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2. Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K, Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G, Hayden, James T, Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte EG, Tops, Bastiaan BJ, Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M, Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J, Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M, Sahm, Felix, Solomon, David A, and Jones, David TW

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Pediatric, Genetics, Rare Diseases, Pediatric Cancer, Cancer, Pediatric Research Initiative, Neurosciences, Brain Cancer, Brain Disorders, Child, Child, Preschool, Female, Humans, Infant, Male, Cell Cycle Proteins, Central Nervous System Neoplasms, DNA Methylation, DNA-Binding Proteins, Neuroectodermal Tumors, Primitive, RNA-Binding Proteins, Transcription Factors, Tumor Suppressor Proteins, Wnt Signaling Pathway, PLAGL1, PLAGL2, Molecular neuro-oncology, Pediatric cancer, Clinical Sciences, Neurology & Neurosurgery
Abstract

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

Published
2023

4. Impact of age on safety of Busulfan-Melphalan followed by autologous hematopoietic stem-cell transplantation versus standard chemotherapy in the patients of the EURO-E.W.I.N.G. 99 and Ewing 2008 clinical trials

Author

Choderlos de Laclos, Xavier, Risbourg, Séverine, Brennan, Bernadette, Bertucci, François, Gaspar, Nathalie, Gelderblom, Hans, Hawkins, Douglas S., Janeway, Katherine, Juergens, Heribert, Kasper, Bernd, Krailo, Mark D., Cécile Le Deley, Marie, Marec-Bérard, Perrine, McCabe, Martin G., Metzler, Markus, Ranft, Andreas, Strauss, Sandra, Tabone, Marie-Dominique, Windsor, Rachael, Dirksen, Uta, and Gandemer, Virginie

Published
2024
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5. Correction to: Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K., Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G., Hayden, James T., Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte E. G., Tops, Bastiaan B. J., Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M., Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J., Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M., Sahm, Felix, Solomon, David A., and Jones, David T. W.

Published
2023
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6. Protocol for the ‘Supporting Young Cancer Survivors who Smoke’ study (PRISM): Informing the development of a smoking cessation intervention for childhood, adolescent and young adult cancer survivors in England

Author

Brown, Morven C., primary, Araújo-Soares, Vera, additional, Skinner, Roderick, additional, Brown, Jamie, additional, Glaser, Adam W., additional, Hanratty, Helena, additional, McCabe, Martin G., additional, Amariutei, Ana-Ecaterina, additional, Mauri, Sabrina, additional, and Sharp, Linda, additional

Published
2024
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7. Comprehensive molecular profiling of sarcomas in adolescent and young adult patients: Results of the EORTC SPECT-AYA international proof-of-concept study

Author

Morfouace, Marie, Horak, Peter, Kreutzfeldt, Simon, Stevovic, Aleksandra, de Rojas, Teresa, Denisova, Evgeniya, Hutter, Barbara, Bautista, Francisco, Oliveira, Júlio, Defachelles, Anne-Sophie, White, Jeff, Kasper, Bernd, Preusser, Matthias, Golfinopoulos, Vassilis, Pfister, Stefan, Van der Graaf, Winette, Wardelmann, Eva, Shenjere, Patrick, Fröhling, Stefan, and McCabe, Martin G.

Published
2022
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11. EANO–EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma

Author

Franceschi, Enrico, Hofer, Silvia, Brandes, Alba A, Frappaz, Didier, Kortmann, Rolf-Dieter, Bromberg, Jacoline, Dangouloff-Ros, Volodia, Boddaert, Nathalie, Hattingen, Elke, Wiestler, Benedikt, Clifford, Steven C, Figarella-Branger, Dominique, Giangaspero, Felice, Haberler, Christine, Pietsch, Torsten, Pajtler, Kristian W, Pfister, Stefan M, Guzman, Raphael, Stummer, Walter, Combs, Stephanie E, Seidel, Clemens, Beier, Dagmar, McCabe, Martin G, Grotzer, Michael, Laigle-Donadey, Florence, Stücklin, Ana S Guerreiro, Idbaih, Ahmed, Preusser, Matthias, van den Bent, Martin, Weller, Michael, and Hau, Peter

Published
2019
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15. Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition

