title: Dose heterogeneity in the target volume and intensity-modulated radiotherapy to escalate the dose in the treatment of non-small-cell lung cancer.
abstract: OBJECTIVE
  To quantify the dose escalation achievable in the treatment of non-small-cell lung cancer (NSCLC) by allowing dose heterogeneity in the target volume or using intensity-modulated radiotherapy (IMRT), or both.
  
  
  METHODS
  Computed tomography data and contours of 10 NSCLC patients with limited movements of the tumor and representing a broad spectrum of clinical cases were selected for this study. Four irradiation techniques were compared: two conformal (CRT) and two IMRT techniques, either prescribing a homogeneous dose in the planning target volume (PTV) (CRT(hom) and IMRT(hom)) or allowing dose heterogeneity (CRT(inhom) and IMRT(inhom)). The dose heterogeneity was allowed only toward high doses, i.e., the minimum dose in the target for CRT(inhom) and IMRT(inhom) could not be lower than for the corresponding homogeneous plan. The dose in the PTV was escalated (fraction size of 2.25 Gy) until either an organ at risk reached the maximum allowed dose or the mean PTV dose reached a maximum level set at 101.25 Gy.
  
  
  RESULTS
  When small and convex tumors were irradiated, CRT(hom) could achieve the maximum dose of 101.25 Gy, whereas for bigger and/or concave PTVs the dose level achievable with CRT(hom) was significantly lower, in 1 case even below 60 Gy. The CRT(inhom) allowed on average a 6% dose escalation with respect to CRT(hom). The IMRT(hom) achieved in all except 1 case a mean PTV dose of at least 75 Gy. The gain in mean PTV dose of IMRT(hom) with respect to CRT(hom) ranged from 7.7 to 14.8 Gy and the IMRT(hom) plans were always more conformal than the corresponding CRT(hom) plans. The IMRT(inhom) provided an additional advantage over IMRT(hom) of at least 5 Gy. For all CRT plans the achievable dose was determined by the lung dose threshold, whereas for more than half of the IMRT plans the esophagus was the dose-limiting organ. The IMRT plans were deliverable with 10-12 segments per beam and did not produce an increase of lung volume irradiated at low doses (<20 Gy).
  
  
  CONCLUSIONS
  The dose in NSCLC treatments can be escalated by loosening the constraints on maximum dose in the target volume or using IMRT, or both. For large and concave tumors, an average dose escalation of 6% and 17% was possible when dose heterogeneity and IMRT were applied alone. When they were combined, the average dose increase was as high as 35%. Intensity-modulated RT delivered in a static mode can produce homogeneous dose distributions in the target and does not lead to an increase of lung volume receiving (very) low doses, even down to 5 Gy.
authors.affiliation: Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Schwarz
authors.forename: Markus
authors.initials: M
authors.lastname: Alber
authors.forename: Joos V
authors.initials: JV
authors.lastname: Lebesque
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Mijnheer
authors.forename: Eugène M F
authors.initials: EM
authors.lastname: Damen
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000532:radiotherapy*; D004947:Esophagus / Q000528:radiation effects; D006321:Heart / Q000528:radiation effects; D006801:Humans; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D020714:Maximum Tolerated Dose; D009010:Monte Carlo Method; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D013116:Spinal Cord / Q000528:radiation effects