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14 results on '"Lopez-Aguilar, E"'

1. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

Author

Nobre, L, Zapotocky, M, Khan, S, Fukuoka, K, Fonseca, A, McKeown, T, Sumerauer, D, Vicha, A, Grajkowska, WA, Trubicka, J, Li, KKW, Ng, H-K, Massimi, L, Lee, JY, Kim, S-K, Zelcer, S, Vasiljevic, A, Faure-Conter, C, Hauser, P, Lach, B, Van Veelen-Vincent, M-L, French, PJ, Van Meir, EG, Weiss, WA, Gupta, N, Pollack, IF, Hamilton, RL, Rao, AAN, Giannini, C, Rubin, JB, Moore, AS, Chambless, LB, Vibhakar, R, Ra, YS, Massimino, M, McLendon, RE, Wheeler, H, Zollo, M, Ferruci, V, Kumabe, T, Faria, CC, Sterba, J, Jung, S, Lopez-Aguilar, E, Mora, J, Carlotti, CG, Olson, JM, Leary, S, Cain, J, Krskova, L, Zamecnik, J, Hawkins, CE, Tabori, U, Huang, A, Bartels, U, Northcott, PA, Taylor, MD, Yip, S, Hansford, JR, Bouffet, E, Ramaswamy, V, Nobre, L, Zapotocky, M, Khan, S, Fukuoka, K, Fonseca, A, McKeown, T, Sumerauer, D, Vicha, A, Grajkowska, WA, Trubicka, J, Li, KKW, Ng, H-K, Massimi, L, Lee, JY, Kim, S-K, Zelcer, S, Vasiljevic, A, Faure-Conter, C, Hauser, P, Lach, B, Van Veelen-Vincent, M-L, French, PJ, Van Meir, EG, Weiss, WA, Gupta, N, Pollack, IF, Hamilton, RL, Rao, AAN, Giannini, C, Rubin, JB, Moore, AS, Chambless, LB, Vibhakar, R, Ra, YS, Massimino, M, McLendon, RE, Wheeler, H, Zollo, M, Ferruci, V, Kumabe, T, Faria, CC, Sterba, J, Jung, S, Lopez-Aguilar, E, Mora, J, Carlotti, CG, Olson, JM, Leary, S, Cain, J, Krskova, L, Zamecnik, J, Hawkins, CE, Tabori, U, Huang, A, Bartels, U, Northcott, PA, Taylor, MD, Yip, S, Hansford, JR, Bouffet, E, and Ramaswamy, V

Abstract

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.

Published
2020

2. Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand?

Author

El-Khouly, F.E. Veldhuijzen van Zanten, S.E.M. Santa-Maria Lopez, V. Hendrikse, N.H. Kaspers, G.J.L. Loizos, G. Sumerauer, D. Nysom, K. Pruunsild, K. Pentikainen, V. Thorarinsdottir, H.K. Rutkauskiene, G. Calvagna, V. Drogosiewicz, M. Dragomir, M. Deak, L. Kitanovski, L. von Bueren, A.O. Kebudi, R. Slavc, I. Jacobs, S. Jadrijevic-Cvrlje, F. Entz-Werle, N. Grill, J. Kattamis, A. Hauser, P. Pears, J. Biassoni, V. Massimino, M. Lopez Aguilar, E. Torsvik, I.K. Joao Gil-da-Costa, M. Kumirova, E. Cruz-Martinez, O. Holm, S. Bailey, S. Hayden, T. Thomale, U.W. Janssens, G.O.R. Kramm, C.M. van Vuurden, D.G.

Abstract

Introduction: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. Methods: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. Results: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. Conclusion: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials. © 2019, The Author(s).

Published
2019

4. Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease

Author

Veldhuijzen van Zanten, S.E.M. Baugh, J. Chaney, B. De Jongh, D. Sanchez Aliaga, E. Barkhof, F. Noltes, J. De Wolf, R. Van Dijk, J. Cannarozzo, A. Damen-Korbijn, C.M. Lieverst, J.A. Colditz, N. Hoffmann, M. Warmuth-Metz, M. Bison, B. Jones, D.T.W. Sturm, D. Gielen, G.H. Jones, C. Hulleman, E. Calmon, R. Castel, D. Varlet, P. Giraud, G. Slavc, I. Van Gool, S. Jacobs, S. Jadrijevic-Cvrlje, F. Sumerauer, D. Nysom, K. Pentikainen, V. Kivivuori, S.-M. Leblond, P. Entz-Werle, N. von Bueren, A.O. Kattamis, A. Hargrave, D.R. Hauser, P. Garami, M. Thorarinsdottir, H.K. Pears, J. Gandola, L. Rutkauskiene, G. Janssens, G.O. Torsvik, I.K. Perek-Polnik, M. Gil-da-Costa, M.J. Zheludkova, O. Shats, L. Deak, L. Kitanovski, L. Cruz, O. Morales La Madrid, A. Holm, S. Gerber, N. Kebudi, R. Grundy, R. Lopez-Aguilar, E. Zapata-Tarres, M. Emmerik, J. Hayden, T. Bailey, S. Biassoni, V. Massimino, M. Grill, J. Vandertop, W.P. Kaspers, G.J.L. Fouladi, M. Kramm, C.M. van Vuurden, D.G. on behalf of the members of the SIOPE DIPG Network

