protocol. Temozolomide demonstrates relatively good efficacy in therapy, but it could also present with several side effects. The resistance of GBM to the drug is currently the subject of work by specialists in the field of oncology, and its use in various regimens and patient groups may bring therapeutic benefits in the future. The aim of this review paper is to summarize the relevance of TMZ in the treatment of GBM based on recent reports.
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- 2024
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41. Is Spirometry a Sufficient Test for Assessing Respiratory Function after Lung Resection?
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Wnuk D, Marjański T, Tomasik B, Żuralska-Wnuk J, and Rzyman W
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- Humans, Female, Male, Aged, Middle Aged, Pneumonectomy methods, Respiratory Function Tests methods, Prospective Studies, Forced Expiratory Volume, Spirometry methods, Lung Neoplasms surgery, Carcinoma, Non-Small-Cell Lung surgery
- Abstract
Background: The prediction of postoperative functional status in non-small cell lung cancer patients based on preoperative assessment of physical and respiratory capacity is inadequate based on recent RCTs., Material and Methods: Prospectively collected spirometry data and the six-minute walk test results of 57 patients treated with lobectomy for non-small cell lung cancer were analyzed. The tests were performed before surgery, and 30 and 90 days after lobectomy. All patients underwent a respiratory functional and physical capacity assessment., Results: All 57 patients underwent lobectomy. Before surgery, mean FEV1 was 2.4 ± 0.7 L, corresponding to %FEV1 of 88.3 ± 17.3%. The mean absolute and expected 6MWT distance was 548 ± 74.6 m and 108.9 ± 14.5%, respectively. At the first postoperative evaluation 30 days after surgery, FEV1 and %FEV1 decreased significantly by an average of 0.5 ± 0.3 L and 15.1 ± 10.7%, while 6MWT and expected 6MWT decreased minimally by an average of 1.0 m and 0.8%, respectively. Three months after lobectomy, FEV1 and %FEV1, compared with the initial assessment, decreased by an average of 0.3 ± 0.3 l and 7.8 ± 10.0%, while 6MWT and its expected score increased to 564.6 ± 84.6 m and 112.8 ± 15.8%, respectively., Conclusions: After lobectomy, FEV1 decreased slightly and less than expected, while 6MWT increased proportionally compared to the preoperative evaluation.
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- 2024
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42. Devices and Methods for Dosimetry of Personalized Photodynamic Therapy of Tumors: A Review on Recent Trends.
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Alekseeva P, Makarov V, Efendiev K, Shiryaev A, Reshetov I, and Loschenov V
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Significance: Despite the widespread use of photodynamic therapy in clinical practice, there is a lack of personalized methods for assessing the sufficiency of photodynamic exposure on tumors, depending on tissue parameters that change during light irradiation. This can lead to different treatment results. Aim: The objective of this article was to conduct a comprehensive review of devices and methods employed for the implicit dosimetric monitoring of personalized photodynamic therapy for tumors. Methods: The review included 88 peer-reviewed research articles published between January 2010 and April 2024 that employed implicit monitoring methods, such as fluorescence imaging and diffuse reflectance spectroscopy. Additionally, it encompassed computer modeling methods that are most often and successfully used in preclinical and clinical practice to predict treatment outcomes. The Internet search engine Google Scholar and the Scopus database were used to search the literature for relevant articles. Results: The review analyzed and compared the results of 88 peer-reviewed research articles presenting various methods of implicit dosimetry during photodynamic therapy. The most prominent wavelengths for PDT are in the visible and near-infrared spectral range such as 405, 630, 660, and 690 nm. Conclusions: The problem of developing an accurate, reliable, and easily implemented dosimetry method for photodynamic therapy remains a current problem, since determining the effective light dose for a specific tumor is a decisive factor in achieving a positive treatment outcome.
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- 2024
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43. Neurotrophic tyrosine receptor kinase gene fusions in adult and pediatric patients with solid tumors: a clinicogenomic biobank and record linkage study of expression frequency and patient characteristics from Finland.
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Zhang W, Schmitz AA, Kallionpää RE, Perälä M, Pitkänen N, Tukiainen M, Alanne E, Jöhrens K, Schulze-Rath R, Farahmand B, and Zong J
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- Humans, Finland epidemiology, Male, Child, Female, Adult, Middle Aged, Adolescent, Child, Preschool, Young Adult, Aged, Biological Specimen Banks, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Gene Fusion, Sarcoma genetics, Sarcoma pathology, Salivary Gland Neoplasms genetics, Salivary Gland Neoplasms pathology, Receptor, trkB genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Infant, Oncogene Proteins, Fusion genetics, Neoplasms genetics, Neoplasms pathology, Lung Neoplasms genetics, Lung Neoplasms pathology, High-Throughput Nucleotide Sequencing, Membrane Glycoproteins, Receptor, trkA genetics, Receptor, trkC genetics
- Abstract
Background: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers. Using the Auria Biobank in Finland, we aimed to identify and characterize patients with these gene fusions, and describe their clinical and tumor characteristics, treatments received, and outcomes., Material and Methods: We evaluated pediatrics with any solid tumor type and adults with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), sarcoma, or salivary gland cancer. We determined tropomyosin receptor kinase (TRK) protein expression by pan-TRK immunohistochemistry (IHC) staining of tumor samples from the Auria Biobank, scored by a certified pathologist. NTRK gene fusion was confirmed by next generation sequencing (NGS). All 2,059 patients were followed-up starting 1 year before their cancer diagnosis., Results: Frequency of NTRK gene fusion tumors was 3.1% (4/127) in pediatrics, 0.7% (8/1,151) for CRC, 0.3% (1/288) for NSCLC, 0.9% (1/114) for salivary gland cancer, and 0% (0/379) for sarcoma. Among pediatrics there was one case each of fibrosarcoma (TPM3::NTRK1), Ewing's sarcoma (LPPR1::NTRK2), primitive neuroectodermal tumor (DAB2IP::NTRK2), and papillary thyroid carcinoma (RAD51B::NTRK3). Among CRC patients, six harbored tumors with NTRK1 fusions (three fused with TPM3), one harbored a NTRK3::GABRG1 fusion, and the other a NTRK2::FXN/LPPR1 fusion. Microsatellite instability was higher in CRC patients with NTRK gene fusion tumors versus wild-type tumors (50.0% vs. 4.4%). Other detected fusions were SGCZ::NTRK3 (NSCLC) and ETV6::NTRK3 (salivary gland cancer). Four patients (three CRC, one NSCLC) received chemotherapy; one patient (with CRC) received radiotherapy., Conclusion: NTRK gene fusions are rare in adult CRC, NSCLC, salivary tumors, sarcoma, and pediatric solid tumors.
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- 2024
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44. EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2024 update on the diagnosis, risk-stratification, and management.
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Malpica L, Marques-Piubelli ML, Beltran BE, Chavez JC, Miranda RN, and Castillo JJ
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Disease Overview: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy., Diagnosis: The diagnosis is established through meticulous pathological evaluation. Detection of EBV-encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO-HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others., Risk-Stratification: The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers., Management: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS., (© 2024 Wiley Periodicals LLC.)
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- 2024
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45. Comments on "Novel strategy of hold-and-drag clip closure with mantis-like claw for post-gastric endoscopic submucosal dissection defect of <30 mm".
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Zhong C, Cao T, and Lan S
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- Humans, Stomach Neoplasms surgery, Wound Closure Techniques instrumentation, Surgical Instruments, Gastric Mucosa surgery, Endoscopic Mucosal Resection methods, Endoscopic Mucosal Resection instrumentation, Endoscopic Mucosal Resection adverse effects
- Abstract
Competing Interests: The authors declare that they have no conflict of interest.
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- 2024
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46. ALK Inhibitor and Chemotherapy Combinations in Models of ALK-Translocated NSCLC.
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Luukkainen MEK and Koivunen JP
- Subjects
- Humans, Cell Line, Tumor, Apoptosis drug effects, Drug Synergism, Drug Resistance, Neoplasm drug effects, Receptor Protein-Tyrosine Kinases antagonists & inhibitors, Receptor Protein-Tyrosine Kinases genetics, Receptor Protein-Tyrosine Kinases metabolism, Piperidines pharmacology, Piperidines administration & dosage, Carbazoles pharmacology, Carbazoles administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Anaplastic Lymphoma Kinase antagonists & inhibitors, Anaplastic Lymphoma Kinase genetics, Anaplastic Lymphoma Kinase metabolism, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Protein Kinase Inhibitors pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cisplatin pharmacology, Cisplatin administration & dosage, Pemetrexed pharmacology, Pemetrexed administration & dosage
- Abstract
Background/aim: Randomized trials have shown the benefit of combining tyrosine kinase inhibitors (TKI) and chemotherapy in the treatment of epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC). For anaplastic lymphoma kinase-rearranged (ALK
+ ) NSCLC, prospective trial results of the combination are not available and have not even been thoroughly investigated in vitro. In this study, we investigated combinations of TKI and chemotherapy using in vitro models of ALK+ NSCLC., Materials and Methods: ALK+ cell line models H3122, H2228, and DFCI032 with differing primary resistance to ALK receptor TKIs were used. We investigated short-(viability assay) and long-term (colony-formation assay) cytotoxicity, apoptosis, and cell signaling in response to the combinations of agents. We selected the most commonly used agents, alectinib, cisplatin, and pemetrexed, to investigate the combination effects., Results: In the combination experiments with short-term exposure, synergism between TKI and pemetrexed was observed, while cisplatin had antagonistic effects. In the long-term experiments, the combination of cisplatin and TKI was synergistic in all lines, while no synergism was observed with pemetrexed. Among the chemotherapy and TKI sequences, cisplatin followed by TKI was more cytotoxic than the opposite in two out of the three models. In the TKI-sensitive H3122 cell line, the combination of chemotherapy and TKI combination increased apoptosis. Interestingly, pemetrexed treatment resulted in the activation of ALK, which was abolished with TKI., Conclusion: Combining TKI and chemotherapy in ALK+ models has some synergistic effects that overcome primary TKI resistance. However, the synergy varies depending on the chemotherapeutic agent, cytotoxic assay, and the cell line used. Prospective clinical trials are warranted to fully characterize the potential of combination chemotherapy with TKIs in ALK+ NSCLC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2024
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47. Assessing Digital Breast Tomosynthesis Impact on Early Cancer Detection: Insights from Consecutive Screening.
