6533b833fe1ef96bd129b93f

RESEARCH PRODUCT

MBCL-07. NON-METASTATIC MEDULLOBLASTOMA OF EARLY CHILDHOOD: RESULTS FROM THE PROSPECTIVE CLINICAL TRIAL HIT-2000 AND AN EXTENDED VALIDATION COHORT

Andreas FaldumDenise ObrechtMonika Warmuth-metzHildegard DohmenAndreas Von DeimlingAndreas Von DeimlingPaul-gerhardt SchlegelAndrey KorshunovAndrey KorshunovElisabeth J. RushingChristine HaberlerMartin MynarekTorsten PietschKatharina FilipskiNicolas U. GerberMarkus J. RiemenschneiderJens SchittenhelmOri StaszewskiBrigitte BisonMartin BeneschKlaus PietschmannClemens SommerOlga ZheludkovaWolfgang BrückHolger OttensmeierAndrey GolanovMatthias MeinhardtStefan RutkowskiTanvi SharmaChristian MawrinNatalie JaegerUlrich SchüllerChristian HartmannFrank DeinleinCamelia-maria MonoranuGudrun FleischhackArend KochAndré O. Von BuerenFelix SahmRobert KwiecienStefan M. PfisterCarsten FriedrichMarcel KoolMichael A. GrotzerMarina RyzhovaMartin SillKatja Von HoffKatja Von HoffMartin HasselblattRolf-dieter KortmannIrene Slavc

subject

MedulloblastomaOncologyCancer Researchmedicine.medical_specialtybusiness.industrymedicine.disease3. Good healthClinical trialOncologyInternal medicinemedicineNon metastaticMedulloblastoma (Clinical)AcademicSubjects/MED00300AcademicSubjects/MED00310Neurology (clinical)Early childhoodbusinessValidation cohort

description

Abstract OBJECTIVE To avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy. PATIENTS AND METHODS Eighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for non-response or progression. After 2006, local radiotherapy was introduced for non-responders or classic (CMB), anaplastic or large-cell medulloblastoma (LCA). Infantile SHH-activated medulloblastomas (SHH_INF) were subdivided by DNA-methylation profiling. Survival in SHH_INF subtypes were also assessed in a validation cohort (n=71). RESULTS Patients with desmoplastic medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) (n=42) had 93% 5-year PFS, 100% 5-year OS and 93% 5-year CSI-free survival. Patients with CMB/LCA (n=45) had 37% 5y-PFS, 62% 5y-OS and 39% 5y-CSI-free survival. Local radiotherapy did not improve survival in CMB/LCA patients. All DMB/MBEN assessed by DNA methylation profiling belonged to the SHH_INF subgroup. Group 3 patients (5y-PFS 36% [n=14]) relapsed more frequently than SHH_INF (5y-PFS 93% [n=28]) or Group 4 patients (5y-PFS 83% [n=6], p<0.001). SHH_INF split into iSHH-I and iSHH-II subtypes in HIT-2000-BIS4 and the validation cohort, without prognostic impact (5y-PFS: iSHH-I 73% vs. iSHH-II 83%, p=0.25, n=99). Mean IQ was 90 (radiotherapy-free survivors) vs. 74 (patients that received CSI) [p=0.012]. CONCLUSION Systemic chemotherapy and intraventricular methotrexate led to favorable survival in both iSHH-subtypes of SHH-activated DMB/MBEN with acceptable neurotoxicity. Survival in non-WNT/non-SHH CMB/LCA patients was not improved by local radiotherapy. Survival was more favorable in patients with Group 4 than in patients with Group 3 medulloblastoma.

yearjournalcountryeditionlanguage
2020-12-01Neuro-Oncology
10.1093/neuonc/noaa222.483http://europepmc.org/articles/PMC7715606