Title | Phase II Study of Nonmetastatic Desmoplastic Medulloblastoma in Children Younger Than 4 Years of Age: A Report of the Children's Oncology Group (ACNS1221) |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Lafay-Cousin L, Bouffet E, Strother D, Rudneva V, Hawkins C, Eberhart C, Horbinski C, Heier L, Souweidane M, Williams-Hughes C, Onar-Thomas A, Billups CA, Fouladi M, Northcott P, Robinson G, Gajjar A |
Journal | J Clin Oncol |
Volume | 38 |
Issue | 3 |
Pagination | 223-231 |
Date Published | 2020 Jan 20 |
ISSN | 1527-7755 |
Abstract | PURPOSE: Nodular desmoplastic medulloblastoma (ND) and medulloblastoma with extensive nodularity (MBEN) have been associated with a more favorable outcome in younger children. However, treatment-related neurotoxicity remains a significant concern in this vulnerable group of patients. PATIENTS AND METHODS: ACNS1221 was a prospective single-arm trial of conventional chemotherapy for nonmetastatic ND and MBEN based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate, aiming to achieve similar outcome (2-year progression-free survival [PFS] ≥ 90%) with reduced treatment-related neurotoxicity. Secondary objectives included feasibility of timely central pathology review and evaluation of tumor molecular profile. RESULTS: Twenty-five eligible patients (15 males and 10 females; median age, 18.7 months) were enrolled. Eighteen patients had ND and 7 had MBEN histology. Three patients had residual disease at baseline. The study closed early because of a higher than expected relapse rate. Twelve patients experienced relapse-local (n= 6), distant (n = 3), and combined (n = 3)-at a median of 9.8 months from diagnosis (range, 8.9-13.7 months), and 2 patients died of disease. Two-year PFS and overall survival rates were 52% (95% CI, 32.4% to 71.6%) and 92% (95% CI, 80.8% to 100.0%) respectively. Patients older than 12 months of age ( = .036) and ND histology ( = .005) were associated with worse PFS. No patients with MBEN histology experienced relapse. All tumor samples clustered within the sonic hedgehog (SHH) group. Methylation analysis delineated 2 subgroups, SHH-I and SHH-II, which were associated with 2-year PFS rates of 30.0% (95% CI, 1.6% to 58.4%) and 66.7% (95% CI, 44.0% to 89.4%), respectively ( = .099). CONCLUSION: The proposed modified regimen of conventional systemic chemotherapy without serial intraventricular methotrexate injection failed to achieve the targeted 2-year PFS of 90%. With this cohort, we prospectively confirmed the existence of two SHH subgroups and observed a trend toward worse outcome for SHH-I patients. |
DOI | 10.1200/JCO.19.00845 |
Alternate Journal | J. Clin. Oncol. |
PubMed ID | 31774708 |
PubMed Central ID | PMC6968798 |
Grant List | U10 CA098413 / CA / NCI NIH HHS / United States U10 CA098543 / CA / NCI NIH HHS / United States U10 CA180886 / CA / NCI NIH HHS / United States U10 CA180899 / CA / NCI NIH HHS / United States |