Recurrent glioblastoma: Combination of high cerebral blood flow with MGMT promoter methylation is associated with benefit from low-dose temozolomide rechallenge at first recurrence

Purpose: To determine if the combination of high cerebral blood flow (CBF) and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation is associated with benefit from a second round of low-dose temozolomide (TMZ) (ie, rechallenge) in patients with glioblastoma at first recurrence. Materials and Methods: The institutional review board approved this retrospective cohort study and waived the requirement for informed consent. Seventy-two patients with recurrent glioblastoma after concurrent TMZ radiation therapy were treated with a low-dose TMZ rechallenge and underwent arterial spin labeling magnetic resonance imaging. The cohort was dichotomized to high-CBF and low-CBF subgroups. MGMT promoter methylation was determined before concurrent TMZ radiation therapy. The coprimary end points were median time to progression (TTP) and 6-month outcome after the initiation of low-dose TMZ. The Cox proportional hazards model was used to assess the association between clinical outcome and CBF status. Results: There was a significant difference between the high- and low-CBF cohorts in median TTP (6 months vs 3 months, respectively; P = .001). Favorable 6-month outcomes occurred in 16 of 31 (52%) patients with high CBF and six of 41 (15%) patients with low CBF (P = .001). At multivariate analysis, high CBF was independently associated with longer TTP (P = .023). The association between high CBF and favorable outcome was significant only in the MGMT promoter methylation group (P = .006 for TTP; P = .005 for 6-month outcome). Conclusion: The combination of high CBF with MGMT methylation may be associated with benefits from a low-dose TMZ rechallenge in patients with recurrent glioblastoma. However, alternative strategies might be needed for patients with both low CBF and a lack of MGMT methylation.