Anna Martling Surgeon, chief physician, professor, dean and research group leader for the ALASCCA study. Anna Martling already has many titles. Now she can add Cancer Researcher of the Year 2021.                          Ingress:

In Sweden (population 11 mill.) circa 7 000 people are diagnosed with colorectal cancer and around 2 700 die from the disease.

Colorectal cancer is the third most common cancer after prostate and breast cancer (apart from skin cancer.)

Worldwide, more than 1,4 million men and women are diagnosed with the disease, and more than 50 percent will die.

Thus, there is a high need for more efficient adjuvant therapies to improve survival in colorectal cancer.

Interview:

Question: Anna Martling, how would you briefly describe the ALASCCA study?

ALASCCA is a prospective, randomized, double blinded, placebo controlled, multicenter, biomarker-based study of

adjuvant treatment with aspirin in colorectal cancer. A total of 3,800 Nordic patients will be screened.

ALASCCA is short for Adjuvant Low Dose Aspirin in Colorectal Cancer.

The primary objective of ALASCCA is to determine whether, adjuvant treatment with 160 mg aspirin once daily for 3 years, can improve time to recurrence in patients with colorectal cancer with somatic alterations in the PI3K signaling pathway. The effect of aspirin is by reducing inflammation.

However, it is not entirely certain how aspirin works in these contexts. Absolutely is inflammatory and COX-2

inhibition, in connection with the then specific mutation Pik3Ca, an important component. However, it may also be the platelet inhibitory effect of aspirin that may be significant.

Question: Why has ALASCCA taken aspirin as a starting point for such a comprehensive study?

Recent retrospective studies suggest that adjuvant treatment with common acetylsalicylic acid – such as trombyl or aspirin – after a colorectal cancer diagnosis significantly improves survival for patients with alterations in the PI3K signaling pathway. Given that alterations in the PI3K signaling pathway are found in 30 – 40 percent of all colorectal cancer this finding, if found to be proven true in a well-designed prospective study, could have tremendous improvement potential in enhancing survival in colorectal cancer.

Question: ALASCCA has been running since March 2016. Even if it is not completed, you may already be able to see what effect daily intake of low-dose aspirin has?

No, the state of knowledge is still unclear.

Observational studies have reported a decrease in colorectal cancer in regular aspirin consumers. Randomized controlled trials have shown a reduced risk of adenoma, but so far, no study specifically had the prevention of recurrence of colorectal cancer as a primary endpoint.

Now patient number 600 is randomized in ALASCCA.

As a result, we have closed the screening for new patients within the study. Now the important work of following the patients who are randomized to study drugs continues.

Our study will be evaluated regarding primary endpoint only in three years (Q2 2024) and then published.

There are 4 – 5 other aspirin studies in parallel with ours in an international perspective. However, no one is fully included and completed. We are the first to have completed inclusion and the only one to use a biomarker to control treatment.

Question: Is there a risk that individuals in the control group take low-dose aspirin and thus affect the end result?

Good question, which we also asked ourselves.

Factual information to the subjects is absolutely essential here. We do not know about ASA at all is effective for this very purpose and that it is the basis for us to do the study.

It is important that the people participating in the study understand. However, we have gradually realized that the risk is small, especially as the subjects neither do not know what the daily dose contains – aspirin or placebo nor if their tumour has the potential predictive biomarker or not. We urge all subjects to avoid aspirin and instead take paracetamol for colds, transient headaches, or the like.

Question: Should not a disease as serious as colorectal cancer be the subject of general health examinations?

The decision to recommend screening for CRC has since long been taken and planning before starting is now underway in some of the country’s 21 regions. Only Stockholm-Gotland has a fully developed screening program so far.

The National Board of Health and Welfare recommends everyone between the ages of 50 and 74 to be screened. The corona pandemic is partly due to delays.

The chance of being cured increases if the disease is detected early.

Question: What advice do at-risk patients receive regarding dietary habits?

At the group level, we know that there are certain risk factors that are linked to our lifestyle. They therefore receive partly the same advice as everyone else

others who want to live healthy; reduce intake of red meat and charcuterie, take control of body weight – avoid obesity. Coffee is good, as is a high intake of fiber.

Question: In an interview in the magazine SJUKHUSLÄKAREN 2/21, you say that “Precision medicine is the only way forward.” You mean cancer treatment.

 Can you develop it?

Precision medicine means a significantly improved ability to provide “the right treatment for the right patient at the right time”.

The ability is based on new possibilities to genetically determine each patient, to map and understand human biological variation. In the area of ​​solid tumors, such as  colorectal cancer, we are currently conducting tests for genetic changes that give us answers to the question of whether the tumor can respond to an individualized specific therapy, so-called “tailored treatment”.

In the future, we will see more and more combinations of treatments at the individual level, such as radiation + one or

several drugs. Interestingly, old drugs such as aspirin can have a renaissance when combined with new genetic and medical-technical methods.

Of course, our opportunities to achieve therapeutic success increase the more information about the patient and the more diagnostic and therapeutic methods and available drugs we have, concludes Anna Martling.      //COB