Author

Kool, Marcel, Jones, David TW, Jäger, Natalie, Northcott, Paul A, Pugh, Trevor J, Hovestadt, Volker, Piro, Rosario M, Esparza, L Adriana, Markant, Shirley L, Remke, Marc, Milde, Till, Bourdeaut, Franck, Ryzhova, Marina, Sturm, Dominik, Pfaff, Elke, Stark, Sebastian, Hutter, Sonja, Şeker-Cin, Huriye, Johann, Pascal, Bender, Sebastian, Schmidt, Christin, Rausch, Tobias, Shih, David, Reimand, Jüri, Sieber, Laura, Wittmann, Andrea, Linke, Linda, Witt, Hendrik, Weber, Ursula D, Zapatka, Marc, König, Rainer, Beroukhim, Rameen, Bergthold, Guillaume, van Sluis, Peter, Volckmann, Richard, Koster, Jan, Versteeg, Rogier, Schmidt, Sabine, Wolf, Stephan, Lawerenz, Chris, Bartholomae, Cynthia C, von Kalle, Christof, Unterberg, Andreas, Herold-Mende, Christel, Hofer, Silvia, Kulozik, Andreas E, von Deimling, Andreas, Scheurlen, Wolfram, Felsberg, Jörg, Reifenberger, Guido, Hasselblatt, Martin, Crawford, John R, Grant, Gerald A, Jabado, Nada, Perry, Arie, Cowdrey, Cynthia, Croul, Sydney, Zadeh, Gelareh, Korbel, Jan O, Doz, Francois, Delattre, Olivier, Bader, Gary D, McCabe, Martin G, Collins, V Peter, Kieran, Mark W, Cho, Yoon-Jae, Pomeroy, Scott L, Witt, Olaf, Brors, Benedikt, Taylor, Michael D, Schüller, Ulrich, Korshunov, Andrey, Eils, Roland, Wechsler-Reya, Robert J, Lichter, Peter, Pfister, Stefan M, and Project, on behalf of the ICGC PedBrain Tumor

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Pediatric Research Initiative, Genetics, Rare Diseases, Cancer, Pediatric, Brain Cancer, Pediatric Cancer, Brain Disorders, Adolescent, Adult, Animals, Base Sequence, Biphenyl Compounds, Cerebellar Neoplasms, Child, Child, Preschool, DEAD-box RNA Helicases, DNA Copy Number Variations, Drug Resistance, Neoplasm, Female, Gene Expression Profiling, Hedgehog Proteins, High-Throughput Nucleotide Sequencing, Humans, Infant, Kruppel-Like Transcription Factors, Male, Medulloblastoma, Mice, Mice, Inbred NOD, Mice, SCID, Molecular Sequence Data, N-Myc Proto-Oncogene Protein, Neoplasm Transplantation, Nuclear Proteins, Oncogene Proteins, Patched Receptors, Patched-1 Receptor, Phosphatidylinositol 3-Kinases, Promoter Regions, Genetic, Proto-Oncogene Proteins c-akt, Pyridines, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Repressor Proteins, Signal Transduction, Smoothened Receptor, Telomerase, Tumor Suppressor Protein p53, Young Adult, Zinc Finger Protein Gli2, ICGC PedBrain Tumor Project, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.

Published
2014

16. Delivered relative dose intensity in adolescent and young adult germ cell tumours in England: Assessment of data quality and consistency from clinical trials compared to national cancer registration data.

Author

Hughes, Nicola F., Cromie, Kirsten J., Feltbower, Richard G., McCabe, Martin G., and Stark, Dan

Subjects
YOUNG adults, GERM cells, CLINICAL trials, DATA quality, TEENAGERS
Abstract

Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens. However, evidence specific to AYA is limited by poor recruitment of AYA to trials and dose delivery outside trials not being well examined. We examined the utility of cancer registration data and a clinical trials dataset to investigate the delivery of relative dose intensity (RDI) in routine National Health Service practice in England, compared to within international clinical trials. Linked data from the Cancer Outcomes and Services Dataset (COSD) and the Systemic Anti‐Cancer Therapy (SACT) dataset, and data from four international clinical trials were analysed. Survival over time was described using Kaplan‐Meier estimation; overall, by age category, International Germ‐Cell Cancer Collaborative Group (IGCCCG) classification, stage, tumour subtype, primary site, ethnicity and deprivation. Cox regression models were used to determine the fully adjusted effect of RDI on mortality risk. The quality of both datasets was critically evaluated and clinically enhanced. RDI was found to be well maintained in all datasets with higher RDIs associated with improved survival outcomes. Real‐world data demonstrated several strengths, including population coverage and inclusion of sociodemographic variables and comorbidity. It is limited in GCT however, by the poor completion of data items enabling risk classification of patients and a higher proportion of missing data. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Precision Medicine for Childhood Cancer: Current Limitations and Future Perspectives.

Author

McCabe, Martin G., Geoerger, Birgit, Chesler, Louis, Hargrave, Darren, Parsons, D. Williams, van Tilburg, Cornelis M., Schleiermacher, Gudrun, Hickman, John A., and George, Sally L.

Subjects
*CHILDHOOD cancer, *INDIVIDUALIZED medicine
Abstract

Greater collaboration needed to realize potential of molecular profiling initiatives for pediatric cancers. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Clonal selection drives genetic divergence of metastatic medulloblastoma.

Author

Wu, Xiaochong, Northcott, Paul A, Dubuc, Adrian, Dupuy, Adam J, Shih, David JH, Witt, Hendrik, Croul, Sidney, Bouffet, Eric, Fults, Daniel W, Eberhart, Charles G, Garzia, Livia, Van Meter, Timothy, Zagzag, David, Jabado, Nada, Schwartzentruber, Jeremy, Majewski, Jacek, Scheetz, Todd E, Pfister, Stefan M, Korshunov, Andrey, Li, Xiao-Nan, Scherer, Stephen W, Cho, Yoon-Jae, Akagi, Keiko, MacDonald, Tobey J, Koster, Jan, McCabe, Martin G, Sarver, Aaron L, Collins, V Peter, Weiss, William A, Largaespada, David A, Collier, Lara S, and Taylor, Michael D

Subjects
Animals, Humans, Mice, Medulloblastoma, Neoplasm Metastasis, Li-Fraumeni Syndrome, Disease Models, Animal, DNA Transposable Elements, Survival Rate, Mutagenesis, Insertional, DNA Methylation, CpG Islands, Germ-Line Mutation, Genes, p53, Clonal Evolution, Disease Models, Animal, Genes, p53, Mutagenesis, Insertional, General Science & Technology
Abstract

Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.

Published
2012

20. Correction to: Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification (Acta Neuropathologica, (2023), 145, 1, (49-69), 10.1007/s00401-022-02516-2)

Author

Keck, Michaela-Kristina, Sill, Martin, Wittmann, Andrea, Joshi, Piyush, Stichel, Damian, Beck, Pengbo, Okonechnikow, Konstantin, Sievers, Philipp, Wefers, Annika K, Roncaroli, Federico, Avula, Shivaram, McCabe, Martin G, Hayden, James T, Wesseling, Pieter, Øra, Ingrid, Nistér, Monica, Kranendonk, Mariëtte E G, Tops, Bastiaan B J, Zapotocky, Michal, Zamecnik, Josef, Vasiljevic, Alexandre, Fenouil, Tanguy, Meyronet, David, von Hoff, Katja, Schüller, Ulrich, Loiseau, Hugues, Figarella-Branger, Dominique, Kramm, Christof M, Sturm, Dominik, Scheie, David, Rauramaa, Tuomas, Pesola, Jouni, Gojo, Johannes, Haberler, Christine, Brandner, Sebastian, Jacques, Tom, Sexton Oates, Alexandra, Saffery, Richard, Koscielniak, Ewa, Baker, Suzanne J, Yip, Stephen, Snuderl, Matija, Ud Din, Nasir, Samuel, David, Schramm, Kathrin, Blattner-Johnson, Mirjam, Selt, Florian, Ecker, Jonas, Milde, Till, von Deimling, Andreas, Korshunov, Andrey, Perry, Arie, Pfister, Stefan M, Sahm, Felix, and Solomon, David A

Subjects
Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc
Abstract

In the original publication, incorrect version of Fig. 6 was published and the correct version (Fig. 6) is given below. The original article has been corrected.

