title: Geometrical Measures Obtained from Pretreatment Postcontrast T1 Weighted MRIs Predict Survival Benefits from Bevacizumab in Glioblastoma Patients.
abstract: BACKGROUND
  Antiangiogenic therapies for glioblastoma (GBM) such as bevacizumab (BVZ), have been unable to extend survival in large patient cohorts. However, a subset of patients having angiogenesis-dependent tumors might benefit from these therapies. Currently, there are no biomarkers allowing to discriminate responders from non-responders before the start of the therapy.
  
  
  METHODS
  40 patients from the randomized GENOM009 study complied the inclusion criteria (quality of images, clinical data available). Of those, 23 patients received first line temozolomide (TMZ) for eight weeks and then concomitant radiotherapy and TMZ. 17 patients received BVZ+TMZ for seven weeks and then added radiotherapy to the treatment. Clinical variables were collected, tumors segmented and several geometrical measures computed including: Contrast enhancing (CE), necrotic, and total volumes; equivalent spherical CE width; several geometric measures of the CE 'rim' geometry and a set of image texture measures. The significance of the results was studied using Kaplan-Meier and Cox proportional hazards analysis. Correlations were assessed using Spearman correlation coefficients.
  
  
  RESULTS
  Kaplan-Meier and Cox proportional hazards analysis showed that total, CE and inner volume (p = 0.019, HR = 4.258) and geometric heterogeneity of the CE areas (p = 0.011, HR = 3.931) were significant parameters identifying response to BVZ. The group of patients with either regular CE areas (small geometric heterogeneity, median difference survival 15.88 months, p = 0.011) or those with small necrotic volume (median survival difference 14.50 months, p = 0.047) benefited substantially from BVZ.
  
  
  CONCLUSIONS
  Imaging biomarkers related to the irregularity of contrast enhancing areas and the necrotic volume were able to discriminate GBM patients with a substantial survival benefit from BVZ. A prospective study is needed to validate our results.
authors.affiliation: Laboratory of Mathematical Oncology (MôLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Edificio Politécnico, Avda. Camilo José Cela 3, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
authors.forename: David
authors.identifier: http://orcid.org/0000-0002-6104-3894
authors.initials: D
authors.lastname: Molina
authors.affiliation: Laboratory of Mathematical Oncology (MôLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Edificio Politécnico, Avda. Camilo José Cela 3, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pérez-Beteta
authors.affiliation: Laboratory of Mathematical Oncology (MôLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Edificio Politécnico, Avda. Camilo José Cela 3, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Martínez-González
authors.affiliation: Medical Oncology Service, Hospital Universitario, 12 de Octubre, Madrid, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Sepúlveda
authors.affiliation: Medical Oncology Service, Hospital Sant Joan de Reus, Reus, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Peralta
authors.affiliation: Medical Oncology Service, Institut Catalá d'Oncologia IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Gil-Gil
authors.affiliation: Medical Oncology Service, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Gaspar
authors.initials: G
authors.lastname: Reynes
authors.affiliation: Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Herrero
authors.affiliation: Medical Oncology Service, Hospital Provincial de Castellón, Castellón, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: De Las Peñas
authors.affiliation: Medical Oncology Service, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Luque
authors.affiliation: Neuroradiology Section. Radiology Service. Hospital del Mar, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Capellades
authors.affiliation: Medical Oncology Service, Institut Català d'Oncologia, IGTP, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Balaña
authors.affiliation: Laboratory of Mathematical Oncology (MôLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Edificio Politécnico, Avda. Camilo José Cela 3, Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain.
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Pérez-García
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000627:therapeutic use; D015415:Biomarkers; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality*; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D000068258:Bevacizumab