gamma-ray mutagen sensitivity and survival in patients with glioma

Despite advances in treatment of brain tumors, cerebral malignant gliomas a re rapidly debilitating with poor survival. Patient age and tumor histology are known to influence survival in glioma patients, but these factors do n ot account for all of the variability in survival time. To identify additio nal useful predictors,,ve tested an assay that measures intrinsic gamma-ray mutagen sensitivity. Our hypothesis was that increased sensitivity of peri pheral blood lymphocytes to chromatid breaks is associated with tumor aggre ssiveness and decreased patient survival. The eligible 76 patients were those with histologically confirmed malignant gliomas, seen at the University of Texas M. D. Anderson Cancer Center betw een 1994 and 1997, for whom we had sufficient blood for the in vitro gamma- radiation assay. After gamma-irradiation of each subject's lymphocytes, the frank chromatid breaks in 50 metaphases were averaged to calculate breaks/ cell, On the basis of our patient series, we established a gamma-ray mutage n sensitivity cutoff point of 0.55 breaks/cell that was confirmed by bootst rap resampling techniques. Patients with values >0.55 breaks/cell were cons idered sensitive. Kaplan-Meier and Cox proportional hazards modeling were u sed for the analysis. The gamma-ray mutagen-sensitive patients had worse survival than the nonsen sitive patients, with an unadjusted hazard rate ratio of 1.6 (95% confidenc e interval, 0.9-2.8; P = 0.15). After adjustment for age, tumor histology, and extent of surgical resection, the hazard rate ratio was 2.4 (95% confid ence interval, 1.3-4.6; P = 0.0081). Our data suggest that gamma-ray mutagen sensitivity is a prognostic indicat or of survival in glioma patients. The significance of these findings needs to be verified in studies with larger samples of patients with histologica lly similar gliomas.