TY  - JOUR
AU  - Robinson, Giles W
AU  - Rudneva, Vasilisa A
AU  - Buchhalter, Ivo
AU  - Billups, Catherine A
AU  - Waszak, Sebastian M
AU  - Smith, Kyle S
AU  - Bowers, Daniel C
AU  - Bendel, Anne
AU  - Fisher, Paul G
AU  - Partap, Sonia
AU  - Crawford, John R
AU  - Hassall, Tim
AU  - Indelicato, Daniel J
AU  - Boop, Frederick
AU  - Klimo, Paul
AU  - Sabin, Noah D
AU  - Patay, Zoltan
AU  - Merchant, Thomas E
AU  - Stewart, Clinton F
AU  - Orr, Brent A
AU  - Korbel, Jan O
AU  - Jones, David
AU  - Sharma, Tanvi
AU  - Lichter, Peter
AU  - Kool, Marcel
AU  - Korshunov, Andrey
AU  - Pfister, Stefan
AU  - Gilbertson, Richard J
AU  - Sanders, Robert P
AU  - Onar-Thomas, Arzu
AU  - Ellison, David W
AU  - Gajjar, Amar
AU  - Northcott, Paul A
TI  - Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial.
JO  - The lancet  / Oncology
VL  - 19
IS  - 6
SN  - 1470-2045
CY  - London
PB  - The Lancet Publ. Group
M1  - DKFZ-2018-00705
SP  - 768 - 784
PY  - 2018
AB  - Young children with medulloblastoma have a poor overall survival compared with older children, due to use of radiation-sparing therapy in young children. Radiotherapy is omitted or reduced in these young patients to spare them from debilitating long-term side-effects. We aimed to estimate event-free survival and define the molecular characteristics associated with progression-free survival in young patients with medulloblastoma using a risk-stratified treatment strategy designed to defer, reduce, or delay radiation exposure.In this multicentre, phase 2 trial, we enrolled children younger than 3 years with newly diagnosed medulloblastoma at six centres in the USA and Australia. Children aged 3-5 years with newly diagnosed, non-metastatic medulloblastoma without any high-risk features were also eligible. Eligible patients were required to start therapy within 31 days from definitive surgery, had a Lansky performance score of at least 30, and did not receive previous radiotherapy or chemotherapy. Patients were stratified postoperatively by clinical and histological criteria into low-risk, intermediate-risk, and high-risk treatment groups. All patients received identical induction chemotherapy (methotrexate, vincristine, cisplatin, and cyclophosphamide), with high-risk patients also receiving an additional five doses of vinblastine. Induction was followed by risk-adapted consolidation therapy: low-risk patients received cyclophosphamide (1500 mg/m2 on day 1), etoposide (100 mg/m2 on days 1 and 2), and carboplatin (area under the curve 5 mg/mL per min on day 2) for two 4-week cycles; intermediate-risk patients received focal radiation therapy (54 Gy with a clinical target volume of 5 mm over 6 weeks) to the tumour bed; and high-risk patients received chemotherapy with targeted intravenous topotecan (area under the curve 120-160 ng-h/mL intravenously on days 1-5) and cyclophosphamide (600 mg/m2 intravenously on days 1-5). After consolidation, all patients received maintenance chemotherapy with cyclophosphamide, topotecan, and erlotinib. The coprimary endpoints were event-free survival and patterns of methylation profiling associated with progression-free survival. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy); biological analyses included all patients with tissue available for methylation profiling. This trial is registered with ClinicalTrials.gov, number NCT00602667, and was closed to accrual on April 19, 2017.Between Nov 27, 2007, and April 19, 2017, we enrolled 81 patients with histologically confirmed medulloblastoma. Accrual to the low-risk group was suspended after an interim analysis on Dec 2, 2015, when the 1-year event-free survival was estimated to be below the stopping rule boundary. After a median follow-up of 5·5 years (IQR 2·7-7·3), 5-year event-free survival was 31·3
LB  - PUB:(DE-HGF)16
C6  - pmid:29778738
DO  - DOI:10.1016/S1470-2045(18)30204-3
UR  - https://inrepo02.dkfz.de/record/135968
ER  -