The DNA-Repair GeneMGMTand the Clinical Response of Gliomas to Alkylating Agents

To the Editor: Esteller and colleagues (Nov.9 issue) 1 claim that methylation of the O 6 -methylguanine-DNA methyltransferase ( MGMT ) promoter is associated with improved responsiveness to carmustine and prolonged survival in patients with high-grade gliomas.We believe there are methodologic flaws in the authors' study that call these results into question.First, the patients in the study were treated with a combination of surgery, radiation therapy, and chemotherapy with cisplatin and carmustine.We do not believe the response to carmustine is a discernible end point in this trial, because multiple treatments were administered along with carmustine.Second, although the difference in age between the group of patients with unmethylated tumors and the group with methylated tumors was not statistically different, there was a trend toward an older age in the group with unmethylated tumors.We are not given the distribution of ages above or below 50 years.Since the prognosis worsens with each additional decade of age, such information would be useful in assessing the balance in age between the two groups. 2,3 Third, the median period of survival was approximately 20 months for the patients with unmethylated tumors and approximately 30 months for those with methylated tumors, as compared with an average of about 12 months in other series. 2,3 Moreover, since no deaths occurred before 12 months, it is unlikely that the patients chosen for this study were representative of most patients with the disease.Finally, the small numbers of deaths in the two groups of patients make the results of a statistical comparison questionable.