Originally published as JCO Early Release 10.1200/JCO.2004.03.036 on February 17 2004

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fernandez-Teijeiro, A. Articles by Pomeroy, S. L. Search for Related Content PubMed PubMed Citation Articles by Fernandez-Teijeiro, A. Articles by Pomeroy, S. L. Related Articles Related Article Related Editorial Social Bookmarking                            What's this?

Combining Gene Expression Profiles and Clinical Parameters for Risk Stratification in Medulloblastomas

From the Division of Neuroscience, Department of Neurology, Department of Medicine, Children's Hospital; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School; Department of Biostatistics, Harvard School of Public Health, Boston; Whitehead Institute/MIT Center of Biomedical Research, MA Institute of Technology, Cambridge, MA; and Unidad de Oncologia Pediatrica, Hospital de Cruces-Baracaldo, Basque Country, Spain

Address reprint requests to Scott L. Pomeroy, MD, PhD, Department of Neurology, Enders 260, Children's Hospital, 300 Longwood Ave, Boston MA 02115; e-mail: scott.pomeroy{at}childrens.harvard.edu

PURPOSE: Stratification of risk in patients with medulloblastoma remains a challenge. As clinical parameters have been proven insufficient for accurately defining disease risk, molecular markers have become the focus of interest. Outcome predictions on the basis of microarray gene expression profiles have been the most accurate to date. We ask in a multivariate model whether clinical parameters enhance survival predictions of gene expression profiles.

PATIENTS AND METHODS: In a cohort of 55 young patients (whose medulloblastoma samples have been analyzed previously for gene expression profile), associations between clinical and gene expression variables and survival were assessed using Cox proportional hazards models. Available clinical variables included age, stage (ie, the presence of disseminated disease at diagnosis), sex, histologic subtype, treatment, and status.

RESULTS: Univariate analysis demonstrated expression profiles to be the only significant clinical prognostic factor (P = .03). In multivariate analysis, gene expression profiles predicted outcome independent of other criteria. Clinical criteria did not significantly contribute additional information for outcome predictions, although an exploratory analysis noted a trend for decreased survival of patients with metastases at diagnosis but favorable gene expression profile.

CONCLUSION: Gene expression profiling predicts medulloblastoma outcome independent of clinical variables. These results need to be validated in a larger prospective study.

Supported in part by NIH grant No. NS35701, an NIH-supported Mental Retardation Research Center HD18655, and the Kyle Mullarkey Medulloblastoma Fund (S.L.P), the Fulbright Scholar Program, the Foundation of Spanish Society of Pediatric Oncology (SEOP), and a grant from the Department of Health of Basque Gouvernement (Spain) (A.F-T).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

• Clinical, Histopathologic, and Molecular Markers of Prognosis: Toward a New Disease Risk Stratification System for Medulloblastoma
  Amar Gajjar, Roberto Hernan, Mehmet Kocak, Christine Fuller, Youngsoo Lee, Peter J. McKinnon, Dana Wallace, Ching Lau, Murali Chintagumpala, David M. Ashley, Stewart J. Kellie, Larry Kun, and Richard J. Gilbertson
  JCO 2004 22: 984-993 [Abstract] [Full Text]

Related Editorial

• Biologic Risk Stratification of Medulloblastoma: The Real Time Is Now
  Paul Graham Fisher, Peter C. Burger, and Charles G. Eberhart
  JCO 2004 22: 971-974 [Full Text]

This article has been cited by other articles:

				M. M. Souweidane The Evolving Role of Surgery in the Management of Pediatric Brain Tumors J Child Neurol, November 1, 2009; 24(11): 1366 - 1374. [Abstract] [PDF]

				S. Pfister, M. Remke, A. Benner, F. Mendrzyk, G. Toedt, J. Felsberg, A. Wittmann, F. Devens, N. U. Gerber, S. Joos, et al. Outcome Prediction in Pediatric Medulloblastoma Based on DNA Copy-Number Aberrations of Chromosomes 6q and 17q and the MYC and MYCN Loci J. Clin. Oncol., April 1, 2009; 27(10): 1627 - 1636. [Abstract] [Full Text] [PDF]

				L. Lafay-Cousin and D. Strother Current Treatment Approaches for Infants with Malignant Central Nervous System Tumors Oncologist, April 1, 2009; 14(4): 433 - 444. [Abstract] [Full Text] [PDF]

				K. C. Lo, C. Ma, B. N. Bundy, S. L. Pomeroy, C. G. Eberhart, and J. K. Cowell Gain of 1q Is a Potential Univariate Negative Prognostic Marker for Survival in Medulloblastoma Clin. Cancer Res., December 1, 2007; 13(23): 7022 - 7028. [Abstract] [Full Text] [PDF]

				V. Oyharcabal-Bourden, C. Kalifa, J.C. Gentet, D. Frappaz, C. Edan, P. Chastagner, E. Sariban, A. Pagnier, A. Babin, F. Pichon, et al. Standard-Risk Medulloblastoma Treated by Adjuvant Chemotherapy Followed by Reduced-Dose Craniospinal Radiation Therapy: A French Society of Pediatric Oncology Study J. Clin. Oncol., July 20, 2005; 23(21): 4726 - 4734. [Abstract] [Full Text] [PDF]

				A. C. Paulino, B. S. Teh, M. Sadeh, K. Seiter, L. Ashby, R. LaRocca, T. Ryken, R. D. Aiken, S. Rutkowski, H. Ottensmeier, et al. Treatment of brain tumors. N. Engl. J. Med., June 2, 2005; 352(22): 2350 - 2353. [Full Text] [PDF]

				P. G. Fisher, P. C. Burger, and C. G. Eberhart Biologic Risk Stratification of Medulloblastoma: The Real Time Is Now J. Clin. Oncol., March 15, 2004; 22(6): 971 - 974. [Full Text] [PDF]