Dynamic history of low-grade gliomas before and after temozolomide treatment.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ricard
Damien
D
Institut National de la Santé et de la Recherche Médicale, U711, Paris, France.
Kaloshi
Gentian
G
Amiel-Benouaich
Alexandra
A
Lejeune
Julie
J
Marie
Yannick
Y
Mandonnet
Emmanuel
E
Kujas
Michèle
M
Mokhtari
Karima
K
Taillibert
Sophie
S
Laigle-Donadey
Florence
F
Carpentier
Antoine F
AF
Omuro
Antonio
A
Capelle
Laurent
L
Duffau
Hugues
H
Cornu
Philippe
P
Guillevin
Rémy
R
Sanson
Marc
M
Hoang-Xuan
Khê
K
Delattre
Jean-Yves
JY
D000328:Adult; D000368:Aged; D000465:Algorithms; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002875:Chromosomes / Q000502:physiology; D004273:DNA, Neoplasm / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53 / Q000235:genetics; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D004273:DNA, Neoplasm; D003606:Dacarbazine; D000077204:Temozolomide