{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T11:43:46Z","timestamp":1793187826648,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Charit\u00e9"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>High-grade astrocytoma with piloid features (HGAP) is a recently described brain tumor entity defined by a specific DNA methylation profile. HGAP has been proposed to be integrated in the upcoming World Health Organization classification of central nervous system tumors expected in 2021. In this series, we present the first single-center experience with this new entity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>During 2017 and 2020, six HGAP were identified. Clinical course, surgical procedure, histopathology, genome-wide DNA methylation analysis, imaging, and adjuvant therapy were collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tumors were localized in the brain stem (n\u2009=\u20091), cerebellar peduncle (n\u2009=\u20091), diencephalon (n\u2009=\u20091), mesencephalon (n\u2009=\u20091), cerebrum (n\u2009=\u20091) and the thoracic spinal cord (n\u2009=\u20092). The lesions typically presented as T1w hypo- to isointense and T2w hyperintense with inhomogeneous contrast enhancement on MRI. All patients underwent initial surgical intervention. Three patients received adjuvant radiochemotherapy, and one patient adjuvant radiotherapy alone. Four patients died of disease, with an overall survival of 1.8, 9.1, 14.8 and 18.1\u00a0months. One patient was alive at the time of last follow-up, 14.6\u00a0months after surgery, and one patient was lost to follow-up. Apart from one tumor, the lesions did not present with high grade histology, however patients showed poor clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Here, we provide detailed clinical, neuroradiological, histological, and molecular pathological information which might aid in clinical decision making until larger case series are published. With the exception of one case, the tumors did not present with high-grade histology but patients still showed short intervals between diagnosis and tumor progression or death even after extensive multimodal therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11060-021-03749-z","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T05:02:52Z","timestamp":1619499772000},"page":"109-120","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["High-grade astrocytoma with piloid features (HGAP): the Charit\u00e9 experience with a new central nervous system tumor entity"],"prefix":"10.1007","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5278-7202","authenticated-orcid":false,"given":"Katja","family":"Bender","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-0385","authenticated-orcid":false,"given":"Eil\u00eds","family":"Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Chirica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Onken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6177-1755","authenticated-orcid":false,"given":"Felix","family":"Ehret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-805X","authenticated-orcid":false,"given":"Philipp","family":"Euskirchen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arend","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-497X","authenticated-orcid":false,"given":"David","family":"Capper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7906-5629","authenticated-orcid":false,"given":"David","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"3749_CR1","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1111\/bpa.12832","volume":"30","author":"DN Louis","year":"2020","unstructured":"Louis DN, Wesseling P, Aldape K, Brat DJ, Capper D, Cree IA, Eberhart C, Figarella-Branger D, Fouladi M, Fuller GN, Giannini C, Haberler C, Hawkins C, Komori T, Kros JM, Ng HK, Orr BA, Park SH, Paulus W, Perry A, Pietsch T, Reifenberger G, Rosenblum M, Rous B, Sahm F, Sarkar C, Solomon DA, Tabori U, van den Bent MJ, von Deimling A, Weller M, White VA, Ellison DW (2020) cIMPACT-NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT-Utrecht meeting on future CNS tumor classification and grading. Brain Pathol 30:844\u2013856. https:\/\/doi.org\/10.1111\/bpa.12832","journal-title":"Brain Pathol"},{"key":"3749_CR2","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nature26000","volume":"555","author":"D Capper","year":"2018","unstructured":"Capper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D, Koelsche C, Sahm F, Chavez L, Reuss DE, Kratz A, Wefers AK, Huang K, Pajtler KW, Schweizer L, Stichel D, Olar A, Engel NW, Lindenberg K, Harter PN, Braczynski AK, Plate KH, Dohmen H, Garvalov BK, Coras R, Holsken A, Hewer E, Bewerunge-Hudler M, Schick M, Fischer R, Beschorner