title: Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Columbia University Medical Center, New York, New York, USA. Electronic address: krishna123@gmail.com.
authors.forename: Krishna
authors.initials: K
authors.lastname: Surapaneni
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Kennedy
authors.affiliation: Department of Neuroscience, Columbia University Medical Center, New York, New York, USA.
authors.forename: Ted K
authors.initials: TK
authors.lastname: Yanagihara
authors.affiliation: Department of Radiology, Columbia University Medical Center, New York, New York, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: DeLaPaz
authors.affiliation: Department of Neurological Surgery, Columbia University Medical Center, New York, New York, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001810:Blood Volume; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D018481:Convection; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage*; D019772:Topotecan / Q000008:administration & dosage*; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D019772:Topotecan
keywords: Convection-enhanced delivery; Perfusion magnetic resonance imaging; Topotecan