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6–6.4 months) and the median overall survival is 11.0 months (95% CI 10.5–11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG. © 2017, The Author(s).

Published
2017

6. Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma

Author

Anne Jouvet, Ana Gutiérrez-Fernández, Namal Abeysundara, Olivier Ayrault, Vijay Ramaswamy, Charles G. Eberhart, Jennifer A. Chan, Johan M. Kros, Xiaochong Wu, Sachin Kumar, Seung-Ki Kim, Maria C. Vladoiu, Noriyuki Kijima, Xose S. Puente, Ian F. Pollack, Robert J. Wechsler-Reya, Boleslaw Lach, Almos Klekner, Ander Diaz-Navarro, Claudia C. Faria, Lincoln Stein, Nicole Gauer, Enrique López-Aguilar, Nada Jabado, Amulya A. Nageswara Rao, Livia Garzia, David Malkin, Stefan M. Pfister, Jiannis Ragoussis, Maura Massimino, James M. Olson, Caterina Giannini, Hamza Farooq, Pim J. French, Florence M.G. Cavalli, Anna Goldenberg, John A. Calarco, Joshua B. Rubin, Maria Luisa Garrè, Betty Luu, László Bognár, Weifan Dong, Shimin Shuai, Antoine Forget, Jun Wang, Ichiyo Shibahara, Pasqualino De Antonellis, William A. Weiss, Marco A. Marra, Lola B. Chambless, Patryk Skowron, Wiesława Grajkowska, Jiao Zhang, Ali Momin, Erwin G. Van Meir, Michelle Fèvre-Montange, Rajeev Vibhakar, Ho Keung Ng, David Przelicki, Hiromichi Suzuki, Kyle Juraschka, Craig Daniels, A. Sorana Morrissy, Toshihiro Kumabe, Xi Huang, Wai Sang Poon, Swneke D. Bailey, Michael D. Taylor, Pathology, Neurology, Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France. 4Université Paris Sud, Université Paris- Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France., Institut Curie [Paris], Suzuki H., Kumar S.A., Shuai S., Diaz-Navarro A., Gutierrez-Fernandez A., De Antonellis P., Cavalli F.M.G., Juraschka K., Farooq H., Shibahara I., Vladoiu M.C., Zhang J., Abeysundara N., Przelicki D., Skowron P., Gauer N., Luu B., Daniels C., Wu X., Forget A., Momin A., Wang J., Dong W., Kim S.-K., Grajkowska W.A., Jouvet A., Fevre-Montange M., Garre M.L., Nageswara Rao A.A., Giannini C., Kros J.M., French P.J., Jabado N., Ng H.-K., Poon W.S., Eberhart C.G., Pollack I.F., Olson J.M., Weiss W.A., Kumabe T., Lopez-Aguilar E., Lach B., Massimino M., Van Meir E.G., Rubin J.B., Vibhakar R., Chambless L.B., Kijima N., Klekner A., Bognar L., Chan J.A., Faria C.C., Ragoussis J., Pfister S.M., Goldenberg A., Wechsler-Reya R.J., Bailey S.D., Garzia L., Morrissy A.S., Marra M.A., Huang X., Malkin D., Ayrault O., Ramaswamy V., Puente X.S., Calarco J.A., Stein L., Taylor M.D., Repositório da Universidade de Lisboa, Suzuki, H., Kumar, S. A., Shuai, S., Diaz-Navarro, A., Gutierrez-Fernandez, A., De Antonellis, P., Cavalli, F. M. G., Juraschka, K., Farooq, H., Shibahara, I., Vladoiu, M. C., Zhang, J., Abeysundara, N., Przelicki, D., Skowron, P., Gauer, N., Luu, B., Daniels, C., Wu, X., Forget, A., Momin, A., Wang, J., Dong, W., Kim, S. -K., Grajkowska, W. A., Jouvet, A., Fevre-Montange, M., Garre, M. L., Nageswara Rao, A. A., Giannini, C., Kros, J. M., French, P. J., Jabado, N., Ng, H. -K., Poon, W. S., Eberhart, C. G., Pollack, I. F., Olson, J. M., Weiss, W. A., Kumabe, T., Lopez-Aguilar, E., Lach, B., Massimino, M., Van Meir, E. G., Rubin, J. B., Vibhakar, R., Chambless, L. B., Kijima, N., Klekner, A., Bognar, L., Chan, J. A., Faria, C. C., Ragoussis, J., Pfister, S. M., Goldenberg, A., Wechsler-Reya, R. J., Bailey, S. D., Garzia, L., Morrissy, A. S., Marra, M. A., Huang, X., Malkin, D., Ayrault, O., Ramaswamy, V., Puente, X. S., Calarco, J. A., Stein, L., Taylor, M. D., and Olivier, AYRAULT

