Chemoradiation for anaplastic oligodendrogliomas: clinical outcomes and prognostic value of molecular markers

Autor: Felice Giangaspero, Riccardo Maurizi Enrici, Giuseppe Minniti, Gaetano Lanzetta, Domenica Di Stefano, Mattia Falchetto Osti, Andrea Pace, Claudia Scaringi, Stefania Scarpino, Antonella Arcella
Rok vydání: 2014
Předmět:
Oncology
Male
Cancer Research
Pathology
medicine.medical_treatment
Loss of Heterozygosity
Procarbazine
drug therapy/radiotherapy
genetics
DNA Modification Methylases
Brain Neoplasms
Middle Aged
Chromosome 1p19q
Isocitrate Dehydrogenase
Treatment Outcome
Neurology
Chromosomes
Human
Pair 1
Anaplastic oligodendroglioma
Pair 1
IDH1
Female
MGMT
Chromosomes
Human
Pair 9
medicine.drug
Human
Pair 9
Adult
Vincristine
medicine.medical_specialty
Adult
Aged
Brain Neoplasms
drug therapy/radiotherapy
Chromosomes
genetics
Chromosomes
genetics
DNA Modification Methylases
genetics
DNA Repair Enzymes
genetics
Disease-Free Survival
Female
Humans
Isocitrate Dehydrogenase
genetics
Loss of Heterozygosity
genetics
Male
Middle Aged
Oligodendroglioma
drug therapy/radiotherapy
Proportional Hazards Models
Retrospective Studies
Treatment Outcome
Tumor Suppressor Proteins
genetics
Young Adult
Oligodendroglioma
Biology
Chromosomes
Disease-Free Survival
Young Adult
Internal medicine
medicine
Temozolomide
Humans
Anaplastic Oligoastrocytoma
Radiotherapy
Aged
Proportional Hazards Models
Retrospective Studies
Tumor Suppressor Proteins
Lomustine
Radiation therapy
DNA Repair Enzymes
Concomitant
Neurology (clinical)
Popis: Combination of procarbazine, lomustine and vincristine (PCV) with radiation therapy (RT) has been associated with longer survival in patients with anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA), especially in those with chromosome 1p/19q codeletion. We report a multicenter retrospective study of 84 consecutive adult patients with AO and AOA treated with RT plus concomitant and adjuvant temozolomide (TMZ) between February 2004 and January 2011. Correlations between chromosome 1p/19q codeletion, isocitrate dehydrogenase1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation with survival outcomes have been analyzed. For all 84 patients the median overall survival (OS) and progression-free survival rates were 55.6 and 45.2 months, respectively. Grade 3 or 4 hematological toxicity occurred in 17 % of patients. Chromosome 1p/19q codeletion was detected in 57 %, IDH1 mutation in 63 %, and MGMT promoter methylation in 74 % of evaluable patients. In multivariate analysis the presence of chromosome 1p/19q codeletion was associated with significant survival benefit (median OS 34 months in noncodeleted tumors and not reached in codeleted tumors; HR 0.16, 95 % CI 0.03-0.45; P = 0.005). IDH1 mutation was also of prognostic significance for longer survival (P = 0.001; HR 0.20, 95 % 0.06-0.41), whereas MGMT promoter methylation was only of borderline significance. The study indicates that RT with concomitant and adjuvant TMZ is a relatively safe treatment associated with longer survival in patients with 1p/19q codeleted and IDH1 mutated tumors. Results from ongoing randomized studies will be essential to clarify if RT plus TMZ may provide survival as good as or better than RT combined with PCV for patients with AO and AOA.
Databáze: OpenAIRE
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