{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:53:06Z","timestamp":1773417186470,"version":"3.50.1"},"reference-count":99,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"DOI":"10.1007\/s12672-026-04639-4","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:09:56Z","timestamp":1770628196000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular convergence enables precision medicine for pediatric low grade gliomas"],"prefix":"10.1007","volume":"17","author":[{"given":"Xuxu","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shepeng","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenjiang","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"4639_CR1","doi-asserted-by":"publisher","first-page":"iii1","DOI":"10.1093\/neuonc\/noab200","volume":"23","author":"QT Ostrom","year":"2021","unstructured":"Ostrom QT, Cioffi G, Waite K, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united States in 2014\u20132018. Neuro Oncol. 2021;23:iii1.","journal-title":"Neuro Oncol"},{"key":"4639_CR2","doi-asserted-by":"publisher","first-page":"v1","DOI":"10.1093\/neuonc\/noac202","volume":"24","author":"QT Ostrom","year":"2022","unstructured":"Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the united States in 2015\u20132019. Neuro Oncol. 2022;24:v1.","journal-title":"Neuro Oncol"},{"key":"4639_CR3","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1093\/neuonc\/noad195","volume":"26","author":"J Fangusaro","year":"2024","unstructured":"Fangusaro J, Jones DT, Packer RJ, et al. Pediatric low-grade glioma: State-of-the-art and ongoing challenges. Neuro Oncol. 2024;26:25.","journal-title":"Neuro Oncol"},{"issue":"Suppl 2","key":"4639_CR4","doi-asserted-by":"publisher","first-page":"ii1","DOI":"10.1093\/neuonc\/not151","volume":"15","author":"QT Ostrom","year":"2013","unstructured":"Ostrom QT, Gittleman H, Farah P, et al. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the united States in 2006\u20132010. Neuro Oncol. 2013;15(Suppl 2):ii1.","journal-title":"Neuro Oncol"},{"key":"4639_CR5","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1016\/j.ccell.2020.03.011","volume":"37","author":"S Ryall","year":"2020","unstructured":"Ryall S, Zapotocky M, Fukuoka K, et al. Integrated molecular and clinical analysis of 1,000 pediatric Low-Grade gliomas. Cancer Cell. 2020;37:569.","journal-title":"Cancer Cell"},{"key":"4639_CR6","doi-asserted-by":"publisher","first-page":"e2300017","DOI":"10.1200\/GO.23.00017","volume":"9","author":"DC Moreira","year":"2023","unstructured":"Moreira DC, Lam CG, Bhakta N, et al. Tackling pediatric Low-Grade gliomas: A global perspective. JCO Glob Oncol. 2023;9:e2300017.","journal-title":"JCO Glob Oncol"},{"key":"4639_CR7","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s40478-020-00902-z","volume":"8","author":"S Ryall","year":"2020","unstructured":"Ryall S, Tabori U, Hawkins C. Pediatric low-grade glioma in the era of molecular diagnostics. Acta Neuropathol Commun. 2020;8:30.","journal-title":"Acta Neuropathol Commun"},{"key":"4639_CR8","first-page":"99","volume":"8","author":"TP Diwanji","year":"2017","unstructured":"Diwanji TP, Engelman A, Snider JW, Mohindra P. Epidemiology, diagnosis, and optimal management of glioma in adolescents and young adults. Adolesc Health Med Ther. 2017;8:99.","journal-title":"Adolesc Health Med Ther"},{"key":"4639_CR9","doi-asserted-by":"publisher","first-page":"4190","DOI":"10.1002\/cncr.29649","volume":"121","author":"AJ Dodgshun","year":"2015","unstructured":"Dodgshun AJ, Elder JE, Hansford JR, Sullivan MJ. Long-term visual outcome after chemotherapy for optic pathway glioma in children: site and age are strongly predictive. Cancer. 2015;121:4190.","journal-title":"Cancer"},{"key":"4639_CR10","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1002\/pbc.22198","volume":"53","author":"G Nicolin","year":"2009","unstructured":"Nicolin G, Parkin P, Mabbott D, et al. Natural history and outcome of optic pathway gliomas in children. Pediatr Blood Cancer. 2009;53:1231.","journal-title":"Pediatr Blood Cancer"},{"key":"4639_CR11","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/S0022-3476(89)80137-4","volume":"114","author":"R Listernick","year":"1989","unstructured":"Listernick R, Charrow J, Greenwald MJ, Esterly NB. Optic gliomas in children with neurofibromatosis type 1. J Pediatr. 1989;114:788.","journal-title":"J Pediatr"},{"key":"4639_CR12","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/ana.21107","volume":"61","author":"R Listernick","year":"2007","unstructured":"Listernick R, Ferner RE, Liu GT, Gutmann DH. Optic pathway gliomas in neurofibromatosis-1: controversies and recommendations. Ann Neurol. 