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1. Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

Author

Quaglino, P., Maule, M., Prince, H.M., Porcu, P., Horwitz, S., Duvic, M., Talpur, R., Vermeer, M., Bagot, M., Guitart, J., Papadavid, E., Sanches, J.A., Hodak, E., Sugaya, M., Berti, E., Ortiz-Romero, P., Pimpinelli, N., Servitje, O., Pileri, A., Zinzani, P.L., Estrach, T., Knobler, R., Stadler, R., Fierro, M.T., Alberti Violetti, S., Amitay-Laish, I., Antoniou, C., Astrua, C., Chaganti, S., Child, F., Combalia, A., Fabbro, S., Fava, P., Grandi, V., Jonak, C., Martinez-Escala, E., Kheterpal, M., Kim, E.J., McCormack, C., Miyagaki, T., Miyashiro, D., Morris, S., Muniesa, C., Nikolaou, V., Ognibene, G., Onida, F., Osella-Abate, S., Porkert, S., Postigo-Llorente, C., Ram-Wolff, C., Ribero, S., Rogers, K., Sanlorenzo, M., Stranzenbach, R., Spaccarelli, N., Stevens, A., Zugna, D., Rook, A.H., Geskin, L.J., Willemze, R., Whittaker, S., Hoppe, R., Scarisbrick, J., and Kim, Y.

Published
2017
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3. Corrigendum: Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: A multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium (Annals of Oncology (2017) 28 (2517-2525) DOI: 10.1093/annonc/mdx352)

Author

Quaglino, P., Maule, M., Prince, H. M., Porcu, P., Horwitz, S., Duvic, M., Talpur, R., Vermeer, M., Bagot, M., Guitart, J., Papadavid, E., Sanches, J. A., Hodak, E., Sugaya, M., Berti, E., Ortiz-Romero, P., Pimpinelli, N., Servitje, O., Pileri, A., Zinzani, P. L., Estrach, T., Knobler, R., Stadler, R., Fierro, M. T., Alberti Violetti, S., Amitay-Laish, I., Antoniou, C., Astrua, C., Chaganti, S., Child, F., Combalia, A., Fabbro, S., Fava, P., Grandi, V., Jonak, C., Martinez-Escala, E., Kheterpal, M., Kim, E. J., Mccormack, C., Miyagaki, T., Miyashiro, D., Morris, S., Muniesa, C., Nikolaou, V., Ognibene, G., Onida, F., Osella-Abate, S., Porkert, S., Postigo-Llorente, C., Ram-Wolff, C., Ribero, S., Rogers, K., Sanlorenzo, M., Stranzenbach, R., Spaccarelli, N., Stevens, A., Zugna, D., Rook, A. H., Geskin, L. J., Willemze, R., Whittaker, S., Hoppe, R., Scarisbrick, J., and Kim, Y.

Published
2019

4. Corrigendum: Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: A multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium (Annals of Oncology (2017) 28 (2517-2525) DOI: 10.1093/annonc/mdx352)

Author

Quaglino, P. Maule, M. Prince, H.M. Porcu, P. Horwitz, S. Duvic, M. Talpur, R. Vermeer, M. Bagot, M. Guitart, J. Papadavid, E. Sanches, J.A. Hodak, E. Sugaya, M. Berti, E. Ortiz-Romero, P. Pimpinelli, N. Servitje, O. Pileri, A. Zinzani, P.L. Estrach, T. Knobler, R. Stadler, R. Fierro, M.T. Alberti Violetti, S. Amitay-Laish, I. Antoniou, C. Astrua, C. Chaganti, S. Child, F. Combalia, A. Fabbro, S. Fava, P. Grandi, V. Jonak, C. Martinez-Escala, E. Kheterpal, M. Kim, E.J. McCormack, C. Miyagaki, T. Miyashiro, D. Morris, S. Muniesa, C. Nikolaou, V. Ognibene, G. Onida, F. Osella-Abate, S. Porkert, S. Postigo-Llorente, C. Ram-Wolff, C. Ribero, S. Rogers, K. Sanlorenzo, M. Stranzenbach, R. Spaccarelli, N. Stevens, A. Zugna, D. Rook, A.H. Geskin, L.J. Willemze, R. Whittaker, S. Hoppe, R. Scarisbrick, J. Kim, Y.

