{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T15:46:16Z","timestamp":1789746376779,"version":"4.0.1"},"reference-count":73,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French Ministry of Health and Institut National du Cancer, and by Soci\u00e9t\u00e9 Fran\u00e7aise de lutte con-tre les Cancers et leuc\u00e9mies de l\u2019Enfant (SFCE)\/ Enfants et sant\u00e9 and from Association de Recher-che sur les Tumeurs C\u00e9r\u00e9brales (ARTC)","award":["PHRC-K 2011-250"],"award-info":[{"award-number":["PHRC-K 2011-250"]}]},{"name":"BMBF ADDRess","award":["01GM1909E"],"award-info":[{"award-number":["01GM1909E"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background. SIOP PNET5 MB was initiated in 2014 as the first European trial using clinical, histological, and molecular parameters to stratify treatments for children and adolescents with standard-risk medulloblastoma. Methods. Stratification by upfront assessment of molecular parameters requires the timely submission of adequate tumour tissue. In the standard-risk phase-III cohort, defined by the absence of high-risk criteria (M0, R0), pathological (non-LCA), and molecular biomarkers (MYCN amplification in SHH\u2013MB or MYC amplification), a randomized intensification by carboplatin concomitant with radiotherapy is investigated. In the LR stratum for localized WNT-activated medulloblastoma and age &lt;16 years, a reduction of craniospinal radiotherapy dose to 18 Gy and a reduced maintenance chemotherapy are investigated. Two additional strata (WNT-HR, SHH-TP53) were implemented during the trial. Results. SIOP PNET5 MB is actively recruiting. The availability of adequate tumour tissue for upfront real-time biological assessments to assess inclusion criteria has proven feasible. Conclusion. SIOP PNET5 MB has demonstrated that implementation of biological parameters for stratification is feasible in a prospective multicentre setting, and may improve risk-adapted treatment. Comprehensive research studies may allow assessment of additional parameters, e.g., novel medulloblastoma subtypes, and identification and validation of biomarkers for the further refinement of risk-adapted treatment in the future.<\/jats:p>","DOI":"10.3390\/cancers13236077","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T21:19:08Z","timestamp":1638479948000},"page":"6077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["SIOP PNET5 MB Trial: History and Concept of a Molecularly Stratified Clinical Trial of Risk-Adapted Therapies for Standard-Risk Medulloblastoma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-2719","authenticated-orcid":false,"given":"Martin","family":"Mynarek","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7267-1052","authenticated-orcid":false,"given":"Till","family":"Milde","sequence":"additional","affiliation":[{"name":"Hopp Children\u2019s Cancer Center (KiTZ), 69120 Heidelberg, Germany"},{"name":"Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), 69120 Heidelberg, Germany"},{"name":"Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3054-6218","authenticated-orcid":false,"given":"Laetitia","family":"Padovani","sequence":"additional","affiliation":[{"name":"Oncology Radiotherapy Department, CRCM Inserm, Aix-Marseille University, UMR1068, CNRS UMR7258, AMU UM105, Genome Instability and Carcinogenesis, Assistance Publique des H\u00f4pitaux de Marseille, 13284 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert O.","family":"Janssens","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands"},{"name":"Princess M\u00e1xima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kwiecien","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Clinical Research, Faculty of Medicine, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Mosseri","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Institut Curie, 75248 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Clifford","sequence":"additional","affiliation":[{"name":"Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9286-4831","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Doz","sequence":"additional","affiliation":[{"name":"SIREDO Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris and Universit\u00e9 de Paris, 75248 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Louis, D.N., Ohgaki, H., Wiestler, O.D., and Cavenee, W.K. (2007). WHO Classification of Tumours of the Central Nervous System, IARC.","DOI":"10.1007\/s00401-007-0278-6"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S1470-2045(04)01424-X","article-title":"Medulloblastoma: Signalling a change in treatment","volume":"5","author":"Gilbertson","year":"2004","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S1470-2045(06)70867-1","article-title":"Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): Long-term results from a prospective, multicentre trial","volume":"7","author":"Gajjar","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1200\/JCO.2006.06.4980","article-title":"Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma","volume":"24","author":"Packer","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/cncr.11095","article-title":"Endocrine and cardiovascular late effects among adult survivors of childhood brain tumors: Childhood Cancer Survivor Study","volume":"97","author":"Gurney","year":"2003","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s11060-004-3009-z","article-title":"Neuropsychological performance and quality of life of 10 year survivors of childhood