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Recursive partitioning analysis of prognostic factors in three Radiation
Therapy Oncology Group malignant glioma trials
WJ Curran Jr, CB Scott, J Horton, JS Nelson, AS Weinstein, AJ
Fischbach, CH Chang, M Rotman, SO Asbell and RE Krisch
Fox Chase Cancer Center, 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 histopathology 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 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.
Source: http://jncicancerspectrum.oupjournals.org/cgi/content/abstract/jnci;85/9/704
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