© 1993 by Oxford University Press
Journal of the National Cancer Institute, Vol. 85, No. 9, 704-710,
May 5, 1993
© 1993 Oxford University Press
Recursive Partitioning Analysis of Prognostic Factors in Three Radiation Therapy Oncology Group Malignant Glioma Trials
1Fox Chase Cancer Center Philadelphia, Pa
2Radiation Therapy Oncology Group Philadelphia, Pa
3Eastern Cooperative Oncology Group, Moffitt Cancer Center Tampa, Fla
4Armed Forces Institute of Pathology Washington, D.C
5Moorestown NJ
6LDS Hospital Salt Lake City, Utah
7Columbia Presbyterian Hospital New York, N.Y.
8State University of New York Brooklyn
9Albert Einstein Medical College Philadelphia, Pa
10Veterans Administraton Medical Center Philadelphia, Pa
11Highland Hospital Rochester, N.Y
*Correspondence to: Walter J. Curran, Jr., M.D., Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111.
Background: Despite notable technical advances in therapy for malignant gliomas during the past decade, improved patient survival has not been clearly documented, suggesting that pretreatment prognostic factors influence outcome more than minor modifications in therapy. Age, performance status, and tumor histopathol-ogy have been identified as the pretreatment variables most predictive of survival outcome. However, an analysis of the association of survival with both pretreatment characteristics and treatment-related variables is necessary to assure reliable evaluation of new approaches for treatment of malignant glioma. Purpose: This study of malignant glioma patients used a non-parametric statistical technique to examine the associations of both pretreatment patient and tumor characteristics and treatment-related variables with survival duration. This technique was used to identify subgroups with survival rates sufficiently different to create improvements in the design and stratification of clinical trials. Methods: We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy (RT) regimens with and without chemotherapy or a radiation sensitizer. This approach creates a regression tree according to prognostic variables that classifies patients into homogeneous subsets by survival. Twenty-six pretreatment characteristics and six treatment-related variables were analyzed. Results: The most significant split occurred by age (<50 versus 
50 years). Patients younger than 50 years old were categorized by histology (astrocytomas with anaplastic or atypical foci [AAF] versus glioblastoma multiforme [GBM]) and subsequently by normal or abnormal mental status for AAF patients and by performance status for
those with GBM. For patients aged 50 years or older, performance status was the most important variable, with normal or abnormal mental status creating the only significant split in the poorer performance status group. Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 (by extent of surgery and RT dose). Median survival times were 4.7–58.6 months for the 12 subgroups resulting from this analysis, which ranged in size from 32 to 256 patients. Conclusions: This approach permits examination of the interaction between prognostic variables not possible with other forms of multivariate analysis. Implications: The recursive partitioning technique can be employed to refine the stratification and design of malignant glioma trials. [J Natl Cancer Inst 85: 704–710, 1993].
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B. J. Fisher, C. Scott, D. R. Macdonald, C. Coughlin, and W. J. Curran Phase I Study of Topotecan Plus Cranial Radiation for Glioblastoma Multiforme: Results of Radiation Therapy Oncology Group Trial 9507 J. Clin. Oncol., February 15, 2001; 19(4): 1111 - 1117. [Abstract] [Full Text] [PDF]
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J. S. Yu, C. J. Wheeler, P. M. Zeltzer, H. Ying, D. N. Finger, P. K. Lee, W. H. Yong, F. Incardona, R. C. Thompson, M. S. Riedinger, et al. Vaccination of Malignant Glioma Patients with Peptide-pulsed Dendritic Cells Elicits Systemic Cytotoxicity and Intracranial T-cell Infiltration Cancer Res., February 1, 2001; 61(3): 842 - 847. [Abstract] [Full Text]
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I. Cokgor, G. Akabani, C.-T. Kuan, H. S. Friedman, A. H. Friedman, R. E. Coleman, R. E. McLendon, S. H. Bigner, X.-G. Zhao, A. M. Garcia-Turner, et al. Phase I Trial Results of Iodine-131-Labeled Antitenascin Monoclonal Antibody 81C6 Treatment of Patients With Newly Diagnosed Malignant Gliomas J. Clin. Oncol., November 15, 2000; 18(22): 3862 - 3872. [Abstract] [Full Text] [PDF]
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F. A. Greco, J. D. Hainsworth, N. Levitan, and A. Dowlati Paclitaxel for limited-stage small-cell lung cancer. J. Clin. Oncol., October 1, 2000; 18(19): 3453 - 3454. [Full Text] [PDF]
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J. Del Rowe, C. Scott, M. Werner-Wasik, J. P. Bahary, W. J. Curran, R. C. Urtasun, and B. Fisher Single-Arm, Open-Label Phase II Study of Intravenously Administered Tirapazamine and Radiation Therapy for Glioblastoma Multiforme J. Clin. Oncol., March 13, 2000; 18(6): 1254 - 1259. [Abstract] [Full Text] [PDF]
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R. Miralbell, F. Mornex, R. Greiner, M. Bolla, G. Storme, M. Hulshof, J. Bernier, J. Denekamp, A. M. Rojas, M. Pierart, et al. Accelerated Radiotherapy, Carbogen, and Nicotinamide in Glioblastoma Multiforme: Report of European Organization for Research and Treatment of Cancer Trial 22933 J. Clin. Oncol., October 1, 1999; 17(10): 3143 - 3149. [Abstract] [Full Text] [PDF]
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