Timing of aspirin and other nonsteroidal anti-inflammatory drug use among patients with colorectal cancer in relation to tumor markers and survival

Xinwei Hua, Amanda I. Phipps, Andrea N. Burnett-Hartman, Scott V. Adams, Sheetal Hardikar, Stacey A. Cohen, Jonathan M. Kocarnik, Dennis J. Ahnen, Noralane Morey Lindor, John A. Baron, Polly A. Newcomb

Research output: Contribution to journalArticle

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Abstract

Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status (Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

Original languageEnglish (US)
Pages (from-to)2806-2813
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number24
DOIs
StatePublished - Aug 20 2017

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Tumor Biomarkers
Aspirin
Colorectal Neoplasms
Anti-Inflammatory Agents
Survival
Pharmaceutical Preparations
Registries
Neoplasms
Microsatellite Instability
Mutation
CpG Islands
Canada
Phenotype

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Timing of aspirin and other nonsteroidal anti-inflammatory drug use among patients with colorectal cancer in relation to tumor markers and survival. / Hua, Xinwei; Phipps, Amanda I.; Burnett-Hartman, Andrea N.; Adams, Scott V.; Hardikar, Sheetal; Cohen, Stacey A.; Kocarnik, Jonathan M.; Ahnen, Dennis J.; Lindor, Noralane Morey; Baron, John A.; Newcomb, Polly A.

In: Journal of Clinical Oncology, Vol. 35, No. 24, 20.08.2017, p. 2806-2813.

Research output: Contribution to journalArticle

Hua, X, Phipps, AI, Burnett-Hartman, AN, Adams, SV, Hardikar, S, Cohen, SA, Kocarnik, JM, Ahnen, DJ, Lindor, NM, Baron, JA & Newcomb, PA 2017, 'Timing of aspirin and other nonsteroidal anti-inflammatory drug use among patients with colorectal cancer in relation to tumor markers and survival', Journal of Clinical Oncology, vol. 35, no. 24, pp. 2806-2813. https://doi.org/10.1200/JCO.2017.72.3569
Hua, Xinwei ; Phipps, Amanda I. ; Burnett-Hartman, Andrea N. ; Adams, Scott V. ; Hardikar, Sheetal ; Cohen, Stacey A. ; Kocarnik, Jonathan M. ; Ahnen, Dennis J. ; Lindor, Noralane Morey ; Baron, John A. ; Newcomb, Polly A. / Timing of aspirin and other nonsteroidal anti-inflammatory drug use among patients with colorectal cancer in relation to tumor markers and survival. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 24. pp. 2806-2813.
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title = "Timing of aspirin and other nonsteroidal anti-inflammatory drug use among patients with colorectal cancer in relation to tumor markers and survival",
abstract = "Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95{\%} CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95{\%} CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95{\%} CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95{\%} CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95{\%} CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status (Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95{\%} CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95{\%} CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.",
author = "Xinwei Hua and Phipps, {Amanda I.} and Burnett-Hartman, {Andrea N.} and Adams, {Scott V.} and Sheetal Hardikar and Cohen, {Stacey A.} and Kocarnik, {Jonathan M.} and Ahnen, {Dennis J.} and Lindor, {Noralane Morey} and Baron, {John A.} and Newcomb, {Polly A.}",
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T1 - Timing of aspirin and other nonsteroidal anti-inflammatory drug use among patients with colorectal cancer in relation to tumor markers and survival

AU - Hua, Xinwei

AU - Phipps, Amanda I.

AU - Burnett-Hartman, Andrea N.

AU - Adams, Scott V.

AU - Hardikar, Sheetal

AU - Cohen, Stacey A.

AU - Kocarnik, Jonathan M.

AU - Ahnen, Dennis J.

AU - Lindor, Noralane Morey

AU - Baron, John A.

AU - Newcomb, Polly A.

PY - 2017/8/20

Y1 - 2017/8/20

N2 - Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status (Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

AB - Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status (Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

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