2007;61:189.","journal-title":"Ann Neurol"},{"key":"4639_CR13","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1136\/adc.2007.125880","volume":"93","author":"FJ O\u2019Callaghan","year":"2008","unstructured":"O\u2019Callaghan FJ, Martyn CN, Renowden S, et al. Subependymal nodules, giant cell Astrocytomas and the tuberous sclerosis complex: a population-based study. Arch Dis Child. 2008;93:751.","journal-title":"Arch Dis Child"},{"key":"4639_CR14","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1111\/j.1469-8749.1996.tb12086.x","volume":"38","author":"DW Webb","year":"1996","unstructured":"Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol. 1996;38:146.","journal-title":"Dev Med Child Neurol"},{"key":"4639_CR15","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1212\/01.WNL.0000142039.14522.1A","volume":"63","author":"S Goh","year":"2004","unstructured":"Goh S, Butler W, Thiele EA. Subependymal giant cell tumors in tuberous sclerosis complex. Neurology. 2004;63:1457.","journal-title":"Neurology"},{"key":"4639_CR16","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1038\/s41431-020-0638-4","volume":"28","author":"T Frebourg","year":"2020","unstructured":"Frebourg T, Bajalica Lagercrantz S, Oliveira C, et al. European reference network GENTURIS. Guidelines for the Li\u2013Fraumeni and heritable TP53-related cancer syndromes. Eur J Hum Genet. 2020;28:1379\u201386.","journal-title":"Eur J Hum Genet"},{"issue":"9","key":"4639_CR17","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1093\/neuonc\/noad042","volume":"25","author":"J Foss-Skiftesvik","year":"2023","unstructured":"Foss-Skiftesvik J, Li S, Rosenbaum A, et al. Multi-ancestry genome-wide association study of 4069 children with glioma identifies 9p21.3 risk locus. Neuro Oncol. 2023;25(9):1709\u201320.","journal-title":"Neuro Oncol"},{"issue":"1","key":"4639_CR18","first-page":"vdab109","volume":"3","author":"JP Whitehouse","year":"2021","unstructured":"Whitehouse JP, Howlett M, Federico A, et al. Defining the molecular features of radiation-induced glioma: A systematic review and meta-analysis. Neurooncol Adv. 2021;3(1):vdab109.","journal-title":"Neurooncol Adv"},{"key":"4639_CR19","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S1470-2045(07)70207-3","volume":"8","author":"S Wilne","year":"2007","unstructured":"Wilne S, Collier J, Kennedy C, et al. Presentation of childhood CNS tumours: a systematic review and meta-analysis. Lancet Oncol. 2007;8:685.","journal-title":"Lancet Oncol"},{"key":"4639_CR20","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s13052-022-01316-4","volume":"48","author":"S Trapani","year":"2022","unstructured":"Trapani S, Bortone B, Bianconi M, et al. Diencephalic syndrome in childhood, a challenging cause of failure to thrive: miniseries and literature review. Ital J Pediatr. 2022;48:147.","journal-title":"Ital J Pediatr"},{"key":"4639_CR21","doi-asserted-by":"publisher","first-page":"e742","DOI":"10.1542\/peds.2004-2237","volume":"115","author":"A Fleischman","year":"2005","unstructured":"Fleischman A, Brue C, Poussaint TY, et al. Diencephalic syndrome: a cause of failure to thrive and a model of partial growth hormone resistance. Pediatrics. 2005;115:e742.","journal-title":"Pediatrics"},{"key":"4639_CR22","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1634\/theoncologist.2013-0345","volume":"19","author":"DA Forst","year":"2014","unstructured":"Forst DA, Nahed BV, Loeffler JS, Batchelor TT. Low-grade gliomas. Oncologist. 2014;19:403.","journal-title":"Oncologist"},{"key":"4639_CR23","unstructured":"Aiman W, Gasalberti DP, Rayi A. StatPearls, StatPearls Publishing, Treasure Island (FL) 2025."},{"key":"4639_CR24","doi-asserted-by":"publisher","first-page":"100169","DOI":"10.1016\/j.ejcped.2024.100169","volume":"4","author":"K Roka","year":"2024","unstructured":"Roka K, Scheinemann K, Avula S, Maduro JH, Thomale UW, Sehested A, Schouten-Van Meeteren AYN. On behalf of the interdisciplinary SIOPe LGG working Group. European standard clinical practice recommendations for primary pediatric low-grade gliomas. EJC Paediatr Oncol. 2024;4:100169.","journal-title":"EJC Paediatr Oncol"},{"issue":"12","key":"4639_CR25","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1093\/neuonc\/noab096","volume":"23","author":"L Marner","year":"2021","unstructured":"Marner L, Lundemann M, Sehested A, et al. Diagnostic accuracy and clinical impact of [^18F]FET PET in childhood CNS tumors. Neuro Oncol. 2021;23(12):2107\u201316.","journal-title":"Neuro Oncol"},{"issue":"11","key":"4639_CR26","doi-asserted-by":"publisher","first-page":"3852","DOI":"10.1007\/s00259-022-05817-6","volume":"49","author":"A Piccardo","year":"2022","unstructured":"Piccardo A, Albert NL, Rossi A, et al. Joint EANM\/SIOPE\/RAPNO practice guidelines\/SNMMI procedure standards for imaging of paediatric gliomas using PET with radiolabelled amino acids and [^18F]FDG: version 1.0. Eur J Nucl Med Mol Imaging. 2022;49(11):3852\u201369.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"1","key":"4639_CR27","first-page":"vdac122","volume":"4","author":"J Haizel-Cobbina","year":"2022","unstructured":"Haizel-Cobbina J, Thakkar R, Richard K, et al. Clinical and molecular features of disseminated pediatric low-grade glioma and glioneuronal tumors: a systematic review and survival analysis. Neurooncol Adv. 2022;4(1):vdac122.","journal-title":"Neurooncol Adv"},{"issue":"3","key":"4639_CR28","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/s00381-012-1970-y","volume":"29","author":"SX Bian","year":"2013","unstructured":"Bian SX, McAleer MF, Vats TS, Mahajan A, Grosshans DR. Pilocytic Astrocytoma with leptomeningeal dissemination. Childs Nerv Syst. 2013;29(3):441\u201350.","journal-title":"Childs Nerv Syst"},{"issue":"2","key":"4639_CR29","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00401-018-1865-4","volume":"136","author":"MY Deng","year":"2018","unstructured":"Deng MY, Sill M, Chiang J, et al. Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features. Acta Neuropathol. 2018;136(2):239\u201353.","journal-title":"Acta Neuropathol"},{"key":"4639_CR30","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.wneu.2020.10.058","volume":"145","author":"M Karthigeyan","year":"2021","unstructured":"Karthigeyan M, Ravishankar S, Shankar SK, Santosh V. Cerebrospinal fluid spread in a child with pleomorphic xanthoastrocytoma: report with cytopathologic evidence. World Neurosurg. 2021;145:443\u20137.","journal-title":"World Neurosurg"},{"key":"4639_CR31","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","volume":"23","author":"DN Louis","year":"2021","unstructured":"Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23:1231.","journal-title":"Neuro Oncol"},{"key":"4639_CR32","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1200\/JCO.2016.71.8726","volume":"35","author":"A Lassaletta","year":"2017","unstructured":"Lassaletta A, Zapotocky M, Mistry M, et al. Therapeutic and prognostic implications of BRAF V600E in pediatric Low-Grade gliomas. J Clin Oncol. 2017;35:2934.","journal-title":"J Clin Oncol"},{"issue":"1","key":"4639_CR33","first-page":"vdae228","volume":"7","author":"K Aldape","year":"2025","unstructured":"Aldape K, Capper D, von Deimling A, et al. cIMPACT-NOW update 9: recommendations on utilization of genome-wide DNA methylation profiling for central nervous system tumor diagnostics. Neurooncol Adv. 2025;7(1):vdae228.","journal-title":"Neurooncol Adv"},{"issue":"6","key":"4639_CR34","doi-asserted-by":"publisher","first-page":"e12838","DOI":"10.1111\/nan.12838","volume":"48","author":"E Schepke","year":"2022","unstructured":"Schepke E, L\u00f6fgren M, Pietsch T, et al. DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study. Neuropathol Appl Neurobiol. 2022;48(6):e12838.","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"10","key":"4639_CR35","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.jmoldx.2023.06.013","volume":"25","author":"CL White","year":"2023","unstructured":"White CL, et al. Implementation of DNA methylation array profiling in pediatric central nervous system tumors: the AIM BRAIN project: an Australian and new Zealand children\u2019s Haematology\/Oncology group study. J Mol Diagn. 2023;25(10):709\u201328.","journal-title":"J Mol Diagn"},{"key":"4639_CR36","unstructured":"WHO Classification of Tumours Editorial Board. Central nervous system tumours: WHO classification of tumours. 5th ed. International Agency for Research on Cancer; 2021."},{"key":"4639_CR37","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1007\/s00381-022-05600-w","volume":"38","author":"K Wi\u015bniewski","year":"2022","unstructured":"Wi\u015bniewski K, Brandel MG, Gonda DD, et al. Prognostic factors in diffuse leptomeningeal glioneuronal tumor (DLGNT): a systematic review. Childs Nerv Syst. 2022;38:1663.","journal-title":"Childs Nerv Syst"},{"key":"4639_CR38","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1007\/s00381-024-06432-6","volume":"40","author":"IY Bajin","year":"2024","unstructured":"Bajin IY, Levine A, Dewan MC, et al. Understanding diffuse leptomeningeal glioneuronal tumors. Childs Nerv Syst. 2024;40:2359.","journal-title":"Childs Nerv Syst"},{"issue":"6","key":"4639_CR39","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1007\/s00401-022-02507-3","volume":"144","author":"J Chiang","year":"2022","unstructured":"Chiang J, Moreira DC, Li X, Furtado LV. Prognostic significance of chromosome arm 1q gain and methylation class in molecularly defined diffuse leptomeningeal glioneuronal tumor. Acta Neuropathol. 