medulloblastoma","volume":"72","author":"Maddrey","year":"2005","journal-title":"J. Neuro-Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1200\/JCO.2001.19.15.3470","article-title":"Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: A Children\u2019s Cancer Group study","volume":"19","author":"Ris","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1200\/JCO.2005.00.703","article-title":"Neurocognitive consequences of risk-adapted therapy for childhood medulloblastoma","volume":"23","author":"Mulhern","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1200\/JCO.2011.39.8719","article-title":"Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: Results from the randomized multicenter HIT-SIOP PNET 4 trial","volume":"30","author":"Lannering","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1200\/JCO.1999.17.3.832","article-title":"Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: Conclusions from the Children\u2019s Cancer Group 921 randomized phase III study","volume":"17","author":"Zeltzer","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000071316","article-title":"Medulloblastoma: Present concepts of stratification into risk groups","volume":"39","author":"Packer","year":"2003","journal-title":"Pediatr. Neurosurg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S1470-2045(05)70252-7","article-title":"Treatment of medulloblastoma with postoperative chemotherapy alone: An SFOP prospective trial in young children","volume":"6","author":"Grill","year":"2005","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1056\/NEJMoa042176","article-title":"Treatment of early childhood medulloblastoma by postoperative chemotherapy alone","volume":"352","author":"Rutkowski","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1056\/NEJM199306173282401","article-title":"Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors","volume":"328","author":"Duffner","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1148\/93.6.1351","article-title":"An operative staging system and a megavoltage radiotherapeutic technic for cerebellar medulloblastomas","volume":"93","author":"Chang","year":"1969","journal-title":"Radiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1016\/j.ejca.2006.02.026","article-title":"Treatment of high risk medulloblastomas in children above the age of 3 years: A SFOP study","volume":"42","author":"Verlooy","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.ejca.2009.01.015","article-title":"Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT\u201991","volume":"45","author":"Hinkes","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1200\/JCO.1999.17.10.3234","article-title":"Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor","volume":"17","author":"Fouladi","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1023\/A:1008363422189","article-title":"Prognostic value of cerebrospinal fluid cytology in pediatric medulloblastoma. Swiss Pediatric Oncology Group","volume":"10","author":"Miralbell","year":"1999","journal-title":"Ann. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4726","DOI":"10.1200\/JCO.2005.00.760","article-title":"Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: A French Society of Pediatric Oncology Study","volume":"23","author":"Kalifa","year":"2005","journal-title":"J. Clin. Onco.l"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/cncr.10189","article-title":"Histopathologic grading of medulloblastomas: A Pediatric Oncology Group study","volume":"94","author":"Eberhart","year":"2002","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/415436a","article-title":"Prediction of central nervous system embryonal tumour outcome based on gene expression","volume":"415","author":"Pomeroy","year":"2002","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1200\/JCO.2010.30.2299","article-title":"Survival and prognostic factors of early childhood medulloblastoma: An international meta-analysis","volume":"28","author":"Rutkowski","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.4161\/cc.5.22.3446","article-title":"Wnt\/Wingless pathway activation and chromosome 6 loss characterize a distinct molecular sub-group of medulloblastomas associated with a favorable prognosis","volume":"5","author":"Clifford","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1200\/JCO.2003.05.116","article-title":"Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology\/United Kingdom Children\u2019s Cancer Study Group PNET-3 Study","volume":"21","author":"Taylor","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7951","DOI":"10.1200\/JCO.2005.01.5479","article-title":"Beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: The United Kingdom Children\u2019s Cancer Study Group Brain Tumour Committee","volume":"23","author":"Ellison","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/S1470-2045(18)30532-1","article-title":"Prognostic effect of whole chromosomal aberration signatures in standard-risk, non-WNT\/non-SHH medulloblastoma: A retrospective, molecular analysis of the HIT-SIOP PNET 4 trial","volume":"19","author":"Goschzik","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"38827","DOI":"10.18632\/oncotarget.5149","article-title":"Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: Results from the multi-center HIT-SIOP-PNET4 clinical trial","volume":"6","author":"Clifford","year":"2015","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00401-011-0800-8","article-title":"Medulloblastoma: Clinicopathological correlates of SHH, WNT, and non-SHH\/WNT molecular subgroups","volume":"121","author":"Ellison","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1200\/JCO.2009.25.7121","article-title":"Adult and pediatric medulloblastomas are genetically distinct and require different algorithms for molecular risk stratification","volume":"28","author":"Korshunov","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5482","DOI":"10.1158\/1078-0432.CCR-03-0721","article-title":"Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients","volume":"10","author":"Lamont","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00401-011-0923-y","article-title":"MYC family amplification and clinical risk-factors interact to predict an extremely poor prognosis in childhood medulloblastoma","volume":"123","author":"Ryan","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00401-012-1077-2","article-title":"DNA methylation profiling of medulloblastoma allows robust subclassification and improved outcome prediction using formalin-fixed biopsies","volume":"125","author":"Schwalbe","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00401-011-0922-z","article-title":"Molecular subgroups of medulloblastoma: The current consensus","volume":"123","author":"Taylor","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41572-019-0063-6","article-title":"Medulloblastoma","volume":"5","author":"Northcott","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1200\/JCO.2012.48.5052","article-title":"Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma","volume":"31","author":"Zhukova","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/S1470-2045(17)30243-7","article-title":"Novel molecular subgroups for clinical classification and outcome prediction in childhood medulloblastoma: A cohort study","volume":"18","author":"Schwalbe","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S1470-2045(18)30242-0","article-title":"Spectrum and prevalence of genetic predisposition in medulloblastoma: A retrospective genetic study and prospective validation in a clinical trial cohort","volume":"19","author":"Waszak","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_40","unstructured":"Louis, D.N., Ohgaki, H., Wiestler, O.D., and Cavenee, W.K. (2016). WHO Classification of Tumours of the Central Nervous System, IARC. [4th ed.]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1200\/JCO.19.03057","article-title":"Nonmetastatic Medulloblastoma of Early Childhood: Results from the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort","volume":"38","author":"Mynarek","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1200\/JCO.1999.17.7.2127","article-title":"Treatment of children with medulloblastomas with Reduced-Dose craniospinal radiation therapy and adjuvant chemotherapy: A Children\u2019s Cancer Group Study","volume":"17","author":"Packer","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1055\/s-2008-1043883","article-title":"Preradiation chemotherapy of children and young adults with malignant brain tumors: Results of the German pilot trial HIT\u203288\/\u203289","volume":"210","author":"Kuhl","year":"1998","journal-title":"Klin. Padiatr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.ijrobp.2007.07.2342","article-title":"Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma","volume":"70","author":"Merchant","year":"2008","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.ijrobp.2005.03.031","article-title":"Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: Results of the French M-SFOP 98 protocol","volume":"63","author":"Carrie","year":"2005","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1200\/JCO.2008.18.6437","article-title":"Online quality control, hyperfractionated radiotherapy alone and reduced boost volume for standard risk medulloblastoma: Long-term results of MSFOP 98","volume":"27","author":"Carrie","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1200\/JCO.20.02730","article-title":"Children\u2019s Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma","volume":"39","author":"Michalski","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1007\/s00066-020-01707-8","article-title":"Pretreatment central quality control for craniospinal irradiation in non-metastatic medulloblastoma: First experiences of the German radiotherapy quality control panel in the SIOP PNET5 MB trial","volume":"197","author":"Dietzsch","year":"2021","journal-title":"Strahlenther. Onkol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/S0360-3016(99)00200-X","article-title":"Impact of targeting deviations on outcome in medulloblastoma: Study of the French Society of Pediatric Oncology (SFOP)","volume":"45","author":"Carrie","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dietzsch, S., Braesigk, A., Seidel, C., Remmele, J., Kitzing, R., Schlender, T., Mynarek, M., Geismar, D., Jablonska, K., and Schwarz, R. (2021). Types of deviation and review criteria in pretreatment central quality control of tumor bed boost in medulloblastoma-an analysis of the German Radiotherapy Quality Control Panel in the SIOP PNET5 MB trial. Strahlenther. Onkol., online ahead of print.","DOI":"10.1007\/s00066-021-01822-0"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s00066-019-01469-y","article-title":"A dedicated cloud system for real-time upfront quality assurance in pediatric radiation therapy","volume":"195","author":"Meroni","year":"2019","journal-title":"Strahlenther. Onkol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3171\/jns.1994.81.5.0690","article-title":"Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy","volume":"81","author":"Packer","year":"1994","journal-title":"J. Neurosurg."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1200\/JCO.2011.40.2792","article-title":"Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: A Children\u2019s Oncology Group Phase I\/II study","volume":"30","author":"Jakacki","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1200\/JCO.2016.71.6902","article-title":"Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy","volume":"35","author":"Teepen","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.mrgentox.2015.05.010","article-title":"A new genotoxicity assay based on p53 target gene induction","volume":"789\u2013790","author":"Zerdoumi","year":"2015","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1200\/JCO.2016.67.2428","article-title":"Treatment of Children and Adolescents with Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters","volume":"34","author":"Kortmann","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1200\/JCO.2010.28.5148","article-title":"Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome","volume":"29","author":"Cho","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/path.2514","article-title":"Beta-catenin status in paediatric medulloblastomas: Correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics","volume":"218","author":"Fattet","year":"2009","journal-title":"J. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s00401-013-1126-5","article-title":"Robust molecular subgrouping and copy-number profiling of medulloblastoma from small amounts of archival tumour material using high-density DNA methylation arrays","volume":"125","author":"Hovestadt","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00401-012-0958-8","article-title":"Molecular subgroups of medulloblastoma: An international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas","volume":"123","author":"Kool","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1200\/JCO.2009.27.4324","article-title":"Medulloblastoma comprises four distinct molecular variants","volume":"29","author":"Northcott","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00401-014-1276-0","article-title":"Prognostic significance of clinical, histopathological, and molecular characteristics of medulloblastomas in the prospective HIT2000 multicenter clinical trial cohort","volume":"128","author":"Pietsch","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1200\/JCO.2005.04.4974","article-title":"Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations","volume":"24","author":"Thompson","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e293","DOI":"10.1016\/S1470-2045(14)71206-9","article-title":"Next-generation (epi)genetic drivers of childhood brain tumours and the outlook for targeted therapies","volume":"16","author":"Northcott","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00401-013-1213-7","article-title":"Medulloblastoma Down Under 2013: A report from the third annual meeting of the International Medulloblastoma Working Group","volume":"127","author":"Gottardo","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ccell.2016.03.002","article-title":"Medulloblastoma Genotype Dictates Blood Brain Barrier Phenotype","volume":"29","author":"Phoenix","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0360-3016(99)00177-7","article-title":"Long-term intellectual outcome in children with posterior fossa tumors according to radiation doses and volumes","volume":"45","author":"Grill","year":"1999","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"iii393","DOI":"10.1093\/neuonc\/noaa222.501","article-title":"Mbcl-25. Pilot Study of a Surgery and Chemotherapyonly Approach in the Upfront Therapy of Children with Wnt-Positive Standard Risk Medulloblastoma: Updated Outcomes","volume":"22","author":"Cohen","year":"2020","journal-title":"Neuro-Oncology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/0959-8049(94)90086-8","article-title":"What is the place of carboplatin in paediatric oncology?","volume":"30A","author":"Doz","year":"1994","journal-title":"Eur. J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1001\/jamaoncol.2021.2224","article-title":"Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children\u2019s Oncology Group","volume":"7","author":"Leary","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1158\/1078-0432.CCR-17-0408","article-title":"Cancer Screening Recommendations for Individuals with Li-Fraumeni Syndrome","volume":"23","author":"Kratz","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e419","DOI":"10.1016\/S1470-2045(18)30364-4","article-title":"Biological material collection to advance translational research and treatment of children with CNS tumours: Position paper from the SIOPE Brain Tumour Group","volume":"19","author":"Rutkowski","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/nan.12716","article-title":"Advanced molecular pathology for rare tumours: A national feasibility study and model for centralised medulloblastoma diagnostics","volume":"47","author":"Crosier","year":"2021","journal-title":"Neuropathol. Appl. Neurobiol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/23\/6077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:38:49Z","timestamp":1760168329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/23\/6077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":73,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cancers13236077"],"URL":"https:\/\/doi.org\/10.3390\/cancers13236077","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]}}}