title: Loss of lung function after chemo-radiotherapy for NSCLC measured by perfusion SPECT/CT: Correlation with radiation dose and clinical morbidity.
abstract: BACKGROUND
  The purpose of the study was to assess dose and time dependence of radiotherapy (RT)-induced changes in regional lung function measured with single photon emission computed tomography (SPECT) of the lung and relate these changes to the symptomatic endpoint of radiation pneumonitis (RP) in patients treated for non-small cell lung cancer (NSCLC).
  
  
  METHODS
  NSCLC patients scheduled to receive curative RT of minimum 60 Gy were included prospectively in the study. Lung perfusion SPECT/CT was performed before and three months after RT. Reconstructed SPECT/CT data were registered to treatment planning CT. Dose to the lung was segmented into regions corresponding to 0-5, 6-20, 21-40, 41-60 and > 60 Gy. Changes (%) in regional lung perfusion before and after RT were correlated with regional dose and symptomatic RP (CTC grade 2-5) outcome.
  
  
  RESULTS
  A total of 58 patients were included, of which 45 had three-month follow-up SPECT/CT scans. Analysis showed a statistically significant dose-dependent reduction in regional perfusion at three-month follow-up. The largest population composite perfusion loss was in 41-60 Gy (42.2%) and > 60 Gy (41.7%) dose bins. Lung regions receiving low dose of 0-5 Gy and 6-20 Gy had corresponding perfusion increase (-7.2% and -6.1%, respectively). Regional perfusion reduction was different in patients with and without RP with the largest difference in 21-40 Gy bin (p = 0.02), while for other bins the difference did not reach statistical significance. The risk of symptomatic RP was higher for the patients with perfusion reduction after RT (p = 0.02), with the relative risk estimate of 3.6 (95% CI 1.1-12).
  
  
  CONCLUSIONS
  Perfusion lung function changes in a dose-dependent manner after RT. The severity of radiation-induced lung symptoms is significantly correlated with SPECT perfusion changes. Perfusion reduction early after RT is associated with a high risk of later development of symptomatic RP.
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus C , Denmark.
authors.forename: Katherina P
authors.initials: KP
authors.lastname: Farr
authors.affiliation: b Department of Medical Physics , Aarhus University Hospital , Aarhus C , Denmark.
authors.forename: Ditte S
authors.initials: DS
authors.lastname: Møller
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus C , Denmark.
authors.forename: Azza A
authors.initials: AA
authors.lastname: Khalil
authors.affiliation: c Department of Nuclear Medicine and PET Centre , Aarhus University Hospital , Aarhus C , Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Kramer
authors.affiliation: c Department of Nuclear Medicine and PET Centre , Aarhus University Hospital , Aarhus C , Denmark.
authors.forename: Anni
authors.initials: A
authors.lastname: Morsing
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus C , Denmark.
authors.forename: Cai
authors.initials: C
authors.lastname: Grau
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D011829:Radiation Dosage; D017564:Radiation Pneumonitis / Q000000981:diagnostic imaging*; D012129:Respiratory Function Tests; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed