Question

An October 25, 2012 article in the New England Journal of Medicine reports the results of a study examining aspirin and survival among patients with colorectal cancer. The following pieces of text are taken directly from the article abstract: (my edits are in italics) “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…… RESULTS Among patients with mutated-PIK3CA colorectal cancers, regular use of aspirin after diagnosis was associated with superior colorectal cancer–specific survival (adjusted relative risk 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 (adjusted relative risk 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 (adjusted relative risk, 0.96; 95% CI, 0.69 to 1.32; P = 0.76 by the log-rank test) ) or overall survival (adjusted relative risk, 0.94; 95% CI, 0.75 to 1.17; P = 0.96 by the log-rank test)” The authors present the following graphic as part of the article: (on the next page) Statistical Reasoning in Public Health 1, 2016: Ho

1. What is the outcome of interest for this study?

2. What is the primary predictor of interest for this study?

3. What type of study design is this?

4. Describe the findings with regards to aspirin and survival in patients with colorectal cancer with respect to the presence or absence of the PIK3CA mutation.

5. Even though the authors estimated the association between aspirin and survival separately for the mutated-PIK3CA and wild-type PIK3CA, each of the two associations was adjusted for multiple factors including age, sex, year of diagnosis etc… Why was it potentially necessary to do this adjustment?

Answer 1

1. The outcome of interest for this study suggests that regular use of aspirin after the diagnosis of colorectal cancer is significantly associated with increased survival among patients with mutated- PIK3CAtumors but not among patients with wild-type PIK3CA tumors.

This relationship appeared to be independent of aspirin use before diagnosis. PIK3CA mutation may serve as a tumor biomarker that predicts the response to the initiation of aspirin therapy in patients with newly diagnosed colorectal cancer.

2. The primary predictor of interest for this study PIK3CA mutation.

3. The study design used for this research article is Cohort design (Prospective Cohort study/ Observational design).

4. Following are the findings with regards to aspirin and survival in patients with colorectal cancer with respect to the presence or absence of the PIK3CA mutation.

• Aspirin use after diagnosis, appeared to prevent progression of disease in patients with mutated PIK3CA tumors- Tumor evolution, tumor cells are subject to changes in their own genome,epigenome, proteome, and metabolome and to changes in the local microenvironment. Thus, their dependence on an inflammatory microenvironment probably varies according to the specific phase of tumor evolution, which may result in the differential interaction of aspirin use and PIK3CA mutation in the early phase of evolution (before diagnosis) versus the late phase (after diagnosis).
• The effect of post-diagnosis use of aspirin on survival is stronger in mutated-PIK3CA colorectal cancer than in wild-type PIK3CA cancer
• Among patients with mutated-PIK3CA tumors, regular use of aspirin after diagnosis was associated with significantly longer cancer-specific survival in contrast among patients with wild type PIK3CA tumors, regular use of aspirin after diagnosis was not associated with cancer-specific survival
• The effect of aspirin on survival among patients with mutated-PIK3CA tumors appeared consistent irrespective of the dose- Only 3 colorectal cancer–specific deaths occurred among 66 patients with mutated-PIK3CA tumors who used aspirin after diagnosis. Among patients with mutated PIK3CA tumors,23 of 90 patients who did not use aspirin after diagnosis(26%) died within 5 years after diagnosis, whereas only 2 of 62 regular users of aspirin after diagnosis (3%) died within 5 years after diagnosis.
• Aspirin acts a promising agent for adjuvant therapy when used in patients who are already diagnosed with colorectal cancer.

Above mentioned is the brief description of findings in regards to aspirin and survival in patients with colorectal cancer with respect to the presence or absence of the PIK3CA mutation.

5. Even though the study has several strengths it also had some limitations.Statistical power was limited, data on cancer treatment were limited. The multivariable survival analysis was adjusted for cancer stage(I, II, III, IV) as the decision making for the treatment was largely based on stage of cancer, also there was limited information about cancer recurrence. Thus due to the limited satastical data few adjustments were made.