Originally published as JCO Early Release 10.1200/JCO.2008.18.7724 on December 8 2008

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Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor

Susan N. Chi, Mary Ann Zimmerman, Xiaopan Yao, Kenneth J. Cohen, Peter Burger, Jaclyn A. Biegel, Lucy B. Rorke-Adams, Michael J. Fisher, Anna Janss, Claire Mazewski, Stewart Goldman, Peter E. Manley, Daniel C. Bowers, Anne Bendel, Joshua Rubin, Christopher D. Turner, Karen J. Marcus, Liliana Goumnerova, Nicole J. Ullrich, Mark W. Kieran

From the Dana-Farber Cancer Institute; Children's Hospital Boston, Boston, MA; Johns Hopkins Medical Center, Baltimore, MD; Children's Hospital of Philadelphia, Philadelphia, PA; Children's Healthcare of Atlanta, Atlanta, GA; Children's Memorial Medical Center, Chicago, IL; Hasbro Children's Hospital, Providence, RI; University of Texas Southwestern Medical Center, Dallas, TX; Children's Hospitals and Clinics of Minnesota, Minneapolis/St Paul, MN; and Washington University at St Louis, St Louis, MO

Corresponding author: Susan Chi, MD, Dana-Farber Cancer Institute, 44 Binney St, SW331, Boston, MA; e-mail: susan_chi{at}dfci.harvard.edu

Purpose Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with a historic median survival ranging from 6 to 11 months. Based on a previous pilot series, a prospective multi-institutional trial was conducted for patients with newly diagnosed CNS ATRT.

Patients and Methods Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy (RT) was prescribed, either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on age and extent of disease at diagnosis.

Results Between 2004 and 2006, 25 patients were enrolled; 20 were eligible for evaluation. Median age at diagnosis was 26 months (range, 2.4 months to 19.5 years). Gross total resection of the primary tumor was achieved in 11 patients. Fourteen patients had M0 disease at diagnosis, one patient had M2 disease, and five patients had M3 disease. Fifteen patients received radiation therapy: 11 focal and four craniospinal. Significant toxicities, in addition to the expected, included radiation recall (n = 2) and transverse myelitis (n = 1). There was one toxic death. Of the 12 patients who were assessable for chemotherapeutic response (pre-RT), the objective response rate was 58%. The objective response rate observed after RT was 38%. The 2-year progression-free and overall survival rates are 53% ± 13% and 70% ± 10%, respectively. Median overall survival has not yet been reached.

Conclusion This intensive multimodality regimen has resulted in a significant improvement in time to progression and overall survival for patients with this previously poor-prognosis tumor.

published online ahead of print at www.jco.org on December 8, 2008

Supported by the Stop and Shop Family Supermarkets Brain Tumor Clinic, the Dana-Farber Cancer Institute Pediatric Brain Tumor Clinical and Research Fund, and a grant from the National Institutes of Health (Grant No. CA46274) to J.A.B.

Presented in part at the International Symposium on Pediatric Neuro-Oncology, June 29-July 2, 2008, Chicago, IL.

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

Clinical trial information can be found for the following: NCT00084838 [ClinicalTrials.gov]

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