Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma

World Neurosurg. 2015 Jul;84(1):163-72. doi: 10.1016/j.wneu.2015.03.008. Epub 2015 Mar 13.


Objective: To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status.

Methods: Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference.

Results: There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. -29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51-1.00).

Conclusion: In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months.

Keywords: Convection-enhanced delivery; Perfusion magnetic resonance imaging; Topotecan.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Blood Volume*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / physiopathology
  • Cerebrovascular Circulation*
  • Convection*
  • Disease Progression
  • Female
  • Glioma / drug therapy*
  • Glioma / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Topoisomerase I Inhibitors / administration & dosage*
  • Topotecan / administration & dosage*
  • Treatment Outcome
  • Tumor Burden


  • Antineoplastic Agents
  • Topoisomerase I Inhibitors
  • Topotecan