Managing Initial Recurrence
If GIST returns after surgery removes the primary tumor it is called a recurrence. A recurrence can occur near the original tumor site (a "local" recurrence) or new tumors can appear in distant sites. If this happens, these tumors are called metastases (or simply, "mets"). If GIST tumors metastasize they usually travel to the liver, or the peritoneum. Metastases to the lymph-nodes and lungs are rare, but do occur. Metastases are usually harder to treat than primary tumors.
Recurrences that occur while a patient is taking adjuvant Gleevec (preventative Gleevec) are typically Gleevec-resistant and should generally be treated as resistant-GIST. If a patient took adjuvant Gleevec and then stopped the drug before they had a recurrence, there would be a good chance that they would still be sensitive to Gleevec (depending on things such as type of mutation). An example of the latter would be a patient that takes adjuvant Gleevec for a year, then stops Gleevec and has a recurrence at the two year mark. See the following table:
|Likely to respond to Gleevec
(depending on mutation)
|Likely to be resistant to Gleevec|
|Never had Gleevec (no adjuvant Gleevec)||Had a recurrence while actively taking adjuvant Gleevec|
|Took adjuvant Gleevec for a period of time (for example, 1 year), stopped Gleevec, then had a recurrence at a later time|
Gleevec-sensitive recurrences are usually managed with drug treatment. Gleevec is the standard treatment for unresectable or metastatic GIST. It has been approved for GIST since 2002 in many countries. For detailed information about Gleevec, see the Gleevec section of this website.
In 2002, Gleevec was filed for registration and received approval from the European Union (EU), the Food and Drug Administration (FDA) in the United States, and other countries for the treatment of adult patients with unresectable and/or metastatic malignant GISTs.
Gleevec is a pill that is taken either once or twice daily, depending on the dose.
Gleevec is different from traditional chemotherapy in that it is very selective. Traditional chemotherapy kills all cells that are dividing quickly. This is what causes so many of the side effects of traditional chemotherapy. In addition to the cancer cells, this type of chemotherapy also kills many of the body's normal cells. Gleevec is much more selective and as a result has fewer side effects. It was designed to block the activity of a mutant type of enzyme (an enzyme is a specific type of protein) that causes Chronic Myeloid Leukemia (CML). This enzyme is called Bcr/Abl. In addition to blocking Bcr/Abl, Gleevec also blocks several other enzymes. These are:
- Platelet Derived Growth Factor Receptors (PDGFR-alpha and PDGFR-beta)
- Various forms of the Abl enzymes
Approximately 85% of GIST patients will respond to Gleevec with either significant shrinkage (about 2/3 of patients) or it will cause the tumors to stop growing (stability). These responses are more durable than many types of chemotherapy, but resistance will eventually develop for most patients. This section of the website deals with managing an initial recurrence. For information on dealing with resistance to Gleevec see: Managing GIST Progression.
CAUTION: The Life Raft Group often hears reports of doctors wanting to stop Gleevec in patients with metastatic disease that have been stable for several years. With rare exceptions, this practice is not recommended and can result in tumor growth. (See Stopping Gleevec for more details and references.)
The Role of Surgery for Metastatic GIST
Perhaps because of the dramatic initial success of Gleevec in phase II and phase III trials in the early 2000's, surgery was not often considered for metastatic GIST during this period. As the limitations of Gleevec therapy become more apparent, the role of surgery in metastatic GIST is being re-evaluated.
A randomized surgery trial for metastatic GIST patients is opening in Europe and one is being planned for the United States1. These trials will be for metastatic GIST patients that are stable on Gleevec.
In the absence of clinical trial data about surgery for metastatic disease, there are 4 or 5 case series (2,3,4,5) that have been published (at least in abstract form). For the most part, the data from these studies seems to be fairly consistent and some 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.
Given the limited data available, the decision on whether or not to have surgery for metastatic disease after responding to Gleevec is a complex decision. It involves many factors such as:
1. Can all disease be removed?
2. How complicated is the surgery?
3. How likely are complications?
Given the complexity of these decisions and the limited data, it is recommended that patients considering surgery after a response to Gleevec be evaluated in a center with recognized GIST expertise. This type of evaluation should include a multidisciplinary review, including an oncologist and a surgeon.
2. Surgery of residual disease following Imatinib mesylate in advanced gastrointestinal stromal tumors (GIST)
Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings. Vol 23, No. 16S, Part I of II (June 1 Supplement), 2005: 9038
A. Gronchi, M. Fiore, R. Bertulli, M. Colecchia, E. Tamborini, S. Pilotti, A. Messina, P. Coco, S. Stacchiotti, P. G. Casali
3. Indication and results of surgery following imatinib treatment of locally advanced or metastatic GI stromal tumors (GIST)
Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 9500
P. Hohenberger, C. Langer, S. Pistorius, I. Iesalnieks, E. Wardelmann, P. Reichardt, Chirurgische Arbeitsgemeinschaft Onkologie (cao-V)
4. Perioperative morbidity in metastatic gastrointestinal stromal tumors (GIST) undergoing surgery of residual disease following imatinib (IM)
ournal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 10043
A. Gronchi, M. Fiore, S. Radaelli, P. Coco, E. Fumagalli, S. Stacchiotti, P. Collini, E. Tamborini, S. Pilotti, P. G. Casali
J Clin Oncol 2006;24: 2325–2331.
C. P. Raut, M. Posner, J. Desai, J. A. Morgan, S. George, D. Zahrieh, C. D. Fletcher, G. D. Demetri, M. M. Bertagnolli