Abstract

In the original article, the affiliation number 16 for authors E. Berti and S. Alberti Violetti was incorrect. It originally read: 'Dermatologic Clinic, University of Milano, Milano, Italy' and has now been changed to 'Department of Dermatology, Fondazione Cà Granda, IRCCS,OMP, Milano, Italy'. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Published
2019

5. Corrections to “Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium”

Author

Quaglino, P., primary, Maule, M., additional, Prince, H.M., additional, Porcu, P., additional, Horwitz, S., additional, Duvic, M., additional, Talpur, R., additional, Vermeer, M., additional, Bagot, M., additional, Guitart, J., additional, Papadavid, E., additional, Sanches, J.A., additional, Hodak, E., additional, Sugaya, M., additional, Berti, E., additional, Ortiz-Romero, P., additional, Pimpinelli, N., additional, Servitje, O., additional, Pileri, A., additional, Zinzani, P.L., additional, Estrach, T., additional, Knobler, R., additional, Stadler, R., additional, Fierro, M.T., additional, Alberti Violetti, S., additional, Amitay-Laish, I., additional, Antoniou, C., additional, Astrua, C., additional, Chaganti, S., additional, Child, F., additional, Combalia, A., additional, Fabbro, S., additional, Fava, P., additional, Grandi, V., additional, Jonak, C., additional, Martinez-Escala, E., additional, Kheterpal, M., additional, Kim, E.J., additional, McCormack, C., additional, Miyagaki, T., additional, Miyashiro, D., additional, Morris, S., additional, Muniesa, C., additional, Nikolaou, V., additional, Ognibene, G., additional, Onida, F., additional, Osella-Abate, S., additional, Porkert, S., additional, Postigo-Llorente, C., additional, Ram-Wolff, C., additional, Ribero, S., additional, Rogers, K., additional, Sanlorenzo, M., additional, Stranzenbach, R., additional, Spaccarelli, N., additional, Stevens, A., additional, Zugna, D., additional, Rook, A.H., additional, Geskin, L.J., additional, Willemze, R., additional, Whittaker, S., additional, Hoppe, R., additional, Scarisbrick, J., additional, and Kim, Y., additional

Published
2019
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7. Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

Author

Alessandro Pileri, K. Rogers, G. Ognibene, C. Postigo-Llorente, Larisa J. Geskin, M. Kheterpal, S. Alberti Violetti, Daniela Zugna, Paolo Fava, Youn H. Kim, V. Nikolaou, A. Stevens, Evangelia Papadavid, Joan Guitart, Nicola Pimpinelli, P L Ortiz-Romero, Emilio Berti, Ch. Antoniou, Iris Amitay-Laish, F. Child, René Stranzenbach, Tomomitsu Miyagaki, Denis Miyashiro, R. Knobler, Pier Luigi Zinzani, Maarten H. Vermeer, Teresa Estrach, Francesco Onida, Stephen Morris, S. Chaganti, Martina Sanlorenzo, Ellen Kim, Cristina Muniesa, José Antonio Sanches, Pietro Quaglino, Makoto Sugaya, M. Duvic, J. Scarisbrick, N. Spaccarelli, Vieri Grandi, Steve Horwitz, Simona Osella-Abate, Alain H. Rook, Martine Bagot, Chiara Astrua, Octavio Servitje, Emmilia Hodak, Rakhshandra Talpur, Sean Whittaker, Milena Maule, Christopher McCormack, S. Fabbro, A. Combalia, Rein Willemze, Rudolf Stadler, Estela Martinez-Escala, Pierluigi Porcu, S. Porkert, M.T. Fierro, Caroline Ram-Wolff, Simone Ribero, Henry Miles Prince, Richard T. Hoppe, Constanze Jonak, Quaglino, P, Maule, M, Prince, H. M, Porcu, P, Horwitz, S, Duvic, M, Talpur, R, Vermeer, M, Bagot, M, Guitart, J, Papadavid, E, Sanches, J. A, Hodak, E, Sugaya, M, Berti, E, Ortiz-Romero, P, Pimpinelli, N, Servitje, O, Pileri, A, Zinzani, P. L, Estrach, T, Knobler, R, Stadler, R, Fierro, M. T, Alberti Violetti, S, Amitay-Laish, I, Antoniou, C, Astrua, C, Chaganti, S, Child, F, Combalia, A, Fabbro, S, Fava, P, Grandi, V, Jonak, C, Martinez-Escala, E, Kheterpal, M, Kim, E. J, Mccormack, C, Miyagaki, T, Miyashiro, D, Morris, S, Muniesa, C, Nikolaou, V, Ognibene, G, Onida, F, Osella-Abate, S, Porkert, S, Postigo-Llorente, C, Ram-Wolff, C, Ribero, S, Rogers, K, Sanlorenzo, M, Stranzenbach, R, Spaccarelli, N, Stevens, A, Zugna, D, Rook, A. H, Geskin, L. J, Willemze, R, Whittaker, S, Hoppe, R, Scarisbrick, J, and Kim, Y.

