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3. Convection-Enhanced Delivery in Children: Techniques and Applications

Author

Aquilina, K., Chakrapani, A., Carr, L., Kurian, M. A., Hargrave, D., Di Rocco, Concezio, Series Editor, Arraez, Miguel A., Editorial Board Member, Froelich, Sebastien, Editorial Board Member, Kato, Yoko, Editorial Board Member, Pang, Dachling, Editorial Board Member, and Tu, Yong-Kwang, Editorial Board Member

Published
2022
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4. A nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: safety, efficacy, visual morbidity, and outcomes

Author

Green, K, Panagopoulou, P, D'Arco, F, O'Hare, P, Bowman, R, Walters, B, Dahl, C, Jorgensen, M, Patel, P, Slater, O, Ahmed, R, Bailey, S, Carceller, F, Collins, R, Corley, E, English, M, Howells, L, Kamal, A, Kilday, J-PJP, Lowis, S, Lumb, B, Pace, E, Picton, S, Pizer, B, Shafiq, A, Uzunova, L, Wayman, H, Wilson, S, Hargrave, D, Opocher, E, Green, K, Panagopoulou, P, D'Arco, F, O'Hare, P, Bowman, R, Walters, B, Dahl, C, Jorgensen, M, Patel, P, Slater, O, Ahmed, R, Bailey, S, Carceller, F, Collins, R, Corley, E, English, M, Howells, L, Kamal, A, Kilday, J-PJP, Lowis, S, Lumb, B, Pace, E, Picton, S, Pizer, B, Shafiq, A, Uzunova, L, Wayman, H, Wilson, S, Hargrave, D, and Opocher, E

Abstract

BACKGROUND: Bevacizumab is increasingly used in children with pediatric low-grade glioma (PLGG) despite limited evidence. A nationwide UK service evaluation was conducted to provide larger cohort "real life" safety and efficacy data including functional visual outcomes. METHODS: Children receiving bevacizumab-based treatments (BBT) for PLGG (2009-2020) from 11 centers were included. Standardized neuro-radiological (RANO-LGG) and visual (logMAR visual acuity) criteria were used to assess clinical-radiological correlation, survival outcomes and multivariate prognostic analysis. RESULTS: Eighty-eight children with PLGG received BBT either as 3rd line with irinotecan (85%) or alongside 1st/2nd line chemotherapies (15%). Toxicity was limited and minimal. Partial response (PR, 40%), stable disease (SD, 49%), and progressive disease (PD, 11%) were seen during BBT. However, 65% progressed at 8 months (median) from BBT cessation, leading to a radiology-based 3 yr-progression-free survival (PFS) of 29%. Diencephalic syndrome (P = .03) was associated with adverse PFS. Pre-existing visual morbidity included unilateral (25%) or bilateral (11%) blindness. Improvement (29%) or stabilization (49%) of visual acuity was achieved, more often in patients' best eyes. Vision deteriorated during BBT in 14 (22%), with 3-year visual-PFS of 53%; more often in patients' worst eyes. A superior visual outcome (P = .023) was seen in neurofibromatosis type 1-associated optic pathway glioma (OPG). Concordance between visual and radiological responses was 36%; optimized to 48% using only best eye responses. CONCLUSIONS: BBTs provide effective short-term PLGG control and delay further progression, with a better sustained visual (best > worst eye) than radiological response. Further research could optimize the role of BBT toward a potentially sight-saving strategy in OPG.

Published
2023

6. IMMU-08. Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: efficacy, safety, biomarker, and pharmacokinetic results from Checkmate 908

Author

Dunkel, IJ, Cohen, K, Foreman, NK, Hargrave, D, Lassaletta, A, André, N, Hansford, JR, Hassall, T, Eyrich, M, Gururangan, S, Bartels, U, Gajjar, A, Howell, L, Warad, D, Pacius, M, Tam, R, Wang, Y, Zhu, L, Doz, F, Dunkel, IJ, Cohen, K, Foreman, NK, Hargrave, D, Lassaletta, A, André, N, Hansford, JR, Hassall, T, Eyrich, M, Gururangan, S, Bartels, U, Gajjar, A, Howell, L, Warad, D, Pacius, M, Tam, R, Wang, Y, Zhu, L, and Doz, F

Abstract

BACKGROUND: Limited data exist regarding checkpoint inhibitor efficacy for pediatric CNS malignancies. METHODS: CheckMate 908 is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO + ipilimumab (IPI) in 5 cohorts of pediatric patients previously treated with standard-of-care (NCT03130959). Patients received NIVO-3mg/kg Q2W or NIVO-3mg/kg + IPI-1mg/kg Q3W (4 doses) followed by NIVO-3mg/kg Q2W. Primary endpoints included OS (newly diagnosed DIPG) and PFS (other CNS cohorts); secondary endpoints included other efficacy metrics/safety. Exploratory endpoints included pharmacokinetics/biomarker analyses. Comparisons between treatments/cohorts were not planned. RESULTS: At data cutoff (13-Jan-2021), 166 patients received NIVO (n=85) or NIVO+IPI (n=81) at median (m) ages of 10.0yrs (range, 1-21) and 11.0yrs (1-21), respectively. In newly diagnosed DIPG, mOS (80% CI) was 11.7mos (10.3-16.5) with NIVO (n=23) and 10.8mos (9.1-15.8) with NIVO+IPI (n=22). In recurrent/progressive HGG, mPFS (80% CI) was 1.7mos (1.4-2.7) with NIVO (n=16) and 1.3mos (1.2-1.5) with NIVO+IPI (n=15). In relapsed/resistant medulloblastoma, mPFS (80% CI) was 1.4mos (1.2-1.4) with NIVO (n=15) and 2.8mos (1.5-4.5) with NIVO+IPI (n=15). In relapsed/resistant ependymoma, mPFS (80% CI) was 1.4mos (1.4-2.6) with NIVO (n=12) and 4.6mos (1.4-5.4) with NIVO+IPI (n=10). In other recurrent/progressive CNS tumors, mPFS (95% CI) was 1.2mos (1.1-1.3) with NIVO (n=19) and 1.6mos (1.3-3.5) with NIVO+IPI (n=19). Median treatment duration was 2.1mos (range, 0-41.7+ [NIVO]/0-29.6+ [NIVO+IPI]). Grade 3/4 treatment-related AEs occurred in 14.1% (NIVO) and 27.2% (NIVO+IPI) of patients. NIVO and IPI first dose trough concentrations were lower in youngest and lowest-weight patients. Baseline tumor PD-L1 expression was not associated with survival. Tumor mutational burden was high in 1 patient (NIVO+IPI) with HGG (OS=11.0mos). CONCLUSIONS: NIVO±IPI demonstrated no clinical benefit in

Published
2022

8. Neurological Symptom Improvement After Re-Irradiation in Patients With Diffuse Intrinsic Pontine Glioma: A Retrospective Analysis of the SIOP-E-HGG/DIPG Project

Author

Chavaz L, Janssens GO, Bolle S, Mandeville H, Ramos-Albiac M, Van Beek K, Benghiat H, Hoeben B, Morales-La Madrid A, Seidel C, Kortmann RD, Hargrave D, Gandola L, Pecori E, van Vuurden DG, Biassoni V, Massimino M, Kramm CM, and von Bueren AO

Subjects
re-irradiation (re-RT), child, diffuse intrinsic pontine glioma (DIPG), adolescent, radiotherapy
Abstract

PURPOSE: The aim of this study is to investigate the spectrum of neurological triad improvement in patients with diffuse intrinsic pontine glioma (DIPG) treated by re-irradiation (re-RT) at first progression. METHODS: We carried out a re-analysis of the SIOP-E retrospective DIPG cohort by investigating the clinical benefits after re-RT with a focus on the neurological triad (cranial nerve deficits, ataxia, and long tract signs). Patients were categorized as "responding" or "non-responding" to re-RT. To assess the interdependence between patients' characteristics and clinical benefits, we used a chi-square or Fisher's exact test. Survival according to clinical response to re-RT was calculated by the Kaplan-Meier method. RESULTS: As earlier reported, 77% (n = 24/31) of patients had any clinical benefit after re-RT. Among 25/31 well-documented patients, 44% (n = 11/25) had improvement in cranial nerve palsies, 40% (n = 10/25) had improvement in long-tract signs, and 44% (11/25) had improvement in cerebellar signs. Clinical benefits were observed in at least 1, 2, or 3 out of 3 symptoms of the DIPG triad, in 64%, 40%, and 24%, respectively. Patients irradiated with a dose =20 Gy versus

Published
2022

13. A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study

Author

Alves, C.A.P.F., primary, Löbel, U., additional, Martin-Saavedra, J.S., additional, Toescu, S., additional, Tsunemi, M.H., additional, Teixeira, S.R., additional, Mankad, K., additional, Hargrave, D., additional, Jacques, T.S., additional, da Costa Leite, C., additional, Gonçalves, F.G., additional, Vossough, A., additional, and D'Arco, F., additional

Published
2021
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14. P86.03 A Phase 2 Study of Erdafitinib in Patients with Advanced Solid Tumors and Fibroblast Growth Factor Receptor Gene Alterations

Author

Pant, S., primary, Tabernero, J., additional, Massard, C., additional, Hyman, D.M., additional, Witt, O., additional, Doi, T., additional, Qin, S., additional, Lu-Emerson, C., additional, Hargrave, D., additional, Garcia-Corbacho, J., additional, Little, S., additional, Tolbert, J., additional, Santiago-Walker, A., additional, Moy, C., additional, Hammond, C., additional, Lau, Y.Y., additional, Sweiti, H., additional, and Schuler, M., additional

Published
2021
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16. 603TiP Phase II, open-label study of erdafitinib in adult and adolescent patients (pts) with advanced solid tumours harboring fibroblast growth factor receptor (FGFR) gene alterations

Author

Schuler, M., primary, Tabernero, J., additional, Massard, C., additional, Iyer, G. Vasudeva, additional, Witt, O., additional, Doi, T., additional, Qin, S., additional, Lu-Emerson, C., additional, Hargrave, D., additional, Garcia-Corbacho, J., additional, Little, S., additional, Xia, Q., additional, Santiago-Walker, A., additional, Moy, C.H., additional, Hammond, C., additional, Lau, Y.Y., additional, Sweiti, H., additional, and Pant, S., additional

Published
2020
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20. Evaluation of the Implementation of the Response Assessment in Neuro-Oncology Criteria in the HERBY Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas

Author

Rodriguez, D., primary, Chambers, T., additional, Warmuth-Metz, M., additional, Aliaga, E. Sanchez, additional, Warren, D., additional, Calmon, R., additional, Hargrave, D., additional, Garcia, J., additional, Vassal, G., additional, Grill, J., additional, Zahlmann, G., additional, Morgan, P.S., additional, and Jaspan, T., additional

Published
2019
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24. Phase II open-label, global study evaluating dabrafenib in combination with trametinib in pediatric patients with BRAF V600–mutant high-grade glioma (HGG) or low-grade glioma (LGG)

Author

Hargrave, D., primary, Witt, O., additional, Cohen, K., additional, Packer, R., additional, Lissat, A., additional, Kordes, U., additional, Laetsch, T.W., additional, Hoffman, L., additional, Lassaletta, A., additional, Gerber, N.U., additional, Gilheeney, S., additional, Holm, S., additional, Kramm, C., additional, Sumerauer, D., additional, Reitmann, C., additional, Russo, M.W., additional, and Bouffet, E., additional

Published
2018
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25. Intra- and extra-cranial Malignant Rhabdoid Tumours share common location-independent clinical and molecular disease characteristics.

Author

Grabovska, Y, additional, Finetti, MA, additional, Selby, MP, additional, Schwalbe, EC, additional, Smith, A, additional, Crosier, S, additional, Pickles, JC, additional, Fairchild, AR, additional, Avery, A, additional, O'Hare, P, additional, Pizer, B, additional, Brennan, B, additional, Lowis, S, additional, Hargrave, D, additional, Anderson, J, additional, Jacques, TS, additional, Bailey, S, additional, Clifford, SC, additional, and Williamson, D, additional

Published
2018
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26. SMARCB1-Dependencies in Malignant Rhabdoid Tumours: A strategy for Pre-Clinical Therapeutic Target Identification in the Absence of Actionable Mutations

Author

Finetti, MA, additional, Ramli, R, additional, Hacking, J, additional, Ridgwell, D, additional, Selby, MP, additional, Grabovska, Y, additional, del-Carpio Pons, A, additional, Batting, S, additional, Wood, JA, additional, Barker, JM, additional, Smith, A, additional, Crosier, S, additional, O'Hare, P, additional, Pizer, B, additional, Brennan, B, additional, Lowis, S, additional, Hargrave, D, additional, Anderson, J, additional, Jacques, TS, additional, Bailey, S, additional, Clifford, SC, additional, and Williamson, D, additional

Published
2018
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27. A multi-disciplinary consensus statement concerning surgical approaches to low-grade, high-grade astrocytomas and diffuse intrinsic pontine gliomas in childhood (CPN Paris 2011) using the Delphi method

Author

Walker, D. A., Liu, J., Kieran, M., Jabado, N., Picton, S., Packer, R., Rose, C. S. t., Van Meeteren, A. S., Carvalho, A., Van Damme, A., Depreitere, B., Gustavsson, B., Due Tonnessen, B. J., Bertozzi Salamon, A. I., Brentrup, A., Raybaud, C., Jones, C., Dufour, C., Dorfer, C., Sainte Rose, C., Malluci, C., Hargrave, D., Walker, D., Van Vuurden, D., De Carli, E., Bouffet, E., Van Calenbergh, F., Frappaz, D., Frassanito, P., Goodrich, J., Baechli, H., Grill, J., Ternier, J., Cappelen, J., Caird, J., Pereira, J., Riffaud, L., Baroncini, M., Walker, M., Ozek, M., Nysom, K., Varlet, P., Goodden, J., Bertolini, P., Perilongo, Giorgio, Mercier, P., Grundy, R., Kortmann, R. D., Pfister, S., Constantini, S., Sgouros, S., Holm, S., Czech, T., Merchant, T., Stokland, T., Ridola, V., and Vandertop, P.

Subjects
Cancer Research, medicine.medical_specialty, Consensus, medicine.medical_treatment, Neurosurgery, Glioma, Biopsy, medicine, Brain Stem Neoplasms, Humans, Neurofibromatosis, Child, medicine.diagnostic_test, business.industry, General surgery, Astrocytoma, medicine.disease, Surgery, Radiation therapy, Clinical trial, Oncology, Practice Guidelines as Topic, Basic and Translational Investigations, Neurology (clinical), Neoplasm Grading, business, Risk assessment
Abstract

Astrocytic tumors account for 42% of childhood brain tumors, arising in all anatomical regions and associated with neurofibromatosis type 1 (NF1) in 15%. Anatomical site determines the degree and risk of resectability; the more complete resection, the better the survival rates. New biological markers and modern radiotherapy techniques are altering the risk assessments of clinical decisions for tumor resection and biopsy. The increasingly distinct pediatric neuro-oncology multidisciplinary team (PNMDT) is developing a distinct evidence base. A multidisciplinary consensus conference on pediatric neurosurgery was held in February 2011, where 92 invited participants reviewed evidence for clinical management of hypothalamic chiasmatic glioma (HCLGG), diffuse intrinsic pontine glioma (DIPG), and high-grade glioma (HGG). Twenty-seven statements were drafted and subjected to online Delphi consensus voting by participants, seeking >70% agreement from >60% of respondents; where

Published
2013
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28. Survival benefit for patients with diffuse intrinsic pontine glioma (DIPG) undergoing re-irradiation at first progression: A matched-cohort analysis on behalf of the SIOP-E-HGG/DIPG working group

Author

Janssens, G.O., Gandola, L., Bolle, S., Mandeville, H., Ramos-Albiac, M., Beek, K., Benghiat, H., Hoeben, B.A., Morales la Madrid, A., Kortmann, R.D., Hargrave, D., Menten, J., Pecori, E., Biassoni, V., Bueren, A.O. von, Vuurden, D.G. van, Massimino, M., Sturm, D., Peters, M., Kramm, C.M., Janssens, G.O., Gandola, L., Bolle, S., Mandeville, H., Ramos-Albiac, M., Beek, K., Benghiat, H., Hoeben, B.A., Morales la Madrid, A., Kortmann, R.D., Hargrave, D., Menten, J., Pecori, E., Biassoni, V., Bueren, A.O. von, Vuurden, D.G. van, Massimino, M., Sturm, D., Peters, M., and Kramm, C.M.