Subjects
0301 basic medicine, Adult, Adolescent, RNA Splicing, [SDV]Life Sciences [q-bio], Biology, Article, 03 medical and health sciences, 0302 clinical medicine, GLI2, RNA, Small Nuclear, medicine, Humans, G%29+of+U1+spliceosomal+small+nuclear+RNAs+%28snRNAs%29%22">subgroups of medulloblastoma, recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs), Hedgehog Proteins, Sonic hedgehog, Cerebellar Neoplasms, Gene, ComputingMilieux_MISCELLANEOUS, Medulloblastoma, Multidisciplinary, Cerebellar Neoplasm, Alternative splicing, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Alternative Splicing, 030104 developmental biology, PTCH1, RNA Splice Site, 030220 oncology & carcinogenesis, RNA splicing, Mutation, Cancer research, biology.protein, RNA Splice Sites, Hedgehog Protein, Small nuclear RNA, Human
Abstract

© The Author(s), under exclusive licence to Springer Nature Limited 2019, In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only

Published
2019

7. Intertumoral Heterogeneity within Medulloblastoma Subgroups

Author

Luca Massimi, Caterina Giannini, Betty Luu, Cynthia Hawkins, Byung Kyu Cho, James T. Rutka, G. Yancey Gillespie, Timothy E. Van Meter, Almos Klekner, Young Shin Ra, Carolina Nor, Anna Goldenberg, Rajeev Vibhakar, Hideo Nakamura, Gaetano Finocchiaro, Massimo Zollo, John Peacock, Marta Perek-Polnik, Keren Isaev, Alvaro Lassaletta, Amulya A. Nageswara Rao, Florence M.G. Cavalli, Maura Massimino, Livia Garzia, Jüri Reimand, Charles G. Eberhart, Maryam Fouladi, Enrique López-Aguilar, Annie Huang, Cécile Faure-Conter, Gary D. Bader, Jaume Mora, Ho Keung Ng, James M. Olson, Jennifer A. Chan, Erwin G. Van Meir, Daniela Pretti da Cunha Tirapelli, Hamza Farooq, Fernando Chico Ponce de León, Linda M. Liau, Kay Ka Wai Li, Shenandoah Robinson, Anne Jouvet, Tomoko Shofuda, José Pimentel, Reid C. Thompson, Yuan Yao Thompson, Ian F. Pollack, Nada Jabado, Boleslaw Lach, Pim J. French, Joshua B. Rubin, Eric Bouffet, Alexandre Vasiljevic, Ali G. Saad, Michael K. Cooper, Satoru Osuka, Peter B. Dirks, Jaroslav Sterba, Johan M. Kros, Claudia C. Faria, Kyu-Chang Wang, Seung-Ki Kim, Shin Jung, Craig Daniels, A. Sorana Morrissy, Ladislav Rampášek, Andrew R. Hallahan, Sarah Leary, Wiesława Grajkowska, Uri Tabori, Marc Remke, Samer K. Elbabaa, Michael D. Taylor, Andrew S. Moore, Toshihiro Kumabe, Mario Perezpeña-Diazconti, Vijay Ramaswamy, Ronald L. Hamilton, Claudia M. Kuzan-Fischer, Marie Lise C. van Veelen, Helen Wheeler, Michal Zapotocky, Ji Yeoun Lee, David Shih, Jeffrey R. Leonard, Karel Zitterbart, Carlos Gilberto Carlotti, Steffen Albrecht, Jonathon Torchia, Peter Hauser, Ute Bartels, William A. Weiss, Sameer Agnihotri, Lola B. Chambless, Neurosurgery, Pathology, Neurology, Cavalli, Fmg, Remke, M, Rampasek, L, Peacock, J, Shih, Djh, Luu, B, Garzia, L, Torchia, J, Nor, C, Morrissy, A, Agnihotri, S, Thompson, Yy, Kuzan-Fischer, Cm, Farooq, H, Isaev, K, Daniels, C, Cho, Bk, Kim, Sk, Wang, Kc, Lee, Jy, Grajkowska, Wa, Perek-Polnik, M, Vasiljevic, A, Faure-Conter, C, Jouvet, A, Giannini, C, Nageswara Rao, Aa, Li, Kkw, Ng, Hk, Eberhart, Cg, Pollack, If, Hamilton, Rl, Gillespie, Gy, Olson, Jm, Leary, S, Weiss, Wa, Lach, B, Chambless, Lb, Thompson, Rc, Cooper, Mk, Vibhakar, R, Hauser, P, van