Correlation of tumor topography and peritumoral edema of recurrent malignant gliomas with therapeutic response to intranasal administration of perillyl alcohol

Invest New Drugs. 2009 Dec;27(6):557-64. doi: 10.1007/s10637-008-9215-3. Epub 2009 Jan 13.


Background: The aim of this study was to establish a correlation of tumor topography and peritumoral brain edema with the therapeutic response to intranasal administration of perillyl alcohol (POH) in a cohort of patients with recurrent malignant gliomas.

Methods: The retrospective study reviewed clinical and neuroradiological data from patients with recurrent malignant gliomas who received intranasal daily administration of POH 440 mg. The following parameters were assessed: demographic characteristics, initial symptoms, overall survival, tumor topography and tumor size, presence of midline shift and extent of peritumoral edema. Statistical analysis was carried out with log rank tests and overall survival as assessed by Kaplan-Meier method including 95% confidence intervals.

Results: A cohort of 67 patients included 52 (78%) with glioblastoma (GBM), ten (15%) with anaplastic astrocytoma (AA) and five (7%) with anaplastic oligodendroglioma (AO). Accordingly to tumor topography lobar localization was present in all (5/5) AO; eight (8/10) and 41 GBM patients whereas in the basal ganglia two AA and 11 GBM patients. It was also observed a relation between the tumor size and area of peritumoral brain edema (PTBE). Patients with good therapeutic response showed reduction of tumor size and PTBE area, but poor prognosis was associated with lack of response to treatment and persistence of high PTBE. Patients with tumor in the basal ganglia survived significantly longer than those with lobar gliomas (log rank test, p = 0.0003). Presence of midline shift (>1 cm) was a statistically significant risk factor for shorter survival (log rank test, p = 0.0062)

Conclusions: This study suggests that: (1) patients with recurrent gliomas with localization in the basal ganglia survive significantly longer than those with tumors at lobar localization; (2) presence of PTBE contributes to symptoms, likely to be implicated in the morbidity and invading potential of malignant gliomas. These findings support the theory that interaction between glioma cells at distinct brain microenvironment can influence the oncobiological behavior of glioma cells and ultimately to the prognosis.

MeSH terms

  • Administration, Intranasal
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Brain Edema / complications
  • Brain Edema / drug therapy
  • Brain Edema / pathology*
  • Brain Neoplasms / complications
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Glioma / complications
  • Glioma / drug therapy*
  • Glioma / pathology*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Monoterpenes / administration & dosage
  • Monoterpenes / therapeutic use*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology*
  • Treatment Outcome


  • Antineoplastic Agents
  • Monoterpenes
  • perillyl alcohol