title: New dose constraint reduces radiation-induced fatal pneumonitis in locally advanced non-small cell lung cancer patients treated with intensity-modulated radiotherapy.
abstract: BACKGROUND
  Intensity-modulated radiotherapy (IMRT) in locally advanced non-small cell lung cancer (NSCLC) allows treatment of patients with large tumour volumes, but radiation pneumonitis (RP) remains a dose limiting complication. The incidence of severe RP using three-dimensional (3D) conformal radiotherapy, was previously reported to be 17%, with 2% lethal RP. The aim of this study was to monitor the incidence of RP following the introduction of IMRT.
  
  
  METHODS
  IMRT was delivered using 4-8 beam arrangements and introduced in three phases. In phase I, 12 patients were treated using only one dose constraint (V20), in which the total lung volume receiving 20 Gy was limited to 40%. In phase II, 25 patients were treated with an additional dose constraint of mean lung dose (MLD) ≤ 20 Gy. In phase III, 50 patients were treated with an extra dose constraint (V5) in which the total lung volume receiving a dose of 5 Gy was ≤ 60%. RP was prospectively documented. The results of phase I & II (IMRT-1) were compared to those in phase III (IMRT-2).
  
  
  RESULTS
  The median follow-up time was 17 months. The introduction of IMRT was associated with an increase in the incidence of RP in Phase I&II (IMRT-1) to 41%, six of 37 (16%) had grade 5 RP (IMRT-1). Introducing the dose constraint V5, led to a significant reduction in the lung volume receiving doses ≤ 20 Gy from 51 ± 2% to 41 ± 1% (p < 0.0001). Introducing V5 constraint did not decrease the incidence of severe (grade ≥ 3) RP, but significantly decreased the lethal pneumonitis to 4% (two of 50 patients), p = 0.05.
  
  
  CONCLUSIONS
  Introducing IMRT resulted in an increase in the incidence of severe and fatal RP, however a new dose constraint to the volume of lung receiving low doses reduced the incidence of lethal pneumonitis.
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Azza A
authors.initials: AA
authors.lastname: Khalil
authors.affiliation: b Department of Medical Physics , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Hoffmann
authors.affiliation: b Department of Medical Physics , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Ditte S
authors.initials: DS
authors.lastname: Moeller
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Katherina P
authors.initials: KP
authors.lastname: Farr
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Marianne M
authors.initials: MM
authors.lastname: Knap
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D017564:Radiation Pneumonitis / Q000453:epidemiology*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*