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Metastatic GIST: Treatment for liver-only metastases

DR LOVE: Dr Eisenberg, how often do you see recurrences five years after surgery in patients with GIST?

DR EISENBERG: It depends on the individual biology of the tumor. In a patient who has a large GIST with a high mitotic rate, one would expect to see recurrences within the first year or two.

This particular patient had a large tumor, but she had minimal mitoses and her Ki-67 was barely positive, suggesting that this tumor was conflicted. It was big enough, but it did not demonstrate the other characteristics that would lead us to believe that its course would be particularly aggressive.

The recurrence was in the liver only, which is a favored site for GIST. When they develop metastatic disease, about half of these patients will have liver-only disease (DeMatteo 2000; [1.4]), which should be confirmed not only by CT but also perhaps by PET.

The workup for liver metastases is similar in the postimatinib era to the workup in the preimatinib era.

Evaluation of whether the patient is a surgical candidate should be based on the volume of liver disease, the age of the patient, comorbidities and the anatomic location of the lesions.

In the preimatinib era, resection of GIST liver metastases was not particularly successful. Long-term survival occurred in only about five or 10 percent of those patients whose liver metastases were successfully resected.

In the postimatinib era, I am certain that has changed. Anecdotally, from several institutional reports, it has changed.

Metastatic GIST: Clinical use of neoadjuvant imatinib for liver-only metastases

DR LOVE: Dr Demetri, in this type of situation with liver-only metastases, do you use preoperative or postoperative systemic therapy or both?

DR DEMETRI: I believe it’s a pretty standard consensus across the world that we would start with systemic therapy with the idea that surgery may play a role.

It’s the opposite of what we often assume, that surgery is the primary modality. In this case, drug therapy is the primary modality.

The fact that systemic treatment, on median, will fail after a couple of years, however, has given us hope for a multimodality approach to managing this form of sarcoma. GIST is a type of sarcoma, and we’re accustomed to multimodality approaches in managing other types of sarcomas.

These approaches generally involve starting with drugs to gain some control of the disease and then considering surgery later to prevent the emergence of resistant clones that are probably hiding in those bulky tumors.

DR LOVE: When the surgeon says a tumor can be resected, what is the thinking about using preoperative systemic therapy at that point, as opposed to using it afterwards as adjuvant therapy?

DR DEMETRI: The advantage is similar to the way we approach the use of chemotherapy in osteosarcoma. You start with the systemic therapy, and usually you’re able to see that the tumor is not rapidly overcoming those drugs, or imatinib in this case.

If the tumor were to progress through imatinib, maybe you wouldn’t benefit the patient by moving right to surgery because even after the best possible surgical resection, other cells are almost certainly left behind.

DR LOVE: What duration of preoperative therapy do you use?

DR DEMETRI: We do not know. The median time to optimal response is approximately four to six months, but there have been patients whose tumors shrink after one year.

So we negotiate with the patient. “What’s good for you? Does that fall on Christmas? Is a big holiday coming up?” When we schedule these resections, we use that sort of personal factor.

DR EISENBERG: One of the advantages we have found in treating this disease systemically first is that it provides an in vivo tumor model. You can see if the agent is working, which tends to help promote post-surgical use of the same agent.

Also, the effect on the tumor is fairly dramatic in terms of degenerative change that makes it much less vascular, which makes the surgery easier.