Evidence map›Paper›PMID 41159377›Full record

ArticleNeuro-oncology2026

An integrated analysis of three medulloblastoma clinical trials refines risk-stratification approaches for reducing toxicity and improving survival.

Kyle S Smith, Sandeep K Dhanda, Catherine A Billups, Edgar Sioson, Congyu Lu, Airen Zaldivar Peraza, Karishma Gangwani, Yimei Li, Qian Li, Tong Lin and 10 more

3 registry-linked trialsAbstract read
In one paragraph

Article in Neuro-oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00085202 phase3completednot on this map

Treatment of Patients With Newly Diagnosed Medulloblastoma, Supratentorial Primitive Neuroectodermal Tumor, or Atypical Teratoid Rhabdoid Tumor

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2003 to 2023Enrolled416ConditionsBrain and Central Nervous System TumorsArmsfilgrastim, cisplatin, cyclophosphamide, vincristine, autologous hematopoietic stem cell transplantation
NCT00085735 phase3completednot on this map

A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial

TypeinterventionalSponsorChildren's Oncology GroupRan2004 to 2024Enrolled549ConditionsMedulloblastomaArmsCisplatin, Craniospinal Irradiation, Cyclophosphamide, Involved-Field Radiation Therapy, Laboratory Biomarker Analysis
NCT00392327 phase3completednot on this map

Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients

TypeinterventionalSponsorChildren's Oncology GroupRan2007 to 2026Enrolled379ConditionsAnaplastic Medulloblastoma, MedulloblastomaArmsBiospecimen Collection, Carboplatin, Cisplatin, Cyclophosphamide, Filgrastim
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Time to adjuvant treatment for newly diagnosed pediatric brain tumors in the molecular era: a single center retrospective study.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Article
  2. Surgical resection in medulloblastoma: a crossroads in the molecular era.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Review
  3. Review
  4. Article
  5. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Kyle S SmithDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis (K.S.S., P.A.N.).
Sandeep K DhandaDivision of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis (S.K.D., A.G., G.W.R.).
Catherine A BillupsDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis (C.A.B., Y.L., Q.L., T.L., A.O.-T.).
Edgar SiosonDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis (E.S., C.L., A.Z.P., K.G., X.Z.).
Congyu LuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis (E.S., C.L., A.Z.P., K.G., X.Z.).
Airen Zaldivar PerazaDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis (E.S., C.L., A.Z.P., K.G., X.Z.).
Karishma GangwaniDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis (E.S., C.L., A.Z.P., K.G., X.Z.).
Yimei LiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis (C.A.B., Y.L., Q.L., T.L., A.O.-T.).
Qian LiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis (C.A.B., Y.L., Q.L., T.L., A.O.-T.).
Tong LinDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis (C.A.B., Y.L., Q.L., T.L., A.O.-T.).
Jeff M MichalskiDepartment of Radiation Oncology, Washington University School of Medicine, St Louis (J.M.M.).
Roger J PackerBrain Tumor Institute, Gilbert Family Neurofibromatosis Institute, Center for Neuroscience and Behavioral Medicine, Children's National Hospital, Washington (R.J.P.).
James M OlsonBen Towne Center for Childhood Cancer and Blood Disorder's Research, Seattle Children's Research Institute, Seattle (J.M.O., S.E.S.L.); Department of Pediatrics, University of Washington, Seattle (J.M.O., S.E.S.L.); Fred Hutchinson Cancer Research Center, Seattle (J.M.O., S.E.S.L.).
Sarah E S LearyBen Towne Center for Childhood Cancer and Blood Disorder's Research, Seattle Children's Research Institute, Seattle (J.M.O., S.E.S.L.); Department of Pediatrics, University of Washington, Seattle (J.M.O., S.E.S.L.); Fred Hutchinson Cancer Research Center, Seattle (J.M.O., S.E.S.L.).
Maryam FouladiNationwide Children's Hospital, Columbus (M.F.).ORCID 0009-0005-3039-3313
Amar GajjarDivision of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis (S.K.D., A.G., G.W.R.).ORCID 0000-0001-5019-0699
Xin ZhouDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis (E.S., C.L., A.Z.P., K.G., X.Z.).ORCID 0000-0003-3979-8200
Arzu Onar-ThomasDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis (C.A.B., Y.L., Q.L., T.L., A.O.-T.).ORCID 0000-0003-1005-2413
Paul A NorthcottDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis (K.S.S., P.A.N.).
Giles W RobinsonDivision of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis (S.K.D., A.G., G.W.R.).ORCID 0000-0001-7441-9486

Funding

Pediatric brain tumors: Improving survival through integration of clinical molecular diagnostics and biologically targeted therapies into clinical trialsR50CA275857 · NCI · SEATTLE CHILDREN'S HOSPITAL · PI Sarah Elisabeth Sherr Leary · 2023 to 2026
$701k
American Lebanese Syrian Associated CharitiesCCSG 5P30CA021765-43 Developmental Funds 1R01CA270785-01A1CCSG 5P30CA021765-43 Developmental Funds P01CA096832NCI NIH HHS R50 CA275857St. Baldrick's Foundationthe National Cancer Institute P30CA021765
6 · The paper itself

Abstract

backgroundThe identification of clinical and molecular heterogeneity in medulloblastoma has produced risk-stratified therapy, but establishing the most effective yet least toxic regimens has remained elusive owing to numerous treatment options. To improve risk-stratification, we performed an integrated analysis from three clinical trials.

methodsMedulloblastoma patients from ACNS0331/NCT00085735, ACNS0332/NCT00392327, and SJMB03/NCT00085202 were included if they had methylation profiling. Molecular groups [WNT, SHH, Group 3 (G3), and Group 4 (G4)], subgroups, and copy number variations were procured from methylation profiles and mutations from next-generation sequencing. Data was assembled into an interactive portal to capture patient characteristics. Cross-trial comparisons, univariable, and multivariable analyses were conducted and used to derive a risk-stratification schema.

resultsEight hundred ninety-eight patients (WNT = 131, SHH = 151, G3 = 220, G4 = 396) were included. Progression-free-survival (PFS) distributions among analogous cross-trial cohorts were not different, demonstrating no survival advantage of any one therapy over another. The addition of carboplatin to high-dose craniospinal irradiation (HDCSI) containing regimen was selectively superior in PFS in G3/G4 subgroup 3 (P = 0.048) and G3/G4 subgroup 2 (P = 0.035) to HDCSI regimens without carboplatin. Nine actionable risk-stratified groups were identified consisting of 2 WNT groups (low, high-risk), 3 SHH groups (low-, average-, very-high-risk), and 4 G3/G4 groups (low-, average-, high-, and very-high-risk).

conclusionsOur integrated cross-trial analysis suggests toxicity can be reduced by eliminating disproportionate differences in therapy in favor of a more uniform treatment backbone. Moreover, we propose and model a risk-classification system that identifies the most appropriate cohorts on which to trial significant dose reductions in craniospinal irradiation or select treatment intensifications.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCerebellar NeoplasmsChemoradiotherapyMedulloblastomaAdolescentAdultChildChild, PreschoolClinical Trials as TopicCraniospinal IrradiationDNA MethylationFemaleFollow-Up StudiesHumansMaleMutationcraniospinal irradiationmedulloblastomamethylationmolecular ­categorizationrisk stratified therapy

Identifiers

PMID41159377
PMCPMC12962632

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.