title: Predicting survival of pancreatic cancer patients treated with gemcitabine using longitudinal tumour size data.
abstract: Measures derived from longitudinal tumour size data have been increasingly utilised to predict survival of patients with solid tumours. The aim of this study was to examine the prognostic value of such measures for patients with metastatic pancreatic cancer undergoing gemcitabine therapy.
  
  
  
  The control data from two Phase III studies were retrospectively used to develop (271 patients) and validate (398 patients) survival models. Firstly, 31 baseline variables were screened from the training set using penalised Cox regression. Secondly, tumour shrinkage metrics were interpolated for each patient by hierarchical modelling of the tumour size time-series. Subsequently, survival models were built by applying two approaches: the first aimed at incorporating model-derived tumour size metrics in a parametric model, and the second simply aimed at identifying empirical factors using Cox regression. Finally, the performance of the models in predicting patient survival was evaluated on the validation set.
  
  
  
  Depending on the modelling approach applied, albumin, body surface area, neutrophil, baseline tumour size and tumour shrinkage measures were identified as potential prognostic factors. The distributional assumption on survival times appeared to affect the identification of risk factors but not the ability to describe the training data. The two survival modelling approaches performed similarly in predicting the validation data.
  
  
  
  A parametric model that incorporates model-derived tumour shrinkage metrics in addition to other baseline variables could predict reasonably well survival of patients with metastatic pancreatic cancer. However, the predictive performance was not significantly better than a simple Cox model that incorporates only baseline characteristics.
authors.affiliation: Manchester Pharmacy School, The University of Manchester, Stopford Building Room 3.32, Oxford Road, Manchester, M13 9PT, UK. thierry.wendling@manchester.ac.uk.|Drug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, 4002, Basel, Switzerland. thierry.wendling@manchester.ac.uk.
authors.forename: Thierry
authors.initials: T
authors.lastname: Wendling
authors.affiliation: Manchester Pharmacy School, The University of Manchester, Stopford Building Room 3.32, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Mistry
authors.affiliation: Manchester Pharmacy School, The University of Manchester, Stopford Building Room 3.32, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Kayode
authors.initials: K
authors.lastname: Ogungbenro
authors.affiliation: Manchester Pharmacy School, The University of Manchester, Stopford Building Room 3.32, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Leon
authors.initials: L
authors.lastname: Aarons
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008962:Models, Theoretical; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D047368:Tumor Burden / Q000187:drug effects*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Gemcitabine; Hierarchical modelling; Metastatic pancreatic cancer; Survival analysis; Tumour size time-series