2022;144(6):1185\u20137.","journal-title":"Acta Neuropathol"},{"issue":"1","key":"4639_CR40","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00401-018-1940-x","volume":"137","author":"J Chiang","year":"2019","unstructured":"Chiang J, Dalton J, Upadhyaya SA, et al. Chromosome arm 1q gain is an adverse prognostic factor in localized and diffuse leptomeningeal glioneuronal tumors with BRAF gene fusion and 1p deletion. Acta Neuropathol. 2019;137(1):179\u201381.","journal-title":"Acta Neuropathol"},{"key":"4639_CR41","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s11910-023-01257-3","volume":"23","author":"SF Sait","year":"2023","unstructured":"Sait SF, Giantini-Larsen AM, Tringale KR, et al. Treatment of pediatric Low-Grade gliomas. Curr Neurol Neurosci Rep. 2023;23:185.","journal-title":"Curr Neurol Neurosci Rep"},{"issue":"1","key":"4639_CR42","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s40478-020-00902-z","volume":"8","author":"S Ryall","year":"2020","unstructured":"Ryall S, Tabori U, Hawkins C. Pediatric\u2002low-grade\u2002glioma\u2002in the\u2002era\u2002of\u2002molecular\u2002diagnostics. Acta Neuropathol Commun. 2020;8(1):30.","journal-title":"Acta Neuropathol Commun"},{"key":"4639_CR43","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1200\/JCO.2011.36.6054","volume":"30","author":"JL Ater","year":"2012","unstructured":"Ater JL, Zhou T, Holmes E, et al. Randomized study of two chemotherapy regimens for treatment of low-grade glioma in young children: a report from the children\u2019s oncology group. J Clin Oncol. 2012;30:2641.","journal-title":"J Clin Oncol"},{"key":"4639_CR44","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1002\/cncr.29987","volume":"122","author":"JL Ater","year":"2016","unstructured":"Ater JL, Xia C, Mazewski CM, et al. Nonrandomized comparison of neurofibromatosis type 1 and non-neurofibromatosis type 1 children who received carboplatin and vincristine for progressive low-grade glioma: A report from the children\u2019s oncology group. Cancer. 2016;122:1928.","journal-title":"Cancer"},{"key":"4639_CR45","doi-asserted-by":"crossref","unstructured":"Lassaletta A, Scheinemann K, Zelcer SM et al. Phase II weekly vinblastine for Chemotherapy-Na\u00efve children with progressive Low-Grade glioma: A Canadian pediatric brain tumor consortium study. J Clin Oncol 2016.","DOI":"10.1200\/JCO.2016.68.1585"},{"key":"4639_CR46","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.ejca.2017.04.019","volume":"81","author":"AK Gnekow","year":"2017","unstructured":"Gnekow AK, WALKer DA, Kandels D, et al. A European randomised controlled trial of the addition of Etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (\u2264\u200916\u2002years) low grade glioma\u2002- A final report. Eur J Cancer. 2017;81:206.","journal-title":"Eur J Cancer"},{"key":"4639_CR47","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1002\/ijc.29711","volume":"138","author":"AJ Dodgshun","year":"2016","unstructured":"Dodgshun AJ, Maixner WJ, Heath JA, et al. Single agent carboplatin for pediatric low-grade glioma: A retrospective analysis shows equivalent efficacy to multiagent chemotherapy. Int J Cancer. 2016;138:481.","journal-title":"Int J Cancer"},{"key":"4639_CR48","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1093\/neuonc\/2.4.213","volume":"2","author":"DH Mahoney Jr","year":"2000","unstructured":"Mahoney DH Jr, Cohen ME, Friedman HS, et al. Carboplatin is effective therapy for young children with progressive optic pathway tumors: a pediatric oncology group phase II study. Neuro Oncol. 2000;2:213.","journal-title":"Neuro Oncol"},{"issue":"4","key":"4639_CR49","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1002\/cncr.23249","volume":"112","author":"L Lafay-Cousin","year":"2008","unstructured":"Lafay-Cousin L, Sung L, Carret AS, et al. Carboplatin hypersensitivity reaction in pediatric patients with low-grade glioma: a Canadian pediatric brain tumor consortium experience. Cancer. 2008;112(4):892\u20139.","journal-title":"Cancer"},{"key":"4639_CR50","doi-asserted-by":"publisher","first-page":"3471","DOI":"10.1002\/ijc.33170","volume":"147","author":"D Kandels","year":"2020","unstructured":"Kandels D, Pietsch T, Bison B, et al. Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low-grade glioma patients-Report from the German SIOP-LGG 2004 cohort. Int J Cancer. 2020;147:3471.","journal-title":"Int J Cancer"},{"key":"4639_CR51","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1093\/neuonc\/nov057","volume":"17","author":"M Chintagumpala","year":"2015","unstructured":"Chintagumpala M, Eckel SP, Krailo M, et al. A pilot study using carboplatin, vincristine, and Temozolomide in children with progressive\/symptomatic low-grade glioma: a children\u2019s oncology group study\u2020. Neuro Oncol. 2015;17:1132.","journal-title":"Neuro Oncol"},{"key":"4639_CR52","doi-asserted-by":"publisher","first-page":"2951","DOI":"10.1200\/JCO.2002.12.008","volume":"20","author":"S Gururangan","year":"2002","unstructured":"Gururangan S, Cavazos CM, Ashley D, et al. Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol. 2002;20:2951.","journal-title":"J Clin Oncol"},{"key":"4639_CR53","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1093\/neuonc\/not154","volume":"16","author":"S Gururangan","year":"2014","unstructured":"Gururangan S, Fangusaro J, Poussaint TY, et al. Efficacy of bevacizumab plus Irinotecan in children with recurrent low-grade gliomas\u2013a pediatric brain tumor consortium study. Neuro Oncol. 2014;16:310.","journal-title":"Neuro Oncol"},{"key":"4639_CR54","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1200\/JCO.2011.34.5843","volume":"30","author":"E Bouffet","year":"2012","unstructured":"Bouffet E, Jakacki R, Goldman S, et al. Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol. 2012;30:1358.","journal-title":"J Clin Oncol"},{"key":"4639_CR55","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1093\/neuonc\/noac223","volume":"25","author":"K Green","year":"2023","unstructured":"Green K, Panagopoulou P, D\u2019Arco F, et al. A nationwide evaluation of bevacizumab-based treatments in pediatric low-grade glioma in the UK: Safety, efficacy, visual morbidity, and outcomes. Neuro Oncol. 2023;25:774.","journal-title":"Neuro Oncol"},{"key":"4639_CR56","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/cam4.1799","volume":"8","author":"N Zhukova","year":"2019","unstructured":"Zhukova N, Rajagopal R, Lam A, et al. Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low-grade glioma. Cancer Med. 2019;8:40.","journal-title":"Cancer Med"},{"key":"4639_CR57","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1001\/jamaophthalmol.2013.5819","volume":"132","author":"RA Avery","year":"2014","unstructured":"Avery RA, Hwang EI, Jakacki RI, Packer RJ. Marked recovery of vision in children with optic pathway gliomas treated with bevacizumab. JAMA Ophthalmol. 2014;132:111.","journal-title":"JAMA Ophthalmol"},{"issue":"24","key":"4639_CR58","doi-asserted-by":"publisher","first-page":"6087","DOI":"10.3390\/cancers14246087","volume":"14","author":"CAM Bennebroek","year":"2022","unstructured":"Bennebroek CAM, van Zwol J, Porro GL, et al. Impact of bevacizumab on visual function, tumor size, and toxicity in pediatric progressive optic pathway glioma: a retrospective nationwide multicentre study. Cancers (Basel). 2022;14(24):6087.","journal-title":"Cancers (Basel)"},{"key":"4639_CR59","unstructured":"ClinicalTrials.gov. Vinblastine alone or with bevacizumab in children with progressive or recurrent pediatric low-grade glioma (NCT02840409). ClinicalTrials.gov. Accessed December 16, 2025."},{"key":"4639_CR60","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1148\/66.4.518","volume":"66","author":"JM TAVERAS","year":"1956","unstructured":"TAVERAS JM, MOUNT LA, WOOD EH. The value of radiation therapy in the management of glioma of the optic nerves and Chiasm. Radiology. 1956;66:518.","journal-title":"Radiology"},{"key":"4639_CR61","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0167-8140(97)00102-3","volume":"45","author":"HS Erkal","year":"1997","unstructured":"Erkal HS, Serin M, Cakmak A. Management of optic pathway and chiasmatic-hypothalamic gliomas in children with radiation therapy. Radiother Oncol. 1997;45:11.","journal-title":"Radiother Oncol"},{"key":"4639_CR62","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1136\/adc.79.4.334","volume":"79","author":"C Cappelli","year":"1998","unstructured":"Cappelli C, Grill J, Raquin M, et al. Long-term follow up of 69 patients treated for optic pathway tumours before the chemotherapy era. Arch Dis Child. 