TY - JOUR
AR - COR-2019-5-117
TI - Fluorothymidine Positron Emission Tomography (FLT-PET) Repeatability and Response Evaluation in Advanced Pancreatic Cancer Patients Treated with Gemcitabine-Based Chemotherapy
AU - Andrew, Cotterill
AU - Angela, Lamarca
AU - Azeem, Saleem
AU - Ioannis, Trigonis
AU - Juan W, Valle
AU - Madhu, Rao
AU - Mahbubunnabi, Tamal
AU - Mairéad G, McNamara
AU - Peter J, Julyan
AU - Prakash, Manoharan
AU - Richard A, Hubner
AU - Zarni, Win
JO - Clinical Oncology and Research
PY - 2019
DA - Wed 27, Nov 2019
SN - 2613-4942
DO - http://dx.doi.org/10.31487/j.COR.2019.5.17
UR - https://www.sciencerepository.org/fluorothymidine-positron-emission-tomography-repeatability-and-response-evaluation-in-advanced-pancreatic-cancer-patients_COR-2019-5-117 
KW - FLT, PET, proliferation, pancreatic cancer, feasibility, repeatability
AB - Purpose: This study aimed to evaluate the feasibility and repeatability of [18F]-fluorothymidine positron emission tomography (FLT-PET) and its utility as a proliferative imaging marker to evaluate response in patients with advanced pancreatic adenocarcinoma (PDAC) receiving gemcitabine-based chemotherapy.
Methods: PDAC patients due to commence gemcitabine-based chemotherapy underwent FLT-PET over 60 minutes, before (baseline) and after 28 days of chemotherapy. Repeatability was assessed by a second FLT-PET scan within 7 days of baseline scan and before starting chemotherapy.  Scans were assessed by two independent physician’s to determine inter-reporter concordance. FLT-PET uptake over 45-60 minutes was estimated as maximum and mean standardised uptake values (SUVmax and SUVmean). Exploratory analysis of tissue biomarkers was performed from archival tissue samples.
Results: All 18 of the 21 patients consented who were imaged had primary tumour in-situ and 83% had metastases with 60% in liver.  17 patients received gemcitabine-based treatment. Thirty-five FLT-PET scans were acquired (89% evaluable) and 26 lesions delineated (17 primary tumours, 9 liver metastases). At baseline, liver metastases showed higher uptake compared with primary tumour with mean (SD) SUVmax [7.2 (1.1) vs 4.5 (1.3); p < 0.001] and SUVmean [4.7 (0.6) vs 2.1 (0.6); p < 0.001)]. There was good intra-patient repeatability and inter-reporter concordance with mean (SD) test-retest difference and inter-reporter Lin’s concordance coefficient being 4.9% (17.6) and 0.703 for SUVmax and -5.4% (SD 9.8) and 0.710 for SUVmean, respectively. However, gemcitabine-capecitabine combination therapy resulted in a higher FLT uptake compared to gemcitabine alone, although this did not translate to clinical benefit. No relationship was observed between tissue markers and FLT in half of the subjects imaged whose tissue was available.
Conclusions: FLT-PET is a feasible and reproducible imaging technique in patients with PDAC to evaluate proliferation-targeting therapy, using a simplified imaging protocol in well-designed clinical trials.