Subjects
Oncology, Male, medicine.medical_treatment, Medical Oncology, Cutaneous lymphoma, 030207 dermatology & venereal diseases, 0302 clinical medicine, Photopheresis, CTCL, Japan, Child, Bexarotene, Aged, 80 and over, treatment, Follow up studies, Hematology, Middle Aged, Chemotherapy regimen, Europe, Mycosis fungoides, Prognosis, Survival, Treatment, 030220 oncology & carcinogenesis, Female, prognosi, Brazil, medicine.drug, mycosis fungoide, Mycosis fungoides/Sezary syndrome, Adult, medicine.medical_specialty, Adolescent, survival, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Sezary Syndrome, Aged, Neoplasm Staging, Retrospective Studies, Patterns of care, Chlorambucil, business.industry, mycosis fungoides, Advanced stage, Australia, Retrospective cohort study, medicine.disease, Dermatology, Gemcitabine, United States, Relative risk, prognosis, business
Abstract

Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.

Published
2017

8. Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium.

Author

Quaglino P, Maule M, Prince HM, Porcu P, Horwitz S, Duvic M, Talpur R, Vermeer M, Bagot M, Guitart J, Papadavid E, Sanches JA, Hodak E, Sugaya M, Berti E, Ortiz-Romero P, Pimpinelli N, Servitje O, Pileri A, Zinzani PL, Estrach T, Knobler R, Stadler R, Fierro MT, Alberti Violetti S, Amitay-Laish I, Antoniou C, Astrua C, Chaganti S, Child F, Combalia A, Fabbro S, Fava P, Grandi V, Jonak C, Martinez-Escala E, Kheterpal M, Kim EJ, McCormack C, Miyagaki T, Miyashiro D, Morris S, Muniesa C, Nikolaou V, Ognibene G, Onida F, Osella-Abate S, Porkert S, Postigo-Llorente C, Ram-Wolff C, Ribero S, Rogers K, Sanlorenzo M, Stranzenbach R, Spaccarelli N, Stevens A, Zugna D, Rook AH, Geskin LJ, Willemze R, Whittaker S, Hoppe R, Scarisbrick J, and Kim Y

Published
2019
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9. Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p.Q575E).

Author

Park J, Yang J, Wenzel AT, Ramachandran A, Lee WJ, Daniels JC, Kim J, Martinez-Escala E, Amankulor N, Pro B, Guitart J, Mendillo ML, Savas JN, Boggon TJ, and Choi J

Subjects
Amino Acid Sequence, Amino Acid Substitution genetics, Base Sequence, Genome, Human, HEK293 Cells, Humans, Jurkat Cells, Microfilament Proteins chemistry, Mutation genetics, NF-kappa B metabolism, Oncogenes, Receptors, Antigen, T-Cell metabolism, Sequence Analysis, DNA, Signal Transduction genetics, rhoA GTP-Binding Protein genetics, Genomics, Lymphoma, T-Cell, Cutaneous genetics, Microfilament Proteins genetics
Abstract