1998;79:334.","journal-title":"Arch Dis Child"},{"key":"4639_CR63","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1093\/jnci\/djp148","volume":"101","author":"GT Armstrong","year":"2009","unstructured":"Armstrong GT, Liu Q, Yasui Y, et al. Long-term outcomes among adult survivors of childhood central nervous system malignancies in the childhood cancer survivor study. J Natl Cancer Inst. 2009;101:946.","journal-title":"J Natl Cancer Inst"},{"key":"4639_CR64","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.ijrobp.2017.07.023","volume":"99","author":"DS Tsang","year":"2017","unstructured":"Tsang DS, Murphy ES, Merchant TE. Radiation therapy for optic pathway and hypothalamic Low-Grade gliomas in children. Int J Radiat Oncol Biol Phys. 2017;99:642.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"4639_CR65","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1200\/JCO.2008.21.2738","volume":"27","author":"TE Merchant","year":"2009","unstructured":"Merchant TE, Conklin HM, Wu S, et al. Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits. J Clin Oncol. 2009;27:3691.","journal-title":"J Clin Oncol"},{"key":"4639_CR66","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.ijrobp.2014.04.053","volume":"89","author":"BA Greenberger","year":"2014","unstructured":"Greenberger BA, Pulsifer MB, Ebb DH, et al. Clinical outcomes and late endocrine, neurocognitive, and visual profiles of proton radiation for pediatric low-grade gliomas. Int J Radiat Oncol Biol Phys. 2014;89:1060.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"4639_CR67","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.radonc.2014.08.017","volume":"113","author":"TI Yock","year":"2014","unstructured":"Yock TI, Bhat S, Szymonifka J, et al. Quality of life outcomes in proton and photon treated pediatric brain tumor survivors. Radiother Oncol. 2014;113:89.","journal-title":"Radiother Oncol"},{"key":"4639_CR68","doi-asserted-by":"publisher","first-page":"5957","DOI":"10.1073\/pnas.1219232110","volume":"110","author":"AJ Sievert","year":"2013","unstructured":"Sievert AJ, Lang SS, Boucher KL, et al. Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric Astrocytomas. Proc Natl Acad Sci U S A. 2013;110:5957.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4639_CR69","doi-asserted-by":"publisher","first-page":"7303","DOI":"10.1158\/1078-0432.CCR-19-2177","volume":"25","author":"DR Hargrave","year":"2019","unstructured":"Hargrave DR, Bouffet E, Tabori U, et al. Efficacy and safety of DaBRAFenib in pediatric patients with BRAF V600 Mutation-Positive relapsed or refractory Low-Grade glioma: results from a phase I\/IIa study. Clin Cancer Res. 2019;25:7303.","journal-title":"Clin Cancer Res"},{"key":"4639_CR70","doi-asserted-by":"publisher","first-page":"83280","DOI":"10.18632\/oncotarget.21059","volume":"8","author":"L Peng","year":"2017","unstructured":"Peng L, Wang Y, Hong Y, et al. Incidence and relative risk of cutaneous squamous cell carcinoma with single-agent BRAF inhibitor and dual BRAF\/MEK inhibitors in cancer patients: a meta-analysis. Oncotarget. 2017;8:83280.","journal-title":"Oncotarget"},{"key":"4639_CR71","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1056\/NEJMoa1105358","volume":"366","author":"F Su","year":"2012","unstructured":"Su F, Viros A, Milagre C, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366:207.","journal-title":"N Engl J Med"},{"key":"4639_CR72","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s41591-023-02668-y","volume":"30","author":"LB Kilburn","year":"2024","unstructured":"Kilburn LB, Khuong-Quang DA, Hansford JR, et al. The type II RAF inhibitor Tovorafenib in relapsed\/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024;30:207.","journal-title":"Nat Med"},{"key":"4639_CR73","volume-title":"[package insert]","author":"OJEMDA (tovorafenib)","year":"2024","unstructured":"OJEMDA (tovorafenib). [package insert]. Brisbane, CA: Day One Biopharmaceuticals, Inc.; 2024."},{"key":"4639_CR74","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12885-024-11820-x","volume":"24","author":"CM van Tilburg","year":"2024","unstructured":"van Tilburg CM, Kilburn LB, Perreault S, et al. LOGGIC\/FIREFLY-2: a phase 3, randomized trial of Tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. BMC Cancer. 2024;24:147.","journal-title":"BMC Cancer"},{"key":"4639_CR75","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1093\/neuonc\/now282","volume":"19","author":"A Banerjee","year":"2017","unstructured":"Banerjee A, Jakacki RI, Onar-Thomas A, et al. A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a pediatric brain tumor consortium (PBTC) study. Neuro Oncol. 2017;19:1135.","journal-title":"Neuro Oncol"},{"key":"4639_CR76","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, et al. 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. 2019;20:1011.","journal-title":"Lancet Oncol"},{"key":"4639_CR77","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s11060-018-2971-9","volume":"140","author":"M Kondyli","year":"2018","unstructured":"Kondyli M, Larouche V, Saint-Martin C, et al. Trametinib for progressive pediatric low-grade gliomas. J Neurooncol. 2018;140:435.","journal-title":"J Neurooncol"},{"key":"4639_CR78","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s11060-020-03592-8","volume":"149","author":"N Manoharan","year":"2020","unstructured":"Manoharan N, Choi J, Chordas C, et al. Trametinib for the treatment of recurrent\/progressive pediatric low-grade glioma. J Neurooncol. 2020;149:253.","journal-title":"J Neurooncol"},{"key":"4639_CR79","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s11060-020-03640-3","volume":"149","author":"F Selt","year":"2020","unstructured":"Selt F, van Tilburg CM, Bison B, et al. Response to Trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020;149:499.","journal-title":"J Neurooncol"},{"key":"4639_CR80","doi-asserted-by":"publisher","first-page":"e2300590","DOI":"10.1200\/PO.23.00590","volume":"8","author":"L Papusha","year":"2024","unstructured":"Papusha L, Zaytseva M, Panferova A, et al. Midline Low-Grade gliomas of early childhood: focus on targeted therapies. JCO Precis Oncol. 2024;8:e2300590.","journal-title":"JCO Precis Oncol"},{"key":"4639_CR81","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1200\/JCO.22.01000","volume":"41","author":"E Bouffet","year":"2023","unstructured":"Bouffet E, Geoerger B, Moertel C, et al. Efficacy and safety of Trametinib monotherapy or in combination with DaBRAFenib in pediatric BRAF V600-Mutant Low-Grade glioma. J Clin Oncol. 2023;41:664.","journal-title":"J Clin Oncol"},{"key":"4639_CR82","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s11523-022-00888-9","volume":"17","author":"T Trippett","year":"2022","unstructured":"Trippett T, Toledano H, Campbell Hewson Q, et al. Cobimetinib in pediatric and young adult patients with relapsed or refractory solid tumors (iMATRIX-cobi): A Multicenter, phase I\/II study. Target Oncol. 2022;17:283.","journal-title":"Target Oncol"},{"key":"4639_CR83","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1056\/NEJMoa2303815","volume":"389","author":"E Bouffet","year":"2023","unstructured":"Bouffet E, Hansford JR, Garr\u00e8 ML, et al. DaBRAFenib plus Trametinib in pediatric glioma with BRAF V600 mutations. N Engl J Med. 2023;389:1108.","journal-title":"N Engl J Med"},{"key":"4639_CR84","doi-asserted-by":"publisher","first-page":"e28787","DOI":"10.1002\/pbc.28787","volume":"68","author":"KD Wright","year":"2021","unstructured":"Wright KD, Yao X, London WB, et al. A POETIC phase II study of continuous oral everolimus in recurrent, radiographically progressive pediatric low-grade glioma. Pediatr Blood Cancer. 2021;68:e28787.","journal-title":"Pediatr Blood Cancer"},{"key":"4639_CR85","doi-asserted-by":"crossref","unstructured":"Lee A, Chou AJ, Williams MP et al. Erdafitinb in patients with FGFR-altered tumors: results from the NCI-COG pediatric MATCH trial arm B (APEC1621B). J Clin Oncol 2023; 41:suppl 16; abstr 1007.","DOI":"10.1200\/JCO.2023.41.16_suppl.10007"},{"key":"4639_CR86","doi-asserted-by":"crossref","unstructured":"Farouk Sait S, Fischer C, Antal Z et al. Slipped capital femoral epiphyses: A major on-target adverse event associated with FGFR tyrosine kinase inhibitors in pediatric patients. Pediatr Blood Cancer 2023;:e30410.","DOI":"10.1002\/pbc.30410"},{"key":"4639_CR87","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1200\/JCO-24-01854","volume":"43","author":"TW Laetsch","year":"2025","unstructured":"Laetsch TW, Voss S, Ludwig K, et al. Larotrectinib for newly diagnosed infantile fibrosarcoma and other pediatric NTRK Fusion-Positive solid tumors (Children\u2019s oncology group ADVL1823). J Clin Oncol. 2025;43:1188.","journal-title":"J Clin Oncol"},{"key":"4639_CR88","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1093\/neuonc\/noab274","volume":"24","author":"F Doz","year":"2022","unstructured":"Doz F, van Tilburg CM, Geoerger B, et al. Efficacy and safety of larotrectinib in TRK fusion-positive primary central nervous system tumors. Neuro Oncol. 2022;24:997.","journal-title":"Neuro Oncol"},{"key":"4639_CR89","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1093\/neuonc\/noac087","volume":"24","author":"AV Desai","year":"2022","unstructured":"Desai AV, Robinson GW, Gauvain K, et al. Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro Oncol. 