|
|
|
|
|
|
||
|
|
||||
|
|
||||
|
||||
Pediatric Neuro-Oncology |
Department of Neurosurgery, University of Pittsburgh School of Medicine and the Children's Hospital of Pittsburgh, Pittsburgh, PA 15213 (I.F.P.); Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105 (J.M.B.); Department of Pathology, Ohio State University, Columbus, OH 43210 (A.J.Y.); Department of Pathology, Johns Hopkins 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 of Pathology, University of California, San Francisco, CA 94143 (R.L.D.); Department of Pediatrics, New York University Medical Center, New York 10016 (J.L.F.); USA
2 Address correspondence to Ian F. Pollack, Children's Oncology Group, P.O. Box 60012, Arcadia, CA 91066-6012, USA (Ian.Pollack{at}chp.edu).
Abstract
To examine the influence of the pathology review mechanism on the results of analyses of therapeutic efficacy and biological prognostic correlates for pediatric high-grade gliomas, we evaluated the effects of using single-expert review or consensus review, as alternatives to institutional classification, in determining outcome results of a large randomized trial. The study group was the randomized cohort of Children's Cancer Group study 945, which compared efficacy of 2 chemotherapy regimens adjuvant to surgery and radiation. Trial eligibility required institutional histopathologic diagnosis of high-grade glioma. Sections of study tumors also were centrally reviewed, initially by a study review neuropathologist and subsequently by 5 neuropathologists, including the review pathologist. Reviews were independent, and reviewers were masked to clinical factors and outcomes, and consensus diagnoses of the panel were then established. Among 172 eligible patients, 42 tumors were classified as discordant on single-expert review and 51 on consensus review. Progression-free survival probabilities calculated for patients with tumors classified as high-grade gliomas by either single-expert or consensus review were inferior to those for the overall, institutionally diagnosed cohort. However, conclusions of the study regarding relative efficacy of treatment and clinical and molecular outcome correlates were unaffected by diagnosis method. Resection extent, proliferation index, and p53 expression were associated strongly with outcome, regardless of diagnosis method. However, comparisons between arms in which inclusion was determined by different review criteria for each arm caused spurious conclusions about efficacy differences between treatments. We conclude that the pathology review mechanism had little effect on within-trial comparisons of therapeutic effects or prognostic correlates in this randomized study, but strongly influenced survival distributions that were calculated for each treatment arm. These results support the implementation of expedited central review in therapeutic studies involving childhood malignant gliomas as a way to prospectively identify and exclude cases with discordant diagnoses and indicate the need for additional measures, such as molecular assessments, to increase the reproducibility of neuro pathologic classification for these tumors.
References
Aldape, K., Simmons, M.L., Davis, R.L., Miike, R., Wiencke, J., Barger, G., Lee, M., Chen, P., and Wrensch, M. (2000) Discrepancies in diagnoses of neuroepithelial neoplasms: The San Francisco Bay Area Adult Glioma Study. Cancer 88,2342 -2349.[CrossRef][ISI][Medline]
Allen, J.C., Aviner, S., Yates, A.J., Boyett, J.M., Cherlow, J.M., Turski, P.A., Epstein, F., and Finlay, J.L. (1998) Treatment of high-grade spinal cord astrocytoma of childhood with "8–in-1" chemotherapy and radiother apy: A pilot study of CCG-945. J. Neurosurg. 88,215 -220.[CrossRef][ISI][Medline]
Childhood Brain Tumor Consortium. (1989) Intraobserver reproducibility in assigning brain tumors to classes in the World Health Organization diagnostic scheme. The Childhood Brain Tumor Consortium. J. Neurooncol. 7,211 -224.[Medline]
Finlay, J.L., Boyett, J.M., Yates, A.J., Wisoff, J.H., Milstein,
J.M., Geyer, J.R., Bertolone, S.J., McGuire, P., Cherlow, J.M., and Tefft, M.
(1995) Randomized phase III trial in childhood high-grade
astrocytoma comparing vincristine, lomustine, and prednisone with the
eight-drugs-in-1–day regimen. Children's Cancer Group. J.
Clin. Oncol. 13,112
-123.
Geyer, J.R., Finlay, J.L., Boyett, J.M., Wisoff, J., Yates, A., Mao, L., and Packer, R.J. (1995) Survival of infants with malignant astrocytomas: A report from the Children's Cancer Group. Cancer 75,1045 -1050.[CrossRef][ISI][Medline]
Kalbfleisch, J.D., and Prentice, R.I. (1980) The Statistical Analysis of Failure Time Data. New York: John Wiley and Sons.
