Surgery

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 recent, large retrospective study reported a median time to recurrence of 19 months.² However, documentd 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.^3,4,5,6,7,8 With the approval of Gleevec in 2002, the median survival of patients with metastatic GIST is much improved. In a phase II study 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. Also, some of the patients in this trial benefited from newer treatments, such as Sutent, but some of the patients in this trial died before Sutent was available.

Exploring Surgical Options for Imatinib-Treated Patients With Advanced GIST (released April, 2004)

GIST: The Potential Role of Resection after Systemic Therapy  (September, 2002) Treatment options for metastatic or recurrent GIST are even more limited. The likelihood of recurrence approaches 100% after second surgery for reappearance or metastasis, with a time to progression of less than 4 months.⁹

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Surgery and Nutritional Support

Short-Bowel Syndrome
Synonyms and related keywords: SBS, short gut syndrome, anenteric malabsorption syndrome, malabsorption, maldigestion, malnutrition, diarrhea, fluid disturbances, electrolyte disturbances, total parenteral nutrition, TPN Diet after surgery Nutrition problems and their solutions

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Surgery or Gleevec?

No controlled clinical trials have been completed to answer this question. We can only offer some factors to consider in making this choice. Each patient is different and it is impossible to give specific medical advise over the internet. The evaluation of each patient by a doctor who is experienced with GIST is required to take into account the unique aspects of each patient.

• In inoperable cases and most metastatic cases, the impressive response rate to Gleevec makes it a fairly easy choice over surgery.

In newly diagnosed GIST patients whose tumors have not metastasized, the choices are more complex.

• Some GIST patients receive long term relief from surgery, and some do not. Therefore the aggressiveness of the cancer is one consideration. Many attempts to classify GIST tumors have been made. The Diagnosis section of this website discusses this issue.

• The difficulty of surgery is one consideration. Many GIST patients lose their stomachs, gall bladders, and other organs. A difficult surgery might be made easier after treatment with Gleevec.

• "...Since (Gleevec) was developed as a therapeutic alternative, surgery for metastatic GIST has largely been replaced by drug therapy, and primary surgery for metastatic GIST should probably be attempted only in patients who have bleeding or obstructive disease. The question of whether surgical resection should be done to remove residual masses, after (Gleevec) therapy, is unanswered and requires further research. We suspect that this approach would be a very reasonable option for patients with low-volume disease." ¹⁰

• View the Slide presentation "GIST: The Potential Role of Resection after Systemic Therapy", given by Dr. Charles Blanke at the London GIST conference.

• The type of KIT or PDGFRa mutation helps predict response to Gleevec. In patients with KIT mutations, exon 11 mutations have the best response rate, exon 9 mutations have an intermediate response rate and "wild-type" KIT has the lowest response rate to Gleevec. In patients with PDGFRA mutations, exon 12 mutations have the best response rate, while some patients with a rare exon 18 mutation, called D842V, do not appear to respond to Gleevec. Clinical testing to determine the type of KIT or PDGFRA mutation a patient has is available. More aggressive surgery might be indicated for patients who are less likely to respond to Gleevec. How do I obtain testing for mutations in KIT/PDGFRA?

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Gleevec after surgery (Adjuvant Gleevec)?

On April 12th 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. However, at this time Gleevec is not approved for adjuvant treatment. It has been submitted to the FDA for registration in the United States, but it is unknown how long this process will take.

Some GIST patients do take adjuvant Gleevec on an "off-label" basis. Insurance companies vary greatly on whether or not they cover Gleevec on an off-label basis.

There are a number of factors to consider about whether or not 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, M.D. Anderson Cancer Center

• 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.
• Should patients with a KIT exon 9 mutation (a type of mutation that responses best to high-dose Gleevec or Sutent) take adjuvant Gleevec? If so; should it be at a higher dose?

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If Gleevec is given after surgery that removed all visible tumors, how long should it be continued?