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Phase III Study of Craniospinal Radiation Therapy Followed by Adjuvant Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma

Roger J. Packer, Amar Gajjar, Gilbert Vezina, Lucy Rorke-Adams, Peter C. Burger, Patricia L. Robertson, Lisa Bayer, Deborah LaFond, Bernadine R. Donahue, MaryAnne H. Marymont, Karin Muraszko, James Langston, Richard Sposto

From the Divisions of Neurology, Pediatrics, Radiology, and Oncology, Children’s National Medical Center; Departments of Neurology, Pediatrics, and Radiology, The George Washington University, Washington, DC; Department of Oncology and Radiology, St Jude Research Hospital, Memphis, TN; Division of Neuropathology, Children’s Hospital of Philadelphia; Department of Pathology, University of Pennsylvania, Philadelphia, PA; Department of Pathology, Johns Hopkins University, Baltimore, MD; Department of Neurology, Pediatrics and Neurosurgery, University of Michigan, Ann Arbor, MI; Division of Pediatric Hematology-Oncology, Weill Medical College of Cornell University; Department of Radiation Oncology, New York University School of Medicine, New York; Department of Radiation Oncology, Maimonides Cancer Center, Brooklyn, NY; Department of Radiation Oncology, Children’s Memorial Hospital; Department of Radiation Oncology, Northwestern University, Chicago, IL; Children’s Hospital of Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles; and the Children’s Oncology Group, Arcadia, CA

Address reprint requests to Roger J. Packer, MD, Department of Neurology, Children’s National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010; e-mail: rpacker{at}cnmc.org

Purpose To determine the event-free survival (EFS) and overall survival of children with average-risk medulloblastoma and treated with reduced-dose craniospinal radiotherapy (CSRT) and one of two postradiotherapy chemotherapies.

Methods Four hundred twenty-one patients between 3 years and 21 years of age with nondisseminated medulloblastoma (MB) were prospectively randomly assigned to treatment with 23.4 Gy of CSRT, 55.8 Gy of posterior fossa RT, plus one of two adjuvant chemotherapy regimens: lomustine (CCNU), cisplatin, and vincristine; or cyclophosphamide, cisplatin, and vincristine.

Results Forty-two of 421 patients enrolled were excluded from analysis. Sixty-six of the remaining 379 patients had incompletely assessable postoperative studies. Five-year EFS and survival for the cohort of 379 patients was 81% ± 2.1% and 86% ± 9%, respectively (median follow-up over 5 years). EFS was unaffected by sex, race, age, treatment regimen, brainstem involvement, or excessive anaplasia. EFS was detrimentally affected by neuroradiographic unassessability. Patients with areas of frank dissemination had a 5-year EFS of 36% ± 15%. Sixty-seven percent of progressions had some component of dissemination. There were seven second malignancies. Infections occurred more frequently on the cyclophosphamide arm and electrolyte abnormalities were more common on the CCNU regimen.

Conclusion This study discloses an encouraging EFS rate for children with nondisseminated MB treated with reduced-dose craniospinal radiation and chemotherapy. Additional, careful, step-wise reductions in CSRT in adequately staged patients may be possible.

Supported by a cooperative group grant to the Children’s Oncology Group (5UI0CA098543-02).

Presented in part at the 33rd Annual Meeting of the Child Neurology Society in Ottawa, Canada, October 15, 2004, and the 11th International Symposium of Pediatric Neuro-Oncology in Boston, MA, on June 14, 2005.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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