Colon Cancer Survival Improved with Aspirin Use Interview with:

M.S. ReimersM.S. Reimers, MD PhD Student
Dr. Jan Liefers MD
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands What are the main findings of the study?

Answer: Aspirin use was associated with an improved survival, as we have published before when investigating this cohort (Bastiaannet et al, Brit J Cancer 2012/ Reimers et al. J Am Geriatr Soc. 2012. In this study we have focused on investigating which patients will benefit from aspirin treatment by investigating some tumor markers, such as PTGS2 expression, HLA class I expression and PIK3CA mutation status. Interestingly, only patients with HLA class I expression on their tumor membrane will benefit from aspirin treatment and have a better outcome. We raise the hypothesize that aspirin inhibits platelet aggregation to circulating tumors cells. By interfering with this process, the metastatic potential of these circulating tumour cells is inhibited, thereby preventing metastasis and colon cancer death.HLA class I expression might be needed for signalling between platelets and circulating tumor cells. If this hypothesis is confirmed by others or in vitro studies, than this might explain the finding that aspirin seems not only beneficial as an adjuvant therapy for colorectal cancer patients, but also for patients with other malignancies (oesophagus, breast, etc). Interestingly, preliminary findings from our team investigating aspirin use in oesophageal cancer also showed that aspirin use in these tumors was associated with an improved survival. Were any of the findings unexpected?

Answer: Yes. We previously hypothesized before starting this study that aspirin use would be associated with a survival benefit in tumors who have lost their HLA class I expression. As soon as cancer cells enter the bloodstream they interact with platelets. Through tumor cell coating, platelets are thought to protect disseminating tumor cells from lysis by immune cells such as Natural Killer cells. Aspirin influences platelet aggregation. Most likely tumor cell coating and platelet-tumor cell interaction are affected as well. In case of aspirin use, tumor cells are now prone for lysis by immune cells. Natural Killer cells preferentially recognize and eliminate cells with low or absent expression of HLA class I, We therefore hypothesized that the survival benefit associated with low dose aspirin use after a cancer diagnosis would be associated with tumors that have low or absent HLA class I expression. What should clinicians and patients take away from your report?

Dr. Reimers:  Aspirin seems to improve survival in colon cancer patients and therefore it might be used as adjuvant treatment in the near future. This study shows that not all patients will benefit from this treatment. In our study, only patients with HLA class I expression on their tumor cell surface showed an improved survival when they used aspirin after a colon cancer diagnosis. However, these results have to be validated first. Furthermore as interesting as it may be, we still need to await the results of ongoing and planned randomized trials for a definite answer.  In the second half of 2014, in the Netherlands, we will start a phase 3, placebo controlled trial (placebo versus aspirin 80 mg) to test aspirin as a valid adjuvant therapy. What recommendations do you have for future research as a result of this study?

Dr. Reimers:  Validation of HLA class I as a predictive biomarker for aspirin benefit needs to be validated in an independent cohort. It is also desirable that different groups investigating the role of aspirin in colon cancer and predictive biomarkers for aspirin treatment join forces and possibly pool their data to increase statistical power of the different cohorts. Furthermore, results from randomized controlled trials are eagerly awaited.


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