Published
2023

21. Comprehensive molecular profiling of sarcomas in adolescent and young adult patients: Results of the EORTC SPECTA-AYA international proof-of-concept study

Author

Morfouace, Marie, primary, Horak, Peter, additional, Kreutzfeldt, Simon, additional, Stevovic, Aleksandra, additional, de Rojas, Teresa, additional, Denisova, Evgeniya, additional, Hutter, Barbara, additional, Bautista, Francisco, additional, Oliveira, Júlio, additional, Defachelles, Anne-Sophie, additional, White, Jeff, additional, Kasper, Bernd, additional, Preusser, Matthias, additional, Golfinopoulos, Vassilis, additional, Pfister, Stefan, additional, Van der Graaf, Winette, additional, Wardelmann, Eva, additional, Shenjere, Patrick, additional, Fröhling, Stefan, additional, and McCabe, Martin G., additional

Published
2023
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22. Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Keck, Michaela-Kristina, primary, Sill, Martin, additional, Wittmann, Andrea, additional, Joshi, Piyush, additional, Stichel, Damian, additional, Beck, Pengbo, additional, Okonechnikow, Konstantin, additional, Sievers, Philipp, additional, Wefers, Annika K., additional, Roncaroli, Federico, additional, Avula, Shivaram, additional, McCabe, Martin G., additional, Hayden, James T., additional, Wesseling, Pieter, additional, Øra, Ingrid, additional, Nistér, Monica, additional, Kranendonk, Mariëtte E. G., additional, Tops, Bastiaan B. J., additional, Zapotocky, Michal, additional, Zamecnik, Josef, additional, Vasiljevic, Alexandre, additional, Fenouil, Tanguy, additional, Meyronet, David, additional, von Hoff, Katja, additional, Schüller, Ulrich, additional, Loiseau, Hugues, additional, Figarella-Branger, Dominique, additional, Kramm, Christof M., additional, Sturm, Dominik, additional, Scheie, David, additional, Rauramaa, Tuomas, additional, Pesola, Jouni, additional, Gojo, Johannes, additional, Haberler, Christine, additional, Brandner, Sebastian, additional, Jacques, Tom, additional, Sexton Oates, Alexandra, additional, Saffery, Richard, additional, Koscielniak, Ewa, additional, Baker, Suzanne J., additional, Yip, Stephen, additional, Snuderl, Matija, additional, Ud Din, Nasir, additional, Samuel, David, additional, Schramm, Kathrin, additional, Blattner-Johnson, Mirjam, additional, Selt, Florian, additional, Ecker, Jonas, additional, Milde, Till, additional, von Deimling, Andreas, additional, Korshunov, Andrey, additional, Perry, Arie, additional, Pfister, Stefan M., additional, Sahm, Felix, additional, Solomon, David A., additional, and Jones, David T. W., additional

Published
2022
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25. Abstract 2005: First results of the EORTC-SPECTA project on comprehensive molecular profiling of adolescent and young adult sarcoma patients

Author

Morfouace, Marie, primary, Horak, Peter, additional, Kreutzfeldt, Simon, additional, Shenjere, Patrick, additional, Wardelmann, Eva, additional, Denisova, Evgeniya, additional, Stevovic, Aleksandra, additional, Bautista, Francisco J., additional, Oliveira, Julio, additional, van der Graaf, Winette, additional, Fröhling, Stefan, additional, and McCabe, Martin G., additional

Published
2022
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26. OTHR-41. Amplification of the PLAG family genes – PLAGL1 and PLAGL2 – is a key feature of a novel embryonal CNS tumor type

Author

Keck, Michaela-Kristina, primary, Sill, Martin, additional, Wittmann, Andrea, additional, Kumar, Piyush Joshi, additional, Stichel, Damian, additional, Sievers, Philipp, additional, Wefers, Annika K, additional, Roncaroli, Federico, additional, Hayden, James, additional, McCabe, Martin G, additional, Kranendonk, Mariëtte E G, additional, Zapotocky, Michal, additional, Vasiljevic, Alexandre, additional, Schüller, Ulrich, additional, Sturm, Dominik, additional, Blattner-Johnson, Mirjam, additional, von Deimling, Andreas, additional, Korshunov, Andrey, additional, Sahm, Felix, additional, Perry, Arie, additional, Solomon, David, additional, Pfister, Stefan, additional, and Jones, David T W, additional

Published
2022
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29. Radiation treatment of benign tumors in NF2-related-schwannomatosis: A national study of 266 irradiated patients showing a significant increase in malignancy/malignant progression.