Abstract

Item does not contain fulltext, BACKGROUND: Overall survival (OS) of patients with diffuse intrinsic pontine glioma (DIPG) is poor. The purpose of this study is to analyse benefit and toxicity of re-irradiation at first progression. METHODS: At first progression, 31 children with DIPG, aged 2-16 years, underwent re-irradiation (dose 19.8-30.0 Gy) alone (n = 16) or combined with systemic therapy (n = 15). At initial presentation, all patients had typical symptoms and characteristic MRI features of DIPG, or biopsy-proven high-grade glioma. An interval of >/=3 months after upfront radiotherapy was required before re-irradiation. Thirty-nine patients fulfilling the same criteria receiving radiotherapy at diagnosis, followed by best supportive care (n = 20) or systemic therapy (n = 19) at progression but no re-irradiation, were eligible for a matched-cohort analysis. RESULTS: Median OS for patients undergoing re-irradiation was 13.7 months. For a similar median progression-free survival after upfront radiotherapy (8.2 versus 7.7 months; P = .58), a significant benefit in median OS (13.7 versus 10.3 months; P = .04) was observed in favour of patients undergoing re-irradiation. Survival benefit of re-irradiation increased with a longer interval between end-of-radiotherapy and first progression (3-6 months: 4.0 versus 2.7; P < .01; 6-12 months: 6.4 versus 3.3; P = .04). Clinical improvement with re-irradiation was observed in 24/31 (77%) patients. No grade 4-5 toxicity was recorded. On multivariable analysis, interval to progression (corrected hazard ratio = .27-.54; P < .01) and re-irradiation (corrected hazard ratio = .18-.22; P < .01) remained prognostic for survival. A risk score (RS), comprising 5 categories, was developed to predict survival from first progression (ROC: .79). Median survival ranges from 1.0 month (RS-1) to 6.7 months (RS-5). CONCLUSIONS: The majority of patients with DIPG, responding to upfront radiotherapy, do benefit of re-irradiation with acceptable tolerability.

Published
2017

30. Biomarker prevalence study and phase I trial of afatinib in children with malignant tumours

Author

Nysom, K., primary, Leblond, P., additional, Frappaz, D., additional, Aerts, I., additional, Varlet, P., additional, Giangaspero, F., additional, Gambart, M., additional, Hargrave, D., additional, Marshall, L., additional, Kearns, P., additional, Makin, G., additional, Gallego, S., additional, Kieran, M., additional, Casanova, M., additional, Lahogue, A., additional, Wind, S., additional, Stolze, B., additional, Roy, D., additional, Uttenreuther-Fischer, M., additional, and Geoerger, B., additional

Published
2017
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31. Melanoma in congenital melanocytic naevi

Author

Kinsler, V.A., primary, O'Hare, P., additional, Bulstrode, N., additional, Calonje, J.E., additional, Chong, W.K., additional, Hargrave, D., additional, Jacques, T., additional, Lomas, D., additional, Sebire, N.J., additional, and Slater, O., additional

Published
2017
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32. A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia

Author

Vormoor, B., primary, Veal, G. J., additional, Griffin, M. J., additional, Boddy, A. V., additional, Irving, J., additional, Minto, L., additional, Case, M., additional, Banerji, U., additional, Swales, K. E., additional, Tall, J. R., additional, Moore, A. S., additional, Toguchi, M., additional, Acton, G., additional, Dyer, K., additional, Schwab, C., additional, Harrison, C. J., additional, Grainger, J. D., additional, Lancaster, D., additional, Kearns, P., additional, Hargrave, D., additional, and Vormoor, J., additional

Published
2016
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33. CNS tumours The first study of dabrafenib in pediatric patients with BRAF V600–mutant relapsed or refractory low-grade gliomas

Author

Kieran, M.W., primary, Bouffet, E., additional, Tabori, U., additional, Broniscer, A., additional, Cohen, K., additional, Hansford, J., additional, Geoerger, B., additional, Hingorani, P., additional, Dunkel, I., additional, Russo, M., additional, Tseng, L., additional, Liu, Q., additional, Nebot, N., additional, Whitlock, J., additional, and Hargrave, D., additional

Published
2016
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34. Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas

Author

Jaspan, T., primary, Morgan, P.S., additional, Warmuth-Metz, M., additional, Sanchez Aliaga, E., additional, Warren, D., additional, Calmon, R., additional, Grill, J., additional, Hargrave, D., additional, Garcia, J., additional, and Zahlmann, G., additional

Published
2016
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35. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria

Author

Jansen, M.H., Veldhuijzen-van Zanten, S.E., Sanchez Aliaga, E., Heymans, M.W., Warmuth-Metz, M., Hargrave, D., Hoeven, E.J. van der, Gidding, C.E.M., Bont, E.S. de, Eshghi, O.S., Reddingius, R., Peeters, C.M., Schouten-van Meeteren, A.Y., Gooskens, R.H., Granzen, B., Paardekooper, G.M., Janssens, G.O.R.J., Noske, D.P., Barkhof, F., Kramm, C.M., Vandertop, W.P., Kaspers, G.J., Vuurden, D.G. van, Jansen, M.H., Veldhuijzen-van Zanten, S.E., Sanchez Aliaga, E., Heymans, M.W., Warmuth-Metz, M., Hargrave, D., Hoeven, E.J. van der, Gidding, C.E.M., Bont, E.S. de, Eshghi, O.S., Reddingius, R., Peeters, C.M., Schouten-van Meeteren, A.Y., Gooskens, R.H., Granzen, B., Paardekooper, G.M., Janssens, G.O.R.J., Noske, D.P., Barkhof, F., Kramm, C.M., Vandertop, W.P., Kaspers, G.J., and Vuurden, D.G. van

Abstract

Item does not contain fulltext, BACKGROUND: Although diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG are sparse. To control for confounding variables in DIPG studies, which generally include relatively small patient numbers, a survival prediction tool is needed. METHODS: A multicenter retrospective cohort study was performed in the Netherlands, the UK, and Germany with central review of clinical data and MRI scans of children with DIPG. Cox proportional hazards with backward regression was used to select prognostic variables (P < .05) to predict the accumulated 12-month risk of death. These predictors were transformed into a practical risk score. The model's performance was validated by bootstrapping techniques. RESULTS: A total of 316 patients were included. The median overall survival was 10 months. Multivariate Cox analysis yielded 5 prognostic variables of which the coefficients were included in the risk score. Age

Published
2015

36. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria

Author

Jansen, M. (Marc), Veldhuijzen Van Zanten, S.E.M. (Sophie), Aliaga, E.S. (Esther Sanchez), Heymans, M.W. (Martijn), Warmuth-Metz, M. (Monika), Hargrave, D. (Darren), Van Der Hoeven, E.J. (Erica J.), Gidding, C.E. (Corrie), Bont, E.S.J.M. (Eveline) de, Eshghi, O.S. (Omid S.), Reddingius, R.E. (Roel), Peeters, C.M. (Cacha M.), Schouten-van Meeteren, A.Y.N. (Antoinette), Gooskens, R.H.J.M. (Rob), Granzen, B. (Bernd), Paardekooper, G.M. (Gabriel M.), Janssens, G.O. (Geert), Noske, D.P. (David), Barkhof, F. (Frederik), Kramm, C.M. (Christof M.), Vandertop, W.P. (Peter), Kaspers, G.J.L. (Gertjan), Vuurden, D.G. (Dannis) van, Jansen, M. (Marc), Veldhuijzen Van Zanten, S.E.M. (Sophie), Aliaga, E.S. (Esther Sanchez), Heymans, M.W. (Martijn), Warmuth-Metz, M. (Monika), Hargrave, D. (Darren), Van Der Hoeven, E.J. (Erica J.), Gidding, C.E. (Corrie), Bont, E.S.J.M. (Eveline) de, Eshghi, O.S. (Omid S.), Reddingius, R.E. (Roel), Peeters, C.M. (Cacha M.), Schouten-van Meeteren, A.Y.N. (Antoinette), Gooskens, R.H.J.M. (Rob), Granzen, B. (Bernd), Paardekooper, G.M. (Gabriel M.), Janssens, G.O. (Geert), Noske, D.P. (David), Barkhof, F. (Frederik), Kramm, C.M. (Christof M.), Vandertop, W.P. (Peter), Kaspers, G.J.L. (Gertjan), and Vuurden, D.G. (Dannis) van

Abstract

Background Although diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG are sparse. To control for confounding variables in DIPG studies, which generally include relatively small patient numbers, a survival prediction tool is needed. Methods A multicenter retrospective cohort study was performed in the Netherlands, the UK, and Germany with central review of clinical data and MRI scans of children with DIPG. Cox proportional hazards with backward regression was used to select prognostic variables (P <. 05) to predict the accumulated 12-month risk of death. These predictors were transformed into a practical risk score. The model's performance was validated by bootstrapping techniques. Results A total of 316 patients were included. The median overall survival was 10 months. Multivariate Cox analysis yielded 5 prognostic variables of which the coefficients were included in the risk score. Age ≤3 years, longer symptom duration at diagnosis, and use of oral and intravenous chemotherapy were favorable predictors, while ring enhancement on MRI at diagnosis was an unfavorable predictor. With increasing risk score categories, overall survival decreased significantl

Published
2015
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37. Investigation of a swimming pool-associated cryptosporidiosis outbreak in the Kimberley region of Western Australia

Author

Ng-Hublin, J.S.Y., Hargrave, D., Combs, B., Ryan, U., Ng-Hublin, J.S.Y., Hargrave, D., Combs, B., and Ryan, U.

