{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317378/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Methylation profiling"],"species":["Homo sapiens"],"gds_type":["Methylation profiling by genome tiling array"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317378"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Integrated biomarker and treatment correlates of prognosis in infant medulloblastoma: Multi-national retrospective cohort studies","description":"This dataset spans two studies which investigate the clinico-pathology and molecular features of infant medulloblastoma, defined as children aged <5 years at diagnosis. Both abstracts follow. Background Infant medulloblastoma (iMB; <3-5-years old at diagnosis) is a major challenge in paediatric oncology. The favourable-risk SHH iMB molecular group with desmoplastic histology (40% of iMB) is commonly spared upfront craniospinal irradiation (CSI) to avoid neurocognitive side-effects. However, clinical studies of the remaining non-WNT/non-SHH iMB group (~60% of iMBs) have not been undertaken, and it is currently considered uniformly high-risk. Understanding the potential for its biological subclassification and clinical stratification is an essential goal towards improved outcomes. This study therefore aimed to directly compare different therapeutic approaches in non-WNT/non-SHH iMB and determine relationships between outcomes and clinico-molecular features. Methods We assembled a global cohort of non-WNT/non-SHH iMBs (n=375). Inclusion criteria was a principal non-WNT/non-SHH MB classification (Group 3 or Group 4); confidence score >0.8) using DNA methylation array-based classification. The survival cohort (n=313) was defined by availability of complete progression-free (PFS) and overall (OS) survival data. Using these cohorts, we characterised their molecular pathology, treatments received, and relationships to outcomes, principally PFS. Findings The total collected cohort (n=375) comprised 262 males and 110 females, with a median age of 3.0 (IQR 2.53-4.0) years. Molecular group 3 tumours (iMBGrp3) predominated (n=246, 66%), primarily molecular subgroups 2 (n=75; 32%), 3 (n=46; 19%) and 4 (n=98; 42%). Regimens incorporating upfront CSI were most common (54% of patients); such patients had significantly better PFS than those treated with focal or no radiotherapy (5-year PFS; CSI, 57.9%; Focal-radiotherapy, 35.3%; No radiotherapy, 26.8%; p<0.001), and equivalent PFS to CSI-treated non-infant patients. Upfront chemotherapy -only approaches were used in 33% (66/199) of iMBGrp3; high-dose (HIGH-DOSE) chemotherapy produced better survival rates (45.7%, 5-year PFS) than intraventricular methotrexate-based (21.1%, 5-year PFS) or standard-dose (11%, 2-year PFS) chemotherapy (p=0.003). Subgroup 4 represents a novel chemo-sensitive iMB group, with 64.3% 5-year PFS using high-dose -chemotherapy-only and with evidence of rescue post-relapse. MYC-amplified iMBGrp3 ( subgroup2/3) have dismal prognosis (0% 2-year overall survival (OS)), with rapid progression regardless of treatment. Remaining subgroup 2/3 patients treated with Chemotherapy-only had 30% 5-year PFS, showed some evidence of post-relapse rescue, and could be randomised to test alternative therapeutic strategies. Interpretation Non-WNT/non-SHH iMB outcomes are associated with specific biomarkers and therapy received. Capturing this ‘real-world’ experience identifies favourable ( subgroup 4) and very-high-risk ( subgroup 2/3-MYC) patient groups, providing a critical foundation for first biomarker-driven iMBGrp3 clinical trials. Background Medulloblastoma in infants (iMB; <5 years) presents the challenge of achieving cure while minimizing deleterious cranio-spinal irradiation (CSI)-associated late-effects. Non-randomised Phase-II studies have examined upfront CSI omission and chemotherapy intensification for favourable-risk desmoplastic/nodular (DN) tumours associated with the SHH molecular group (iMBSHH). Comparison of these therapies in large molecularly-defined iMBSHH cohorts, alongside investigations of prognostic biomarkers in therapy-specific context, is urgently required to define future therapeutic strategies. Methods A multi-national cohort of molecularly and clinically-annotated iMBSHH (n=267), not previously reported in clinical trials, was assembled. We investigated molecular pathology, upfront treatments, and relationships to outcome, in this ‘real-world’ setting. Findings iMBSHH patients treated upfront with intensified chemotherapy-only regimens (n=132) based on intraventricular methotrexate (IVT-MTX; 5-year progression-free survival (PFS), 72.6%) or high-dose (HD; 73.0%) therapy, achieved (PFS) outcomes comparable to upfront CSI-based regimens (n=49; 74.0%)(p=0.51). Lower-intensity standard-dose chemotherapy-only regimens