Veelen, Mc, Kros, Jm, French, Pj, Ra, Y, Kumabe, T, López-Aguilar, E, Zitterbart, K, Sterba, J, Finocchiaro, G, Massimino, M, Van Meir, Eg, Osuka, S, Shofuda, T, Klekner, A, Zollo, M, Leonard, Jr, Rubin, Jb, Jabado, N, Albrecht, S, Mora, J, Van Meter, Te, Jung, S, Moore, A, Hallahan, Ar, Chan, Ja, Tirapelli, Dpc, Carlotti, Cg, Fouladi, M, Pimentel, J, Faria, Cc, Saad, Ag, Massimi, L, Liau, Lm, Wheeler, H, Nakamura, H, Elbabaa, Sk, Perezpeña-Diazconti, M, Chico Ponce de León, F, Robinson, S, Zapotocky, M, Lassaletta, A, Huang, Weiping, Hawkins, Ce, Tabori, U, Bouffet, E, Bartels, U, Dirks, Pb, Rutka, Jt, Bader, Gd, Reimand, J, Goldenberg, A, Ramaswamy, V, Taylor, Md, Cavalli F.M.G., Remke M., Rampasek L., Peacock J., Shih D.J.H., Luu B., Garzia L., Torchia J., Nor C., Morrissy A.S., Agnihotri S., Thompson Y.Y., Kuzan-Fischer C.M., Farooq H., Isaev K., Daniels C., Cho B.-K., Kim S.-K., Wang K.-C., Lee J.Y., Grajkowska W.A., Perek-Polnik M., Vasiljevic A., Faure-Conter C., Jouvet A., Giannini C., Nageswara Rao A.A., Li K.K.W., Ng H.-K., Eberhart C.G., Pollack I.F., Hamilton R.L., Gillespie G.Y., Olson J.M., Leary S., Weiss W.A., Lach B., Chambless L.B., Thompson R.C., Cooper M.K., Vibhakar R., Hauser P., van Veelen M.-L.C., Kros J.M., French P.J., Ra Y.S., Kumabe T., Lopez-Aguilar E., Zitterbart K., Sterba J., Finocchiaro G., Massimino M., Van Meir E.G., Osuka S., Shofuda T., Klekner A., Zollo M., Leonard J.R., Rubin J.B., Jabado N., Albrecht S., Mora J., Van Meter T.E., Jung S., Moore A.S., Hallahan A.R., Chan J.A., Tirapelli D.P.C., Carlotti C.G., Fouladi M., Pimentel J., Faria C.C., Saad A.G., Massimi L., Liau L.M., Wheeler H., Nakamura H., Elbabaa S.K., Perezpena-Diazconti M., Chico Ponce de Leon F., Robinson S., Zapotocky M., Lassaletta A., Huang A., Hawkins C.E., Tabori U., Bouffet E., Bartels U., Dirks P.B., Rutka J.T., Bader G.D., Reimand J., Goldenberg A., Ramaswamy V., and Taylor M.D.

Subjects
0301 basic medicine, Cancer Research, medulloblastoma, CURRENT CONSENSUS, copy number, Bioinformatics, subgroups, Cohort Studies, Individual data, Cluster Analysis, R PACKAGE, Precision Medicine, GENECHIP DATA, Sonic hedgehog, ADULT MEDULLOBLASTOMA, DNA Copy Number Variation, Cancer, Pediatric, Genomics, methylation, CANCER, 3. Good health, Oncology, DNA methylation, Human, Pediatric Research Initiative, DNA Copy Number Variations, Pediatric Cancer, Oncology and Carcinogenesis, Computational biology, Biology, Article, CLASSIFICATION, Homogeneous clusters, 03 medical and health sciences, Rare Diseases, Genetics, medicine, Humans, Oncology & Carcinogenesis, Cerebellar Neoplasms, RECURRENCE, neoplasms, Medulloblastoma, Cluster Analysi, gene expression, MUTATIONS, subgroup, Gene Expression Profiling, Human Genome, Neurosciences, integrative clustering, DNA Methylation, medicine.disease, Precision medicine, MEDULOBLASTOMA, Brain Disorders, nervous system diseases, Brain Cancer, Gene expression profiling, stomatognathic diseases, 030104 developmental biology, Genomic, biology.protein, MOLECULAR SUBGROUPS, GENOMIC DATA, Cohort Studie
Abstract

