© 2003 by Society
© 2003 by the Society forNeuro-Oncology
The influence of central review on outcome associations in childhoodmalignant gliomas: Results from the CCG-945 experience
Department of Neurosurgery, University of PittsburghSchool of Medicine and the Children's Hospital of Pittsburgh, Pittsburgh, PA15213 (I.F.P.); Department of Biostatistics, St. JudeChildren's Research Hospital, Memphis, TN 38105 (J.M.B.); Department of Pathology, Ohio State University, Columbus,OH 43210 (A.J.Y.); Department of Pathology, JohnsHopkins University School of Medicine, Baltimore, MD 21205 (P.C.B); Department of Pathology, University of Southern California,Los Angeles, CA 90027 (F.H.G.); Department ofPathology, University of California, San Francisco, CA 94143 (R.L.D.); Department of Pediatrics, New York University MedicalCenter, New York 10016 (J.L.F.); USA
2 Address correspondence to Ian F. Pollack, Children's Oncology Group, P.O. Box60012, Arcadia, CA 91066-6012, USA(Ian.Pollack{at}chp.edu).
 |
Abstract |
|---|
To examine the influence of the pathology review mechanism on the resultsof analyses of therapeutic efficacy and biological prognostic correlates forpediatric high-grade gliomas, we evaluated the effects of using single-expertreview or consensus review, as alternatives to institutional classification,in determining outcome results of a large randomized trial. The study groupwas the randomized cohort of Children's Cancer Group study 945, which comparedefficacy of 2 chemotherapy regimens adjuvant to surgery and radiation. Trialeligibility required institutional histopathologic diagnosis of high-gradeglioma. Sections of study tumors also were centrally reviewed, initially by astudy review neuropathologist and subsequently by 5 neuropathologists,including the review pathologist. Reviews were independent, and reviewers weremasked to clinical factors and outcomes, and consensus diagnoses of the panelwere then established. Among 172 eligible patients, 42 tumors were classifiedas discordant on single-expert review and 51 on consensus review.Progression-free survival probabilities calculated for patients with tumorsclassified as high-grade gliomas by either single-expert or consensus reviewwere inferior to those for the overall, institutionally diagnosed cohort.However, conclusions of the study regarding relative efficacy of treatment andclinical and molecular outcome correlates were unaffected by diagnosis method.Resection extent, proliferation index, and p53 expression were associatedstrongly with outcome, regardless of diagnosis method. However, comparisonsbetween arms in which inclusion was determined by different review criteriafor each arm caused spurious conclusions about efficacy differences betweentreatments. We conclude that the pathology review mechanism had little effecton within-trial comparisons of therapeutic effects or prognostic correlates inthis randomized study, but strongly influenced survival distributions thatwere calculated for each treatment arm. These results support theimplementation of expedited central review in therapeutic studies involvingchildhood malignant gliomas as a way to prospectively identify and excludecases with discordant diagnoses and indicate the need for additional measures,such as molecular assessments, to increase the reproducibility of neuropathologic classification for these tumors.
Received March 17, 2003; Accepted March 27, 2003
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Fangusaro Pediatric High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas J Child Neurol, November 1, 2009; 24(11): 1409 - 1417. [Abstract] [PDF]
|
|
|
|
 |
|
 V. Suri, P. Das, A. Jain, M. C. Sharma, S. A. Borkar, A. Suri, D. Gupta, and C. Sarkar Pediatric glioblastomas: A histopathological and molecular genetic study Neuro Oncology, June 1, 2009; 11(3): 274 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. G. Gottardo and A. Gajjar Chemotherapy for Malignant Brain Tumors of Childhood J Child Neurol, October 1, 2008; 23(10): 1149 - 1159. [Abstract] [PDF]
|
|
|
|
|
|
R. I. Jakacki, A. Yates, S. M. Blaney, T. Zhou, R. Timmerman, A. M. Ingle, L. Flom, M. D. Prados, P. C. Adamson, and I. F. Pollack A phase I trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood Neuro Oncology, August 1, 2008; 10(4): 569 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. F. Pollack, R. L. Hamilton, R. W. Sobol, J. Burnham, A. J. Yates, E. J. Holmes, T. Zhou, and J. L. Finlay O6-Methylguanine-DNA Methyltransferase Expression Strongly Correlates With Outcome in Childhood Malignant Gliomas: Results From the CCG-945 Cohort J. Clin. Oncol., July 20, 2006; 24(21): 3431 - 3437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. G. Barker II, W. T. Curry Jr., and B. S. Carter Surgery for primary supratentorial brain tumors in the United States,1988 to 2000: The effect of provider caseload and centralization of care Neuro Oncology, January 1, 2005; 7(1): 49 - 63. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Broniscer and A. Gajjar Supratentorial High-Grade Astrocytoma and Diffuse Brainstem Glioma: Two Challenges for the Pediatric Oncologist Oncologist, April 1, 2004; 9(2): 197 - 206. [Abstract] [Full Text] [PDF]
|
|