title: Imaging Tumor Response and Tumoral Heterogeneity in Non-Small Cell Lung Cancer Treated With Antiangiogenic Therapy: Comparison of the Prognostic Ability of RECIST 1.1, an Alternate Method (Crabb), and Image Heterogeneity Analysis.
abstract: OBJECTIVE
  We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab.
  
  
  METHODS
  Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression.
  
  
  RESULTS
  Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors.
  
  
  CONCLUSIONS
  The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.
authors.affiliation: *Division of Imaging Sciences and Biomedical Engineering, King's College London Departments of #Clinical Oncology **Radiology, Guy's & St Thomas' NHS Foundation Trust, London ¶Statsconsultancy Ltd, Buckinghamshire, United Kingdom †Department of Radiation Oncology, National Cancer Centre, Singapore, Singapore ‡Department of Thoracic Imaging, Hospital Calmette §Faculty of Medicine, Henri Warembourg ∥Department of Pulmonary and Thoracic Oncology, University of Lille Nord de France, Lille, France.
authors.forename: Connie
authors.initials: C
authors.lastname: Yip
authors.forename: Nunzia
authors.initials: N
authors.lastname: Tacelli
authors.forename: Martine
authors.initials: M
authors.lastname: Remy-Jardin
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherpereel
authors.forename: Alexis
authors.initials: A
authors.lastname: Cortot
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lafitte
authors.forename: Frederic
authors.initials: F
authors.lastname: Wallyn
authors.forename: Jacques
authors.initials: J
authors.lastname: Remy
authors.forename: Paul
authors.initials: P
authors.lastname: Bassett
authors.forename: Musib
authors.initials: M
authors.lastname: Siddique
authors.forename: Gary J R
authors.initials: GJ
authors.lastname: Cook
authors.forename: David B
authors.initials: DB
authors.lastname: Landau
authors.forename: Vicky
authors.initials: V
authors.lastname: Goh
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D005260:Female; D006801:Humans; D007472:Iohexol / Q000031:analogs & derivatives; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011857:Radiographic Image Interpretation, Computer-Assisted / Q000379:methods*; D066066:Response Evaluation Criteria in Solid Tumors; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D000068258:Bevacizumab; D007472:Iohexol; C038192:iopromide