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

Published
2017

8. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author

Iska Moxon-Emre, Livia Garzia, Karin M. Muraszko, Thomas Hielscher, Satoru Osuka, Xing Fan, Andrew S. Moore, Toshihiro Kumabe, Betty Luu, Cynthia Hawkins, Tibor Hortobágyi, David T.W. Jones, Leos Kren, Sridharan Gururangan, Peter Hauser, Peter B. Dirks, David Shih, Jeffrey R. Leonard, Andrey Korshunov, Michael K. Cooper, Gerald A. Grant, Naoki Kagawa, Andrew R. Hallahan, Claudia C. Faria, Pim J. French, Donald J. Mabbott, Joshua B. Rubin, Jaume Mora, Sarah Leary, Michael A. Grotzer, Cécile Faure-Conter, Stefan M. Pfister, Erwin G. Van Meir, Rajeev Vibhakar, Bognár László, Shin Jung, Yoon Jae Cho, Reid C. Thompson, Nada Jabado, Alexander G. Weil, David C.Y. Low, Karel Zitterbart, Enrique López-Aguilar, Alice Carvalho, Kenneth Tou En Chang, Ho Keung Ng, Ana Nikolic, Eric M. Thompson, Jennifer A. Chan, James T. Rutka, Kay Ka Wai Li, Yu Yao, Paul A. Northcott, Vijay Ramaswamy, Roger E. McLendon, Wan Tew Seow, Wendy J. Ingram, Wiesława Grajkowska, Ronald L. Hamilton, Marcel Kool, Caterina Giannini, William A. Weiss, Luca Massimi, Ian F. Pollack, Marie Lise C. van Veelen, Jaroslav Sterba, David Lyden, Ji Yeoun Lee, Ulrich Schüller, Sébastien Perreault, Nalin Gupta, Johan M. Kros, Arman Jahangiri, Roger J. Packer, Brandyn A. Castro, Lola B. Chambless, Jeffrey J. Olson, Seung-Ki Kim, Almos Klekner, Woo Youl Jang, Uri Tabori, Michelle Fèvre-Montange, Marc Remke, Takafumi Wataya, Michael D. Taylor, Sofia Nunes, Marta Perek-Polnik, Tímea Pócza, Amulya A. Nageswara Rao, James M. Drake, Tenzin Gayden, Alexandre Vasiljevic, Eric S. Lipp, Christian Schneider, Alvaro Lassaletta, Jennifer Adamski, Tarek Shalaby, Darell D. Bigner, Teiji Tominaga, Naoya Hashimoto, Anne Jouvet, Abhaya V. Kulkarni, Noriyuki Kijima, Tomoko Shofuda, José Pimentel, Eric Bouffet, Maria Luisa Garrè, Thompson E.M., Hielscher T., Bouffet E., Remke M., Luu B., Gururangan S., McLendon R.E., Bigner D.D., Lipp E.S., Perreault S., Cho Y.-J., Grant G., Kim S.-K., Lee J.Y., Rao A.A.N., Giannini C., Li K.K.W., Ng H.-K., Yao Y., Kumabe T., Tominaga T., Grajkowska W.A., Perek-Polnik M., Low D.C.Y., Seow W.T., Chang K.T.E., Mora J., Pollack I.F., Hamilton R.L., Leary S., Moore A.S., Ingram W.J., Hallahan A.R., Jouvet A., Fevre-Montange M., Vasiljevic A., Faure-Conter C., Shofuda T., Kagawa N., Hashimoto N., Jabado N., Weil A.G., Gayden T., Wataya T., Shalaby T., Grotzer M., Zitterbart K., Sterba J., Kren L., Hortobagyi T., Klekner A., Laszlo B., Pocza T., Hauser P., Schuller U., Jung S., Jang W.-Y., French P.J., Kros J.M., van Veelen M.-L.C., Massimi L., Leonard J.R., Rubin J.B., Vibhakar R., Chambless L.B., Cooper M.K., Thompson R.C., Faria C.C., Carvalho A., Nunes S., Pimentel J., Fan X., Muraszko K.M., Lopez-Aguilar E., Lyden D., Garzia L., Shih D.J.H., Kijima N., Schneider C., Adamski J., Northcott P.A., Kool M., Jones D.T.W., Chan J.A., Nikolic A., Garre M.L., Van Meir E.G., Osuka S., Olson J.J., Jahangiri A., Castro B.A., Gupta N., Weiss W.A., Moxon-Emre I., Mabbott D.J., Lassaletta A., Hawkins C.E., Tabori U., Drake J., Kulkarni A., Dirks P., Rutka J.T., Korshunov A., Pfister S.M., Packer R.J., Ramaswamy V., Taylor M.D., Neurology, Pathology, and Neurosurgery

Subjects
Adult, Male, medicine.medical_specialty, Canada, medicine.medical_treatment, Klinikai orvostudományok, Article, Disease-Free Survival, Brain Neoplasm, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, medicine, Humans, Child, Retrospective Studies, Medulloblastoma, Chemotherapy, Proportional hazards model, business.industry, Brain Neoplasms, Hazard ratio, Cancer, Infant, Retrospective cohort study, Orvostudományok, medicine.disease, Prognosis, Combined Modality Therapy, Magnetic Resonance Imaging, 3. Good health, Surgery, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, Disease Progression, Female, business, 030217 neurology & neurosurgery, Chemoradiotherapy, Human
Abstract

BACKGROUND: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. METHODS: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. FINDINGS: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models of progression-free and overall survival. We found that the prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. We identified a progression-free survival benefit for gross total resection over sub-total resection (hazard ratio [HR] 1·45, 95% CI 1·07-1·96, p=0·16) but no overall survival benefit (HR 1·23, 0·87-1·72, p=0·24). We saw no progression-free survival or overall survival benefit for gross total resection compared with near-total resection (HR 1·05, 0·71-1·53, p=0·8158 for progression-free survival and HR 1·14, 0·75-1·72, p=0·55 for overall survival). No significant survival benefit existed for greater extent of resection for patients with WNT, SHH, or group 3 tumours (HR 1·03, 0·67-1·58, p=0·89 for sub-total resection vs gross total resection). For patients with group 4 tumours, gross total resection conferred a benefit to progression-free survival compared with sub-total resection (HR 1·97, 1·22-3·17, p=0·0056), especially for those with metastatic disease (HR 2·22, 1·00-4·93, p=0·050). However, gross total resection had no effect on overall survival compared with sub-total resection in patients with group 4 tumours (HR 1·67, 0·93-2·99, p=0·084). INTERPRETATION: The prognostic benefit of increased extent of resection for patients with medulloblastoma is attenuated after molecular subgroup affiliation is taken into account. Although maximum safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high because there is no definitive benefit to gross total resection compared with near-total resection. FUNDING: Canadian Cancer Society Research Institute, Terry Fox Research Institute, Canadian Institutes of Health Research, National Institutes of Health, Pediatric Brain Tumor Foundation, and the Garron Family Chair in Childhood Cancer Research.

Published
2016

9. Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand?

Author

El-Khouly FE, Veldhuijzen van Zanten SEM, Santa-Maria Lopez V, Hendrikse NH, Kaspers GJL, Loizos G, Sumerauer D, Nysom K, Pruunsild K, Pentikainen V, Thorarinsdottir HK, Rutkauskiene G, Calvagna V, Drogosiewicz M, Dragomir M, Deak L, Kitanovski L, von Bueren AO, Kebudi R, Slavc I, Jacobs S, Jadrijevic-Cvrlje F, Entz-Werle N, Grill J, Kattamis A, Hauser P, Pears J, Biassoni V, Massimino M, Lopez Aguilar E, Torsvik IK, Joao Gil-da-Costa M, Kumirova E, Cruz-Martinez O, Holm S, Bailey S, Hayden T, Thomale UW, Janssens GOR, Kramm CM, and van Vuurden DG

Subjects
Biopsy, Combined Modality Therapy, Disease Progression, Humans, Prognosis, Brain Stem Neoplasms diagnosis, Brain Stem Neoplasms therapy, Diffuse Intrinsic Pontine Glioma diagnosis, Diffuse Intrinsic Pontine Glioma therapy
Abstract

Introduction: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines., Methods: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively., Results: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials., Conclusion: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.

Published
2019
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10. Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease.

