Girish Dhall1, Sharon H O'Neil2, Lingyun Ji3, Kelley Haley4, Ashley M Whitaker4, Marvin D Nelson5, Floyd Gilles6, Sharon L Gardner7, Jeffrey C Allen7, Albert S Cornelius8, Kamnesh Pradhan9, James H Garvin10, Randal S Olshefski11, Juliette Hukin12, Melanie Comito13, Stewart Goldman14, Mark P Atlas15, Andrew W Walter16, Stephen Sands17, Richard Sposto4, Jonathan L Finlay11. 1. Division of Pediatric Hematology-Oncology, University of Alabama Birmingham, Birmingham, Alabama, USA. 2. Division of Neurology and The Saban Research Institute, Children's Hospital Los Angeles (CHLA), Los Angeles, California, USA. 3. Department of Preventive Medicine, Keck School of Medicine at the University of Southern California, Los Angeles, California, USA. 4. Division of Hematology-Oncology CHLA, Los Angeles, California, USA. 5. Department of Radiology CHLA, Los Angeles, California, USA. 6. Department of Pathology CHLA, Los Angeles, California, USA. 7. Division of Pediatric Hematology-Oncology, NYU Medical Center, New York, New York, USA. 8. Division of Pediatric Hematology-Oncology, Helen DeVos Children's Hospital, Grand Rapids, Michigan, USA. 9. Division of Pediatric Hematology-Oncology, Riley Hospital for Children, Indianapolis, Indiana, USA. 10. Division of Pediatric Hematology-Oncology, New York Presbyterian Hospital, New York, New York, USA. 11. Division of Pediatric Hematology-Oncology, Nationwide Children's Hospital, Columbus, Ohio, USA. 12. Division of Pediatric Hematology-Oncology, British Columbia Children's Hospital, Vancouver, British Columbia, Canada. 13. Division of Pediatric Hematology-Oncology, Penn State Hershey Children's Hospital, Hershey, Pennsylvania, USA. 14. Division of Pediatric Hematology-Oncology, Lurie Children's Hospital, Chicago, Illinois, USA. 15. Division of Pediatric Hematology-Oncology, Children's Medical Center of New York, New York, New York, USA. 16. Division of Pediatric Hematology-Oncology, Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA. 17. Departments of Psychiatry and Behavioral Sciences and Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
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.
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) medulloblastomapatients 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 medulloblastomapatients. 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.
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