Inoperable GIST with Liver Metastases

Jonathan Strosberg, MD:This case describes a 65-year-old man who presented with abdominal pain and was found to have a very large tumor occupying pretty much his entire stomach, invading into the spleen. There was also a small liver lesion. Biopsy of the stomach confirmed a gastrointestinal stromal tumor with a high mutation rate more than 5 mitoses/50 high-powered fields,KIT-positive on staining. And mutational analysis revealed anexon 11mutation.

This is a case of a patient with a very large primary tumor. Resecting that tumor would be a large, potentially risky surgery. The patient also has a liver metastasis. So, I think we want to think about surgery eventually, but we want to start with neoadjuvant imatinib.

When we’re faced with a tumor that’s technically resectable but that we think the morbidity of surgery would be reduced with neoadjuvant treatment, we generally start patients on imatinib and monitor them closely over time. We generally scan every 3 months. Sometimes we’ll start with an initial PET scan as well and repeat the PET scan several weeks later just to make sure that the tumor is sensitive. Mutational analysis also helps in that sense because we know thatexon 11mutations tend to be quite sensitive to imatinib, and the expectation is that most patients will have tumor shrinkage with the standard doses.

So, as far as length of treatment, it can take a long time to achieve maximal response, and usually we treat until maximum response. Sometimes that can take a year and even longer, although there’s some controversy over whether it’s appropriate to continue neoadjuvant treatment beyond 1 year. What you want to avoid is progression during neoadjuvant treatment, and that’s why it’s important to monitor patients closely during this period.

When you’re talking about a tumor that’s high-risk, locally advanced, or with limited metastases, you need close communication between the surgeon and the medical oncologist in terms of whether neoadjuvant therapy is appropriate, the timing of neoadjuvant therapy, the feasibility of surgery, and also with respect to postoperative adjuvant therapy. It’s ideal if patients are treated in a multidisciplinary setting, where the surgeon and the medical oncologist are within the same institution, although that’s not always possible or necessary.

At 3 months of imatinib therapy, the tumor was reduced from 14 cm to 8 cm. Another 3 months later, the tumor had shrunk down to 5 cm. But at 9 months, there wasn’t any further shrinkage, and so the patient proceeded to undergo partial gastrectomy, splenectomy, and partial hepatectomy for removal of the liver metastases.

This patient actually had metastatic disease to start with. So, in this case, I would definitely proceed with adjuvant therapy after resection of the primary tumor and the liver metastasis. I would actually probably continue with lifetime adjuvant treatment after surgery because the risk of recurrence is extremely high and the likelihood of micrometastases is high in this patient who had metastatic disease to start with. What we think is that imatinib suppresses micrometastases. We’re not sure it actually eradicates micrometastases, and so in this particular case, a fixed duration of adjuvant treatment may not make sense.

In patients with nonmetastatic disease, the risk of recurrence is based on several factors, including mitotic rate, size of the tumor, and also the location of the tumor—stomach versus small intestine versus colorectum. Mitotic rate is probably the most important of these, although location is also an important factor. So, for example, small intestinal tumors have the higher risk of recurrence than gastric tumors. In the case of a patient with resected metastatic disease, we know that the risk of recurrence after surgery is extremely high, particularly in a case like this where the mitotic rate was fairly high at the outset.

Transcript edited for clarity.

• A 65—year-old male presented with severe abdominal discomfort
  • Past medical history included mild back pain and joint pain that was treated with NSAIDs
• Abdominal CT findings showed a large mass with a diameter of 14 cm involving the cardia, fundus, and body of the stomach; splenic involvement was also noted.
• A small lesion was detected in the liver
• Biopsy and histological examination confirmed that the mass was a gastrointestinal stromal tumor
  • IHC indicated that the tumor was positive for c-KIT
  • Genetic analyses showed a mutation in exon 11 of c-KIT
  • The tumor showed high mitotic activity with >5 mitoses/50 high-power fields
• She was diagnosed with GIST of the stomach and liver metastasis
• Treatment was initiated with neoadjuvant imatinib with the goal to achieve reduction of operative risk for the primary tumor and for functional preservation
  • The tumor size was reduced to 8 cm at 3 months and to 5 cm after 6 months
  • No further reduction was noted at 9 months
• At 10 months, the patient underwent total gastrectomy, splenectomy, and partial hepatectomy