Kaplan, E.L., and Meier, P. (1958). Nonparametric estimation from incomplete observations. J. Am. Stat. Assoc. 53,457 -481.[CrossRef][ISI]
Kleihues, P., Burger, P.C., and Scheithauer, B.W. (1993) Histological typing of tumours of the central nervous system, 2nd ed. International Histological Classification of Tumours 21. Berlin: Springer, pp.11 -16.
Mantel, N. (1966). Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 50,163 -170.[Medline]
Papahill, P.A., Ramsay, D.A., and Del Maestro, R.F. (1996) Pleomorphic xanthoastrocytoma: Case report and analysis of the literature concerning efficacy of resection and the significance of necrosis. Neurosurgery 38,822 -829.[ISI][Medline]
Pendergrass, T.W., Milstein, J.M., Geyer, J.R., Mulne, A.F.,
Kosnik, E.J., Mor ris, J.D., Heideman, R.L., Ruymann, F.B., Stuntz, J.T., and
Bleyer, W.A. (1987) Eight drugs in one day chemotherapy for brain
tumors: Experience with 107 children and rationale for preradiation
chemotherapy. J. Clin. Oncol.
5,1221
-1231.
Peto, R., Pike, M.C., Armitage, P., Breslow, N.E., Cox, D.R., Howard, S.V., Mantel, N., McPherson, K., Peto, J., and Smith, P.G. (1976) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design Br. J. Cancer 34,585 -612.[ISI][Medline]
Peto, R., Pike, M.C., Armitage, P., Breslow, N.E., Cox, D.R., Howard, S.V., Mantel, N., McPherson, K., Peto, J., and Smith, P.G. (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br. J. Cancer 35,1 -39.[ISI][Medline]
Pollack, I.F., Hamilton, R.L., Finkelstein, S.D., Campbell, J.W.,
Martinez, A.J., Sherwin, R.N., Bozik, M.E., and Gollin, S.M.
(1997) The relationship between TP53 mutations and
overexpression of p53 and prognosis in malignant gliomas of childhood.
Cancer Res. 57,304
-309.
Pollack, I.F., Hamilton, R.L., Burnham, J., Holmes, E.J., Finkelstein, S.D., Sposto, R., Yates, A.J., Boyett, J.M., and Finlay, J.L. (2002a) The impact of proliferation index on outcome in childhood malignant gliomas: Results in a multi-institutional cohort. Neurosurgery 50,1238 -1244.[CrossRef][Medline]
Pollack, I.F., Finkelstein, S.D., Woods, J., Burnham, J., Holmes,
E.J., Hamilton, R.L., Yates, A.J., Boyett, J.M., Finlay, J.L., and Sposto, R.
(2002b) Expression of p53 and prognosis in children with
malignant gliomas. N. Engl. J. Med.
346,420
-427.
Qu, Y., Tan, M., and Kutner, M.H. (1996) Random effects models in latent class analysis for evaluating accuracy of diagnostic tests. Biometrics 52,797 -810.[CrossRef][ISI][Medline]
Sanford, A., Kun, L., Sposto, R., Holmes, E., Wisoff, J.H., Heier, L., and McGuire-Cullen, P. (2002) Low-grade gliomas of childhood: Impact of surgical resection. A report from the Children's Oncology Group. J. Neurosurg. 96,427 -428.
Schwartz, D., and Lellouch, J. (1967) Explanatory and pragmatic attitudes in therapeutical trials. J. Chronic Dis. 20,637 -648.[CrossRef][ISI][Medline]
Tsiatis, A. (1990) Analysis and interpretation of trial results: Intent-to-treat analysis. J. Acquir. Immune Defic. Syndr. 3 (Suppl. 2),S120 -S123.
Wisoff, J.H., Boyett, J.M., Berger, M.S., Brant, C., Li, H., Yates, A.J., McGuire-Cullen, P., Turski, P.A., Sutton, L.N., Allen, J.C., Packer, R.J., and Finlay, J.L. (1998) Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: A report of the Children's Cancer Group trial no. CCG-945. J. Neurosurg. 89, 52-59.[ISI][Medline]
Yung, W.K., Prados, M.D., Yaya-Tur, R., Rosenfeld, S.S., Brada, M.,
Fried man, H.S., Albright, R., Olson, J., Chang, S.M., O'Neill, A.M.,
Friedman, A.H., Bruner, J., Yue, N., Dugan, M., Zaknoen, S., and Levin, V.A.
(1999) Multicenter phase II trial of temozolomide in patients
with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse.
Temodal Brain Tumor Group [erratum in J. Clin. Oncol. 17,
3693, 1999]. J. Clin. Oncol.
17,2762
-2771.
This article has been cited by other articles:
|
|
 |
|
  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-oncol, 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-oncol, 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]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
