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Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis.

ABSTRACT: BACKGROUND:Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer. METHODS:We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model. RESULTS:A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers. For colorectal cancer, a benefit that was associated with postdiagnosis aspirin use was observed for overall survival and cancer-specific survival [HR?=?0.83, 95%CI(0.75, 0.9.);HR?=?0.78, 95%CI(0.66, 0.92), respectively. However, a prediagnosis of aspirin use did not provide a benefit for overall or cancer-specific survival in colorectal cancer. HR values for overall and cancer-specific survival benefits for colorectal cancer associated with both prediagnosis and postdiagnosis aspirin were as follows: HR?=?0.75, 95%CI(0.61, 0.92) and HR?=?0.78, 95%CI(0.73, 0.85), respectively. In addition, the survival benefit of postdiagnosis aspirin use appeared to be confined to patients with mutated PIK3CA tumors [HR?=?0.78, 95%CI(0.50, 0.99)] and was positive for PTGS2 (COX-2) expression [HR?=?0.75, 95%CI(0.43, 1.30)]. CONCLUSIONS:These findings provide further indications that postdiagnosis aspirin use improves overall survival and cancer-specific survival in colorectal cancer, especially for patients who are positive for PTGS2 (COX-2) expression and PIK3CA-mutated tumors. However, aspirin therapy does not improve overall survival in esophageal and gastric cancers, although the meta-analysis was mainly limited to retrospective studies.

SUBMITTER: Lin JL

PROVIDER: S-EPMC7350580 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis.

Lin Ju-Li JL Lin Jian-Xian JX Zheng Chao-Hui CH Li Ping P Xie Jian-Wei JW Wang Jia-Bin JB Lu Jun J Chen Qi-Yue QY Cao Long-Long LL Lin Mi M Huang Chang-Ming CM

BMC cancer 20200709 1

<h4>Background</h4>Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer.<h4>Methods</h4>We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Over ...[more]

PMID: 32646396

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Project description:BackgroundEpidemiological evidence suggests that use of aspirin after the diagnosis of colorectal cancer can lengthen survival. However, the supporting data vary between studies, and this hypothesis remains controversial. We conducted a meta-analysis to provide a quantitative assessment of the association between use of aspirin after diagnosis of colorectal cancer and patient survival.MethodsWe searched the Medline and Embase databases up to April 2014 to identify studies related to aspirin use after diagnosis and all-cause mortality or colorectal cancer-specific mortality. Summary effect estimates with 95% confidence intervals (CIs) were derived using a fixed or random effects model, depending on the heterogeneity between the included studies.ResultsSeven epidemiologic studies that consisted of six cohort studies and one nested case-control study were included in this meta-analysis. The hazard ratio (HR) of the association between aspirin use after colorectal cancer diagnosis and overall mortality, which was reported in five studies, was 0.74 (95% CI, 0.62-0.89) using a random model (heterogeneity test P=0.003, I(2)=75.3%), and for colorectal cancer-specific mortality (four studies), it was 0.75 (95% CI, 0.51-1.10) using a random model (heterogeneity test P=0.001, I(2)=84.1%). In addition, we analysed postdiagnosis aspirin use according to whether aspirin was also used before diagnosis. The HR for the overall mortality of patients who did not use aspirin before diagnosis, which was reported in four studies, was 0.84 (95% CI, 0.70-1.00), and for colorectal cancer-specific mortality (three studies), it was 0.79 (95% CI, 0.61-1.02). For those who did use aspirin before diagnosis, the HR for overall mortality (four studies) was 0.88 (95% CI, 0.83-0.93), and for colorectal cancer-specific mortality (three studies), it was 0.80 (95% CI, 0.59-1.09). Subgroup analysis showed that use of aspirin after diagnosis was associated with longer overall survival among patients with the variant PIK3CA gene but not for those with wild-type PIK3CA.ConclusionsBased on current evidence, the use of aspirin after diagnosis does not reduce colorectal cancer-specific mortality, but it does reduce all-cause mortality for colorectal cancer patients.

