Factors Impacting Risk Assessment for Developing Metastases or Recurrent GIST After Surgery

In this video, Edwin Choy, MD, PhD, Massachusetts General Hospital, Boston, explains risk factors for developing metastases or recurrent GIST after surgery and discusses the treatment course for a 49-year-old patient who underwent partial gastrectomy for GIST.

Transcript:

Thank you for joining us today. My name is Edwin Choy. I'm an oncologist at Massachusetts General Hospital. I have the pleasure of discussing this case that you see over here. So a quick summary, the patient is a 49-year-old woman who was diagnosed with a gastric mass, had a biopsy that showed a GIST, and then underwent a complete excision of this tumor through a partial gastrectomy.

So before we go on to talking about the clinical question that's presented here, just a couple salient features about the case. One is, in this case, the patient presented with about a 10-pound weight loss and some dull abdominal aching and pain. I just wanted to point out that in many situations, GISTs can actually be asymptomatic and they are often found incidentally for a CAT scan done for a different reason. And so they don't always present with pain or weight loss or early satiety. That's something to keep in mind.

Additionally, in this case, the patient did undergo an endoscopic ultrasound biopsy (EUS). However, on CAT scan, the features of a gist include a mass that's growing within the gastric wall. And if you see such a mass and it's not necessarily fungating inside the stomach or appearing to be a gastric cancer, then often you can make a diagnosis of GIST even without a biopsy. So many surgeons can take the patient straight to a surgical excision and bypass a biopsy if the radiologic features on the scans are convincing enough for a GIST.

Having said that, after the tumor was resected, the case mentioned several features of the tumor itself. First of all, the case mentioned that immunohistochemistry staining was positive for CD117 and DOG1. These are markers for GIST, but not necessarily germane to prognosis. And so having these markers help make the diagnosis, but it doesn't tell you whether or not the tumor is high risk for metastasis or not.

The case talked about how the tumor showed 7 mitosis per 50 high power fields. And so anytime you see 5 or greater mitosis per 50 high power field, we consider that a high grade. And so that would be a high-risk feature for GIST. Additionally, tumors that are 5 centimeters or larger are also thought to be higher risk features. And then any location of tumor outside of the stomach would also be considered a high-risk feature.

And so in this case, the tumor arose from the stomach itself, and so that would be the one low risk characteristic of this tumor. And so overall, I tend to risk stratify a GIST by looking at tumor size, number of mitosis and tumor location. And in this case, the patient has 2 of the 3 high-risk characteristics and only 1 of the 3 was a low-risk characteristic.

So overall, when you look at this patient's risk for developing a relapse of her disease, I would say having 2 out of the 3 high-risk features puts her at a relatively high risk for relapse, high risk meaning greater than 50% chance of a relapse.

And so if we go to the clinical question, the case asks, the following factors, impact risk assessment for developing metastasis or recurrent GIST after surgery, except for, and one answer would be tumor size greater than 5 centimeters, because that is a high risk feature for GIST, that would not be a correct answer. Second option is mitosis over 5 per 50 high power field. That is a risk factor for GIST, so would not be a right answer. The location of tumor in the stomach, that's actually a low-risk feature. So again, that would not be a right answer because it is a risk factor or rather a low-risk factor because it's located in the stomach.

And then option four or D is concurrent positive staining for CD117 and DOG1, like I said earlier in this presentation, CD117 and DOG1 would help you make the diagnosis, but it doesn't really impact risk. And so that is the correct answer because expression of DOG1 would not be part of the risk assessment.

So for this patient, having 2 out of 3 risk factors puts her at high risk. And so when she meets with the medical oncologist, the right move at this time would be to recommend adjuvant therapy. And so for adjuvant therapy, I typically start with imatinib at a dose of 400 milligrams per day. At the same time, I would order a sequencing of her tumor DNA, and if the tumor DNA showed a mutation in exon 11, that would be considered a imatinib sensitive mutation. And she would continue on adjuvant imatinib therapy for anywhere from 3 to 6 years.

So if the mutation was in exon 9, then she should still be considered for imatinib therapy. But some oncologists, if they know that she has an exon 9 mutation, would prefer to start her at 800 milligrams per day as a more effective dose for patients with a slightly more imatinib-resistant mutation in exon 9.

If she has mutations in exons 13, 14, 17, or 18, those are considered imatinib resistant exons in the KIT protein. And so you actually may consider watching her without adjuvant therapy because we know that imatinib has less efficacy in GIST tumors with mutations in those exons in the KIT gene.

And then earlier I said we would consider giving Imatinib for 3 to 6 years. Typically, we've been giving adjuvant therapy for 3 years. But in a recent publication in Annals of Oncology, we have new data suggesting that in patients with higher risk GIST, where the risk of relapse is closer to 70%, giving 6 years of imatinib as adjuvant therapy may lead to a better long-term tumor control. And so for patients with particularly high risk of relapse, I would consider extending adjuvant therapy to 6 years rather than the more traditional 3 years of adjuvant therapy.