The management of gastrointestinal stromal tumors (GIST) involves close collaboration between pathologists, medical oncologists, surgeons, and imaging experts. Treatment may involve surgery and/or the use of a unique precision cancer medicine called a tyrosine kinase inhibitor (TKI).
Complete surgical removal of localized tumors appears to prolong survival and standard chemotherapy and radiation are rarely used. Patients should consider participation in a clinical trial utilizing new, innovative therapies also provides promising treatment.1,2,3
- Tyrosine Kinase Inhibitors
- Radiation Therapy
- Strategies to Improve Treatment
Surgery may be used as initial therapy to completely remove GIST and to remove metastatic tumors. Patients with large tumors or difficult-to-access small GIST that are considered difficult to remove may benefit from TKI therapy prior to surgery to shrink the tumor.3,4 This approach may allow some patients who were initially diagnosed with inoperable disease to undergo surgery once their cancer has responded to the TKI.
For patients with localized GIST, surgery is the standard treatment and should be performed whenever possible. Surgery is best performed by a surgical oncologist; a doctor that specializes in treating cancer with surgery.
The goal of surgery is complete removal of the tumor with an intact pseudocapsule and negative microscopic margins. Laparoscopic surgery in the management of GIST has also been performed and several studies, indicate a role for this surgical approach with gastric tumors.5,6,7
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.
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.3
Precision Treatment with TKI’s
Tyrosine kinase is a protein that is overproduced in GIST cells as a result of a genetic mutation and is responsible for helping the cancer cells survive and grow. A TKI is a precision cancer medicine that blocks tyrosine kinase activity slowing the growth of the cancer. TKI’s are the main medical treatment for GIST.
Gleevec® (imatinib mesylate): Gleevec was the first TKI approved for the treatment of GIST and has become the standard initial treatment. The results with Gleevec are quite remarkable given the fact that both chemotherapy and radiotherapy are ineffective in the treatment of GIST.2
Gleevec is given after surgery (called adjuvant therapy) and is usually given indefinitely because GIST has the ability to recur even after being surgically removed and can spread to other organs. Some GISTs have a higher risk of returning or spreading than others and clinical trials are still being performed to determine out how long Gleevec should be given after surgery to help delay or prevent a recurrence.
The usual dose of Gleevec is 400 milligrams daily. For some patients, the dose may be raised to 800 mg daily, especially for those who have an exon 9 genetic mutation in the KIT gene.8
Sutent (sunitinib): 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. Results of clinical trials 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. Sutent may also be used when the side effects of Gleeve are too serious.9
Stivarga (regorafenib): Stivarga is a multi-kinase inhibitor that targets multiple biological pathways involved in GIST development. It works in many different ways to slow tumor growth, including blockade of the KIT molecule and blocking blood vessel growth into tumors. Stivarga was approved in 2013 for people with later-stage GIST that could not be surgically removed or progressed after treatment with Gleevec and Sutent because it delayed the time to GIST recurrence and prolonged survival.9
Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells and is only rarely used in for the treatment of GIST. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. When radiation treatment is given using implants, it is called internal radiation therapy or brachytherapy. Learn more about radiation here.
Chemotherapy is the use of drugs to destroy cancer cells, usually by ending the cancer cells’ ability to grow and divide. However, standard chemotherapy is not effective for treating GIST and should not be used.1,2,3
When a recurrence occurs, a new cycle of genomic testing is required to learn as much as possible about the recurrence. After this testing is done a new treatment plan is developed based on the results of the tests. The treatment plan may include additional surgery, targeted therapy or participation in a clinical trial evaluating new ways to treat GIST.
1 Demetri GD: Gastrointestinal stromal tumor. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1060-73.
2 Judson I, Demetri G: Advances in the treatment of gastrointestinal stromal tumours. Ann Oncol 18 (Suppl 10): x20-4, 2007.
3 Demetri GD, Benjamin RS, Blanke CD, et al.: NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)–update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 5 (Suppl 2): S1-29; quiz S30, 2007.
4 Bonvalot S, Eldweny H, Péchoux CL, et al.: Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol 13 (12): 1596-603, 2006.
5 Huguet KL, Rush RM Jr, Tessier DJ, et al.: Laparoscopic gastric gastrointestinal stromal tumor resection: the mayo clinic experience. Arch Surg 143 (6): 587-90; discussion 591, 2008.
6 Otani Y, Furukawa T, Yoshida M, et al.: Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases. Surgery 139 (4): 484-92, 2006.
7 Novitsky YW, Kercher KW, Sing RF, et al.: Long-term outcomes of laparoscopic resection of gastric gastrointestinal stromal tumors. Ann Surg 243 (6): 738-45; discussion 745-7, 2006.
8 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.
9 Demetri GD, van Oosterom AT, Garrett CR, et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368 (9544): 1329-38, 2006.