Caitlin Murphy1, Natalie Turner2, Hui-Li Wong2, Mathu Sinnathamby3, Jeanne Tie1,2,3, Belinda Lee2, Jayesh Desai2,3, Iain Skinner4, Michael Christie2,5,6, Ryan Hutchinson6, Sebastian Lunke6, Paul Waring6, Peter Gibbs1,2,3, Ben Tran1,2,3. 1. Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia. 2. Colorectal Translational Oncology Group, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. 3. Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, Victoria, Australia. 4. Colorectal Unit, Department of Surgery, Western Health, Melbourne, Victoria, Australia. 5. Department of Anatomical Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia. 6. Centre for Translational Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
Abstract
BACKGROUND/AIM: 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.
BACKGROUND/AIM: 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: Shuji Ogino; Jonathan A Nowak; Tsuyoshi Hamada; Danny A Milner; Reiko Nishihara Journal: Annu Rev Pathol Date: 2018-08-20 Impact factor: 23.472
Authors: Charles S Fuchs; Zhi Rong Qian; Shuji Ogino; Mancang Gu; Reiko Nishihara; Yang Chen; Wanwan Li; Yan Shi; Yohei Masugi; Tsuyoshi Hamada; Keisuke Kosumi; Li Liu; Annacarolina da Silva; Jonathan A Nowak; Tyler Twombly; Chunxia Du; Hideo Koh; Wenbin Li; Jeffrey A Meyerhardt; Brian M Wolpin; Marios Giannakis; Andrew J Aguirre; Adam J Bass; David A Drew; Andrew T Chan Journal: Oncotarget Date: 2017-09-18
Authors: Peter C Elwood; Janet E Pickering; Gareth Morgan; Julieta Galante; Alison L Weightman; Delyth Morris; Marcus Longley; Malcolm Mason; Richard Adams; Sunil Dolwani; John Chia W K; Angel Lanas Journal: PLoS One Date: 2018-09-25 Impact factor: 3.240