This collection contains data from the Children’s Oncology Group (COG) Clinical Trial NCT00392327, "Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET". The Study Chair was James M. Olson, M.D., Ph.D. It was sponsored by NCI and performed by the Children's Oncology Group under study number ACNS0332. This randomized phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma.  Select patient-level clinical data from this trial is available via the following link: https://nctn-data-archive.nci.nih.gov/node/838.

Trial Description

Children with histologically diagnosed high-risk medulloblastoma, supratentorial primitive neuro-ectodermal tumor of the CNS (CNS-PNET), and pineoblastoma (PBL) have had poor survival despite intensive treatment.  The Children’s Oncology Group (COG) study ACNS0332 was designed to test two approaches for treatment intensification for these patients: addition of carboplatin during irradiation and/or addition of isotretinoin to the adjuvant regimen. Carboplatin has demonstrated preclinical and clinical efficacy in these tumors and is well tolerated in children, whereas isotretinoin crosses the blood-brain barrier efficiently and is effective against preclinical models of medulloblastoma (MB).  Molecular profiling later revealed tumor heterogeneity that was not detectable at protocol inception. Enrollment of patients with CNS-PNET/PBL was subsequently discontinued, and outcomes for this part of the study reported.  Eighty-five participants with institutionally diagnosed CNS-PNETs/PBLs were enrolled. Of 60 patients with sufficient tissue, 31 had tumors that were non-pineal in location. Twenty-two patients (71%) of those 31 were diagnosed with tumor types not intended for trial inclusion, including 18 high-grade (HGGs), two atypical teratoid rhbdoid tumors, and 2 ependymomas. Outcomes across tumor types were strikingly different. Neither carboplatin, nor isotretinoin significantly altered outcomes for all patients. Survival for patients with HGG was similar to that of historic studies that avoid craniospinal irradiation and intensive chemotherapy.  For patients with CNS-PNET/PBL, prognosis is considerably better than previously assumed when molecularly confirmed HGGs are removed. Identification of molecular HGGs may spare affected children from unhelpful intensive treatment. This trial highlights the challenges of a histology-based diagnosis for pediatric brain tumors and indicates that molecular profiling should become a standard component of initial diagnosis.

Pre-operative and post-operative MRI scans of the brain with and without contrast and spinal MRI with and without contrast were required.  All scans underwent central review.

Trial Outcomes

Results of the trial have been reported in the following publication:

Hwang, E. I., Kool, M., Burger, P. C., Capper, D., Chavez, L., Brabetz, S., Williams-Hughes, C., Billups, C., Heier, L., Jaju, A., Michalski, J., Li, Y., Leary, S., Zhou, T., von Deimling, A., Jones, D. T. W., Fouladi, M., Pollack, I. F., Gajjar, A., … Olson, J. M. (2018). Extensive Molecular and Clinical Heterogeneity in Patients With Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children’s Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology, 36(34), 3388–3395. https://doi.org/10.1200/jco.2017.76.4720. Epub ahead of print. PMID: 30332335.