title: Dynamic history of low-grade gliomas before and after temozolomide treatment.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U711, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ricard
authors.forename: Gentian
authors.initials: G
authors.lastname: Kaloshi
authors.forename: Alexandra
authors.initials: A
authors.lastname: Amiel-Benouaich
authors.forename: Julie
authors.initials: J
authors.lastname: Lejeune
authors.forename: Yannick
authors.initials: Y
authors.lastname: Marie
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mandonnet
authors.forename: Michèle
authors.initials: M
authors.lastname: Kujas
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Sophie
authors.initials: S
authors.lastname: Taillibert
authors.forename: Florence
authors.initials: F
authors.lastname: Laigle-Donadey
authors.forename: Antoine F
authors.initials: AF
authors.lastname: Carpentier
authors.forename: Antonio
authors.initials: A
authors.lastname: Omuro
authors.forename: Laurent
authors.initials: L
authors.lastname: Capelle
authors.forename: Hugues
authors.initials: H
authors.lastname: Duffau
authors.forename: Philippe
authors.initials: P
authors.lastname: Cornu
authors.forename: Rémy
authors.initials: R
authors.lastname: Guillevin
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Khê
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
mesh_terms: 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
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004273:DNA, Neoplasm; D003606:Dacarbazine; D000077204:Temozolomide