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

• Published in: Annals of neurology Vol. 61; no. 5; pp. 484 - 490
• Main Authors: Ricard, Damien, Kaloshi, Gentian, Amiel-Benouaich, Alexandra, Lejeune, Julie, Marie, Yannick, Mandonnet, Emmanuel, Kujas, Michèle, Mokhtari, Karima, Taillibert, Sophie, Laigle-Donadey, Florence, Carpentier, Antoine F., Omuro, Antonio, Capelle, Laurent, Duffau, Hugues, Cornu, Philippe, Guillevin, Rémy, Sanson, Marc, Hoang-Xuan, Khê, Delattre, Jean-Yves
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2007; Willey-Liss
• Subjects: Adult; Aged; Algorithms; Antineoplastic agents; Antineoplastic Agents, Alkylating - therapeutic use; Biological and medical sciences; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Chemotherapy; Chromosomes - physiology; Dacarbazine - analogs & derivatives; Dacarbazine - therapeutic use; DNA, Neoplasm - genetics; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Genes, p53 - genetics; Glioma - drug therapy; Glioma - pathology; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Molecular Biology; Neurology; Pharmacology. Drug treatments; Tumors of the nervous system. Phacomatoses; Tumor; Nervous system diseases; Treatment; Temozolomide; Glioma; Central nervous system disease
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.21125

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. Interpretation 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