2022;24:1776.","journal-title":"Neuro Oncol"},{"key":"4639_CR90","unstructured":"ClinicalTrials.gov. HM95573 in Combination With Either Cobimetinib or Cetuximab in Patients With Locally Advanced or Metastatic Solid Tumors. ClinicalTrials.gov Identifier: NCT03284502. Accessed December 16, 2025."},{"key":"4639_CR91","unstructured":"Nobre L, Zapotocky M, Ramaswamy V et al. Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF Inhibition. JCO Precis Oncol 2020; 4."},{"key":"4639_CR92","doi-asserted-by":"publisher","first-page":"1074726","DOI":"10.3389\/fonc.2022.1074726","volume":"12","author":"M Capogiri","year":"2022","unstructured":"Capogiri M, De Micheli AJ, Lassaletta A, et al. Response and resistance to BRAFV600E Inhibition in gliomas. Roadblocks ahead? Front Oncol. 2022;12:1074726.","journal-title":"Roadblocks ahead? Front Oncol"},{"issue":"5","key":"4639_CR93","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.3390\/cancers12051152","volume":"12","author":"KL Collins","year":"2020","unstructured":"Collins KL, Pollack IF. Pediatric low-grade gliomas. Cancers (Basel). 2020;12(5):1152.","journal-title":"Cancers (Basel)"},{"key":"4639_CR94","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00701-014-2299-y","volume":"157","author":"AMN El-Shehaby","year":"2015","unstructured":"El-Shehaby AMN, Reda WAH, Abdel Karim KM, et al. Gamma knife radiosurgery for low-grade tectal gliomas. Acta Neurochir (Wien). 2015;157:247\u201356.","journal-title":"Acta Neurochir (Wien)"},{"key":"4639_CR95","doi-asserted-by":"crossref","unstructured":"Strauss I, Gabay S, Roth J. Laser interstitial thermal therapy (LITT) for pediatric low-grade glioma\u2014case presentations and lessons learned. Childs Nerv Syst Published Online April 16, 2024.","DOI":"10.21203\/rs.3.rs-4249271\/v1"},{"key":"4639_CR96","doi-asserted-by":"crossref","unstructured":"Zeller S, Kaye J, Jumah F et al. Current applications and safety profile of laser interstitial thermal therapy in the pediatric population: a systematic review of the literature. J Neurosurg Pediatr. 2021.","DOI":"10.3171\/2021.2.PEDS20721"},{"key":"4639_CR97","doi-asserted-by":"publisher","first-page":"1120286","DOI":"10.3389\/fneur.2023.1120286","volume":"14","author":"B Spacca","year":"2023","unstructured":"Spacca B, Di Maurizio M, Grandoni M, Tempesti S, Genitori L. Laser interstitial thermal therapy (LITT) for pediatric patients affected by intracranial tumors. Front Neurol. 2023;14:1120286.","journal-title":"Front Neurol"},{"issue":"1","key":"4639_CR98","first-page":"vdz035","volume":"1","author":"KG Holste","year":"2019","unstructured":"Holste KG, Orringer DA. Laser interstitial thermal therapy. Neurooncol Adv. 2019;1(1):vdz035.","journal-title":"Neurooncol Adv"},{"issue":"10","key":"4639_CR99","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1007\/s00381-016-3193-0","volume":"32","author":"Z Tovar-Spinoza","year":"2016","unstructured":"Tovar-Spinoza Z, Choi H. MRI-guided laser interstitial thermal therapy for the treatment of low-grade gliomas in children: a case-series review, description of the current technologies and perspectives. Childs Nerv Syst. 2016;32(10):1947\u201356.","journal-title":"Childs Nerv Syst"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-04639-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-04639-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-04639-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:02:54Z","timestamp":1773406974000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-026-04639-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":99,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4639"],"URL":"https:\/\/doi.org\/10.1007\/s12672-026-04639-4","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"assertion":[{"value":"29 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This is a narrative review article based on published literature. No primary research involving human participants, human data, or human tissue was conducted as part of this study. All information presented is derived from previously published and publicly available sources. Not applicable. This is a review article that does not involve any direct participation of human subjects. No informed consent was required as no original patient data or human participants were included in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable. This manuscript does not contain any individual person\u2019s data in any form (including individual details, images, or videos). All authors have reviewed and approved the final version of the manuscript and consent to its publication in Discover Oncology.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"423"}}