Author

Veldhuijzen van Zanten SEM, Baugh J, Chaney B, De Jongh D, Sanchez Aliaga E, Barkhof F, Noltes J, De Wolf R, Van Dijk J, Cannarozzo A, Damen-Korbijn CM, Lieverst JA, Colditz N, Hoffmann M, Warmuth-Metz M, Bison B, Jones DTW, Sturm D, Gielen GH, Jones C, Hulleman E, Calmon R, Castel D, Varlet P, Giraud G, Slavc I, Van Gool S, Jacobs S, Jadrijevic-Cvrlje F, Sumerauer D, Nysom K, Pentikainen V, Kivivuori SM, Leblond P, Entz-Werle N, von Bueren AO, Kattamis A, Hargrave DR, Hauser P, Garami M, Thorarinsdottir HK, Pears J, Gandola L, Rutkauskiene G, Janssens GO, Torsvik IK, Perek-Polnik M, Gil-da-Costa MJ, Zheludkova O, Shats L, Deak L, Kitanovski L, Cruz O, Morales La Madrid A, Holm S, Gerber N, Kebudi R, Grundy R, Lopez-Aguilar E, Zapata-Tarres M, Emmerik J, Hayden T, Bailey S, Biassoni V, Massimino M, Grill J, Vandertop WP, Kaspers GJL, Fouladi M, Kramm CM, and van Vuurden DG

Subjects
Child, Child, Preschool, Europe, Female, Humans, Image Processing, Computer-Assisted, Male, Pons diagnostic imaging, Young Adult, Brain Stem Neoplasms diagnostic imaging, Glioma diagnostic imaging, Information Services, International Cooperation, Magnetic Resonance Imaging, Registries
Abstract

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.

Published
2017
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11. Onychomycosis in immunosuppressed children receiving chemotherapy.

Author

García-Romero MT, Lopez-Aguilar E, and Arenas R

Subjects
Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Antineoplastic Agents adverse effects, Immunocompromised Host, Neoplasms drug therapy, Onychomycosis immunology
Abstract

Onychomycosis in children has a low incidence worldwide; certain conditions such as immunosuppression have been described as risk factors for it. We studied 72 children receiving chemotherapy for different neoplasms to determine the frequency of onychomycosis. Only one patient had white superficial onychomycosis from Trichophyton rubrum, a frequency of 1.3%, not different from that reported in healthy patients., (© 2012 Wiley Periodicals, Inc.)

Published
2014
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12. Gene expression profiling from formalin-fixed paraffin-embedded tumors of pediatric glioblastoma.

Author

Haque T, Faury D, Albrecht S, Lopez-Aguilar E, Hauser P, Garami M, Hanzély Z, Bognár L, Del Maestro RF, Atkinson J, Nantel A, and Jabado N

Subjects
Adolescent, Brain Neoplasms metabolism, Child, Child, Preschool, Female, Glioblastoma metabolism, Humans, Immunohistochemistry, Infant, Lasers, Male, Oligonucleotide Array Sequence Analysis, RNA, Messenger metabolism, Brain Neoplasms genetics, Brain Neoplasms pathology, Formaldehyde chemistry, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma genetics, Glioblastoma pathology, Paraffin chemistry
Abstract

Purpose: Gene expression profiling has proved crucial for understanding the biology of cancer. In rare diseases, including pediatric glioblastoma (pGBM), the lack of readily available fresh frozen (FF) material limits the feasibility of this analysis, as well as its validation, on independent data sets, a step needed to ensure relevance, mandating the use of alternate RNA sources. To overcome the limitation of material number and to validate results we obtained on FF pGBM, we did microarray analysis on RNA extracted from formalin-fixed, paraffin-embedded archival samples from pGBM and control brains, wherein we had no control on the fixation process., Experimental Design: RNA from 16 pGBM and 3 control brains was extracted and linearly amplified. Reverse transcription-PCR on housekeeping and formerly identified tumor-associated genes and microarray analysis were done on this RNA source. Results were validated by immunohistochemistry., Results: Despite extensive RNA degradation, microarray analysis was possible on 16 of 19 samples and reproduced the pattern of results obtained on FF pGBM. Gene lists and ontology subgrouping were highly concordant in both sample types. Similar to the findings on FF samples, we were able to identify two subsets of pGBM based on their association/lack of association with evidence consistent with an active Ras pathway., Conclusions: Archival formalin-fixed, paraffin-embedded tissues are an invaluable resource as they are the most widely available materials often accessible in conjunction with clinical and follow-up data. Gene expression profiling on this material is feasible and may represent a significant advance for understanding the biology of rare human diseases.

Published
2007
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13. Molecular profiling identifies prognostic subgroups of pediatric glioblastoma and shows increased YB-1 expression in tumors.

Author

Faury D, Nantel A, Dunn SE, Guiot MC, Haque T, Hauser P, Garami M, Bognár L, Hanzély Z, Liberski PP, Lopez-Aguilar E, Valera ET, Tone LG, Carret AS, Del Maestro RF, Gleave M, Montes JL, Pietsch T, Albrecht S, and Jabado N

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Apoptosis, Brain Neoplasms etiology, Brain Neoplasms mortality, Child, Child, Preschool, ErbB Receptors genetics, Female, Glioblastoma etiology, Glioblastoma mortality, Humans, Infant, Male, Middle Aged, Nuclear Proteins, Phosphorylation, Prognosis, Proto-Oncogene Proteins c-akt physiology, Proto-Oncogene Proteins p21(ras) physiology, Signal Transduction, Y-Box-Binding Protein 1, Brain Neoplasms genetics, DNA-Binding Proteins genetics, Gene Expression Profiling, Glioblastoma genetics
Abstract

Purpose: Pediatric glioblastoma (pGBM) is a rare, but devastating brain tumor. In contrast to GBM in adults (aGBM), little is known about the mechanisms underlying its development. Our aim is to gain insight into the molecular pathways of pGBM., Materials and Methods: Thirty-two pGBM and seven aGBM samples were investigated using biochemical and transcriptional profiling. Ras and Akt pathway activation was assessed through the phosphorylation of downstream effectors, and gene expression profiles were generated using the University Health Network Human 19K cDNA arrays. Results were validated using real-time polymerase chain reaction and immunohistochemistry and compared with existing data sets on aGBM., Results: There are at least two subsets of pGBM. One subset, associated with Ras and Akt pathway activation, has very poor prognosis and exhibits increased expression of genes related to proliferation and to a neural stem-cell phenotype, similar to findings in aggressive aGBM. This subset was still molecularly distinguishable from aGBM after unsupervised and supervised analysis of expression profiles. A second subset, with better prognosis, is not associated with activation of Akt and Ras pathways, may originate from astroglial progenitors, and does not express gene signatures and markers shown to be associated with long-term survival in aGBM. Both subsets of pGBM show overexpression of Y-box-protein-1 that may help drive oncogenesis in this tumor., Conclusion: Our work, the first study of gene expression profiles in pGBM, provides valuable insight into active pathways and targets in a cancer with minimal survival, and suggests that these tumors cannot be understood exclusively through studies of aGBM.

Published
2007
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14. Survival of patients with medulloblastoma treated with carboplatin and etoposide before and after radiotherapy.

Author

Lopez-Aguilar E, Sepulveda-Vildosola AC, Rivera-Marquez H, Cerecedo-Diaz F, Santacruz-Castillo E, Valdez-Sanchez M, Arias-Gomez J, and Quintana-Roldan G

Subjects
Adolescent, Antineoplastic Combined Chemotherapy Protocols adverse effects, Brain Neoplasms drug therapy, Brain Neoplasms radiotherapy, Carboplatin administration & dosage, Child, Child, Preschool, Combined Modality Therapy, Disease-Free Survival, Dose Fractionation, Radiation, Etoposide administration & dosage, Humans, Infant, Medulloblastoma drug therapy, Medulloblastoma radiotherapy, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Brain Neoplasms therapy, Medulloblastoma therapy
Abstract

Background: Medulloblastoma represents 20% of all tumors of the central nervous system. Patients with partial resection of the tumor and those with extension into the neuraxis at diagnosis have been identified as high-risk patients. The objective of our study was to determine tumor response, survival rates and toxicity with a new scheme of treatment with carboplatin, etoposide and radiotherapy., Methods: All patients received chemotherapy with carboplatin and etoposide every 4 weeks for four courses, hyperfractionated radiotherapy, and another four courses of the above chemotherapy scheme. Tumor response was classified, and global and disease-free survival rates were calculated according to the actuarial survival method., Results: A total of 26 patients were included, with a median age of 6.9 years. Nineteen achieved complete response after the first four courses of chemotherapy, and two more had a complete response after radiotherapy. A total of seven children have died, three of whom did not respond to initial treatment. Global and disease-free survival rates were 69% and 64%, respectively, at 60 months of follow-up. There was no renal or auditory toxicity. Hematological toxicity was transitory and reversible., Conclusions: This scheme of treatment is effective and can be safely used for pediatric patients with high-risk medulloblastomas. Toxicity was not significant, and survival is similar to other reports.

Published
1998

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