Author

Evans, D Gareth, Halliday, Dorothy, Obholzer, Rupert, Afridi, Shazia, Forde, Claire, Rutherford, Scott A, Hammerbeck-Ward, Charlotte, Lloyd, Simon K, Freeman, Simon M, Pathmanaban, Omar N, Thomas, Owen M, Laitt, Roger D, Stivaros, Stavros, Kilday, John-Paul, Vassallo, Grace, McBain, Catherine, Lavin, Timothy, Paterson, Chay, Whitfield, Gillian, and McCabe, Martin G

Published
2023
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31. International variation in childhood cancer mortality rates from 2001 to 2015: Comparison of trends in the International Cancer Benchmarking Partnership countries

Author

Smith, Lesley, primary, Stiller, Charles A., additional, Aitken, Joanne F., additional, Hjalgrim, Lisa L., additional, Johannesen, Tom, additional, Lahteenmaki, Paivi, additional, McCabe, Martin G., additional, Phillips, Robert, additional, Pritchard‐Jones, Kathy, additional, Steliarova‐Foucher, Eva, additional, Winther, Jeanette F., additional, Woods, Ryan R., additional, Glaser, Adam W., additional, and Feltbower, Richard G., additional

Published
2021
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33. COVID-19 in children with haematological malignancies

Author

Millen, Gerard Cathal, primary, Arnold, Roland, additional, Cazier, Jean-Baptiste, additional, Curley, Helen, additional, Feltbower, Richard, additional, Gamble, Ashley, additional, Glaser, Adam, additional, Grundy, Richard G, additional, Kirton, Laura, additional, Lee, Lennard Y W, additional, McCabe, Martin G, additional, Palles, Claire, additional, Phillips, Bob, additional, Stiller, Charles A, additional, Varnai, Csilla, additional, and Kearns, Pamela, additional

Published
2021
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34. Development of Randomized Trials in Adults with Medulloblastoma—The Example of EORTC 1634-BTG/NOA-23

Author

Hau, Peter, primary, Frappaz, Didier, additional, Hovey, Elizabeth, additional, McCabe, Martin G., additional, Pajtler, Kristian W., additional, Wiestler, Benedikt, additional, Seidel, Clemens, additional, Combs, Stephanie E., additional, Dirven, Linda, additional, Klein, Martin, additional, Anazodo, Antoinette, additional, Hattingen, Elke, additional, Hofer, Silvia, additional, Pfister, Stefan M., additional, Zimmer, Claus, additional, Kortmann, Rolf-Dieter, additional, Sunyach, Marie-Pierre, additional, Tanguy, Ronan, additional, Effeney, Rachel, additional, von Deimling, Andreas, additional, Sahm, Felix, additional, Rutkowski, Stefan, additional, Berghoff, Anna S., additional, Franceschi, Enrico, additional, Pineda, Estela, additional, Beier, Dagmar, additional, Peeters, Ellen, additional, Gorlia, Thierry, additional, Vanlancker, Maureen, additional, Bromberg, Jacoline E. C., additional, Gautier, Julien, additional, Ziegler, David S., additional, Preusser, Matthias, additional, Wick, Wolfgang, additional, and Weller, Michael, additional

Published
2021
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35. Oral etoposide as a single agent in childhood and young adult cancer in England: Still a poorly evaluated palliative treatment

Author

Fraser, Jess, primary, Wills, Lorna, additional, Fardus‐Reid, Fahmina, additional, Irvine, Lucy, additional, Elliss‐Brookes, Lucy, additional, Fern, Lorna, additional, Cameron, Alison L., additional, Pritchard‐Jones, Kathy, additional, Feltbower, Richard G., additional, Shelton, Jon, additional, Stiller, Charles, additional, and McCabe, Martin G., additional

Published
2021
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39. Disease course of neurofibromatosis type 2: a 30-year follow-up study of 353 patients seen at a single institution

Author

Forde, Claire, primary, King, Andrew T, additional, Rutherford, Scott A, additional, Hammerbeck-Ward, Charlotte, additional, Lloyd, Simon K, additional, Freeman, Simon R, additional, Pathmanaban, Omar N, additional, Stapleton, Emma, additional, Thomas, Owen M, additional, Laitt, Roger D, additional, Stivaros, Stavros, additional, Kilday, John-Paul, additional, Vassallo, Grace, additional, McBain, Catherine, additional, Kerrigan, Simon, additional, Smith, Miriam J, additional, McCabe, Martin G, additional, Harkness, Elaine F, additional, and Evans, D Gareth, additional

