title: Isotoxic dose escalation in the treatment of lung cancer by means of heterogeneous dose distributions in the presence of respiratory motion.
abstract: OBJECTIVE
  To test, in the presence of intrafractional respiration movement, a margin recipe valid for a homogeneous and conformal dose distribution and to test whether the use of smaller margins combined with heterogeneous dose distributions allows an isotoxic dose escalation when respiratory motion is considered.
  
  
  METHODS
  Twenty-three Stage II-III non-small-cell lung cancer patients underwent four-dimensional computed tomography scanning. The gross tumor volume and clinical target volume (CTV) were outlined in the mid-ventilation phase. The CTV-to-planning target volume (PTV) margin was calculated by use of a standard margin recipe and the patient-specific respiration pattern. Standard three-dimensional treatment plans were generated and recalculated on the remaining respiration phases. The planning was repeated for a CTV-to-PTV margin decreased by 2.5 and 5 mm relative to the initial margin in all directions. Time-averaged dose-volume histograms (four-dimensional dose-volume histograms) were calculated to evaluate the CTV-to-PTV margin. Finally, the dose was escalated in the plans with decreased PTV such that the mean lung dose (predictor of radiation-induced pneumonitis) was equal to mean lung dose in the plan by use of the initially calculated margin.
  
  
  RESULTS
  A reduction of the standard margin by 2.5 mm compared with the recipe resulted in too low of a minimum dose for some patients. A combination of dose escalation and use of heterogeneous dose distribution was able to increase the minimum dose to the target by approximately 10% and 20% for a CTV-to-PTV margin reduction of 2.5 mm and 5.0 mm, respectively.
  
  
  CONCLUSIONS
  The margin recipe is valid for intrafractional respiration-induced tumor motions. It is possible to increase the dose to the target without increased mean lung dose with an inhomogeneous dose distribution.
authors.affiliation: Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark.
authors.forename: Mariwan
authors.initials: M
authors.lastname: Baker
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
authors.forename: Olfred
authors.initials: O
authors.lastname: Hansen
authors.forename: Jonas Westberg
authors.initials: JW
authors.lastname: Jahn
authors.forename: Stine
authors.initials: S
authors.lastname: Korreman
authors.forename: Carsten
authors.initials: C
authors.lastname: Brink
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D056973:Four-Dimensional Computed Tomography; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009068:Movement; D058958:Organs at Risk / Q000528:radiation effects; D017564:Radiation Pneumonitis / Q000209:etiology / Q000517:prevention & control; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods*; D061089:Radiotherapy, Image-Guided / Q000379:methods; D012119:Respiration; D047368:Tumor Burden