Diana S Osorio1, Neha Patel2, Lingyun Ji3, Richard Sposto3, Joseph Stanek4, Sharon L Gardner5, Jeffrey C Allen5, Albert Cornelius6, Geoffrey B McCowage7, Amanda Termuhlen3, Ira J Dunkel8, Melanie Comito9, James Garvin10, Jonathan L Finlay4. 1. Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA. Diana.Osorio@nationwidechildrens.org. 2. Division of Pediatric Hematology/Oncology, University of Wisconsin, Madison, WI, USA. 3. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. 4. Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, USA. 5. Division of Pediatric Oncology, New York University Langone Medical Center, New York, NY, USA. 6. Division of Pediatric Hematology/Oncology, Helen DeVos Children's Hospital, Grand Rapids, MI, USA. 7. Department of Oncology, The Children's Hospital at Westmead, Sydney, Australia. 8. Department of Pediatrics, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. 9. Division of Pediatric Hematology/Oncology, Penn State Hershey Medical Center, Hershey, PA, USA. 10. Division of Pediatric Hematology/Oncology & Stem Cell Transplant, Columbia University Medical Center, New York, NY, USA.
Abstract
BACKGROUND: The dismal outcome in children with high-grade brainstem gliomas (BSG) accentuates the need for effective therapeutic strategies. We investigated the role of intensive, including marrow-ablative, chemotherapy regimens in the treatment of young children with newly-diagnosed high-grade BSG. METHODS: Between 1991-and-2002, 15 eligible children less than 10 years of age with a diagnosis of high-grade BSG were treated on "Head-Start" I and II protocols (HSI and HSII). Treatment included Induction with 4-5 cycles of one of three intensive chemotherapy regimens followed by Consolidation with one cycle of marrow-ablative chemotherapy (thiotepa, carboplatin and etoposide) with autologous hematopoietic cell rescue (AHCR). Irradiation was required for children over 6 years of age or for those with residual tumor at the end of Consolidation. RESULTS: We had two long-term survivors who were found retrospectively to harbor low-grade glial tumors and thus were not included in the survival analysis. Of the remaining 13 patients, the 1-year event-free (EFS) and overall (OS) survival for these children were 31% (95% CI 9-55%) and 38% (95% CI 14-63%), respectively. Median EFS and OS were 6.6 (95% CI 2.7, 12.7) and 8.7 months (95% CI 6.9, 20.9), respectively. Eight patients developed progressive disease during study treatment (seven during Induction and one at the end of Consolidation). Ten children received focal irradiation, five for residual tumor (three following Induction and two following Consolidation) and five due to disease progression. CONCLUSIONS: Children with high-grade BSG did not benefit from this intensive chemotherapy strategy administered prior to irradiation.
BACKGROUND: The dismal outcome in children with high-grade brainstem gliomas (BSG) accentuates the need for effective therapeutic strategies. We investigated the role of intensive, including marrow-ablative, chemotherapy regimens in the treatment of young children with newly-diagnosed high-grade BSG. METHODS: Between 1991-and-2002, 15 eligible children less than 10 years of age with a diagnosis of high-grade BSG were treated on "Head-Start" I and II protocols (HSI and HSII). Treatment included Induction with 4-5 cycles of one of three intensive chemotherapy regimens followed by Consolidation with one cycle of marrow-ablative chemotherapy (thiotepa, carboplatin and etoposide) with autologous hematopoietic cell rescue (AHCR). Irradiation was required for children over 6 years of age or for those with residual tumor at the end of Consolidation. RESULTS: We had two long-term survivors who were found retrospectively to harbor low-grade glial tumors and thus were not included in the survival analysis. Of the remaining 13 patients, the 1-year event-free (EFS) and overall (OS) survival for these children were 31% (95% CI 9-55%) and 38% (95% CI 14-63%), respectively. Median EFS and OS were 6.6 (95% CI 2.7, 12.7) and 8.7 months (95% CI 6.9, 20.9), respectively. Eight patients developed progressive disease during study treatment (seven during Induction and one at the end of Consolidation). Ten children received focal irradiation, five for residual tumor (three following Induction and two following Consolidation) and five due to disease progression. CONCLUSIONS:Children with high-grade BSG did not benefit from this intensive chemotherapy strategy administered prior to irradiation.
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