Dynamic history of low-grade gliomas before and after temozolomide treatment
Article first published online: 27 APR 2007
Copyright © 2007 American Neurological Association
Annals of Neurology
Volume 61, Issue 5, pages 484–490, May 2007
How to Cite
Ricard, D., Kaloshi, G., Amiel-Benouaich, A., Lejeune, J., Marie, Y., Mandonnet, E., Kujas, M., Mokhtari, K., Taillibert, S., Laigle-Donadey, F., Carpentier, A. F., Omuro, A., Capelle, L., Duffau, H., Cornu, P., Guillevin, R., Sanson, M., Hoang-Xuan, K. and Delattre, J.-Y. (2007), Dynamic history of low-grade gliomas before and after temozolomide treatment. Ann Neurol., 61: 484–490. doi: 10.1002/ana.21125
- Issue published online: 27 APR 2007
- Article first published online: 27 APR 2007
- Manuscript Accepted: 11 FEB 2007
- Manuscript Revised: 31 JAN 2007
- Manuscript Received: 22 AUG 2006
- Assistance Publique-Hopitaux de Paris
- Direction de la Recherche clinique et du development. Grant Numbers: MUL 03012, CRC 05021
- Ligue Nationale contre le Cancer, comité d'Ille et Vilaine
To evaluate the natural progression and the impact of temozolomide in low-grade gliomas and to correlate these changes with the profile of genetic alterations.
The mean tumor diameter (MTD) of low-grade gliomas was evaluated on serial magnetic resonance images before (n = 39), during, and after (n = 107) treatment with neoadjuvant temozolomide. MTD growth curves were correlated with chromosomes 1p-19q loss and p53 overexpression in the tumors.
Before temozolomide onset, MTD increased linearly over time, indicating a continuous growth that was significantly slower in 1p-19q deleted tumors (3.4 vs 5.9mm/year; p = 0.0016) and in tumors that did not overexpress p53 (4.2 vs 6.3mm/year; p = 0.05). During temozolomide treatment, almost all patients (92%) experienced initial decrease of MTD. Subsequently, some tumors started to resume growth despite continuous administration of temozolomide, with a lower rate of relapse in 1p-19q deleted tumors (16.6 vs 58%; p = 0.0004) and in tumors that did not overexpress p53 (26 vs 68%; p = 0.003). When temozolomide was discontinued in the absence of tumor progression, a majority of tumors resumed their progressive growth within a year.
Untreated low-grade gliomas grow continuously at a rate that is influenced by the genetic alterations of the tumors. Temozolomide reverses this pattern at the onset, but this effect is often brief in patients whose tumors overexpress p53 and do not harbor the 1p-19q codeletion, suggesting acquired chemoresistance. A majority of tumors will resume their growth when treatment is discontinued, raising the issue of the optimal duration of treatment in continuously responding patients. Ann Neurol 2007;61:484–490