Abstract

Cryptosporidiosis is a gastroenteric disease caused by the protozoan parasite Cryptosporidium, which manifests primarily as watery diarrhoea. Transmitted via the faecal-oral route, infection with the parasite can occur through ingestion of water, food or other fomites contaminated with its infective oocyst stage. In the months of November and December 2012, there were 18 notified cases of cryptosporidiosis from Broome, Western Australia. The 5-year average for the Kimberley region for this period is <1 case. Interviews conducted by Broome local government staff on the notified cases revealed that 11/18 cases had been swimming at the Broome public swimming pool. Molecular analyses of extracted DNA performed on 8/18 microscopy-positive faecal samples from interviewed cases and three water samples from different locations at the hypervariable glycoprotein 60 (gp60) gene, identified the C. hominis IbA10G2 subtype in all human samples and one water sample

Published
2015

38. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria

Author

Jansen, MH, Veldhuijzen van Zanten, Sophie E., Aliaga, ES, Heymans, MW, Warmuth-Metz, M, Hargrave, D, van der Hoeven, EJ, Gidding, CE, de Bont, ES, Eshghi, OS, Reddingius, Roel, Peeters, CM, Schouten-van Meeteren, AYN, Gooskens, RHJ, Granzen, B, Paardekooper, GM, Janssens, GO, Noske, DP, Barkhof, F, Kramm, CM, Vandertop, WP, Kaspers, GJ, van Vuurden, DG, Jansen, MH, Veldhuijzen van Zanten, Sophie E., Aliaga, ES, Heymans, MW, Warmuth-Metz, M, Hargrave, D, van der Hoeven, EJ, Gidding, CE, de Bont, ES, Eshghi, OS, Reddingius, Roel, Peeters, CM, Schouten-van Meeteren, AYN, Gooskens, RHJ, Granzen, B, Paardekooper, GM, Janssens, GO, Noske, DP, Barkhof, F, Kramm, CM, Vandertop, WP, Kaspers, GJ, and van Vuurden, DG

Published
2015

41. A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

Author

Vormoor, B., Veal, G. J., Griffin, M. J., Boddy, A. V., Irving, J., Minto, L., Case, M., Banerji, U., Swales, K. E., Tall, J. R., Moore, A. S., Toguchi, M., Acton, G., Dyer, K., Schwab, C., Harrison, C. J., Grainger, J. D., Lancaster, D., Kearns, P., and Hargrave, D.

Published
2017
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42. The Herby Study: a Phase 2 Open-Label, Randomized, Multicenter Study of Bevacizumab-Based Therapy in Pediatric Patients with Newly Diagnosed High-Grade Glioma

Author

Grill, J., primary, Hargrave, D., additional, Varlet, P., additional, Jaspan, T., additional, Jones, C., additional, Massimino, M., additional, Cañete, A., additional, Azizi, A.A., additional, Le Deley, M., additional, Saran, F., additional, Morgan, P., additional, Zahlmann, G., additional, Zheng, M., additional, Fuerst-Recktenwald, S., additional, Berger, C., additional, Bouffet, E., additional, and Vassal, G., additional

Published
2014
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44. CRANIOPHARYNGIOMA

Author

Sattar, A., primary, Saleem, A., additional, Pettorini, B., additional, Pizer, B., additional, Bhatti, I., additional, Narenthiran, G., additional, Mallucci, C., additional, Hoffmann, A., additional, Gebhardt, U., additional, Sterkenburg, A., additional, Warmuth-Metz, M., additional, Muller, H. L., additional, Postma, F. P., additional, Pietsch, T., additional, Pohl, F., additional, Kortmann, R.-D., additional, Calaminus, G., additional, Sterkenburg, A. S., additional, Faldum, A., additional, Perelberg, D., additional, Morillon, P., additional, Ederies, A., additional, Aquilina, K., additional, Dorward, N., additional, Michalski, A., additional, Hargrave, D., additional, Chang, Y.-C., additional, Bozorgi, N., additional, James, S., additional, Korbonits, M., additional, Drake, W., additional, Akker, S., additional, Blair, J., additional, Kamaly, I., additional, Clayton, P., additional, Spoudeas, H., additional, Wisoff, J., additional, Elliott, R., additional, Gump, J., additional, Donson, A., additional, Birks, D., additional, Handler, M., additional, Foreman, N., additional, and Hankinson, T., additional

Published
2014
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45. MEDULLOBLASTOMA

