Prognostic factors in medulloblastoma, including DNA ploidy.
OBJECTIVE
DNA ploidy status, completeness of surgical resection, use of chemotherapy, adequacy of radiation therapy, metastatic stage, sex, and age at diagnosis were evaluated as predictors of relapse in 58 patients with cerebellar medulloblastoma.


METHODS
Flow cytometry (FCM) and/or image analysis (IA) were used to characterize tumor DNA ploidy. Twelve tumors (21%) were found to be aneuploid, 11 (19%) tetraploid, and 35 (60%) diploid.


RESULTS
The most significant predictors of relapse in univariate analyses were the adequacy of radiation (> or = 50 Gy) (P = .02), metastatic staging (P = .05), completeness of resection (P = .085), and DNA ploidy status (diploid/tetraploid v aneuploid; P = .11). When the 52 patients who received > or = 50 Gy were included in a multivariate Cox model analysis, those with diploid/tetraploid tumors had fewer recurrences than those with aneuploid tumors (relative risk, 0.33; 95% confidence interval, 0.12 to 0.89; P = .03). Patients with complete resections (P = .07), or with stage M0 disease (P = .06) had fewer recurrences than other patients, but these factors were not independent predictors of outcome. DNA ploidy status was correlated with age; 10 of the 12 aneuploid tumors were found in children ages 3 to 10 years. Age, sex, and the use of chemotherapy were not prognostically significant in these analyses.


CONCLUSIONS
The adequacy of radiation dose and DNA ploidy were the most important prognostic factors in this series. Contrary to previous reports, when corrected for adequacy of treatment, DNA aneuploidy was associated with a poor outcome. By multivariate analyses, DNA ploidy was an independent variable, even when controlling for extent of surgical resection and metastatic stage.
Zerbini
C
C
Department of Pathology, Children's Hospital, Boston, MA 02115.
Gelber
R D
RD
Weinberg
D
D
Sallan
S E
SE
Barnes
P
P
Kupsky
W
W
Scott
R M
RM
Tarbell
N J
NJ
D000782:Aneuploidy; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011003:Ploidies; D011379:Prognosis; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D015996:Survival Rate
D004273:DNA, Neoplasm