Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial. Issue 12 (18th April 2020)

• Record Type: Journal Article
• Authors: Dhall, Girish; O'Neil, Sharon H; Ji, Lingyun; Haley, Kelley; Whitaker, Ashley M; Nelson, Marvin D; Gilles, Floyd; Gardner, Sharon L; Allen, Jeffrey C; Cornelius, Albert S; Pradhan, Kamnesh; Garvin, James H; Olshefski, Randal S; Hukin, Juliette; Comito, Melanie; Goldman, Stewart; Atlas, Mark P; Walter, Andrew W; Sands, Stephen; Sposto, Richard; Finlay, Jonathan L
• Is Part Of: Neuro-oncology. Volume 22:Issue 12(2020)
• Page Start: 1862
• Page End: 1872
• Publication Date: 2020-04-18
• Subjects: desmoplastic -- infants -- medulloblastoma -- myeloablative chemotherapy; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa102
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: "Head Start" III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma. Methods: Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction. Results: Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ± 5% and 62 ± 5% for all patients, 61 ± 8% and 77 ± 7% for localized medulloblastoma, and 35 ± 7% and 52 ± 7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ± 6% and 89 ± 6% compared with 26 ± 6% and 53 ± 7% for classic and 38 ± 13% and 46 ± 14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex ( P <0.0001). Five-year irradiation-free EFS was 78 ± 8% for ND and 21 ± 5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average. Conclusion: We report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.