Looking Within: Exploring Genomic Testing for GI Cancers

SOME OF TODAY’S MOST effective and least grueling treatments for gastrointestinal (GI) cancers come in the form of targeted drugs, which work when disease is driven by specific genetic mutations. Some immunotherapies, too, work best on cancers that express certain genetic alterations.

But before doctors can treat a cancer with this kind of personalized medicine, they must ask for next-generation sequencing or other tests of the tumor tissue so that they know which mutations an individual tumor expresses. The next step should be choosing the medications most likely to bring about a response based on the tumor’s genomic profile.

To offer help in matching a cancer’s genetic alterations with the most appropriate medications, the American Society of Clinical Oncology (ASCO) provides its 2016 document “Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer”. The recommendation is a joint consensus by ASCO, the Association for Molecular Pathology and the College of American Pathologists.

Also helpful is guidance that ASCO released in 2006 and updated in 2009; specific to GI cancers, the recommendations spell out the use of tumor biomarkers to prevent, screen, treat and keep a close watch on these conditions.

“It is important that the guidelines are followed so that, ideally, every patient has that fundamental baseline treatment,” explains Shirley Michelle Shiller, D.O. In an interview during the 2017 OncLive® State of the Science Summit™ on Gastrointestinal Cancers, Shiller, a pathologist at Baylor Scott & White Health in Dallas, discussed progress in precision medicine for patients with GI cancers. OncLive is a sister publication of CURE.

OncLive®: Can you discuss some of the highlights of the ASCO guidelines?

Shiller: The guidelines are intended to help direct clinicians, especially those who may be in more remote areas, as to what any patient should receive in terms of treatment. Some (genetic) alterations, such as KRAS mutations, indicate that a patient would not respond to select therapies (such as EGFR inhibitors), and (this) helps direct the therapy to a more meaningful and efficacious treatment.

Can you discuss the current role of liquid biopsies that can identify mutations by examining cancer cells or their DNA that are found in blood or urine?

That is an emerging technology. The plasma-based testing we know the most about is in the lung cancer space, but it has opportunity in colon cancer, so some people are starting to use it there.

The detection rate is lower in plasma versus in a solid tumor, and that is largely based on our experience: We have more experience testing solid tumors. When you move into the liquid space, there are some sensitivity issues that we are working on, as well as the other variables that you cannot control as much. For example, when you draw blood, it is not certain that the tumor is shedding at that time or that the mutations you hope to detect are shedding enough of a quantity to be detected.

What role will liquid biopsies play in the future of this treatment landscape?

I am certain that they will play a role in all cancers. Ultimately, we will understand how to utilize the information in terms of an initial diagnosis on the tumor, but what might be more relevant are the biomarkers. Once we know what we are looking to monitor, then we can watch those patterns prior to a patient presenting with a recurrence (or drug resistance, and in a much less invasive way than with repeated tissue biopsies).

Some (pharmaceutical) companies are hoping to detect cancer before an actual lesion is even present. That is very far in the research future, but I believe that will become reality at some point.

What impact has precision medicine had on treatment thus far for these patients?

We are having growing pains because some of the testing can be more expensive than a routine blood test or chemistries. However, the information is very important if you are contemplating what therapy to give patients. We are in a power struggle with third-party payers as we get our feet on the ground to demonstrate the benefit of the test and how that saves money downstream in terms of not delivering ineffective therapy: The patient is getting therapy that is more specifically targeted to their actual cancer, which is the essence of precision medicine.

Since many of those therapies are targeted, their (side effect) profile is more tolerable because they are not killing rapidly dividing cells. The patients can tolerate it on an outpatient basis, making their quality of life much higher. In my opinion, cancer (treated this way) is likely to become more of a chronic disease.

Are there unmet needs that should be addressed?

The largest unmet need is for education — not only for the oncologist but even for my pathology colleagues and other health care providers. There are varying levels of implications to the tests, such as testing the tumor to determine whether it has a marker that can be hit. Some of the tests can also imply other things about the patient, such as a hereditary predisposition.

When you start combining those different technologies out there into one result, you have an exponential range of possibilities.