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
Institut National de la Santé et de la Recherche Médicale, U711, Paris, France.
Ann Neurol. 2007 May;61(5):484-90. doi: 10.1002/ana.21125.
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.
评估替莫唑胺对低级别胶质瘤的自然病程及影响，并将这些变化与基因改变特征相关联。
在新辅助替莫唑胺治疗前（n = 39）、治疗期间及治疗后（n = 107），通过系列磁共振成像评估低级别胶质瘤的平均肿瘤直径（MTD）。MTD生长曲线与肿瘤中的1p - 19q缺失及p53过表达相关联。
在替莫唑胺开始治疗前，MTD随时间呈线性增加，表明肿瘤持续生长，在1p - 19q缺失的肿瘤中生长明显较慢（3.4 vs 5.9mm/年；p = 0.0016），在未过表达p53的肿瘤中也是如此（4.2 vs 6.3mm/年；p = 0.05）。在替莫唑胺治疗期间，几乎所有患者（92%）的MTD最初都下降。随后，尽管持续使用替莫唑胺，一些肿瘤仍开始恢复生长，1p - 19q缺失的肿瘤复发率较低（16.6% vs 58%；p = 0.0004），未过表达p53的肿瘤也是如此（26% vs 68%；p = 0.003）。当在无肿瘤进展的情况下停用替莫唑胺时，大多数肿瘤在一年内恢复进行性生长。
未经治疗的低级别胶质瘤以受肿瘤基因改变影响的速率持续生长。替莫唑胺在开始时可逆转这种模式，但对于肿瘤过表达p53且无1p - 19q共缺失的患者，这种效果通常是短暂的，提示获得性化疗耐药。当治疗停止时，大多数肿瘤将恢复生长，这就提出了持续缓解患者的最佳治疗持续时间问题。