- Author
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Jögi A, Johnson K, Wittgren S, Sundgren V, Tomic H, Olinder J, Åkesson A, Andersson I, Zackrisson S, and Bakic PR
- Subjects
- Aged, Female, Humans, Middle Aged, Breast diagnostic imaging, Mass Screening methods, Prospective Studies, Sweden, Breast Neoplasms diagnostic imaging, Early Detection of Cancer methods, Mammography methods
- Abstract
Background Analysis of how digital breast tomosynthesis (DBT) screening affects consecutive screening performance is important to estimate its future value in screening. Purpose To evaluate whether DBT contributes to early detection of breast cancer by assessing cancer detection rates (CDRs), including the fraction of invasive cancers and cancer subtypes in consecutive routine digital mammography (DM). Materials and Methods The paired prospective Malmö Breast Tomosynthesis Screening Trial (MBTST) was performed between January 2010 and February 2015. Participating women underwent one-view DBT and two-view DM at one screening occasion. In this secondary analysis, women were followed up through their first (DM1) and second (DM2) consecutive two-view DM screening rounds after MBTST participation. Cancer diagnoses were identified by referencing records. A logistic regression model, adjusted for age, was used to calculate the odds of luminal A-like cancers with use of the MBTST as reference. Results There were 14 848 final participants in the MBTST (median age, 57 years [IQR, 49-65 years]). Of those, 12 876 women were screened in DM1 (median age, 58 years [IQR, 50-66 years]) and 10 883 were screened in DM2 (median age, 59 years [IQR, 51-67 years]). Compared with CDRs in the trial of 6.5 of 1000 women (95% CI: 5.2, 7.9) for DM and 8.7 of 1000 women (95% CI: 7.3, 10.3) for DBT, the CDR was lower in DM1 (4.6 of 1000 women [95% CI: 3.6, 5.9]) and DM2 (5.3 of 1000 women [95% CI: 4.1, 6.9]). The proportion of invasive cancers was 84.9% (118 of 139 cancers) in the MBTST; the corresponding numbers were 66% (39 of 59 cancers) for DM1 and 83% (50 of 60 cancers) for DM2. The odds of luminal A-like cancers were lower in DM1 at 0.28 (95% CI: 0.12, 0.66 [ P = .004]) but not in DM2 at 0.80 (95% CI: 0.40, 1.58 [ P = .52]) versus screening in the MBTST. Conclusion CDR and the fraction of invasive cancers were lower in DM1 and then increased in DM2 following the MBTST, indicating earlier cancer detection mainly due to increased detection of luminal A-like cancers in DBT screening. Clinical trials registration no. NCT01091545 © RSNA, 2024 See also the editorial by Hooley and Philpotts in this issue.
- Published
- 2024
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48. Survival of patients with ruptured gastrointestinal stromal tumour treated with adjuvant imatinib in a randomised trial.
