title: 3'-Deoxy-3'-¹⁸F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer.
abstract: OBJECTIVE
  3'-Deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CTKSF) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy.
  
  
  METHODS
  Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy.
  
  
  RESULTS
  Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PETKSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35%). Maximum standardised uptake value at 60 min post-injection (SUV60,max) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV60,max increase of ≥ 12% resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100%, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV60,max were not predictive of survival.
  
  
  CONCLUSIONS
  FLT PET/CT detected changes in proliferation, with early increase in SUV60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer.
authors: Department of Surgery & Cancer, Imperial College London (ICL), London, UK.
authors: Amarnath
authors: A
authors: Challapalli
authors: Tara
authors: T
authors: Barwick
authors: Rachel A
authors: RA
authors: Pearson
authors: Shairoz
authors: S
authors: Merchant
authors: Francesco
authors: F
authors: Mauri
authors: Elizabeth C
authors: EC
authors: Howell
authors: Katherine
authors: K
authors: Sumpter
authors: Ross J
authors: RJ
authors: Maxwell
authors: Eric O
authors: EO
authors: Aboagye
authors: Rohini
authors: R
authors: Sharma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015224:Dideoxynucleosides; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D014057:Tomography, X-Ray Computed; D000093542:Gemcitabine
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; D003841:Deoxycytidine; C002854:alovudine; D000093542:Gemcitabine