Pdct-12. Outcomes for Non Metastatic Desmoplastic/ Nodular Infant Medulloblastoma Treated With Reduced Intensity Chemotherapy and Oral Maintenance Chemotherapy
Year: 2016
Type: conference-abstract
Abstract: Young children with non-metastatic (M0) gross totally resected (GTR) medulloblastoma with extensive nodularity (MBEN) or desmoplastic/nodular (DN) pathology have a reported 5-year progression free survival (PFS) of > 85% with high dose chemotherapy. Herein we evaluate if a dose-reduced chemotherapy regimen can achieve a similarly high PFS, while averting the adverse effects of high dose chemotherapy. Children < 3 years of age with M0 DN/MBEN and GTR were prospectively enrolled on a multi-institutional, risk adapted protocol, SJYC07. All participants were prescribed 4 courses of induction therapy- systemic methotrexate, vincristine, cisplatin and cyclophosphamide, 2 courses of consolidation therapy - carboplatin/VP-16 and 6 months oral maintenance chemotherapy - alternating cycles of cyclophosphamide/topotecan and erlotinib. DNA methylation profiling using the Infinium Human-Methylation 450K BeadChip array was performed to determine molecular subgroup of MB. Enrollment was stopped early after 23 patients, when the observed 1-year PFS fell below the monitoring threshold of 80%. At the time of analysis with median follow up of 5.1 years from treatment initiation, 20/23 patients (87%) are alive with 5 year PFS=60% (SE, 12.7%). All 23 belonged to the SHH subgroup. Nine patients progressed at a median time of 9.3 months from start of therapy- 5 local, 3 distant and 1 combined. At median follow up of 2.3 years from progression, 6/9 patients are alive after salvage with surgery, focal/craniospinal radiotherapy and/or chemotherapy. There were no treatment related deaths in the cohort. The majority of children with M0 DN/MBEN can be successfully and less morbidly treated with reduced dose chemotherapy regimen, however outcomes are inferior to prior reports. These results heighten the need for improved stratification of patients within this population. We propose that additional predictive molecular risk factors be sought to identify subset of children who stand to benefit from this dose-reduced regimen.
Source: Neuro-Oncology
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2588824862