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NEUROLOGY 2008;70:590-595
© 2008 American Academy of Neurology

Genetic markers predictive of chemosensitivity and outcome in gliomatosis cerebri

G. Kaloshi, MD, S. Everhard, MSc, F. Laigle-Donadey, MD, Y. Marie, MSc, S. Navarro, MD, K. Mokhtari, MD, A. Idbaih, MD, PhD, F. Ducray, MD, J. Thillet, PhD, K. Hoang-Xuan, MD, PhD, J.-Y Delattre, MD and M. Sanson, MD, PhD

From Service de Neurologie Mazarin (G.K., F.L.-D., A.I., F.D., K.H.-X., J.-Y.D., M.S.), Service de Neurochirurgie (S.N.), and laboratoire de neuropathologie R Escourolle (K.M.), AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Biologie des Interactions Neurones & Glie, INSERM, U711, Paris, France (S.E., Y.M., A.I., F.D., J.T., K.H.-X., J.-Y.D., M.S.); and Faculté de Médecine, Université Pierre et Marie Curie, Paris, France (K.H.-X., J.-Y.D., M.S.).

Address correspondence and reprint requests to Dr. Marc Sanson, Service de neurologie Mazarin, Hôpital de la Salpêtrière, 47, Bd de l’Hôpital, 75013 Paris, France marc.sanson{at}psl.aphp.fr

Background: Up-front temozolomide (TMZ) has been recently proposed as a treatment for gliomatosis cerebri (GC), but no predictive or prognostic markers have been identified so far. Because 1p19q codeletion and methylguanine methyl transferase promoter (MGMTP) methylation have been correlated with chemosensitivity of gliomas, their value was investigated in a cohort of patients with GC treated with TMZ.

Methods: A cohort of 25 GC patients who were treated with TMZ was investigated for 1p19q codeletion and O6-methylguanine DNA.

Results: Patients with a 1p/19q codeletion had a higher response rate (88% [8/9] vs 25% [4/16], p = 0.002), higher progression-free survival (24.5 vs 13.7 months, p = 0.017), and higher overall survival (66.8 vs 15.2 months, p = 0.011) than patients without 1p/19q codeletion. Fourteen of 19 evaluable tumors for MGMTP status were methylated. MGMTP methylation was associated with 1p/19q codeletion (p = 0.045). Patients with unmethylated MGMTP tended to have a shorter progression-free survival and a higher rate of progressive disease.

Conclusion: Response rate to temozolomide and prognosis seem tightly correlated to 1p19q loss. The impact of methylguanine methyl transferase promoter methylation status on gliomatosis cerebri is still unsettled in this population.

Abbreviations: A = astrocytoma; FLAIR = fluid-attenuated inversion recovery; GC = gliomatosis cerebri; KPS = Karnofsky Performance Scale; LOH = loss of heterozygosity; MGMT = methylguanine methyl transferase; MGMTP = methylguanine methyl transferase promoter; MR = minor response; NS = not significant; O = oligodendroglioma; OA = oligoastrocytoma; OS = overall survival; PD = progressive disease; PFS = progression-free survival; PR = partial response; R = response; RT = radiation therapy; TMZ = temozolomide.

Supported by the Délégation à la Recherche Clinique (AP-HP; grant no. MUL 03012).

Disclosure: The authors report no conflicts of interest.

Received June 8, 2007. Accepted in final form September 25, 2007.






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