TY - JOUR
T1 - γ-ray mutagen sensitivity and survival in patients with glioma
AU - Sigurdson, Alice J.
AU - Bondy, Melissa L.
AU - Hess, Kenneth R.
AU - Toms, Steven A.
AU - Kyritsis, Athanassios P.
AU - Gu, Jun
AU - Wang, Li E.
AU - Wang, Xinzhi
AU - Adatto, Phyllis
AU - Bruner, Janet L.
AU - Yung, W. K.Alfred
AU - Levin, Victor A.
AU - Wei, Qingyi
PY - 1998
Y1 - 1998
N2 - Despite advances in treatment of brain tumors, cerebral malignant gliomas are rapidly debilitating with poor survival. Patient age and tumor histology are known to influence survival in glioma patients, but these factors do not account for all of the variability in survival time. To identify additional useful predictors, we tested an assay that measures intrinsic γ-ray mutagen sensitivity. Our hypothesis was that increased sensitivity of peripheral blood lymphocytes to chromatid breaks is associated with tumor aggressiveness 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 between 1994 and 1997, for whom we had sufficient blood for the in vitro y-radiation assay. After y- 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 y-ray mutagen sensitivity cutoff point of 0.55 breaks/cell that was confirmed by bootstrap resampling techniques. Patients with values >0.55 breaks/cell were considered sensitive. Kaplan- Meier and Cox proportional hazards modeling were used for the analysis. The γ-ray mutagen-sensitive patients had worse survival than the nonsensitive patients, with an unadjusted hazard rate ratio of 1.6 (95% confidence 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% confidence interval, 1.3-4.6; P = 0.0081). Our data suggest that γ-ray mutagen sensitivity is a prognostic indicator of survival in glioma patients. The significance of these findings needs to be verified in studies with larger samples of patients with histologically similar gliomas.
AB - Despite advances in treatment of brain tumors, cerebral malignant gliomas are rapidly debilitating with poor survival. Patient age and tumor histology are known to influence survival in glioma patients, but these factors do not account for all of the variability in survival time. To identify additional useful predictors, we tested an assay that measures intrinsic γ-ray mutagen sensitivity. Our hypothesis was that increased sensitivity of peripheral blood lymphocytes to chromatid breaks is associated with tumor aggressiveness 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 between 1994 and 1997, for whom we had sufficient blood for the in vitro y-radiation assay. After y- 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 y-ray mutagen sensitivity cutoff point of 0.55 breaks/cell that was confirmed by bootstrap resampling techniques. Patients with values >0.55 breaks/cell were considered sensitive. Kaplan- Meier and Cox proportional hazards modeling were used for the analysis. The γ-ray mutagen-sensitive patients had worse survival than the nonsensitive patients, with an unadjusted hazard rate ratio of 1.6 (95% confidence 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% confidence interval, 1.3-4.6; P = 0.0081). Our data suggest that γ-ray mutagen sensitivity is a prognostic indicator of survival in glioma patients. The significance of these findings needs to be verified in studies with larger samples of patients with histologically similar gliomas.
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M3 - Article
C2 - 9865917
AN - SCOPUS:17444379728
SN - 1078-0432
VL - 4
SP - 3031
EP - 3035
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -