Patients’ CpG island methylator phenotype (CIMP) status and methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter are the most informative in identifying patients with grade III glioma who might benefit from adding procarbazine, CCNU, and vincristine (PCV) to radiation therapy. This status was assessed in the European Organisation for the Research and Treatment of Cancer trial 26951, which was presented June 2 at the 2013 annual conference of the American Society of Clinical Oncology in Chicago, Illinois.
Prior results had shown that PCV chemotherapy following standard radiation therapy delayed tumor growth and extended the lives of patients with anaplastic oligodendroglial tumors, which are a hard-to-treat form of brain cancer. Earlier trials have found that administering both PCV and radiation therapy also led to improvements in survival for oligodendroglial tumor patients with specific deletions of genetic material in chromosomes 1p and 19q, but not for patients without the mutation.
Nevertheless, up to 30% of oligodendroglial tumors do not have a 1p/19q deletion but may still respond to chemotherapy. Analyses had suggested that other molecularly defined subsets of grade III tumors might benefit as well.
This study profiled the methylation patterns of 115 patients using Infinium HumanMethylation27 or Infinium HumanMethylation450 BeadChip kits. These analyses found two markers, CIMP and MGMT-STP27 methylation status, that were considered promising in being able to differentiate between patients who will and will not respond to PCV chemotherapy. Two other markers, IDH mutation status and 1p/19q chromosomal deletion, had less strength in achieving this differentiation.
“This is further evidence pointing towards a central role of methylation in the behavior of IDH (isocitrate dehydrogenase) mutated glioma and, more in general, of the MGMT gene function in glioma when treated with chemotherapy,” said study coordinator Martin J. Van Den Bent of the Erasmus Medical Centre Cancer Institute in Rotterdam, The Netherlands.