Author

Vaidyanathan, G., primary, Gururangan, S., additional, Bigner, D., additional, Zalutsky, M., additional, Morfouace, M., additional, Shelat, A., additional, Megan, J., additional, Freeman, B. B., additional, Robinson, S., additional, Throm, S., additional, Olson, J. M., additional, Li, X.-N., additional, Guy, K. R., additional, Robinson, G., additional, Stewart, C., additional, Gajjar, A., additional, Roussel, M., additional, Sirachainan, N., additional, Pakakasama, S., additional, Anurathapan, U., additional, Hansasuta, A., additional, Dhanachai, M., additional, Khongkhatithum, C., additional, Hongeng, S., additional, Feroze, A., additional, Lee, K.-S., additional, Gholamin, S., additional, Wu, Z., additional, Lu, B., additional, Mitra, S., additional, Cheshier, S., additional, Northcott, P., additional, Lee, C., additional, Zichner, T., additional, Lichter, P., additional, Korbel, J., additional, Wechsler-Reya, R., additional, Pfister, S., additional, Project, I. P. T., additional, Li, K. K.-W., additional, Xia, T., additional, Ma, F. M. T., additional, Zhang, R., additional, Zhou, L., additional, Lau, K.-M., additional, Ng, H.-K., additional, Lafay-Cousin, L., additional, Chi, S., additional, Madden, J., additional, Smith, A., additional, Wells, E., additional, Owens, E., additional, Strother, D., additional, Foreman, N., additional, Packer, R., additional, Bouffet, E., additional, Wataya, T., additional, Peacock, J., additional, Taylor, M. D., additional, Ivanov, D., additional, Garnett, M., additional, Parker, T., additional, Alexander, C., additional, Meijer, L., additional, Grundy, R., additional, Gellert, P., additional, Ashford, M., additional, Walker, D., additional, Brent, J., additional, Cader, F. Z., additional, Ford, D., additional, Kay, A., additional, Walsh, R., additional, Solanki, G., additional, Peet, A., additional, English, M., additional, Shalaby, T., additional, Fiaschetti, G., additional, Baulande, S., additional, Gerber, N., additional, Baumgartner, M., additional, Grotzer, M., additional, Hayase, T., additional, Kawahara, Y., additional, Yagi, M., additional, Minami, T., additional, Kanai, N., additional, Yamaguchi, T., additional, Gomi, A., additional, Morimoto, A., additional, Hill, R., additional, Kuijper, S., additional, Lindsey, J., additional, Schwalbe, E., additional, Barker, K., additional, Boult, J., additional, Williamson, D., additional, Ahmad, Z., additional, Hallsworth, A., additional, Ryan, S., additional, Poon, E., additional, Ruddle, R., additional, Raynaud, F., additional, Howell, L., additional, Kwok, C., additional, Joshi, A., additional, Nicholson, S. L., additional, Crosier, S., additional, Wharton, S., additional, Robson, K., additional, Michalski, A., additional, Hargrave, D., additional, Jacques, T., additional, Pizer, B., additional, Bailey, S., additional, Swartling, F., additional, Petrie, K., additional, Weiss, W., additional, Chesler, L., additional, Clifford, S., additional, Kitanovski, L., additional, Prelog, T., additional, Kotnik, B. F., additional, Debeljak, M., additional, Grotzer, M. A., additional, Gevorgian, A., additional, Morozova, E., additional, Kazantsev, I., additional, Iukhta, T., additional, Safonova, S., additional, Kumirova, E., additional, Punanov, Y., additional, Afanasyev, B., additional, Zheludkova, O., additional, Grajkowska, W., additional, Pronicki, M., additional, Cukrowska, B., additional, Dembowska-Baginska, B., additional, Lastowska, M., additional, Murase, A., additional, Nobusawa, S., additional, Gemma, Y., additional, Yamazaki, F., additional, Masuzawa, A., additional, Uno, T., additional, Osumi, T., additional, Shioda, Y., additional, Kiyotani, C., additional, Mori, T., additional, Matsumoto, K., additional, Ogiwara, H., additional, Morota, N., additional, Hirato, J., additional, Nakazawa, A., additional, Terashima, K., additional, Fay-McClymont, T., additional, Walsh, K., additional, Mabbott, D., additional, Sturm, D., additional, Northcott, P. A., additional, Jones, D. T. W., additional, Korshunov, A., additional, Pfister, S. M., additional, Kool, M., additional, Hooper, C., additional, Hawes, S., additional, Kees, U., additional, Gottardo, N., additional, Dallas, P., additional, Siegfried, A., additional, Bertozzi, A. I., additional, Sevely, A., additional, Loukh, N., additional, Munzer, C., additional, Miquel, C., additional, Bourdeaut, F., additional, Pietsch, T., additional, Dufour, C., additional, Delisle, M. B., additional, Kawauchi, D., additional, Rehg, J., additional, Finkelstein, D., additional, Zindy, F., additional, Phoenix, T., additional, Gilbertson, R., additional, Trubicka, J., additional, Borucka-Mankiewicz, M., additional, Ciara, E., additional, Chrzanowska, K., additional, Perek-Polnik, M., additional, Abramczuk-Piekutowska, D., additional, Jurkiewicz, D., additional, Luczak, S., additional, Kowalski, P., additional, Krajewska-Walasek, M., additional, Sheila, C., additional, Lee, S., additional, Foster, C., additional, Manoranjan, B., additional, Pambit, M., additional, Berns, R., additional, Fotovati, A., additional, Venugopal, C., additional, O'Halloran, K., additional, Narendran, A., additional, Hawkins, C., additional, Ramaswamy, V., additional, Taylor, M., additional, Singhal, A., additional, Hukin, J., additional, Rassekh, R., additional, Yip, S., additional, Singh, S., additional, Duhman, C., additional, Dunn, S., additional, Chen, T., additional, Rush, S., additional, Fuji, H., additional, Ishida, Y., additional, Onoe, T., additional, Kanda, T., additional, Kase, Y., additional, Yamashita, H., additional, Murayama, S., additional, Nakasu, Y., additional, Kurimoto, T., additional, Kondo, A., additional, Sakaguchi, S., additional, Fujimura, J., additional, Saito, M., additional, Arakawa, T., additional, Arai, H., additional, Shimizu, T., additional, Jurkiewicz, E., additional, Daszkiewicz, P., additional, Drogosiewicz, M., additional, Hovestadt, V., additional, Buchhalter, I., additional, Jager, N. N., additional, Stuetz, A., additional, Johann, P., additional, Schmidt, C., additional, Ryzhova, M., additional, Landgraf, P., additional, Hasselblatt, M., additional, Schuller, U., additional, Yaspo, M.-L., additional, von Deimling, A., additional, Eils, R., additional, Modi, A., additional, Patel, M., additional, Berk, M., additional, Wang, L.-x., additional, Plautz, G., additional, Camara-Costa, H., additional, Resch, A., additional, Lalande, C., additional, Kieffer, V., additional, Poggi, G., additional, Kennedy, C., additional, Bull, K., additional, Calaminus, G., additional, Grill, J., additional, Doz, F., additional, Rutkowski, S., additional, Massimino, M., additional, Kortmann, R.-D., additional, Lannering, B., additional, Dellatolas, G., additional, Chevignard, M., additional, Solecki, D., additional, McKinnon, P., additional, Olson, J., additional, Hayden, J., additional, Ellison, D., additional, Buss, M., additional, Remke, M., additional, Lee, J., additional, Caspary, T., additional, Castellino, R., additional, Sabel, M., additional, Gustafsson, G., additional, Fleischhack, G., additional, Benesch, M., additional, Navajas, A., additional, Reddingius, R., additional, Delisle, M.-B., additional, Lafon, D., additional, Sevenet, N., additional, Pierron, G., additional, Delattre, O., additional, Ecker, J., additional, Oehme, I., additional, Mazitschek, R., additional, Lodrini, M., additional, Deubzer, H. E., additional, Kulozik, A. E., additional, Witt, O., additional, Milde, T., additional, Patmore, D., additional, Boulos, N., additional, Wright, K., additional, Boop, S., additional, Janicki, T., additional, Burzynski, S., additional, Burzynski, G., additional, Marszalek, A., additional, Triscott, J., additional, Green, M., additional, Rassekh, S. R., additional, Toyota, B., additional, Dunham, C., additional, Dunn, S. E., additional, Liu, K.-W., additional, Pei, Y., additional, Genovesi, L., additional, Ji, P., additional, Davis, M., additional, Ng, C. G., additional, Cho, Y.