R, Schittenhelm J, Staszewski O, Wani K, Varlet P, Pages M, Temming P, Lohmann D, Selt F, Witt H, Milde T, Witt O, Aronica E, Giangaspero F, Rushing E, Scheurlen W, Geisenberger C, Rodriguez FJ, Becker A, Preusser M, Haberler C, Bjerkvig R, Cryan J, Farrell M, Deckert M, Hench J, Frank S, Serrano J, Kannan K, Tsirigos A, Bruck W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Hanggi D, Hans V, Rozsnoki S, Hansford JR, Kohlhof P, Kristensen BW, Lechner M, Lopes B, Mawrin C, Ketter R, Kulozik A, Khatib Z, Heppner F, Koch A, Jouvet A, Keohane C, Muhleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG, Driever PH, Kramm CM, Muller HL, Rutkowski S, von Hoff K, Fruhwald MC, Gnekow A, Fleischhack G, Tippelt S, Calaminus G, Monoranu CM, Perry A, Jones C, Jacques TS, Radlwimmer B, Gessi M, Pietsch T, Schramm J, Schackert G, Westphal M, Reifenberger G, Wesseling P, Weller M, Collins VP, Blumcke I, Bendszus M, Debus J, Huang A, Jabado N, Northcott PA, Paulus W, Gajjar A, Robinson GW, Taylor MD, Jaunmuktane Z, Ryzhova M, Platten M, Unterberg A, Wick W, Karajannis MA, Mittelbronn M, Acker T, Hartmann C, Aldape K, Schuller U, Buslei R, Lichter P, Kool M, Herold-Mende C, Ellison DW, Hasselblatt M, Snuderl M, Brandner S, Korshunov A, von Deimling A, Pfister SM (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469\u2013474. https:\/\/doi.org\/10.1038\/nature26000","journal-title":"Nature"},{"key":"3749_CR3","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","volume":"30","author":"MJ Aryee","year":"2014","unstructured":"Aryee MJ, Jaffe AE, Corrada-Bravo H, Ladd-Acosta C, Feinberg AP, Hansen KD, Irizarry RA (2014) Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Bioinformatics 30:1363\u20131369. https:\/\/doi.org\/10.1093\/bioinformatics\/btu049","journal-title":"Bioinformatics"},{"key":"3749_CR4","doi-asserted-by":"crossref","unstructured":"Krijthe JH (2015) Rtsne: T-distributed stochastic neighbor embedding using a barnes-hut implementation.","DOI":"10.32614\/CRAN.package.Rtsne"},{"key":"3749_CR5","first-page":"85","volume":"9","author":"LJP Van der Maaten","year":"2008","unstructured":"Van der Maaten LJP, Hinton GE (2008) Visualizing data using t-SNE. J Mach Learn Res 9:85","journal-title":"J Mach Learn Res"},{"key":"3749_CR6","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s00401-018-1837-8","volume":"136","author":"A Reinhardt","year":"2018","unstructured":"Reinhardt A, Stichel D, Schrimpf D, Sahm F, Korshunov A, Reuss DE, Koelsche C, Huang K, Wefers AK, Hovestadt V, Sill M, Gramatzki D, Felsberg J, Reifenberger G, Koch A, Thomale U-W, Becker A, Hans VH, Prinz M, Staszewski O, Acker T, Dohmen H, Hartmann C, Mueller W, Tuffaha MSA, Paulus W, He\u00df K, Brokinkel B, Schittenhelm J, Monoranu C-M, Kessler AF, Loehr M, Buslei R, Deckert M, Mawrin C, Kohlhof P, Hewer E, Olar A, Rodriguez FJ, Giannini C, Nageswararao AA, Tabori U, Nunes NM, Weller M, Pohl U, Jaunmuktane Z, Brandner S, Unterberg A, H\u00e4nggi D, Platten M, Pfister SM, Wick W, Herold-Mende C, Jones DTW, Von Deimling A, Capper D (2018) Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A\/B and ATRX alterations. Acta Neuropathol 136:273\u2013291. https:\/\/doi.org\/10.1007\/s00401-018-1837-8","journal-title":"Acta Neuropathol"},{"key":"3749_CR7","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1186\/s40478-019-0801-8","volume":"7","author":"A Reinhardt","year":"2019","unstructured":"Reinhardt A, Stichel D, Schrimpf D, Koelsche C, Wefers AK, Ebrahimi A, Sievers P, Huang K, Casalini MB, Fernandez-Klett F, Suwala A, Weller M, Gramatzki D, Felsberg J, Reifenberger G, Becker A, Hans VH, Prinz M, Staszewski O, Acker T, Dohmen H, Hartmann C, Paulus W, Hess K, Brokinkel B, Schittenhelm J, Buslei R, Deckert M, Mawrin C, Hewer E, Pohl U, Jaunmuktane Z, Brandner S, Unterberg A, Hanggi D, Platten M, Pfister SM, Wick W, Herold-Mende C, Korshunov A, Reuss DE, Sahm F, Jones DTW, Capper D, von Deimling A (2019) Tumors diagnosed as cerebellar glioblastoma comprise distinct molecular entities. Acta Neuropathol Commun 7:163. https:\/\/doi.org\/10.1186\/s40478-019-0801-8","journal-title":"Acta Neuropathol Commun"},{"key":"3749_CR8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s00401-019-02088-8","volume":"139","author":"A Gareton","year":"2020","unstructured":"Gareton A, Tauziede-Espariat A, Dangouloff-Ros V, Roux A, Saffroy R, Castel D, Kergrohen T, Fina F, Figarella-Branger D, Pages M, Bourdeaut F, Doz F, Puget S, Dufour C, Lechapt E, Chretien F, Grill J, Varlet P (2020) The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population. Acta Neuropathol 139:287\u2013303. https:\/\/doi.org\/10.1007\/s00401-019-02088-8","journal-title":"Acta