title: Examining the impact of regular aspirin use and PIK3CA mutations on survival in stage 2 colon cancer.
abstract: OBJECTIVE
  Data suggest aspirin improves survival in colorectal cancer (CRC) harbouring PIK3CA mutations. The impact of aspirin is thought predominantly to be through an anti-inflammatory effect. The aim of this study is to explore the effect of aspirin use on survival in a real-world cohort of stage 2 colon cancer (CC) patients.
  
  
  METHODS
  A prospective CRC database identified patients diagnosed with stage 2 CC between 2000 and 2011. PIK3CA mutation status was determined by next generation sequencing. Neutrophil-lymphocyte ratio greater than 5 at diagnosis represented systemic inflammation. Chart review was used to record regular aspirin use at diagnosis. Clinico-pathological features and survival data were available. Survival analyses used the Cox proportional hazards method.
  
  
  RESULTS
  Of 488 patients with stage 2 CC, 95 patients were aspirin users and 70 patients had PIK3CA mutations. Aspirin users were more likely to be older (median: 76.4 years vs 68.3 years, P < 0.001), to be less fit (American Society of Anaesthetists Score 3-4: 58% vs 31%, P < 0.001) and to have systemic inflammation (neutrophil-lymphocyte ratio > 5: 39% vs 27%, P = 0.027). Regular aspirin use did not significantly improve recurrence-free survival. In the PIK3CA mutated group, there was a trend towards improved recurrence-free survival (hazard ratio: 0.45, P = 0.42).
  
  
  CONCLUSIONS
  Our study did not demonstrate a significant survival advantage from aspirin use in stage 2 PIK3CA mutated CC. The 'real-world' nature of our cohort and the subsequent uncontrolled differences in age and fitness in aspirin users are likely to have contributed to this result. Defining the true impact of aspirin in CRC requires prospective randomised clinical trials.
authors: Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.
authors: Caitlin
authors: C
authors: Murphy
authors: Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
authors: Natalie
authors: N
authors: Turner
authors: Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
authors: Hui-Li
authors: HL
authors: Wong
authors: Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Mathu
authors: M
authors: Sinnathamby
authors: Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.|Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Jeanne
authors: J
authors: Tie
authors: Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
authors: Belinda
authors: B
authors: Lee
authors: Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Jayesh
authors: J
authors: Desai
authors: Colorectal Unit, Department of Surgery, Western Health, Melbourne, Victoria, Australia.
authors: Iain
authors: I
authors: Skinner
authors: Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Anatomical Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.|Centre for Translational Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Michael
authors: M
authors: Christie
authors: Centre for Translational Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Ryan
authors: R
authors: Hutchinson
authors: Centre for Translational Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Sebastian
authors: S
authors: Lunke
authors: Centre for Translational Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Paul
authors: P
authors: Waring
authors: Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.|Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Peter
authors: P
authors: Gibbs
authors: Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.|Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.|Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors: Ben
authors: B
authors: Tran
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001315:Australia; D058534:Class I Phosphatidylinositol 3-Kinases; D003110:Colonic Neoplasms / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D016208:Databases, Factual; D005260:Female; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D001241:Aspirin
keywords: 
  
  PIK3CA
  
  ; aspirin; colon cancer; colorectal cancer; real-world data