Gastrointestinal stromal tumors (GISTs) are relatively rare cancers that originate in the cells of Cajal, which are specialized cells lining the digestive tract responsible for initiating the rhythmic movement that propels food and solid waste through the GI tract.
GISTs are characterized by specific genetic abnormalities that cause overactivity of a specific gene, called the c-kit protooncogene, and overproduction of certain proteins. Together, these abnormalities lead to uncontrolled growth and limited cell death among malignant GIST cells.
GISTs may be cancerous (malignant) or noncancerous (benign). Malignant GISTs can occur in any part of the gastrointestinal tract—from the esophagus to the rectum—but occur most commonly in the stomach and small intestine. GISTs of the stomach wall are considered malignant when they exceed 5 to 10 centimeters, have a high rate of cell division, or have metastasized (spread). GISTs of the small bowel are considered malignant if they have any mitoses or are greater than 2 centimeters.
GISTs may spread to distant sites in the body, mainly the peritoneal cavity and the liver. Location of metastatic tumors can be determined through PET (positron emission tomography) or gadolinium-enhanced magnetic resonance imaging (MRI). Diagnosis is often made surgically or by needle biopsy with the assistance of imaging to guide the needle to the tumor.
Until the development of targeted therapy, there was no effective systemic treatment for this tumor, and the prognosis for patients with recurrent local disease or metastatic disease was poor.
About this GIST Treatment Information
The following is a general overview of treatment for GISTs. Cancer treatment may consist of surgery, targeted therapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques—called multi-modality care—has become an important approach for increasing a patient’s chance of cure and prolonging survival.
Participation in a clinical trial utilizing new, innovative therapies also provides promising treatment.
Circumstances unique to each patient’s situation influence which treatment or treatments are utilized. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this Web site is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
Patients with an advanced GIST have an average survival of 9 to 20 months following standard treatment. These are relatively rare tumors and in order to improve treatment, virtually all patients with this disease need to be enrolled in clinical trials.
Role of Surgery in the Treatment of GIST
Surgery may be used as initial therapy to completely remove the primary tumor and may also be used to remove metastatic tumors. Patients with more advanced disease may undergo targeted therapy followed by surgery once they have responded to treatment. This approach may allow some patients who were initially diagnosed with inoperable disease to undergo surgery once their cancer has responded to the targeted therapy.
Surgery as initial treatment: An evaluation of surgery for 33 patients with GIST, two-thirds of which had high-grade tumors, has shown that these cancers can be completely removed with surgery in the majority of patients. Approximately eight out of ten patients were able to have their cancer completely removed with surgery; this included some patients with metastatic disease. On average, patients survived 2.5 years. The researchers estimated that nearly half of the patients would survive more than 2.5 years. Outcomes were less favorable among patients with cancer that was not completely removed.1
Surgery combined with targeted therapy: Patients with advanced GISTs who have limited progression or stable disease with targeted therapy have been shown to experience prolonged overall survival when they also undergo surgery to remove the majority of their remaining cancer, then continue with targeted therapy.
Patients who respond to initial targeted therapy have been shown to experience the best outcomes. For patients who experienced stable disease following treatment with targeted therapy, four out of five had no evidence of disease after surgery and were free of cancer progression one year after surgery. Patients with some progressive disease with targeted therapy also benefited from surgery, but fewer experienced a complete disappearance of their cancer (one-quarter) and freedom from disease progression at one year (one third). Surgery was not found to benefit patients whose cancer progressed widely after targeted therapy; none of these patients survived one year after surgery. Overall, 95% of patients who responded to targeted therapy survived one year or more after surgery. This figure was 86% for patients with limited progression.2
While surgery after targeted therapy appears to shrink the cancer so that it may be completely removed in some patients, research also shows that targeted therapy must be continued indefinitely to reduce the risk of relapse. Among 19 patients who were treated with Gleevec, followed by surgery and continued with Gleevec therapy, there was only one relapse.3
Targeted Therapy for GIST
A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Targeted therapy is the first choice of treatment for GIST that cannot be removed completely with surgery.
