Molecular Testing Advancements Leading Field of GI Cancers

Shirley Michelle Shiller, DO

With the advent of next-generation sequencing and novel technologies, the understanding of the molecular alterations in gastrointestinal (GI) cancers has significantly improved.

In addition, the development of the ASCO guidelines for GI cancers has given oncologists a baseline of treatment options when a mutation or molecular alteration is identified in an individual tumor.

For example, ASCO has updated its provisional clinical opinion on testing patients with metastatic colorectal cancer (CRC) for KRAS mutations to determine whether they should receive anti-EGFR monoclonal antibody as treatment.¹

“It is important that the guidelines are followed so that, ideally, every patient has that fundamental baseline treatment,” explains Shirley Michelle Shiller, DO.

OncLive: Please provide an overview of your presentation.

In an interview during the 2017 OncLive^® State of the Science Summit^TM on Gastrointestinal Cancers, Shiller, a pathologist at Baylor Scott and White Health, discussed progress with precision medicine for patients with gastrointestinal cancers.Shiller: I discussed the recent guidelines and recommendations, which were a collaborative effort between ASCO and various pathology organizations to ensure that we are streamlining testing.

Can you discuss some of the highlights of these guidelines?

Can you discuss the current role of liquid biopsies?

Additionally, I spoke about liquid biopsies and expanded testing, as well as immuno-oncology therapy that is newer but also very effective. I gave hints about some technology to look forward to in the future.The guidelines are intended to help direct clinicians, especially those who may be in more remote areas, to have a baseline as to what any patient should receive in terms of treatment. Some alterations, such as KRAS mutations, indicate that a patient would not respond to select therapies and therefore helps to direct the therapy to a more meaningful and efficacious treatment for the patient.That is one of the emerging technologies. It has met some clinical utility, but it has been utilized more in the lung cancer space thus far. We are still learning a lot with it. A liquid biopsy could be from plasma or urine, although urine is the least understood. 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.

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

The detection rate is lower in plasma versus in a solid tumor and, at this time, 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 that you are hoping to detect are shedding enough of a quantity to be detected.I am certain that it will play a role in all cancers. Lung cancer has the head start, although the diagnosis of leukemia is done on bone marrow specimens and blood. We are now applying it to solid tumors, but it is different because that solid tumor does not exist in the bloodstream. Those are the challenges, but we will get better with time.

Ultimately, we will understand how to utilize the information that we are receiving in terms of an initial diagnosis on the tumor. The histologic diagnosis may not even matter in the long term, 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.

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

Looking to the future, there are some [pharmaceutical] companies that are hoping to detect cancer before an actual lesion is even present. That is very far [off] in the research future but I believe that will become reality at some point. Ultimately, there are several layers. First and foremost, 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 pairs 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. Therefore, 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 adverse event 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, that cancer is likely to become more of a chronic disease.

Are there any unmet needs that should be addressed?

Some of the other things that I discussed are combinatorial therapy. I would not be administering that therapy as a pathologist, but as we understand these biomarkers, we will start to understand sequences of progression and how to control that cancer. We are learning as we go, but cancer will become a chronic disease.The largest unmet need is the need for education—not only for the oncologist, but even for my pathology colleagues and other healthcare 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. Sometimes some of the tests can also imply other things about the patient, such as if they have a hereditary predisposition.

There are multitudes to the technologies out there and, when you start combining those different technologies into one result, you have an exponential range of possibilities. The educational gap is the greatest unmet need.

ASCO updates guideline to include testing for new RAS mutations. American Society of Clinical Oncology. https://gicasym.org/asco-updates-guideline-include-testing-new-ras-mutations. Published January 15, 2016. Accessed December 12, 2017.