title: Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone.
abstract: OBJECTIVE
  Changes in tumour 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability.
  
  
  METHODS
  Sixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5-11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUV(mean) and SUV(max)) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions.
  
  
  RESULTS
  In all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUV(mean) reproducibility in primary tumours (SD 8.9%) was better than SUV(max) reproducibility (SD 12.6%). In nodes, SUV(mean) and SUV(max) reproducibilities (SD 18.0 and 17.2%) were comparable but worse than for primary tumours. After 5-11 RT fractions, primary tumour SUV(mean) decreased significantly by 25% (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31% (p = 0.020) with a larger SUV(mean) decrease of 40% (p < 0.0001). Similar changes were found for SUV(max).
  
  
  CONCLUSIONS
  Across this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.
authors: Institute of Population Health, Wolfson Molecular Imaging Centre, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, M20 3LJ, UK, ioannis.trigonis@postgrad.manchester.ac.uk.
authors: Ioannis
authors: I
authors: Trigonis
authors: Pek Keng
authors: PK
authors: Koh
authors: Ben
authors: B
authors: Taylor
authors: Mahbubunnabi
authors: M
authors: Tamal
authors: David
authors: D
authors: Ryder
authors: Mark
authors: M
authors: Earl
authors: Jose
authors: J
authors: Anton-Rodriguez
authors: Kate
authors: K
authors: Haslett
authors: Helen
authors: H
authors: Young
authors: Corinne
authors: C
authors: Faivre-Finn
authors: Fiona
authors: F
authors: Blackhall
authors: Alan
authors: A
authors: Jackson
authors: Marie-Claude
authors: MC
authors: Asselin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D015224:Dideoxynucleosides / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D015203:Reproducibility of Results
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine