Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas

Introduction: Allelic loss of the short arm of chromosome 1 predicts radiog raphic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with olig odendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when rad iotherapy was part of the initial treatment of these patients. Materials and Methods: We measured progression-free survival following radi otherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free s urvival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multiv ariate statistical analyses. For the subset of patients with newly diagnose d 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 mo nths for patients whose tumors harbored 1p loss vs. 6.2 months for those pa tients whose tumors retained both copies of chromosome 1p (p < 0.001). On b oth univariate and multivariate analyses, chromosome 1p loss was the princi pal 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 tho se patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004) . Conclusion: These data suggest allelic loss of chromosome 1p in patients wi th oligodendroglial neoplasms predicts longer progression-free survival amo ng patients receiving radiotherapy +/- chemotherapy as part of their initia l treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma. (C) 2000 Elsevier Scien ce Inc.