Project description:BACKGROUND:Regular use of aspirin after a diagnosis of colon cancer has been associated with a superior clinical outcome. Experimental evidence suggests that inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2) (also known as cyclooxygenase-2) by aspirin down-regulates phosphatidylinositol 3-kinase (PI3K) signaling activity. We hypothesized that the effect of aspirin on survival and prognosis in patients with cancers characterized by mutated PIK3CA (the phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit alpha polypeptide gene) might differ from the effect among those with wild-type PIK3CA cancers. METHODS:We obtained data on 964 patients with rectal or colon cancer from the Nurses' Health Study and the Health Professionals Follow-up Study, including data on aspirin use after diagnosis and the presence or absence of PIK3CA mutation. We used a Cox proportional-hazards model to compute the multivariate hazard ratio for death. We examined tumor markers, including PTGS2, phosphorylated AKT, KRAS, BRAF, microsatellite instability, CpG island methylator phenotype, and methylation of long interspersed nucleotide element 1. RESULTS:Among patients with mutated-PIK3CA colorectal cancers, regular use of aspirin after diagnosis was associated with superior colorectal cancer-specific survival (multivariate hazard ratio for cancer-related death, 0.18; 95% confidence interval [CI], 0.06 to 0.61; P<0.001 by the log-rank test) and overall survival (multivariate hazard ratio for death from any cause, 0.54; 95% CI, 0.31 to 0.94; P=0.01 by the log-rank test). In contrast, among patients with wild-type PIK3CA, regular use of aspirin after diagnosis was not associated with colorectal cancer-specific survival (multivariate hazard ratio, 0.96; 95% CI, 0.69 to 1.32; P=0.76 by the log-rank test; P=0.009 for interaction between aspirin and PIK3CA variables) or overall survival (multivariate hazard ratio, 0.94; 95% CI, 0.75 to 1.17; P=0.96 by the log-rank test; P=0.07 for interaction). CONCLUSIONS:Regular use of aspirin after diagnosis was associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. The findings from this molecular pathological epidemiology study suggest that the PIK3CA mutation in colorectal cancer may serve as a predictive molecular biomarker for adjuvant aspirin therapy. (Funded by The National Institutes of Health and others.).

Project description:ImportancePopulation-based East Asian data have corroborated reports from non-Asian settings on the association between low-dose aspirin and a lower risk of colorectal cancer (CRC).ObjectiveTo evaluate the association between duration and recency of low-dose aspirin use and CRC risk.Design, setting, and participantsThis nested case-control study included individuals who initiated aspirin use and matched individuals who did not use aspirin. Data were collected from Taiwan National Health Insurance and Taiwan Cancer Registry from 2000 through 2015. CRC cases were age- and sex-matched in a 1:4 ratio with individuals in a control group, identified from a cohort of individuals who used and did not use aspirin through risk-set sampling. Data analysis was conducted from June 2018 to July 2019.ExposuresLow-dose aspirin use was defined as receiving less than 150 mg per day, whereas 100 mg/d was most commonly used. Based on duration and recency of low-dose aspirin use between cohort entry (initiation date of low-dose aspirin for aspirin use group or randomly assigned date for those who did not use aspirin) and index date (CRC diagnosis date for individuals in the case group and the diagnosis date for the 4 corresponding matched individuals in the control group), the 3 following mutually exclusive exposure groups served as the basis for analysis: (1) long-term current low-dose aspirin use, (2) episodic low-dose aspirin use, and (3) no low-dose aspirin use (the reference group).Main outcomes and measuresCRC risk among the 3 exposure groups.ResultsAmong 4 710 504 individuals (2 747 830 [51.7%] men; median [interquartile range] age at cohort entry in initiator group, 61 [52-71] years; median [interquartile range] age at cohort entry in nonuse group, 59 [51-68] years), 79 095 CRC cases (1.7% of study cohort) were identified. Compared with no low-dose aspirin use, the adjusted odds ratio (OR) for long-term current low-dose aspirin use and CRC risk was 0.89 (95% CI, 0.85-0.93); for episodic use, 0.88 (95% CI, 0.86-0.89). Adjusted ORs of 0.69 (95% CI, 0.63-0.76) and 0.64 (95% CI, 0.61-0.67) were observed for long-term current use and episodic low-dose aspirin use within the subcohort of individuals who initiated low-dose aspirin between age 40 and 59 years.Conclusions and relevanceIn this study, low-dose aspirin use was associated with 11% lower CRC risk in an East Asian population, and this association was larger when low-dose aspirin use started before age 60 years.

Dataset Information

Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis.

Publications

Relationship between aspirin use of esophageal, gastric and colorectal cancer patient survival: a meta-analysis.

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