Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas.
BACKGROUND
Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients.


METHODS
We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined.


RESULTS
Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy. The median radiation dose was 54 Gy in 30 fractions. Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19. Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome lp loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004).


CONCLUSIONS
These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma.
Bauman
G S
GS
Department of Oncology, University of Western Ontario and London Regional Cancer Centre, London, Ontario, Canada. glenn.bauman@lrcc.on.ca
Ino
Y
Y
Ueki
K
K
Zlatescu
M C
MC
Fisher
B J
BJ
Macdonald
D R
DR
Stitt
L
L
Louis
D N
DN
Cairncross
J G
JG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*