title: Lung volume measurements as a surrogate marker for patient response in malignant pleural mesothelioma.
abstract: BACKGROUND
  The purpose of this study was to investigate the continuous changes in three distinct response assessment methods during treatment as a marker of response for patients with mesothelioma. Linear tumor thickness measurements, disease volume measurements, and lung volume measurements (a physiological correlate of disease volumes) were investigated in this study.
  
  
  METHODS
  Serial computed tomography scans were obtained during the course of clinically standard chemotherapy for 61 patients. For each of the 216 computed tomography scans, the aerated lung volumes were segmented using a fully automated method, and the pleural disease volume was segmented using a semiautomated method. Modified Response Evaluation Criteria in Solid Tumors linear-thickness measurements were acquired clinically. Diseased (ipsilateral) lung volumes were normalized by the respective contralateral lung volumes to account for the differences in inspiration between scans for each patient. Relative changes in each metric from baseline were tracked over the course of follow-up imaging. Survival modeling was performed using Cox proportional hazards models with time-varying covariates.
  
  
  RESULTS
  Median survival from pretreatment baseline imaging was 12.7 months. A negative correlation was observed between measurements of lung volume and disease volume, and a positive correlation was observed between linear-thickness measurements and disease volume. As continuous numerical parameters, all three response assessment methods were significant imaging biomarkers of patient prognosis in independent survival models.
  
  
  CONCLUSIONS
  Analysis of trajectories of linear-thickness measurements, disease volume measurements, and lung volume measurements during chemotherapy for patients with mesothelioma indicates that increasing linear thickness, increasing disease volume, and decreasing lung volume are all significantly and independently associated with poor patient prognosis.
authors.affiliation: Department of Radiology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zacariah E
authors.initials: ZE
authors.lastname: Labby
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Armato
authors.forename: James J
authors.initials: JJ
authors.lastname: Dignam
authors.forename: Christopher
authors.initials: C
authors.lastname: Straus
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Kindler
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008176:Lung Volume Measurements; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor