title: Non-Small Cell Lung Cancer Treated with Erlotinib: Heterogeneity of (18)F-FDG Uptake at PET-Association with Treatment Response and Prognosis.
abstract: OBJECTIVE
  To determine if first-order and high-order textural features on fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) images of non-small cell lung cancer (NSCLC) (a) at baseline, (b) at 6 weeks, or (c) the percentage change between baseline and 6 weeks can predict response or survival in patients treated with erlotinib.
  
  
  METHODS
  Institutional review board approval was obtained for post hoc analysis of data from a prospective single-center study for which informed consent was obtained. The study included 47 patients with NSCLC who underwent (18)F-FDG PET/computed tomography (CT) at baseline (n = 47) and 6 weeks (n = 40) after commencing treatment with erlotinib. First-order and high-order primary tumor texture features reflecting image heterogeneity, standardized uptake values, metabolic tumor volume, and total lesion glycolysis were measured for all (18)F-FDG PET studies. Response to erlotinib was assessed by using the Response Evaluation Criteria in Solid Tumors (RECIST) on CT images obtained at 12 weeks (n = 32). Associations between PET parameters, overall survival (OS), and RECIST-based treatment response were tested by Cox and logistic regression analyses, respectively.
  
  
  RESULTS
  Median OS was 14.1 months. According to CT RECIST at 12 weeks, there were 21 nonresponders and 11 responders. Response to erlotinib was associated with reduced heterogeneity (first-order standard deviation, P = .01; entropy, P = .001; uniformity, P = .001). At multivariable analysis, high-order contrast at 6 weeks (P = .002) and percentage change in first-order entropy (P = .03) were independently associated with survival. Percentage change in first-order entropy was also independently associated with treatment response (P = .01).
  
  
  CONCLUSIONS
  Response to erlotinib is associated with reduced heterogeneity at (18)F-FDG PET. Changes in first-order entropy are independently associated with OS and treatment response.
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Gary J R
authors.initials: GJ
authors.lastname: Cook
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Mary E
authors.initials: ME
authors.lastname: O'Brien
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Muhammad
authors.initials: M
authors.lastname: Siddique
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Sugama
authors.initials: S
authors.lastname: Chicklore
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Hoi Y
authors.initials: HY
authors.lastname: Loi
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Sharma
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Ravi
authors.initials: R
authors.lastname: Punwani
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Paul
authors.initials: P
authors.lastname: Bassett
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Vicky
authors.initials: V
authors.lastname: Goh
authors.affiliation: From the Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, England (G.J.R.C., M.S., S.C., V.G.); the Lung Unit (M.E.O., R.P.) and Department of Nuclear Medicine and PET (H.Y.L., B.S., S.C.), the Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, England; and Statsconsultancy, Amersham, Buckinghamshire, England (P.B.).
authors.forename: Sue
authors.initials: S
authors.lastname: Chua
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011379:Prognosis; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000069347:Erlotinib Hydrochloride