were inferior (SD; 48.4% PFS)(p=0.006). Rescue was common post-relapse after IVT-MTX/HD protocols and translated into 5-year overall survival (OS) of 85.6% and 88.6%, respectively. iMBSHH encompassed SHH-1 (38%), SHH-2 (47%) and SHH-3 (14%) WHO subgroups. In CSI-naïve iMBSHH, SD associated with worse PFS in SHH-1 (p=0.001), but not SHH-2. Non-DN/MBEN histology (21.2% of iMBSHH) conferred worse PFS in upfront CSI-treated and SD (p<0.001 and p=0.003, respectively) groups. Metastatic disease only associated with prognosis with upfront IVT-MTX-only therapies (p=0.013), while established high-risk features of non-infant MBSHH (TP53-mutation, LCA-histology, MYCN-amplification) only associated with poor prognosis in older SHH-3 (7/7 relapsed). Finally, CSI-naïve PFS findings were validated in a re-evaluation of smaller historical trials cohorts. Interpretation iMBSHH outcomes and prognostic biomarkers are therapy-dependent. Non-metastatic iMBSHH treated with HD or IVT-MTX chemotherapy-only have equivalent favourable outcomes, independent of histology and subgroup. With outcomes established, clinical trials must now focus on quality-of-life following different intensified approaches, to identify kindest curative strategies.","dates":{"publication":"2026/05/29"},"accession":"GSE317378","cross_references":{"GSM":["GSM9470912","GSM9470911","GSM9470914","GSM9470913","GSM9470910","GSM9470919","GSM9470916","GSM9470915","GSM9470918","GSM9470917","GSM9470901","GSM9470900","GSM9470903","GSM9470902","GSM9470909","GSM9470908","GSM9470905","GSM9470904","GSM9470907","GSM9470906","GSM9470956","GSM9470955","GSM9470958","GSM9470957","GSM9471008","GSM9470952","GSM9471129","GSM9470951","GSM9471009","GSM9470954","GSM9471127","GSM9471006","GSM9470953","GSM9471128","GSM9471007","GSM9470959","GSM9471136","GSM9471015","GSM9471137","GSM9471016","GSM9471134","GSM9471013","GSM9470961","GSM9471014","GSM9471135","GSM9470960","GSM9471011","GSM9471132","GSM9471133","GSM9471012","GSM9471130","GSM9471131","GSM9471010","GSM9470945","GSM9470944","GSM9470947","GSM9470946","GSM9470941","GSM9471118","GSM9471119","GSM9470940","GSM9471116","GSM9470943","GSM9470942","GSM9471117","GSM9470949","GSM9470948","GSM9471125","GSM9471004","GSM9471005","GSM9471126","GSM9471123","GSM9470950","GSM9471002","GSM9471124","GSM9471003","GSM9471121","GSM9471000","GSM9471122","GSM9471001","GSM9471120","GSM9470934","GSM9470933","GSM9470936","GSM9471109","GSM9470935","GSM9470930","GSM9471107","GSM9471108","GSM9471105","GSM9470932","GSM9470931","GSM9471106","GSM9470938","GSM9470937","GSM9470939","GSM9471114","GSM9471115","GSM9471112","GSM9471113","GSM9471110","GSM9471111","GSM9470923","GSM9470922","GSM9470925","GSM9470924","GSM9470921","GSM9470920","GSM9470927","GSM9470926","GSM9470929","GSM9470928","GSM9471103","GSM9471104","GSM9471101","GSM9471102","GSM9471100","GSM9470999","GSM9470996","GSM9470995","GSM9470998","GSM9470997","GSM9471051","GSM9471052","GSM9471050","GSM9471059","GSM9471057","GSM9471058","GSM9471055","GSM9471056","GSM9471053","GSM9471054","GSM9470989","GSM9470988","GSM9470985","GSM9470984","GSM9471039","GSM9470987","GSM9470986","GSM9471040","GSM9471041","GSM9471048","GSM9470992","GSM9470991","GSM9471049","GSM9470994","GSM9471046","GSM9470993","GSM9471047","GSM9471044","GSM9471045","GSM9470990","GSM9471042","GSM9471043","GSM9470978","GSM9470977","GSM9470979","GSM9470974","GSM9470973","GSM9471028","GSM9470976","GSM9471149","GSM9470975","GSM9471029","GSM9471150","GSM9471151","GSM9471030","GSM9471037","GSM9470981","GSM9471038","GSM9470980","GSM9471035","GSM9470983","GSM9471036","GSM9470982","GSM9471033","GSM9471034","GSM9471031","GSM9471152","GSM9471153","GSM9471032","GSM9470967","GSM9470966","GSM9470969","GSM9470968","GSM9471019","GSM9470963","GSM9470962","GSM9470965","GSM9471017","GSM9471138","GSM9471139","GSM9471018","GSM9470964","GSM9471140","GSM9470970","GSM9471147","GSM9471026","GSM9471148","GSM9471027","GSM9471145","GSM9471024","GSM9470972","GSM9471025","GSM9470971","GSM9471146","GSM9471143","GSM9471022","GSM9471144","GSM9471023","GSM9471141","GSM9471020","GSM9471142","GSM9471021","GSM9471095","GSM9471096","GSM9471093","GSM9471094","GSM9471091","GSM9471092","GSM9471090","GSM9471099","GSM9471097","GSM9471098","GSM9471084","GSM9471085","GSM9471082","GSM9471083","GSM9471080","GSM9471081","GSM9471088","GSM9471089","GSM9471086","GSM9471087","GSM9470897","GSM9470896","GSM9470899","GSM9470898","GSM9471073","GSM9471074","GSM9471071","GSM9471072","GSM9471070","GSM9471079","GSM9471077","GSM9471078","GSM9471075","GSM9471076","GSM9470889","GSM9471062","GSM9471063","GSM9471060","GSM9471061","GSM9470893","GSM9470892","GSM9471068","GSM9470895","GSM9470894","GSM9471069","GSM9471066","GSM9471067","GSM9470891","GSM9471064","GSM9470890","GSM9471065"],"GPL":["21145","13534"],"GSE":["317378"],"taxon":["Homo sapiens"]}}