- Author
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Joensuu H, Reichardt A, Eriksson M, Hohenberger P, Boye K, Cameron S, Lindner LH, Jost PJ, Bauer S, Schütte J, Lindskog S, Kallio R, Jaakkola PM, Goplen D, Wardelmann E, and Reichardt P
- Subjects
- Humans, Female, Male, Chemotherapy, Adjuvant, Middle Aged, Aged, Adult, Gastrointestinal Neoplasms drug therapy, Gastrointestinal Neoplasms mortality, Gastrointestinal Neoplasms pathology, Disease-Free Survival, Aged, 80 and over, Rupture, Spontaneous, Gastrointestinal Stromal Tumors drug therapy, Gastrointestinal Stromal Tumors mortality, Gastrointestinal Stromal Tumors pathology, Imatinib Mesylate therapeutic use, Antineoplastic Agents therapeutic use
- Abstract
Background: Patients with ruptured gastrointestinal stromal tumour (GIST) have poor prognosis. Little information is available about how adjuvant imatinib influences survival., Methods: We explored recurrence-free survival (RFS) and overall survival (OS) of patients with ruptured GIST who participated in a randomised trial (SSG XVIII/AIO), where 400 patients with high-risk GIST were allocated to adjuvant imatinib for either 1 year or 3 years after surgery. Of the 358 patients with confirmed localised GIST, 73 (20%) had rupture reported. The ruptures were classified retrospectively using the Oslo criteria., Results: Most ruptures were major, four reported ruptures were reclassified unruptured. The 69 patients with rupture had inferior RFS and OS compared with 289 patients with unruptured GIST (10-year RFS 21% vs. 55%, OS 59% vs. 78%, respectively). Three-year adjuvant imatinib did not significantly improve RFS or OS of the patients with rupture compared with 1-year treatment, but in the largest mutational subset with KIT exon 11 deletion/indel mutation OS was higher in the 3-year group than in the 1-year group (10-year OS 94% vs. 54%)., Conclusions: About one-fifth of ruptured GISTs treated with adjuvant imatinib did not recur during the first decade of follow-up. Relatively high OS rates were achieved despite rupture., Clinical Trial Registration: NCT00116935., (© 2024. The Author(s).)
- Published
- 2024
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49. Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial.
- Author
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Peters S, Gadgeel SM, Mok T, Nadal E, Kilickap S, Swalduz A, Cadranel J, Sugawara S, Chiu CH, Yu CJ, Moskovitz M, Tanaka T, Nersesian R, Shagan SM, Maclennan M, Mathisen M, Bhagawati-Prasad V, Diarra C, Assaf ZJ, Archer V, and Dziadziuszko R
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, Aged, 80 and over, Liquid Biopsy, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Indazoles therapeutic use, Indazoles adverse effects, Benzamides therapeutic use, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins metabolism, Protein-Tyrosine Kinases antagonists & inhibitors, Protein-Tyrosine Kinases genetics
- Abstract
Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 ., (© 2024. The Author(s).)
- Published
- 2024
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50. Long-term effects of aromatase inhibitor withdrawal on bone mineral density in early breast cancer patients: 10-year follow-up results of the BREX study.
- Author
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Blomqvist C, Vehmanen L, Kellokumpu-Lehtinen PL, Huovinen R, Ruohola J, Penttinen H, Sievänen H, Nikander R, Utriainen M, and Saarto T
- Subjects
- Humans, Female, Middle Aged, Follow-Up Studies, Adult, Aged, Absorptiometry, Photon, Postmenopause, Bone Density drug effects, Breast Neoplasms drug therapy, Aromatase Inhibitors adverse effects, Aromatase Inhibitors therapeutic use
- Abstract
Purpose: We aimed to provide long-term bone mineral density (BMD) data on early breast cancer patients of the BREX (Breast Cancer and Exercise) study. The effects of exercise and adjuvant endocrine treatment 10 years after randomization were analyzed, with special emphasis on aromatase inhibitor (AI) therapy discontinuation at 5 years., Methods: The BREX study randomized 573 pre- and postmenopausal breast cancer patients into a 1-year supervised exercise program or a control group. 372 patients were included into the current follow-up analysis. BMD (g/cm
2 ) was measured by dual-energy X-ray absorptiometry at lumbar spine (LS), left femoral neck (FN), and the total hip. Separate groups were displayed according to baseline menopausal status, and whether the patient had discontinued AI therapy at 5 years or not., Results: The BMD change from 5 to 10 years did not significantly differ between the two randomized arms. AI discontinuation at 5 years had statistically significant BMD effects. The FN BMD continued to decrease in patients who discontinued AI therapy during the first 5-year off-treatment, but the decrease was three-fold less than in patients without AI withdrawal (- 1.4% v. - 3.8%). The LS BMD increased (+ 2.6%) in patients with AI withdrawal during the first 5 years following treatment discontinuation, while a BMD decrease (-1.3%) was seen in patients without AI withdrawal., Conclusion: This study is to our knowledge the first to quantify the long-term impact of AI withdrawal on BMD. Bone loss associated with AI therapy seems partially reversible after stopping treatment., Trial Registration: http://www., Clinicaltrials: gov/ (Identifier Number NCT00639210)., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
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