Neuropathol"},{"key":"3749_CR9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/s11060-020-03513-9","volume":"148","author":"MJ Mair","year":"2020","unstructured":"Mair MJ, W\u00f6hrer A, Furtner J, Simonovska A, Kiesel B, Oberndorfer S, Ungersb\u00f6ck K, Marosi C, Sahm F, Hainfellner JA, R\u00f6ssler K, Preusser M, Widhalm G, Berghoff AS (2020) Clinical characteristics and prognostic factors of adult patients with pilocytic astrocytoma. J Neurooncol 148:187\u2013198. https:\/\/doi.org\/10.1007\/s11060-020-03513-9","journal-title":"J Neurooncol"},{"key":"3749_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010114","author":"M Lobbous","year":"2020","unstructured":"Lobbous M, Bernstock JD, Coffee E, Friedman GK, Metrock LK, Chagoya G, Elsayed G, Nakano I, Hackney JR, Korf BR, Nabors LB (2020) An update on neurofibromatosis type 1-associated gliomas. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers12010114","journal-title":"Cancers (Basel)"},{"key":"3749_CR11","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.clineuro.2016.06.005","volume":"147","author":"M Fiechter","year":"2016","unstructured":"Fiechter M, Hewer E, Knecht U, Wiest R, Beck J, Raabe A, Oertel MF (2016) Adult anaplastic pilocytic astrocytoma\u2014a diagnostic challenge? A case series and literature review. Clin Neurol Neurosurg 147:98\u2013104. https:\/\/doi.org\/10.1016\/j.clineuro.2016.06.005","journal-title":"Clin Neurol Neurosurg"},{"key":"3749_CR12","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/S1470-2045(19)30277-3","volume":"20","author":"J Fangusaro","year":"2019","unstructured":"Fangusaro J, Onar-Thomas A, Young Poussaint T, Wu S, Ligon AH, Lindeman N, Banerjee A, Packer RJ, Kilburn LB, Goldman S, Pollack IF, Qaddoumi I, Jakacki RI, Fisher PG, Dhall G, Baxter P, Kreissman SG, Stewart CF, Jones DTW, Pfister SM, Vezina G, Stern JS, Panigrahy A, Patay Z, Tamrazi B, Jones JY, Haque SS, Enterline DS, Cha S, Fisher MJ, Doyle LA, Smith M, Dunkel IJ, Fouladi M (2019) Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial. Lancet Oncol 20:1011\u20131022. https:\/\/doi.org\/10.1016\/S1470-2045(19)30277-3","journal-title":"Lancet Oncol"},{"key":"3749_CR13","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/S1470-2045(17)30429-1","volume":"18","author":"MA Davies","year":"2017","unstructured":"Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Marquez-Rodas I, Del Vecchio M, Lebbe C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV (2017) Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol 18:863\u2013873. https:\/\/doi.org\/10.1016\/S1470-2045(17)30429-1","journal-title":"Lancet Oncol"},{"key":"3749_CR14","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/cncr.32547","volume":"126","author":"K Holbrook","year":"2020","unstructured":"Holbrook K, Lutzky J, Davies MA, Davis JM, Glitza IC, Amaria RN, Diab A, Patel SP, Amin A, Tawbi H (2020) Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: a case series. Cancer 126:523\u2013530. https:\/\/doi.org\/10.1002\/cncr.32547","journal-title":"Cancer"},{"key":"3749_CR15","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1097\/CMR.0000000000000527","volume":"29","author":"JZ Drago","year":"2019","unstructured":"Drago JZ, Lawrence D, Livingstone E, Zimmer L, Chen T, Giobbie-Hurder A, Amann VC, Mangana J, Siano M, Zippelius A, Dummer R, Goldinger SM, Sullivan RJ (2019) Clinical experience with combination BRAF\/MEK inhibitors for melanoma with brain metastases: a real-life multicenter study. Melanoma Res 29:65\u201369. https:\/\/doi.org\/10.1097\/CMR.0000000000000527","journal-title":"Melanoma Res"}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-021-03749-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-021-03749-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-021-03749-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T10:46:46Z","timestamp":1724928406000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11060-021-03749-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,27]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["3749"],"URL":"https:\/\/doi.org\/10.1007\/s11060-021-03749-z","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,27]]},"assertion":[{"value":"5 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"DK received travel grants from Accuray and is a member of the advisory board for Novocure, he has no competing interest related to the presented work. DC declared a patent pending for a method to classify tumors according to DNA methylation signatures. The other authors declare that they have no competing interest related to the presented work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Charit\u00e9 Universit\u00e4tsmedizin Berlin (EA2\/150\/20).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}