Cutaneous T-cell lymphoma (CTCL) is an incurable non-Hodgkin lymphoma of the skin-homing T cell. In early-stage disease, lesions are limited to the skin, but in later-stage disease, the tumor cells can escape into the blood, the lymph nodes, and at times the visceral organs. To clarify the genomic basis of CTCL, we performed genomic analysis of 220 CTCLs. Our analyses identify 55 putative driver genes, including 17 genes not previously implicated in CTCL. These novel mutations are predicted to affect chromatin ( BCOR , KDM6A , SMARCB1 , TRRAP ), immune surveillance ( CD58 , RFXAP ), MAPK signaling ( MAP2K1 , NF1 ), NF-κB signaling ( PRKCB , CSNK1A1 ), PI-3-kinase signaling ( PIK3R1 , VAV1 ), RHOA/cytoskeleton remodeling ( ARHGEF3 ), RNA splicing ( U2AF1 ), T-cell receptor signaling ( PTPRN2 , RLTPR ), and T-cell differentiation ( RARA ). Our analyses identify recurrent mutations in 4 genes not previously identified in cancer. These include CK1α (encoded by CSNK1A1 ) (p.S27F; p.S27C), PTPRN2 (p.G526E), RARA (p.G303S), and RLTPR (p.Q575E). Last, we functionally validate CSNK1A1 and RLTPR as putative oncogenes. RLTPR encodes a recently described scaffolding protein in the T-cell receptor signaling pathway. We show that RLTPR (p.Q575E) increases binding of RLTPR to downstream components of the NF-κB signaling pathway, selectively upregulates the NF-κB pathway in activated T cells, and ultimately augments T-cell-receptor-dependent production of interleukin 2 by 34-fold. Collectively, our analysis provides novel insights into CTCL pathogenesis and elucidates the landscape of potentially targetable gene mutations., (© 2017 by The American Society of Hematology.)

Published
2017
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10. The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome.

Author

da Silva Almeida AC, Abate F, Khiabanian H, Martinez-Escala E, Guitart J, Tensen CP, Vermeer MH, Rabadan R, Ferrando A, and Palomero T

Subjects
Case-Control Studies, Chromosome Deletion, DNA Mutational Analysis, Epigenesis, Genetic, Exome genetics, Genetic Loci, Humans, Immunoblotting, Lymphoma, T-Cell, Cutaneous metabolism, Lymphoma, T-Cell, Cutaneous pathology, Risk Factors, Sezary Syndrome metabolism, Sezary Syndrome pathology, Signal Transduction, Skin Neoplasms metabolism, Skin Neoplasms pathology, Gene Expression Regulation, Neoplastic, Genetic Markers genetics, Lymphoma, T-Cell, Cutaneous genetics, Mutation genetics, Sezary Syndrome genetics, Skin Neoplasms genetics
Abstract

Sézary syndrome is a leukemic and aggressive form of cutaneous T cell lymphoma (CTCL) resulting from the malignant transformation of skin-homing central memory CD4(+) T cells. Here we performed whole-exome sequencing of tumor-normal sample pairs from 25 patients with Sézary syndrome and 17 patients with other CTCLs. These analyses identified a distinctive pattern of somatic copy number alterations in Sézary syndrome, including highly prevalent chromosomal deletions involving the TP53, RB1, PTEN, DNMT3A and CDKN1B tumor suppressors. Mutation analysis identified a broad spectrum of somatic mutations in key genes involved in epigenetic regulation (TET2, CREBBP, KMT2D (MLL2), KMT2C (MLL3), BRD9, SMARCA4 and CHD3) and signaling, including MAPK1, BRAF, CARD11 and PRKG1 mutations driving increased MAPK, NF-κB and NFAT activity upon T cell receptor stimulation. Collectively, our findings provide new insights into the genetics of Sézary syndrome and CTCL and support the development of personalized therapies targeting key oncogenically activated signaling pathways for the treatment of these diseases.

Published
2015
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