Published
2020
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40. Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project

Author

Millen, Gerard C., primary, Arnold, Roland, additional, Cazier, Jean-Baptiste, additional, Curley, Helen, additional, Feltbower, Richard G., additional, Gamble, Ashley, additional, Glaser, Adam W., additional, Grundy, Richard G., additional, Lee, Lennard Y. W., additional, McCabe, Martin G., additional, Phillips, Robert S., additional, Stiller, Charles A., additional, Várnai, Csilla, additional, and Kearns, Pamela R., additional

Published
2020
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42. International variation in childhood cancer mortality rates from 2001 to 2015: Comparison of trends in the International Cancer Benchmarking Partnership countries.

Author

Smith, Lesley, Stiller, Charles A., Aitken, Joanne F., Hjalgrim, Lisa L., Johannesen, Tom, Lahteenmaki, Paivi, McCabe, Martin G., Phillips, Robert, Pritchard‐Jones, Kathy, Steliarova‐Foucher, Eva, Winther, Jeanette F., Woods, Ryan R., Glaser, Adam W., and Feltbower, Richard G.

Subjects
DEATH rate, CANCER-related mortality, CHILDHOOD cancer, AGE groups, CENTRAL nervous system tumors, SURVIVAL rate, MORTALITY, NURSE practitioners
Abstract

Despite improved survival rates, cancer remains one of the most common causes of childhood death. The International Cancer Benchmarking Partnership (ICBP) showed variation in cancer survival for adults. We aimed to assess and compare trends over time in cancer mortality between children, adolescents and young adults (AYAs) and adults in the six countries involved in the ICBP: United Kingdom, Denmark, Australia, Canada, Norway and Sweden. Trends in mortality between 2001 and 2015 in the six original ICBP countries were examined. Age standardised mortality rates (ASR per million) were calculated for all cancers, leukaemia, malignant and benign central nervous system (CNS) tumours, and non‐CNS solid tumours. ASRs were reported for children (age 0‐14 years), AYAs aged 15 to 39 years and adults aged 40 years and above. Average annual percentage change (AAPC) in mortality rates per country were estimated using Joinpoint regression. For all cancers combined, significant temporal reductions were observed in all countries and all age groups. However, the overall AAPC was greater for children (−2.9; 95% confidence interval = −4.0 to −1.7) compared to AYAs (−1.8; −2.1 to −1.5) and adults aged >40 years (−1.5; −1.6 to −1.4). This pattern was mirrored for leukaemia, CNS tumours and non‐CNS solid tumours, with the difference being most pronounced for leukaemia: AAPC for children −4.6 (−6.1 to −3.1) vs AYAs −3.2 (−4.2 to −2.1) and over 40s −1.1 (−1.3 to −0.8). AAPCs varied between countries in children for all cancers except leukaemia, and in adults over 40 for all cancers combined, but not in subgroups. Improvements in cancer mortality rates in ICBP countries have been most marked among children aged 0 to 14 in comparison to 15 to 39 and over 40 year olds. This may reflect better care, including centralised service provision, treatment protocols and higher trial recruitment rates in children compared to older patients. What's new? Cancer mortality rates and trends are a function of both cancer incidence and survival and reflect the success of public health policy. Here, the authors compared mortality among children, adolescents and young adults, and older adults across six high‐income, universal health‐coverage nations between 2001 and 2015. They found a consistent temporal reduction in mortality rates in all populations. Changes in cancer mortality rates were larger among children than among adolescent and young adults or older adults. This may reflect the more centralised cancer care provision, more consistent uptake of treatment protocols, and higher trial recruitment rates in children compared to other age groups in these high‐income countries. [ABSTRACT FROM AUTHOR]

Published
2022
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43. Dissecting the genomic complexity underlying medulloblastoma

