Precision oncology in surgery: patient selection for operable pancreatic cancer

Dreyer, S. B. et al. (2018) Precision oncology in surgery: patient selection for operable pancreatic cancer. Annals of Surgery, (doi:10.1097/SLA.0000000000003143) (PMID:30570546) (Early Online Publication)

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Abstract

Objective: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. Background: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. Method: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram. Results: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables. Conclusions: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

Item Type:Articles
Additional Information:The study was supported by Wellcome Trust Senior Investigator Award: 103721/Z/14/Z; Cancer Research UK Programme: C29717/ A17263 and C29717/A18484; Cancer Research UK Glasgow Centre: C596/ A18076; Cancer Research UK Clinical Training Award: C596/A20921; Scottish Genome Partnership SEHHD-CSO 1175759/2158447; Pancreatic Cancer UK Future Research Leaders Fund FLF2015_04_Glasgow; MRC/EPSRC Glasgow Molecular Pathology Node; The Howat Foundation; Precision Panc; The National Health and Medical Research Council of Australia, The Cancer Council NSW, Cancer Institute NSW, Royal Australasian College of Surgeons, St Vincent’s Clinic Foundation and R. T. Hall Trust; and The Avner Pancreatic Cancer Foundation.
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Duthie, Dr Fraser and Carter, Mr Christopher and Moran-Jones, Dr Kim and Jones, Mr Marc and Jamieson, Dr Nigel and Dreyer, Dr Stephan and Cooke, Dr Susanna and Bailey, Dr Peter and McKay, Mr Colin and Chang, Dr David and Biankin, Professor Andrew and Musgrove, Dr Elizabeth
Authors: Dreyer, S. B., Pinese, M., Jamieson, N. B., Scarlett, C. J., Colvin, E. K., Pajic, M., Johns, A. L., Humphris, J. L., Wu, J., Cowley, M. J., Chou, A., Nagrial, A. M., Chantrill, L., Chin, V. T., Jones, M. D., Moran-Jones, K., Carter, C. R., Dickson, E. J., Samra, J. S., Merrett, N. D., Gill, A. J., Kench, J. G., Duthie, F., Miller, D. K., Cooke, S., Aust, D., Knösel, T., Rümmele, P., Grützmann, R., Pilarsky, C., Nguyen, N. Q., Musgrove, E. A., Bailey, P. J., McKay, C. J., Biankin, A. V., and Chang, D. K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Annals of Surgery
Publisher:Lippincott, Williams and Wilkins
ISSN:0003-4932
ISSN (Online):1528-1140
Published Online:30 November 2018

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656911Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOTR)103721/Z/14/ZICS - TRANSLATIONAL RESEARCH CENTRE
645512Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CRUK)C29717/A18484ICS - TRANSLATIONAL RESEARCH CENTRE
696321Development Award: Measurement of Small Molecule Pharmacokinetics in invasive Regions of GlioblastomaAnthony ChalmersCancer Research UK (CRUK)C596/A18076ICS - CLINICAL TRIALS RESEARCH
710321Clinical Training Award Cycle 2Iain McNeishCancer Research UK (CRUK)C596/A20921RI CANCER SCIENCES
742501The Scottish Genomes PartnershipAndrew BiankinChief Scientist office (CSO)1175759/2158447ICS - TRANSLATIONAL RESEARCH CENTRE