-J., additional, Jenkins, N., additional, Copeland, N., additional, Wainwright, B., additional, Tang, Y., additional, Schubert, S., additional, Nguyen, B., additional, Masoud, S., additional, Lee, A., additional, Willardson, M., additional, Bandopadhayay, P., additional, Bergthold, G., additional, Atwood, S., additional, Whitson, R., additional, Qi, J., additional, Beroukhim, R., additional, Tang, J., additional, Oro, A., additional, Link, B., additional, Bradner, J., additional, Vallero, S. G., additional, Bertin, D., additional, Basso, M. E., additional, Milanaccio, C., additional, Peretta, P., additional, Cama, A., additional, Mussano, A., additional, Barra, S., additional, Morana, G., additional, Morra, I., additional, Nozza, P., additional, Fagioli, F., additional, Garre, M. L., additional, Darabi, A., additional, Sanden, E., additional, Visse, E., additional, Stahl, N., additional, Siesjo, P., additional, Vaka, D., additional, Vasquez, F., additional, Weir, B., additional, Cowley, G., additional, Keller, C., additional, Hahn, W., additional, Gibbs, I. C., additional, Partap, S., additional, Yeom, K., additional, Martinez, M., additional, Vogel, H., additional, Donaldson, S. S., additional, Fisher, P., additional, Perreault, S., additional, Guerrini-Rousseau, L., additional, Pujet, S., additional, Kieffer-Renaux, V., additional, Raquin, M. A., additional, Varlet, P., additional, Longaud, A., additional, Sainte-Rose, C., additional, Valteau-Couanet, D., additional, Staal, J., additional, Lau, L. S., additional, Zhang, H., additional, Ingram, W. J., additional, Cho, Y. J., additional, Hathout, Y., additional, Brown, K., additional, Rood, B. R., additional, Handler, M., additional, Hankinson, T., additional, Kleinschmidt-Demasters, B. K., additional, Hutter, S., additional, Jones, D. T., additional, Kagawa, N., additional, Hirayama, R., additional, Kijima, N., additional, Chiba, Y., additional, Kinoshita, M., additional, Takano, K., additional, Eino, D., additional, Fukuya, S., additional, Yamamoto, F., additional, Nakanishi, K., additional, Hashimoto, N., additional, Hashii, Y., additional, Hara, J., additional, Yoshimine, T., additional, Wang, J., additional, Guo, C., additional, Yang, Q., additional, Chen, Z., additional, Filipek, I., additional, Swieszkowska, E., additional, Tarasinska, M., additional, Perek, D., additional, Kebudi, R., additional, Koc, B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Wolff, J., additional, Darendeliler, E., additional, Kerl, K., additional, Gronych, J., additional, McGlade, J., additional, Endersby, R., additional, Hii, H., additional, Johns, T., additional, Sastry, J., additional, Murphy, D., additional, Ronghe, M., additional, Cunningham, C., additional, Cowie, F., additional, Jones, R., additional, Calisto, A., additional, Sangra, M., additional, Mathieson, C., additional, Brown, J., additional, Phuakpet, K., additional, Larouche, V., additional, Bartels, U., additional, Ishida, T., additional, Hasegawa, D., additional, Miyata, K., additional, Ochi, S., additional, Saito, A., additional, Kozaki, A., additional, Yanai, T., additional, Kawasaki, K., additional, Yamamoto, K., additional, Kawamura, A., additional, Nagashima, T., additional, Akasaka, Y., additional, Soejima, T., additional, Yoshida, M., additional, Kosaka, Y., additional, von Bueren, A., additional, Goschzik, T., additional, Kortmann, R., additional, von Hoff, K., additional, Friedrich, C., additional, Muehlen, A. z., additional, Warmuth-Metz, M., additional, Soerensen, N., additional, Deinlein, F., additional, Zwiener, I., additional, Faldum, A., additional, Kuehl, J., additional, KRAMER, K., additional, -Taskar, N. P., additional, Zanzonico, P., additional, Humm, J. L., additional, Wolden, S. L., additional, Cheung, N.-K. V., additional, Venkataraman, S., additional, Alimova, I., additional, Harris, P., additional, Birks, D., additional, Balakrishnan, I., additional, Griesinger, A., additional, Foreman, N. K., additional, Vibhakar, R., additional, Margol, A., additional, Robison, N., additional, Gnanachandran, J., additional, Hung, L., additional, Kennedy, R., additional, Vali, M., additional, Dhall, G., additional, Finlay, J., additional, Erdrich-Epstein, A., additional, Krieger, M., additional, Drissi, R., additional, Fouladi, M., additional, Gilles, F., additional, Judkins, A., additional, Sposto, R., additional, Asgharzadeh, S., additional, Peyrl, A., additional, Chocholous, M., additional, Holm, S., additional, Grillner, P., additional, Blomgren, K., additional, Azizi, A., additional, Czech, T., additional, Gustafsson, B., additional, Dieckmann, K., additional, Leiss, U., additional, Slavc, I., additional, Babelyan, S., additional, Dolgopolov, I., additional, Pimenov, R., additional, Mentkevich, G., additional, Gorelishev, S., additional, Laskov, M., additional, von Bueren, A. O., additional, Nowak, J., additional, Kortmann, R. D., additional, Mynarek, M., additional, Muller, K., additional, Gerber, N. U., additional, Ottensmeier, H., additional, Kwiecien, R., additional, Yankelevich, M., additional, Boyarshinov, V., additional, Glekov, I., additional, Ozerov, S., additional, Gorelyshev, S., additional, Popa, A., additional, Subbotina, N., additional, Martin, A. M., additional, Nirschl, C., additional, Polanczyk, M., additional, Bell, R., additional, Martinez, D., additional, Sullivan, L. M., additional, Santi, M., additional, Burger, P. C., additional, Taube, J. M., additional, Drake, C. G., additional, Pardoll, D. M., additional, Lim, M., additional, Li, L., additional, Wang, W.-G., additional, Pu, J.-X., additional, Sun, H.-D., additional, Ruggieri, R., additional, Symons, M. H., additional, Vanan, M. I., additional, Bolin, S., additional, Schumacher, S., additional, Zeid, R., additional, Yu, F., additional, Vue, N., additional, Gibson, W., additional, Paolella, B., additional, Swartling, F. J., additional, Kieran, M. W., additional, Bradner, J. E., additional, Maher, O., additional, Khatua, S., additional, Tarek, N., additional, Zaky, W., additional, Gupta, T., additional, Mohanty, S., additional, Kannan, S., additional, Jalali, R., additional, Kapitza, E., additional, Denkhaus, D., additional, Muhlen, A. z., additional, van Vuurden, D. G., additional, Garami, M., additional, Fangusaro, J., additional, Davidson, T. B., additional, da Costa, M. J. G., additional, Sterba, J., additional, Clifford, S. C., additional, Finlay, J. L., additional, Schmidt, R., additional, Felsberg, J., additional, Skladny, H., additional, Cremer, F., additional, Reifenberger, G., additional, Kunder, R., additional, Sridhar, E., additional, Moiyadi, A. A., additional, Goel, A., additional, Goel, N., additional, Shirsat, N., additional, Othman, R., additional, Storer, L., additional, Kerr, I., additional, Coyle, B., additional, Law, N., additional, Smith, M. L., additional, Greenberg, M., additional, Laughlin, S., additional, Malkin, D., additional, Liu, F., additional, Moxon-Emre, I., additional, Scantlebury, N., additional, Nasir, A., additional, Onion, D., additional, Lourdusamy, A., additional, Grabowska, A., additional, Cai, Y., additional, Bradshaw, T., additional, de Medeiros, R. S. S., additional, Beaugrand, A., additional, Soares, S., additional, Epelman, S., additional, Wang, W., additional, Sultan, M., additional, Wechsler-Reya, R. J., additional, Zapatka, M., additional, Radlwimmer, B., additional, Alderete, D., additional, Baroni, L., additional, Lubinieki, F., additional, Auad, F., additional, Gonzalez, M. L., additional, Puya, W., additional, Pacheco, P., additional, Aurtenetxe, O., additional, Gaffar, A., additional, Gros, L., additional, Cruz, O., additional, Calvo, C., additional, Shinojima, N., additional, Nakamura, H., additional, Kuratsu, J.-i., additional, Hanaford, A., additional, Eberhart, C., additional, Archer, T., additional, Tamayo, P., additional, Pomeroy, S., additional, Raabe, E., additional, De Braganca, K., additional, Gilheeney, S., additional, Khakoo, Y., additional, Kramer, K., additional, Wolden, S., additional, Dunkel, I., additional, Lulla, R. R., additional, Laskowski, J., additional, Goldman, S., additional, Gopalakrishnan, V., additional, Shih, D., additional, Wang, X., additional, Faria, C., additional, Raybaud, C., additional, Tabori, U., additional, Rutka, J., additional, Jacobs, S., additional, De Vathaire, F., additional, Diallo, I., additional, Llanas, D., additional, Verez, C., additional, Diop, F., additional, Kahlouche, A., additional, Puget, S., additional, Thompson, E., additional, Prince, E., additional, Amani, V., additional, Sin-Chan, P., additional, Lu, M., additional, Kleinman, C., additional, Spence, T., additional, Picard, D., additional, Ho, K. C., additional, Chan, J., additional, Majewski, J., additional, Jabado, N., additional, Dirks, P., additional, Huang, A., additional, Madden, J. R., additional, Donson, A. M., additional, Mirsky, D. M., additional, Dubuc, A., additional, Mack, S., additional, Gendoo, D., additional, Luu, B., additional, MacDonald, T., additional, Van Meter, T., additional, Croul, S., additional, Laureano, A., additional, Brugmann, W., additional, Denman, C., additional, Singh, H., additional, Huls, H., additional, Moyes, J., additional, Sandberg, D., additional, Silla, L., additional, Cooper, L., additional, and Lee, D., additional

Published
2014
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46. HIGH GRADE GLIOMAS AND DIPG

Author

Classen, C. F., primary, William, D., additional, Linnebacher, M., additional, Farhod, A., additional, Kedr, W., additional, Elsabe, B., additional, Fadel, S., additional, Van Gool, S., additional, De Vleeschouwer, S., additional, Koks, C., additional, Garg, A., additional, Ehrhardt, M., additional, Riva, M., additional, Agostinis, P., additional, Graf, N., additional, Yao, T.-W., additional, Yoshida, Y., additional, Zhang, J., additional, Ozawa, T., additional, James, D., additional, Nicolaides, T., additional, Kebudi, R., additional, Cakir, F. B., additional, Gorgun, O., additional, Agaoglu, F. Y., additional, Darendeliler, E., additional, Al-Kofide, A., additional, Al-Shail, E., additional, Khafaga, Y., additional, Al-Hindi, H., additional, Dababo, M., additional, Haq, A. U., additional, Anas, M., additional, Barria, M. G., additional, Siddiqui, K., additional, Hassounah, M., additional, Ayas, M., additional, van Zanten, S. V., additional, Jansen, M., additional, van Vuurden, D., additional, Huisman, M., additional, Vugts, D., additional, Hoekstra, O., additional, van Dongen, G., additional, Kaspers, G., additional, Cockle, J., additional, Ilett, E., additional, Scott, K., additional, Bruning-Richardson, A., additional, Picton, S., additional, Short, S., additional, Melcher, A., additional, Benesch, M., additional, Warmuth-Metz, M., additional, von Bueren, A. O., additional, Hoffmann, M., additional, Pietsch, T., additional, Kortmann, R.-D., additional, Eyrich, M., additional, Rutkowski, S., additional, Fruhwald, M. C., additional, Faber, J., additional, Kramm, C., additional, Porkholm, M., additional, Valanne, L., additional, Lonnqvist, T., additional, Holm, S., additional, Lannering, B., additional, Riikonen, P., additional, Wojcik, D., additional, Sehested, A., additional, Clausen, N., additional, Harila-Saari, A., additional, Schomerus, E., additional, Thorarinsdottir, H. K., additional, Lahteenmaki, P., additional, Arola, M., additional, Thomassen, H., additional, Saarinen-Pihkala, U. M., additional, Kivivuori, S.-M., additional, Buczkowicz, P., additional, Hoeman, C., additional, Rakopoulos, P., additional, Pajovic, S., additional, Morrison, A., additional, Bouffet, E., additional, Bartels, U., additional, Becher, O., additional, Hawkins, C., additional, Gould, T. W. A., additional, Rahman, C. V., additional, Smith, S. J., additional, Barrett, D. A., additional, Shakesheff, K. M., additional, Grundy, R. G., additional, Rahman, R., additional, Barua, N., additional, Cronin, D., additional, Gill, S., additional, Lowisl, S., additional, Hochart, A., additional, Maurage, C.-A., additional, Rocourt, N., additional, Vinchon, M., additional, Kerdraon, O., additional, Escande, F., additional, Grill, J., additional, Pick, V. K., additional, Leblond, P., additional, Burzynski, G., additional, Janicki, T., additional, Burzynski, S., additional, Marszalek, A., additional, Ramani, N., additional, Zaky, W., additional, Kannan, G., additional, Morani, A., additional, Sandberg, D., additional, Ketonen, L., additional, Maher, O., additional, Corrales-Medina, F., additional, Meador, H., additional, Khatua, S., additional, Brassesco, M., additional, Delsin, L., additional, Roberto, G., additional, Silva, C., additional, Ana, L., additional, Rego, E., additional, Scrideli, C., additional, Umezawa, K., additional, Tone, L., additional, Kim, S. J., additional, Kim, C.-Y., additional, Kim, I.-A., additional, Han, J. H., additional, Choi, B.-S., additional, Ahn, H. S., additional, Choi, H. S., additional, Haque, F., additional, Layfield, R., additional, Grundy, R., additional, Gandola, L., additional, Pecori, E., additional, Biassoni, V., additional, Schiavello, E., additional, Chiruzzi, C., additional, Spreafico, F., additional, Modena, P., additional, Bach, F., additional, Pignoli, E., additional, Massimino, M., additional, Drogosiewicz, M., additional, Dembowska-Baginska, B., additional, Jurkiewicz, E., additional, Filipek, I., additional, Perek-Polnik, M., additional, Swieszkowska, E., additional, Perek, D., additional, Bender, S., additional, Jones, D. T., additional, Warnatz, H.-J., additional, Hutter, B., additional, Zichner, T., additional, Gronych, J., additional, Korshunov, A., additional, Eils, R., additional, Korbel, J. O., additional, Yaspo, M.-L., additional, Lichter, P., additional, Pfister, S. M., additional, Yadavilli, S., additional, Becher, O. J., additional, Kambhampati, M., additional, Packer, R. J., additional, Nazarian, J., additional, Lechon, F. C., additional, Fowkes, L., additional, Khabra, K., additional, Martin-Retortillo, L. M., additional, Marshall, L. V., additional, Vaidya, S., additional, Koh, D.-M., additional, Leach, M. O., additional, Pearson, A. D., additional, Zacharoulis, S., additional, Schrey, D., additional, Barone, G., additional, Panditharatna, E., additional, Stampar, M., additional, Siu, A., additional, Gordish-Dressman, H., additional, Devaney, J., additional, Hwang, E. I., additional, Chung, A. H., additional, Mittapalli, R. K., additional, Elmquist, W. 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P., additional, Tsoli, M., additional, Vanniasinghe, A., additional, Luk, P., additional, Dilda, P., additional, Haber, M., additional, Hogg, P., additional, Ziegler, D., additional, Simon, S., additional, Monje, M., additional, Gurova, K., additional, Gudkov, A., additional, Zapotocky, M., additional, Churackova, M., additional, Malinova, B., additional, Zamecnik, J., additional, Kyncl, M., additional, Tichy, M., additional, Puchmajerova, A., additional, Stary, J., additional, Sumerauer, D., additional, Boult, J., additional, Vinci, M., additional, Perryman, L., additional, Box, G., additional, Jury, A., additional, Popov, S., additional, Ingram, W., additional, Eccles, S., additional, Robinson, S., additional, Emir, S., additional, Demir, H. A., additional, Bayram, C., additional, Cetindag, F., additional, Kabacam, G. B., additional, Fettah, A., additional, Li, J., additional, Jamin, Y., additional, Cummings, C., additional, Bamber, J., additional, Sinkus, R., additional, Nandhabalan, M., additional, Bjerke, L., additional, Burford, A., additional, von Bueren, A., additional, Baudis, M., additional, Clarke, P., additional, Collins, I., additional, Workman, P., additional, Olaciregui, N., additional, Mora, J., additional, Carcaboso, A., additional, Bullock, A., additional, Alonso, M., additional, de Torres, C., additional, Cruz, O., additional, Pencreach, E., additional, Moussalieh, F. M., additional, Guenot, D., additional, Namer, I., additional, Pollack, I., additional, Jakacki, R., additional, Butterfield, L., additional, Hamilton, R., additional, Panigrahy, A., additional, Potter, D., additional, Connelly, A., additional, Dibridge, S., additional, Whiteside, T., additional, Okada, H., additional, Ahsan, S., additional, Raabe, E., additional, Haffner, M., additional, Warren, K., additional, Quezado, M., additional, Ballester, L., additional, Eberhart, C., additional, Rodriguez, F., additional, Ramachandran, C., additional, Nair, S., additional, Quirrin, K.-W., additional, Khatib, Z., additional, Escalon, E., additional, Melnick, S., additional, Classen, C. F., additional, Hofmann, M., additional, Schmid, I., additional, Simon, T., additional, Maass, E., additional, Russo, A., additional, Fleischhack, G., additional, Becker, M., additional, Hauch, H., additional, Sander, A., additional, Grasso, C., additional, Berlow, N., additional, Liu, L., additional, Davis, L., additional, Huang, E., additional, Woo, P., additional, Tang, Y., additional, Ponnuswami, A., additional, Chen, S., additional, Huang, Y., additional, Hutt-Cabezas, M., additional, Dret, L., additional, Meltzer, P., additional, Mao, H., additional, Abraham, J., additional, Fouladi, M., additional, Svalina, M. N., additional, Wang, N., additional, Hulleman, E., additional, Li, X.-N., additional, Keller, C., additional, Spellman, P. T., additional, Pal, R., additional, Jansen, M. H. A., additional, Sewing, A. C. P., additional, Lagerweij, T., additional, Vuchts, D. J., additional, van Vuurden, D. G., additional, Caretti, V., additional, Wesseling, P., additional, Kaspers, G. J. L., additional, Cohen, K., additional, Pearl, M., additional, Kogiso, M., additional, Zhang, L., additional, Qi, L., additional, Lindsay, H., additional, Lin, F., additional, Berg, S., additional, Muscal, J., additional, Amayiri, N., additional, Tabori, U., additional, Campbel, B., additional, Bakry, D., additional, Aronson, M., additional, Durno, C., additional, Gallinger, S., additional, Malkin, D., additional, Qaddumi, I., additional, Musharbash, A., additional, Swaidan, M., additional, Al-Hussaini, M., additional, Shandilya, S., additional, McCully, C., additional, Murphy, R., additional, Akshintala, S., additional, Cole, D., additional, Macallister, R. P., additional, Cruz, R., additional, Widemann, B., additional, Salloum, R., additional, Smith, A., additional, Glaunert, M., additional, Ramkissoon, A., additional, Peterson, S., additional, Baker, S., additional, Chow, L., additional, Sandgren, J., additional, Pfeifer, S., additional, Popova, S., additional, Alafuzoff, I., additional, de Stahl, T. D., additional, Pietschmann, S., additional, Kerber, M. J., additional, Zwiener, I., additional, Henke, G., additional, Muller, K., additional, Sieow, N. Y.-F., additional, Hoe, R. H. M., additional, Tan, A. M., additional, Chan, M. Y., additional, Soh, S. Y., additional, Burrell, K., additional, Chornenkyy, Y., additional, Remke, M., additional, Golbourn, B., additional, Barzczyk, M., additional, Taylor, M., additional, Rutka, J., additional, Dirks, P., additional, Zadeh, G., additional, Agnihotri, S., additional, Hashizume, R., additional, Ihara, Y., additional, Andor, N., additional, Chen, X., additional, Lerner, R., additional, Huang, X., additional, Tom, M., additional, Solomon, D., additional, Mueller, S., additional, Petritsch, C., additional, Zhang, Z., additional, Gupta, N., additional, Waldman, T., additional, Dujua, A., additional, Co, J., additional, Hernandez, F., additional, Doromal, D., additional, Hegde, M., additional, Wakefield, A., additional, Brawley, V., additional, Grada, Z., additional, Byrd, T., additional, Chow, K., additional, Krebs, S., additional, Heslop, H., additional, Gottschalk, S., additional, Yvon, E., additional, Ahmed, N., additional, Cornilleau, G., additional, Paulsson, J., additional, Andreiuolo, F., additional, Guerrini-Rousseau, L., additional, Geoerger, B., additional, Vassal, G., additional, Ostman, A., additional, Parsons, D. W., additional, Trevino, L. R., additional, Gao, F., additional, Shen, X., additional, Hampton, O., additional, Kosigo, M., additional, Baxter, P. A., additional, Su, J. M., additional, Chintagumpala, M., additional, Dauser, R., additional, Adesina, A., additional, Plon, S. E., additional, Wheeler, D. A., additional, Lau, C. C., additional, Gielen, G., additional, Muehlen, A. z., additional, Kwiecien, R., additional, Wolff, J., additional, Lulla, R. R., additional, Laskowski, J., additional, Goldman, S., additional, Gopalakrishnan, V., additional, Fangusaro, J., additional, Kieran, M., additional, Fontebasso, A., additional, Papillon-Cavanagh, S., additional, Schwartzentruber, J., additional, Nikbakht, H., additional, Gerges, N., additional, Fiset, P.-O., additional, Bechet, D., additional, Faury, D., additional, De Jay, N., additional, Ramkissoon, L., additional, Corcoran, A., additional, Jones, D., additional, Sturm, D., additional, Johann, P., additional, Tomita, T., additional, Nagib, M., additional, Bendel, A., additional, Goumnerova, L., additional, Bowers, D. C., additional, Leonard, J. R., additional, Rubin, J. B., additional, Alden, T., additional, DiPatri, A., additional, Browd, S., additional, Leary, S., additional, Jallo, G., additional, Prados, M. 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L., additional, Majewski, J., additional, Jabado, N., additional, Cordero, F., additional, Halvorson, K., additional, Taylor, I., additional, Hutt, M., additional, Weingart, M., additional, Price, A., additional, Kantar, M., additional, Onen, S., additional, Kamer, S., additional, Turhan, T., additional, Kitis, O., additional, Ertan, Y., additional, Cetingul, N., additional, Anacak, Y., additional, Akalin, T., additional, Ersahin, Y., additional, Mason, G., additional, Ho, C., additional, Crozier, F., additional, Vezina, G., additional, Packer, R., additional, Hwang, E., additional, Gilheeney, S., additional, Millard, N., additional, DeBraganca, K., additional, Khakoo, Y., additional, Kramer, K., additional, Wolden, S., additional, Donzelli, M., additional, Fischer, C., additional, Petriccione, M., additional, Dunkel, I., additional, Afzal, S., additional, Fleming, A., additional, Larouche, V., additional, Zelcer, S., additional, Johnston, D. L., additional, Kostova, M., additional, Mpofu, C., additional, Decarie, J.-C., additional, Strother, D., additional, Lafay-Cousin, L., additional, Eisenstat, D., additional, Fryer, C., additional, Hukin, J., additional, Hsu, M., additional, Lasky, J., additional, Moore, T., additional, Liau, L., additional, Davidson, T., additional, Prins, R., additional, Hassal, T., additional, Baugh, J., additional, Kirkendall, J., additional, Doughman, R., additional, Leach, J., additional, Jones, B., additional, Miles, L., additional, Hargrave, D., additional, Jacques, T., additional, Savage, S., additional, Saunders, D., additional, Wallace, R., additional, Flutter, B., additional, Morgenestern, D., additional, Blanco, E., additional, Howe, K., additional, Lowdell, M., additional, Samuel, E., additional, Michalski, A., additional, Anderson, J., additional, Arakawa, Y., additional, Umeda, K., additional, Watanabe, K.-i., additional, Mizowaki, T., additional, Hiraoka, M., additional, Hiramatsu, H., additional, Adachi, S., additional, Kunieda, T., additional, Takagi, Y., additional, Miyamoto, S., additional, Venneti, S., additional, Santi, M., additional, Felicella, M. M., additional, Sullivan, L. M., additional, Dolgalev, I., additional, Martinez, D., additional, Perry, A., additional, Lewis, P. W., additional, Allis, D. C., additional, Thompson, C. B., additional, and Judkins, A. R., additional

