title: Respiratory-gated (4D) FDG-PET detects tumour and normal lung response after stereotactic radiotherapy for pulmonary metastases.
abstract: BACKGROUND
  Response assessment after stereotactic ablative body radiotherapy (SABR) in lung can be confounded by radiation-induced inflammation, fibrosis and subsequent alteration of tumour motion. The purpose of this prospective pilot study was to evaluate the utility of four-dimensional (4D) FDG-PET/CT for post-SABR tumour and normal lung response assessment in pulmonary oligometastases.
  
  
  METHODS
  Patients enrolled from February 2010 to December 2011 in this prospective ethics approved study had 1-2 pulmonary metastases on staging FDG-PET. Serial contemporaneous 3D and 4D FDG-PET/CT scans were performed at baseline, 14 days and 70 days after a single fraction of 26 Gy SABR. Tumour response was evaluated in 3D and 4D using SUVmax, RECIST and PERCIST criteria. Normal lung radiotoxicity was evaluated using SUVmean within 0-2 Gy, 2-5 Gy, 5-10 Gy, 10-20 Gy and 20 + Gy isodose volumes.
  
  
  RESULTS
  In total, 17 patients were enrolled of which seven were ineligible due to interval progression from staging PET to baseline 4D-PET. The mean time between scans was 62 days. At a median follow-up of 16 months, 10 patients with 13 metastases received SABR, with no patient having local progression. The vector of tumour motion was larger in patients with discordant 3D and 4D PET PERCIST response (p < 0.01), with a mean (± SEM) motion of 10.5 mm (± 0.96 mm) versus 6.14 mm (± 0.81 mm) in those patients with concordant 3D and 4D response. Surrounding normal lung FDG uptake at 70 days was strongly correlated to delivered radiation dose (r(2) = 0.99, p < 0.01), with significant elevations across all dose levels (p ≤ 0.05), except the < 2 Gy volume (p = 0.30).
  
  
  CONCLUSIONS
  We demonstrate high rates of interval progression between staging PET scans in patients with oligometastases. We found that tumour response on conventional 3D PET is not concordant with 4D PET for tumours with large motion. Normal lung metabolic uptake is strongly dose dependent after SABR, a novel finding that should be further validated.
authors.affiliation: a Sir Peter MacCallum Department of Oncology , The University of Melbourne , Parkville, Victoria , Australia.
authors.forename: Shankar
authors.initials: S
authors.lastname: Siva
authors.forename: Jason W
authors.initials: JW
authors.lastname: Callahan
authors.forename: Tomas
authors.initials: T
authors.lastname: Kron
authors.forename: Brent
authors.initials: B
authors.lastname: Chesson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Barnett
authors.forename: Michael P
authors.initials: MP
authors.lastname: Macmanus
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: David L
authors.initials: DL
authors.lastname: Ball
mesh_terms: D000368:Aged; D005260:Female; D019788:Fluorodeoxyglucose F18; D056973:Four-Dimensional Computed Tomography / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D016634:Radiosurgery; D011880:Radiotherapy Planning, Computer-Assisted
chemical_list: D019788:Fluorodeoxyglucose F18