Author

Jones, David T. W., Jäger, Natalie, Kool, Marcel, Zichner, Thomas, Hutter, Barbara, Sultan, Marc, Cho, Yoon-Jae, Pugh, Trevor J., Hovestadt, Volker, Stütz, Adrian M., Rausch, Tobias, Warnatz, Hans-Jörg, Ryzhova, Marina, Bender, Sebastian, Sturm, Dominik, Pleier, Sabrina, Cin, Huriye, Pfaff, Elke, Sieber, Laura, Wittmann, Andrea, Remke, Marc, Witt, Hendrik, Hutter, Sonja, Tzaridis, Theophilos, Weischenfeldt, Joachim, Raeder, Benjamin, Avci, Meryem, Amstislavskiy, Vyacheslav, Zapatka, Marc, Weber, Ursula D., Wang, Qi, Lasitschka, Bärbel, Bartholomae, Cynthia C., Schmidt, Manfred, von Kalle, Christof, Ast, Volker, Lawerenz, Chris, Eils, Jürgen, Kabbe, Rolf, Benes, Vladimir, van Sluis, Peter, Koster, Jan, Volckmann, Richard, Shih, David, Betts, Matthew J., Russell, Robert B., Coco, Simona, Tonini, Gian Paolo, Schüller, Ulrich, Hans, Volkmar, Graf, Norbert, Kim, Yoo-Jin, Monoranu, Camelia, Roggendorf, Wolfgang, Unterberg, Andreas, Herold-Mende, Christel, Milde, Till, Kulozik, Andreas E., von Deimling, Andreas, Witt, Olaf, Maass, Eberhard, Rössler, Jochen, Ebinger, Martin, Schuhmann, Martin U., Frühwald, Michael C., Hasselblatt, Martin, Jabado, Nada, Rutkowski, Stefan, von Bueren, André O., Williamson, Dan, Clifford, Steven C., McCabe, Martin G., Collins, Peter V., Wolf, Stephan, Wiemann, Stefan, Lehrach, Hans, Brors, Benedikt, Scheurlen, Wolfram, Felsberg, Jörg, Reifenberger, Guido, Northcott, Paul A., Taylor, Michael D., Meyerson, Matthew, Pomeroy, Scott L., Yaspo, Marie-Laure, Korbel, Jan O., Korshunov, Andrey, Eils, Roland, Pfister, Stefan M., and Lichter, Peter

Published
2012
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44. Results of the second interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES).

Author

McCabe, Martin G., primary, Kirton, Laura, additional, Khan, Maria, additional, Fenwick, Nicola, additional, Dirksen, Uta, additional, Gaspar, Nathalie, additional, Kanerva, Jukka, additional, Kuehne, Thomas, additional, Longhi, Alessandra, additional, Luksch, Roberto, additional, Mata, Cristina, additional, Phillips, Marianne, additional, Safwat, Akmal, additional, Strauss, Sandra J., additional, Sundby Hall, Kirsten, additional, Valverde Morales, Claudia Maria, additional, Westwood, Andrew J., additional, Winstanley, Mark, additional, Whelan, Jeremy, additional, and Wheatley, Keith, additional

Published
2020
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45. Correlation of response with progression-free (PFS) and overall (OS) survival in relapsed/refractory Ewing sarcoma (RR-ES): Results from the rEECur trial.

Author

Wheatley, Keith, primary, Kadir, Bryar, additional, Khan, Maria, additional, Fenwick, Nicola, additional, Gaspar, Nathalie, additional, Kanerva, Jukka, additional, Kuehne, Thomas, additional, Longhi, Alessandra, additional, Mata, Cristina, additional, Phillips, Marianne, additional, Hall, Kirsten, additional, Safwat, Akmal, additional, Valverde Morales, Claudia, additional, Westwood, Andrew J., additional, Winstanley, Mark, additional, Evans, Abigail, additional, Strauss, Sandra J, additional, Dirksen, Uta, additional, Whelan, Jeremy, additional, and McCabe, Martin G., additional

Published
2020
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46. Cardiac Mortality Among 200 000 Five-Year Survivors of Cancer Diagnosed at 15 to 39 Years of Age

Author

Henson, Katherine E., Reulen, Raoul C., Winter, David L., Bright, Chloe J., Fidler, Miranda M., Frobisher, Clare, Guha, Joyeeta, Wong, Kwok F., Kelly, Julie, Edgar, Angela B., McCabe, Martin G., Whelan, Jeremy, Cutter, David J., Darby, Sarah C., and Hawkins, Mike M.

