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Treatment Outcomes in 1p19q Co-deleted/Partially Deleted Gliomas

  • Mairéad G. McNamara (a1) (a2), Haiyan Jiang (a3), Mary Jane Lim-Fat (a1), Solmaz Sahebjam (a4), Tim-Rasmus Kiehl (a5), Jason Karamchandani (a6), Claire Coire (a7), Caroline Chung (a8) (a9), Barbara-Ann Millar (a8), Normand Laperriere (a8) and Warren P. Mason (a1)...

Abstract

Background: Radiotherapy with procarbazine, lomustine, and vincristine improves overall survival (OS) in patients with 1p19q co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma. Methods: This retrospective analysis investigated outcomes in patients with 1p19q co-deleted/partially deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and prognostic factors using the Cox proportional hazard model. Results: A total of 106 patients (between December 1997 and December 2013) were included. Median age was 40 years (19-66), 58 were male (55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients (75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27 (25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients, respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85 patients with sufficient material. Upfront treatment was given in 72 (68%) patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47 patients (44%) was 34.7 months and 41.2 months in 9 patients with co-deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma who received upfront temozolomide alone. Median OS was not reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On multivariable analysis for all patients, receipt of therapy upfront versus none (p=0.04), PS 1 versus 0 (p<0.001) and 1p19q co-deletion/incomplete deletion versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate dehydrogenase-1 status was not prognostic for PFS. Conclusions: With similar survival patterns in low-grade/anaplastic gliomas, molecular characteristics may be more important than histological grade. Longer follow-up and results of prospective trials are needed for definitive guidance on treatment of these patients.

Résultats d’un traitement appliqué à des gliomes associés à des codélétions 1p/19q et des délétions partielles. Contexte: À l’instar de la procarbazine, de la lomustine et de la vincristine, les traitements de radiothérapie améliorent le taux de survie général des patients atteints d’oligodendrogliomes/oligoastrocytomes anaplasiques associés à des codélétions 1p/19q. Méthodes: Cette analyse rétrospective s’est penchée sur les résultats d’un traitement offert à des patients atteints d’oligodendrogliomes/oligoastrocytomes et d’oligodendrogliomes/oligoastrocytomes anaplasiques associés à des codélétions/délétions partielles. La survie générale (overall survival) et la survie sans progression (SSP) ont été analysées au moyen de l’estimateur de Kaplan-Meier et de facteurs pronostiques faisant appel au modèle à risques proportionnels de Cox. Résultats: Entre décembre 1997 et décembre 2013, un total de 106 patients ont été inclus dans cette étude. Leur âge médian était de 40 ans (19-66) ; 55% d’entre eux étaient de sexe masculin (n=58). L’échelle de l’Eastern Cooperative Oncology Group était de 0 chez 80 patients (75%). Des codélétions 1p/19q ont été observées chez 66 patients (62%) ; des codélétions incomplètes ont été observées chez 27 d’entre eux (25%) ; enfin, des pertes liées aux chromosomes 1p ou 19q ont été notées chez quatre (4%) et neuf (8%) patients respectivement. On est aussi parvenus à détecter une mutation de l'isocitrate déshydrogénase-1 R132H chez 67 patients sur les 85 qui possédaient assez de matériel génétique. Un traitement initial a été administré à 72 patients (68%), par exemple uniquement de la témozolomide à 52 d’entre eux (49%). Chez 47 patients (44%), la durée médiane de radiothérapie a été de 34,7 mois ; dans le cas de 9 patients atteints d’oligodendrogliomes/oligoastrocytomes anaplasiques associés à des codélétions complètes ou incomplètes à qui l’on n’avait administré qu’un traitement initial à la témozolomide, elle a été de 41,2 mois. Il n’a pas été possible d’obtenir la survie générale moyenne ; toutefois, une survie générale de 5 ans a été de 91% pour tous les groupes (suivi médian : 5,1 ans). Une analyse multivariable de tous les patients a aussi révélé les résultats suivants : administration d’un traitement initial contre aucun traitement (p=0,04) ; échelle de performance 1 contre 0 (p<0,001) ; et codélétion complète/incomplète 1p/19q contre les seules pertes de chromosomes 1p ou 19q (p=0,005). Ces résultats ont été pronostiqués en ce qui regarde la SSP. L’état de l’isocitrate déshydrogénase-1n’a, quant à lui, pas été pronostiqué en ce qui regarde la SSP. Conclusions: Compte tenu des profils de survie similaires en ce qui a trait aux gliomes anaplasiques de bas grade, il se peut que des caractéristiques moléculaires soient plus importantes que le grade histologique. Un suivi à plus long terme ainsi que des études prospectives sont donc nécessaires afin de pouvoir compter sur des orientations définitives concernant le traitement de ces patients.

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Corresponding author

Address correspondence to: Mairéad G. McNamara, Department of Medical Oncology, The Christie NHS Foundation Trust/University of Manchester, Institute of Cancer Sciences, Manchester M20 4BX, UK Email: Mairead.McNamara@christie.nhs.uk

References

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