Expanding Options for Relapsed/Refractory Gastrointestinal Stromal Tumors - Episode 1

Challenges Associated with GIST Management

Andrew Wagner, MD: Hello, and thank you for joining this Targeted Oncology™ presentation titled “Expanding Options for Relapsed/Refractory Gastrointestinal Stromal Tumors.” Over the past 2 decades, the treatment of GIST [gastrointestinal stromal tumors] with tyrosine kinase inhibitors has improved patients’ prognosis and outcomes. However, a percentage of patients present without an identifiable mutation, and others will relapse after 1 or multiple lines of therapy.

Today we’re going to talk about a novel approach to treatment for these patients that received FDA-approved treatment of advanced GIST in mid-May 2020. I’m Dr Andrew Wagner, medical director of ambulatory oncology at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School in Boston, Massachusetts. Joining me today is Dr Shreyaskumar Patel, medical director of the sarcoma center and a tenured professor of medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas. Thank you so much for joining us.

Let’s begin. Hi, Shreyaskumar. How are you? Could you start by describing gastrointestinal stromal tumor and some of the challenges associated with this management? In particular, how many people are diagnosed with GIST each year? What are the risk factors, frequent symptoms, stage at diagnosis, and effect on prognosis?

Shreyaskumar Patel, MD: Thank you, Andy. Most of the audience in this day and age is aware of the diagnosis of gastrointestinal stromal tumors. But for a bit of historical perspective, in the dark ages there was this tumor that we used to call gastrointestinal [GI] leiomyosarcomas. It got redefined toward the late 1990s into gastrointestinal stromal tumors.

Because this is a relatively newer entity, the true incidence is a little debatable. But the best estimates that we have tell us that in the United States, we have somewhere between 5000 and 6000 new cases. It’s called gastrointestinal stromal tumors, implying that the vast majority of these tumors originate from the gastrointestinal tract. But from an embryo logic standpoint, the same cells that give rise to the gut, give rise to some of the other intra-abdominal structures.

There is this tongue twister diagnosis of extra gastrointestinal stromal tumors that there could occasionally be arising from the omentum or the peritoneum. Most common sites or locations happened to be the stomach, followed by the small bowel, followed by a variety of other locations. The very upper and very lower end of gut happened to be relatively infrequent. The presenting symptoms again are very dependent on the site of origin and obviously the bulk of the tumor. A typical gastric tumor that is large and eroding the mucosal lining is going to cause some GI bleeds.

A young, otherwise-healthy person presents within near syncopal episode or some dizziness to the emergency department. This is found to have a hemoglobin count of 5.8 g/dL. Let’s say, for example, a work-up eventually reveals a large abdominal mass with or without other areas of involvement. The typical metastatic pattern is that it tends to lead to peritoneum, liver, bone, and then very rarely in the later stages of the disease it can go to the lungs and other parts of the body.

Andrew Wagner, MD: Can you discuss a little about the location of gastrointestinal stromal tumors and how that affects diagnosis and prognosis? What’s the likelihood of developing metastasis, and are there prognostic features that help us understand that risk?

Shreyaskumar Patel, MD: Good question. It’s important for us to remind our audience that this does fall in this family of tumors that we call soft tissue sarcoma. Some of the same prognostic factors apply. The grade of the tumor reflected here specifically in gastrointestinal stromal tumors as mitotic activity is probably the most prognostic significance. The location of the tumor and the clinical site also happens to be prognostic where the stomach appears to be a more favorable side compared with the small bowel and other sites.

In terms of predicting the risk of recurrence, there are several risk-assessment models out there. The pure clinical ones take into account the size of the tumor, the location of the tumor, and the mitotic activity. Added to that could be some other prognostic factors: Was there a rupture at the time of surgical operation, for example? Mutational analysis, as we will come back to a little later, seems to be predictive, but not as much prognostic in terms of what the overall outcomes tend to be.

Transcript edited for clarity.

Andrew Wagner, MD, reports the following disclosures: Consulting with Deciphera, Daiichi-Sankyo, NanoCarrier. He also reports research funding to his institution with Daiichi-Sankyo, Eli Lilly, Karyopharm, Plexxikon, Aadi Biosciences.