TMZ is well tolerated and provides a substantial rate of response in LGOT. Chromosome 1p loss is correlated with radiographic response and could be a helpful marker for guiding therapeutic decision making in LGOT.

Objective:To evaluate the predictive impact of chromosome 1p/19q deletions on the response and outcome of progressive low-grade gliomas (LGG) treated with up-front temozolomide (TMZ) chemotherapy. Methods: Adult These tumors share an invasive and malignant potential. Gross total surgical resection, whenever possible, is recommended. Radiotherapy is considered as a postoperative standard treatment for LGG, although the optimal timing of this treatment (i.e., immediate vs at progression) remains debatable. 3,4 We and others have recently provided some evidence based on small studies that temozolomide (TMZ), an oral alkylating agent, may represent an interesting alternative option as a primary treatment after surgery in diffuse LGG. [5][6][7] We have reported preliminary results suggesting that chromosome 1p deletion is correlated with radiographic response of LGG to TMZ and might represent a helpful molecular tumor marker for guiding therapeutic decision-making. 6 In the present study we report additional data from an extended series of patients with longer follow-up confirming the efficacy of TMZ in progressive LGG and the predictive value of 1p/19q loss both in terms of prognosis and chemosensitivity.From APHP, Service de

BACKGROUND.In contrast to oligodendrogliomas, molecular predictors of prognosis have not been consistently found in glioblastomas. However, genetic studies show that glioblastomas consist of several genetic subtypes and raise the possibility that molecular alterations could be predictive of survival. METHODS.A search for loss of heterozygosity (LOH) on chromosome 1p, 9p, 10q, 19q, EGFR (epidermal growth factor receptor), CDK4, and MDM2 (mouse double minute) amplifications, CDKN2A (INK4A/ARF) homozygous deletions, p53 expression, was performed in a series of 220 primary glioblastomas. The molecular alterations were then correlated with each other to identify distinct molecular pathways and with clinical parameters and the course of the disease to identify prognostic markers. RESULTS.Nonrandom associations were found between EGFR amplification and LOH10q, LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4 amplification, whereas mutual exclusions were found between p53 expression and EGFR amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and CDK4 amplification. Age (P ϭ 4.10 -5 ) and performance status (P ϭ .003) were the main predictors of outcome. In contrast, molecular markers were of limited impact: MDM2 amplification correlated with poor outcome on both univariate and multivariate analysis (P ϭ .01) and EGFR amplification with good prognosis on multivariate analysis (P ϭ .02). CONCLUSION.Despite their limited prognostic impact, the genetic markers investigated here outline distinct molecular pathways involved in glioblastoma tumorigenesis and warrant broader molecular screening.