title: Locoregional control of non-small cell lung cancer in relation to automated early assessment of tumor regression on cone beam computed tomography.
abstract: OBJECTIVE
  Large interindividual variations in volume regression of non-small cell lung cancer (NSCLC) are observable on standard cone beam computed tomography (CBCT) during fractionated radiation therapy. Here, a method for automated assessment of tumor volume regression is presented and its potential use in response adapted personalized radiation therapy is evaluated empirically.
  
  
  METHODS
  Automated deformable registration with calculation of the Jacobian determinant was applied to serial CBCT scans in a series of 99 patients with NSCLC. Tumor volume at the end of treatment was estimated on the basis of the first one third and two thirds of the scans. The concordance between estimated and actual relative volume at the end of radiation therapy was quantified by Pearson's correlation coefficient. On the basis of the estimated relative volume, the patients were stratified into 2 groups having volume regressions below or above the population median value. Kaplan-Meier plots of locoregional disease-free rate and overall survival in the 2 groups were used to evaluate the predictive value of tumor regression during treatment. Cox proportional hazards model was used to adjust for other clinical characteristics.
  
  
  RESULTS
  Automatic measurement of the tumor regression from standard CBCT images was feasible. Pearson's correlation coefficient between manual and automatic measurement was 0.86 in a sample of 9 patients. Most patients experienced tumor volume regression, and this could be quantified early into the treatment course. Interestingly, patients with pronounced volume regression had worse locoregional tumor control and overall survival. This was significant on patient with non-adenocarcinoma histology.
  
  
  CONCLUSIONS
  Evaluation of routinely acquired CBCT images during radiation therapy provides biological information on the specific tumor. This could potentially form the basis for personalized response adaptive therapy.
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Denmark; Laboratory of Radiation Physics, Odense University Hospital, Denmark. Electronic address: carsten.brink@rsyd.dk.
authors.forename: Carsten
authors.initials: C
authors.lastname: Brink
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Denmark; Laboratory of Radiation Physics, Odense University Hospital, Denmark.
authors.forename: Uffe
authors.initials: U
authors.lastname: Bernchou
authors.affiliation: Laboratory of Radiation Physics, Odense University Hospital, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Bertelsen
authors.affiliation: Institute of Clinical Research, University of Southern Denmark, Denmark; Department of Oncology, Odense University Hospital, Denmark.
authors.forename: Olfred
authors.initials: O
authors.lastname: Hansen
authors.affiliation: Department of Oncology, Odense University Hospital, Denmark.
authors.forename: Tine
authors.initials: T
authors.lastname: Schytte
authors.affiliation: Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Soren M
authors.initials: SM
authors.lastname: Bentzen
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D054893:Cone-Beam Computed Tomography; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012074:Remission Induction; D047368:Tumor Burden / Q000528:radiation effects