Subjects
Adult, Male, heart diseases, Time Factors, Adolescent, neoplasms, mortality, Young Adult, Risk Factors, Original Research Articles, cardiac deaths, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Humans, epidemiology, Female, Survivors
Abstract

Supplemental Digital Content is available in the text., Background: Survivors of teenage and young adult cancer are acknowledged as understudied. Little is known about their long-term adverse health risks, particularly of cardiac disease that is increased in other cancer populations where cardiotoxic treatments have been used. Methods: The Teenage and Young Adult Cancer Survivor Study cohort comprises 200 945 5-year survivors of cancer diagnosed at 15 to 39 years of age in England and Wales from 1971 to 2006, and followed to 2014. Standardized mortality ratios, absolute excess risks, and cumulative risks were calculated. Results: Two thousand sixteen survivors died of cardiac disease. For all cancers combined, the standardized mortality ratios for all cardiac diseases combined was greatest for individuals diagnosed at 15 to 19 years of age (4.2; 95% confidence interval, 3.4–5.2) decreasing to 1.2 (95% confidence interval, 1.1–1.3) for individuals aged 35 to 39 years (2P for trend

Published
2016

48. Description of the BRIGHTLIGHT Cohort: the evaluation of teenagers and young adult cancer services in England

Author

Taylor, Rachel, Fern, Lorna, Barber, Julie, Alvarez Galvez, Javier, Morris, Stephen, Feltbower, Richard, Hooker, Louise, McCabe, Martin G, Gibson, Faith, Raine, Rosalind, Stark, Dan, and Whelan, Jeremy

Abstract

Objective: International recognition of the unique needs of young people with cancer is growing. Many countries have developed specialist age-appropriate cancer services believing them to be of value. In England, 13 specialist Principal Treatment Centres (PTC) deliver cancer care to young people. Despite this expansion of specialist care, systematic investigation of associated outcomes and costs has to date, been lacking. The aim of this paper is to describe recruitment and baseline characteristics of the BRIGHTLIGHT cohort, and the development of the bespoke measures of levels of care and disease severity, which will inform the evaluation of cancer services in England. Design: Prospective, longitudinal, observational study. Setting: Ninety-seven NHS hospitals in England. Participants: A total of 1,114 participants were recruited diagnosed between July 2012 and December 2014: 55% (n=618) male, mean age was 20.1 years (SD=3.3), most (86%) were white and most common diagnoses were lymphoma (31%), germ cell tumour (19%) and leukaemia (13%). Results: At diagnosis, median quality of life score was significantly lower than a published control threshold (69.7 points); 40% had borderline-severe anxiety, and 21% had borderlinesevere depression. There was minimal variation in other patient-reported outcomes according to age, diagnosis or severity of illness. Survival was significantly worse in the Cohort than for young people diagnosed during the same period who were not recruited (cumulative survival probability 4 years after diagnosis: 88% vs. 92%). Conclusions: Data collection was completed in March 2018. Longitudinal comparisons will determine outcomes and costs associated with access/exposure to PTCs. Findings will inform international intervention and policy initiatives to improve outcomes for young people with cancer.

Published
2019

49. Disease course of neurofibromatosis type 2: a 30-year follow-up study of 353 patients seen at a single institution.

Author

Forde, Claire, King, Andrew T, Rutherford, Scott A, Hammerbeck-Ward, Charlotte, Lloyd, Simon K, Freeman, Simon R, Pathmanaban, Omar N, Stapleton, Emma, Thomas, Owen M, Laitt, Roger D, Stivaros, Stavros, Kilday, John-Paul, Vassallo, Grace, McBain, Catherine, Kerrigan, Simon, Smith, Miriam J, McCabe, Martin G, Harkness, Elaine F, and Evans, D Gareth

Published
2021
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50. Supplemental_Material – Supplemental material for Discussing factors associated with quality of life in cancer follow-up appointments: a preliminary test of a pragmatic model for clinical practice

Author

Lindner, Oana C, McCabe, Martin G, Boele, Florien, Mayes, Andrew, Talmi, Deborah, Radford, John, and Wearden, Alison

Subjects
FOS: Clinical medicine, 110604 Sports Medicine, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases, 110314 Orthopaedics
Abstract

Supplemental material, Supplemental_Material for Discussing factors associated with quality of life in cancer follow-up appointments: a preliminary test of a pragmatic model for clinical practice by Oana C Lindner, Martin G McCabe, Florien Boele, Andrew Mayes, Deborah Talmi, John Radford and Alison Wearden in Clinical Rehabilitation

Published
2018
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