Published
2014
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47. Hypofractionation vs Conventional Radiation Therapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Matched-Cohort Analysis

Author

Janssens, G.O.R.J., Jansen, M.H., Lauwers, S.J., Nowak, P.J., Oldenburger, F.R., Bouffet, E., Saran, F., Kamphuis-van Ulzen, K., Lindert, E.J. van, Schieving, J.H., Boterberg, T., Kaspers, G.J.L., Span, P.N., Kaanders, J.H.A.M., Gidding, C.E.M., Hargrave, D., Janssens, G.O.R.J., Jansen, M.H., Lauwers, S.J., Nowak, P.J., Oldenburger, F.R., Bouffet, E., Saran, F., Kamphuis-van Ulzen, K., Lindert, E.J. van, Schieving, J.H., Boterberg, T., Kaspers, G.J.L., Span, P.N., Kaanders, J.H.A.M., Gidding, C.E.M., and Hargrave, D.

Abstract

Item does not contain fulltext, PURPOSE: Despite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To reduce patient burden, we investigated the role of hypofractionation radiation therapy given over 3 to 4 weeks. A 1:1 matched-cohort analysis with conventional radiation therapy was performed to assess response and survival. METHODS AND MATERIALS: Twenty-seven children, aged 3 to 14, were treated according to 1 of 2 hypofractionation regimens over 3 to 4 weeks (39/3 Gy, n=16 or 44.8/2.8 Gy, n=11). All patients had symptoms for /=2 signs of the neurologic triad (cranial nerve deficit, ataxia, long tract signs), and characteristic features of DIPG on magnetic resonance imaging. Twenty-seven patients fulfilling the same diagnostic criteria and receiving at least 50/1.8 to 2.0 Gy were eligible for the matched-cohort analysis. RESULTS: With hypofractionation radiation therapy, the overall survival at 6, 9, and 12 months was 74%, 44%, and 22%, respectively. Progression-free survival at 3, 6, and 9 months was 77%, 43%, and 12%, respectively. Temporary discontinuation of steroids was observed in 21 of 27 (78%) patients. No significant difference in median overall survival (9.0 vs 9.4 months; P=.84) and time to progression (5.0 vs 7.6 months; P=.24) was observed between hypofractionation vs conventional radiation therapy, respectively. CONCLUSIONS: For patients with newly diagnosed DIPG, a hypofractionation regimen, given over 3 to 4 weeks, offers equal overall survival with less treatment burden compared with a conventional regimen of 6 weeks.

Published
2013

48. Innovative Therapies for Children with Cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors.

Author

Geoerger, B, Hargrave, D, Thomas, F, Ndiaye, A, Frappaz, D, Andreiuolo, F, Varlet, P, Aerts, I, Riccardi, Riccardo, Jaspan, T, Chatelut, E, Le Deley, Mc, Paoletti, X, Saint Rose, C, Leblond, P, Morland, B, Gentet, Jc, Meresse, V, Vassal, G., Riccardi, Riccardo (ORCID:0000-0001-7515-6622), Geoerger, B, Hargrave, D, Thomas, F, Ndiaye, A, Frappaz, D, Andreiuolo, F, Varlet, P, Aerts, I, Riccardi, Riccardo, Jaspan, T, Chatelut, E, Le Deley, Mc, Paoletti, X, Saint Rose, C, Leblond, P, Morland, B, Gentet, Jc, Meresse, V, Vassal, G., and Riccardi, Riccardo (ORCID:0000-0001-7515-6622)

Abstract

This multicenter phase I study aimed to establish the recommended dose (RD) of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, given as monotherapy or with radiotherapy to children with malignant brain tumors. Group 1 included patients with refractory or relapsing brain tumors receiving erlotinib alone, and group 2 included newly diagnosed patients with brainstem gliomas receiving radiotherapy and erlotinib. A conventional 3 + 3 dose escalation and a continual reassessment method, respectively, were utilized in 4 dose levels: 75, 100, 125, and 150 mg/m2 per day. Fifty-one children were enrolled (30 and 21, respectively); 50 received treatment. The RD of erlotinib was 125 mg/m2 per day as monotherapy or in combination with radiotherapy. Overall, 230 adverse events in 44 patients were possibly treatment related (216, grades 1 and 2; 9, grade 3; 1, grade 4; 4, grade 5). Dermatologic and neurologic symptoms were common; intratumoral hemorrhage was confirmed in 3 patients. In group 1, 8 of 29 patients (28%) had stable disease with tumor regression approaching 50% in a malignant glioma and an anaplastic oligoastrocytoma. In group 2, overall survival was 12.0 months. EGFR overexpression by immunohistochemistry was found in 17 of 38 (45%) tumor samples analyzed, with a partial gain of 7p11.2 in 1 glioblastoma; phosphate and tensin homolog loss was frequent in brainstem glioma (15 of 19). Mean (95% CI) apparent clearance and volume of distribution for erlotinib were 4.0 L/h (3.4-4.5 L/h) and 98.6 L (69.8-127.0 L), respectively, and were independent of the dose level; mean half-life was 16.6 hours. Thus, erlotinib 125 mg/m2 per day has an acceptable tolerability profile in pediatric patients with brain tumors and can be combined with radiotherapy

Published
2011

50. Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy – Results of a United Kingdom phase II trial (CNS 2007 04)

Author

Bailey, S., primary, Howman, A., additional, Wheatley, K., additional, Wherton, D., additional, Boota, N., additional, Pizer, B., additional, Fisher, D., additional, Kearns, P., additional, Picton, S., additional, Saran, F., additional, Gibson, M., additional, Glaser, A., additional, Connolly, D.J.A., additional, and Hargrave, D., additional

Published
2013
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