Gleevec® (imatinib mesylate) in the treatment of GIST: Gleevec is a type of targeted therapy that works by inhibiting a protein called tyrosine kinase. Tyrosine kinase is overproduced in GIST cells and is responsible for helping the cancer cells survive and grow. Gleevec was developed for the treatment of chronic myeloid leukemia, and is a very active treatment for that disease. Results of early clinical trials involving small numbers of patients indicate that Gleevec produces remarkable anticancer responses among patients with GIST. Since those early trials, Gleevec has become the standard treatment for GIST.
Clinical trial results indicate that over half of the patients with locally recurrent or metastatic GISTs experienced a partial anticancer response with Gleevec. While none experienced a complete anticancer response, an additional 28% had their disease stabilized with treatment. After approximately six months, less than half of the patients had progressed. Researchers have concluded that these are remarkable results given the fact that both chemotherapy and radiotherapy are ineffective in the treatment of GIST.4
The U.S. Food and Drug Administration (FDA) approved the use of Gleevec for the treatment of metastatic and/or inoperable GISTs in 2002 based primarily on the above data.
Sutent® (sunitinib) in the treatment of GIST: Like Gleevec, Sutent inhibits the tyrosine kinase protein. Sutent appears to be an active treatment option for patients with GIST whose disease has progressed with Gleevec or who are unable to tolerate treatment with Gleevec. Early results of a clinical trial indicate that Sutent delayed the time it takes for existing or new tumors to grow in patients with Gleevec-resistant disease. On average, the time before tumor progression for patients treated with Sutent was more than six months (27 weeks) compared to six weeks for patients who were not treated.5
Sutent was FDA-approved for the treatment of GIST in early 2006.
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of GISTs will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of GISTs include the following:
Individualized Treatment: GISTs differ according to genetic abnormalities they express. Research indicates that GISTs with certain abnormalities are more likely to respond to Gleevec treatment, resulting in a longer time before the cancer progresses.6 This finding suggests that patients with GIST may benefit from undergoing genetic testing to determine the genetic characteristics of their cancer.
Earlier Treatment with Targeted Therapy: The targeted therapies Gleevec and Sutent have revolutionized the treatment of advanced GISTs. Research aimed at determining if these treatments may also benefit patients with earlier stage disease is ongoing.7
1 El-Zohairy M, Khalil el-SA, Fakhy I, et al. Gastrointestinal stromal tumor (Gist)’s surgical treatment, NCI experience. J Egypt Natl Canc Inst. 2005; 17:56-66.
2 Raut CP, Posner M, Desai J, Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. Journal of Clinical Oncology. 2006;24(15):2325-31.
3 Rutkowshi P, Nowecki Z, Nyckowshi P, et al. Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. Journal of Surgical Oncology. 2006;93:304-311.
4 Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. New England Journal of Medicine. 2002;347:472-480.
5 Demetri GD, van Oosterom AT, Blackstein M, et al: Phase III, multicenter, randomized, double-blind, placebo-controlled trial of SU11248 in patients following failure of imatinib for metastatic GIST. Journal of Clinical Oncology. 2005;23:308s, Abstract #4000.
6 Heinrich M, Shoemaker J, Corless C, et al. Correlation of target kinase genotype with clinical activity in imatinib mesylate (IM) in patients with metastatic GI stromal tumors (GISTs) expressing KIT. Proceedings from the 2005 annual meeting of the American Society of Clinical Oncology. Presented May 16, 2005 at a plenary session. Abstract #7.
7 Gold JS, Dematteo RP. Combined surgical and molecular therapy: the gastrointestinal stromal tumor model. Annals of Surgery. 2006;244(2):176-84.
Copyright © 2017 Omni Health Media. All Rights Reserved.