title: Parametric response maps of perfusion MRI may identify recurrent glioblastomas responsive to bevacizumab and irinotecan.
abstract: BACKGROUND
  Perfusion weighted imaging (PWI) can be used to measure key aspects of tumor vascularity in vivo and recent studies suggest that perfusion imaging may be useful in the early assessment of response to angiogenesis inhibitors. Aim of this work is to compare Parametric Response Maps (PRMs) with the Region Of Interest (ROI) approach in the analysis of tumor changes induced by bevacizumab and irinotecan in recurrent glioblastomas (rGBM), and to evaluate if changes in tumor blood volume measured by perfusion MRI may predict clinical outcome.
  
  
  METHODS
  42 rGBM patients with KPS ≥ 50 were treated until progression, as defined by MRI with RANO criteria. Relative cerebral blood volume (rCBV) variation after 8 weeks of treatment was calculated through semi-automatic ROI placement in the same anatomic region as in baseline. Alternatively, rCBV variations with respect to baseline were calculated into the evolving tumor region using a voxel-by-voxel difference. PRMs were created showing where rCBV significantly increased, decreased or remained unchanged.
  
  
  RESULTS
  An increased blood volume in PRM (PRMCBV+) higher than 18% (first quartile) after 8 weeks of treatment was associated with increased progression free survival (PFS; 24 versus 13 weeks, p = 0.045) and overall survival (OS; 38 versus 25 weeks, p = 0.016). After 8 weeks of treatment ROI analysis showed that mean rCBV remained elevated in non responsive patients (4.8 ± 0.9 versus 5.1 ± 1.2, p = 0.38), whereas decreased in responsive patients (4.2 ± 1.3 versus 3.8 ± 1.6 p = 0.04), and re-increased progressively when patients approached tumor progression.
  
  
  CONCLUSIONS
  Our data suggest that PRMs can provide an early marker of response to antiangiogenic treatment and warrant further confirmation in a larger cohort of GBM patients.
authors.affiliation: Neuro-Radiology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Aquino
authors.affiliation: General Neurology Unit, Fondazione IRCCS Istituto Neurologico Nazionale C. Mondino, Pavia, Italy.
authors.forename: Anna Luisa
authors.initials: AL
authors.lastname: Di Stefano
authors.affiliation: Neuro-Radiology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scotti
authors.affiliation: Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Cuppini
authors.affiliation: Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.affiliation: Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.affiliation: Neuro-Radiology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Bruzzone
authors.affiliation: Molecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy.
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000077146:Irinotecan; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D055420:Perfusion Imaging / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin