In spite of the impressive advances in targeted therapy for GIST, surgery remains the standard treatment for GIST. The majority of GIST patients will have surgery at some point during their treatment.
Surgery is used at three main times to treat GIST. It is most commonly used as the initial treatment after a patient is diagnosed, especially if the patient has only one tumor that can be removed fairly easily (primary surgery). If the patient has a single tumor but surgery appears to be more difficult, they may be given Gleevec before surgery in order to try to shrink the tumor making surgery easier (neoadjuvant Gleevec). And in some cases, surgery will be used for metastatic disease either before or during treatment with Gleevec.
Prior to 2001, surgery was the only successful treatment option for GIST. However, even for patients whose tumors are completely removed and have microscopically clean margins, there is a high probability of local tumor recurrence in the abdomen. Reports of median time to recurrence vary widely (from 7 months to 2 years)1 and a large retrospective study reported a median time to recurrence of 19 months.2 However, documented GIST recurrence over 20 years after primary surgery underscores the need for long-term follow-up of patients after apparently successful tumor resection.
Prior to Gleevec, if tumors were unresectable, the median survival of patients was short, ranging from 10 to 21 months. With the approval of Gleevec in 2002, the median survival of patients with metastatic GIST is much improved. In a phase II trial for patients taking adjuvant Gleevec (preventative Gleevec after surgery to remove a primary tumor), the 3 year survival rate was 97%. In the first phase II trial for GIST patients with metastatic disease, the median survival was about 5 years. The majority of these patients had very advanced GIST however, as there was no effective therapy prior to this trial.
The removal of the stomach, or other parts of the GI tract can require lifestyle changes. Patients with gastrectomy may have to eat smaller, more frequent meals. They may have more difficulty absorbing some nutrients and may suffer from "dumping syndrome". See this link for more info about gastrectomies and dumping syndrome. Also see the LRG Side Effects page.
Synonyms and related keywords: SBS, short gut syndrome, anenteric malabsorption syndrome, malabsorption, maldigestion, malnutrition, diarrhea, fluid disturbances, electrolyte disturbances, total parenteral nutrition, TPN
After surgery, a type of scar tissue called adhesions can form. These adhesions can cause pain and in some cases a bowel obstruction. For more information about adhesions, see adhesions.org.
Other articles on Adjuvant Gleevec
Preguntas a considerar para tratamiento adyuvante (Word Document)
|Positive results prompt US NCI to make Gleevec available to patients in post-surgical study|
On April 12, 2007, the American College of Surgeons announced that the Z9001 phase III adjuvant Gleevec trial has successfully met its endpoint. Gleevec does increase time to recurrence in a highly significant manner.
On December 19, 2008, the Federal Drug Administration (FDA) approved adjuvant treatment for GIST in the United States. On May 7, 2009, Glivec (international spelling) received approval from the European Commission (EC) for adjuvant treatment of GIST. Approval of Gleevec for adjuvant therapy was based on the interim results of the Z9001 phase III adjuvant Gleevec trial.
There are a number of factors to consider about whether adjuvant Gleevec is suitable for a particular patient. Some factors that might be considered are:
"Even with this new data the decision (to take adjuvant Gleevec) should be individualized between a patient and their physician taking into consideration the many risks and benefits."
Jon Trent, M.D., Medical Oncologist, MD Anderson Cancer Center
1. How likely is the tumor to reoccur?
- A small GIST tumor with a low mitotic rate found incidentally during surgery might be unlikely to reoccur, or if it did reoccur, it might be many years later.
- A large GIST tumor with a high mitotic rate that ruptured during surgery might be very likely to reoccur. In this scenario a strong case could be made for Gleevec after surgery.
2. How likely is the tumor to respond to Gleevec?
- A patient with a less responsive type of tumor might be less inclined to take adjuvant Gleevec. See Mutational Testing.
3. What is the anxiety level of the patient?
- A patient with more anxiety might derive psychological benefit from adjuvant Gleevec (as well as potential medical benefit).
- A patient with less anxiety might be more inclined to take a watchful waiting approach, especially if they were low risk or had a less responsive mutation type.
4. After starting adjuvant Gleevec, how well the patient is tolerating Gleevec can become a factor. If a patient is not tolerating Gleevec well, then they might stop Gleevec and take a watchful waiting approach, especially if they were low risk or had a less responsive mutation type.
In the Z9001 trial (see the preceding section), the patients that received Gleevec took it for one year. Other trials are underway comparing longer durations. At this time the optimal duration of treatment is not defined. The FDA prescribing information for Gleevec does not specify a time frame. In the absence of other guidance, we could speculate that for higher risk patients, longer duration times (even indefinitely) might be considered.
In 2008, Dr. Ronald De Matteo (Memorial Sloan-Kettering Cancer Center) presented data from the Z9000 trial at the ASCO GI Cancers Symposium that showed that patients with KIT exon 9 mutations had a high rate of recurrence beginning at about the one year mark (shortly after the prescribed course of Gleevec). In both the Z9001 trial and the Z9000 trial, the drug was given for one year. Although preliminary, this data suggests that patients with exon 9 mutations may need to be on Gleevec for longer periods; perhaps indefinitely. The proper dose for adjuvant treatment of exon 9 tumors remains a question mark. Exon 9 tumors respond better to higher doses of Gleevec in the metastatic setting, but only standard dose Gleevec has been given in the adjuvant trials, so no data exists as to whether higher doses are better for adjuvant therapy.
Surgery for Advanced and Metastatic GIST
|Molecular Therapy and Surgery Combined in GIST, by Dr. Ronald DeMatteo|
|Surgery and Genotyping Studies Highlighted at ASCO|
|Exploring Surgical Options for Advanced GIST|
In the absence of clinical trial data about surgery for metastatic disease, there are 4 or 5 case series that have been presented in abstract form (preliminary information). For the most part, the data from these studies seems to be fairly consistent and some tentative conclusions can be reached. One of the most solid conclusions seems to be that surgery is of little benefit for patients with widespread progression of metastatic disease. Surgery for limited progression (one or two tumors) appears to have some benefit. Few patients die as a result of surgery, but non-fatal complications can arise.
There are also some areas where it is difficult to reach any conclusions. From these studies we know that patients with stable disease do pretty well after surgery; but we do not know how well they would have done with Gleevec alone. It will probably be quite some time before any trial can answer that question (none are in progress).
Given the limited data available, the decision on whether to have surgery for metastatic disease after responding to Gleevec is a complex decision. It involves many factors such as:
- Can all disease be removed?
- How complicated is the surgery?
- How likely are complications?
Given the complexity of these decisions and the limited data, it is recommended that patients be seen in a center with recognized GIST expertise. This type of evaluation should include a multidisciplinary review, including an oncologist and a surgeon.
For a more thorough discussion of this subject, see the links for Surgery and Advanced/Metastatic GIST at the top of this section.
Exploring Surgical Options for Imatinib-Treated Patients With Advanced GIST (released April, 2004)
Choi H, Charnsangavej C,
Macapinlac HA, et al.
Correlation of computerized
tomography (CT) and proton
emission tomography (PET) in
patients with metastatic GIST
treated at a single institution
with imatinib mesylate
Proc Am Soc Clin Oncol. 2003;22:819. Abstract 3290.
van Coevorden F, Peterse H,
Rodenhuis S. Is there a role for
post imatinib (salvage) surgery
in gastrointestinal stromal
Program of the Connective Tissue Oncology Society 9th Annual Scientific Meeting. 2003:40. Abstract 147.