Answer: Hereditary GIST is extremely rare so it is highly unlikely that your children will inherit this cancer. However, if you have several family members that have had GIST, gastrointestinal leiomyosarcoma, or stomach cancer you should notify your physician. If you would like to know more about the inheritance of GIST there are several publications on the topic (Kleinbaum et al, International Journal of Cancer 2008 Feb 1;122 (3):711-8).
A: It is not a common side-effect of Gleevec but has been described. It may also be a side effect of surgical resection. Either way I favor the initial use of calciumcontaining antacids that are available over the counter. These may help with heartburn but also provide a good source of calcium and may help with muscle cramps that patients get while on Gleevec. If this does not relieve heartburn one should consult their physician for diagnostic evaluation.
A: When I see patients with GIST who have failed Gleevec and Sutent I start over at the beginning. Our sarcoma pathologists review the tumor specimen to make sure it is truly a GIST. Sometimes patients may have other types of sarcoma such as leiomyosarcoma, desmoid tumor, or schwannoma rather than GIST. These types of sarcoma are treated very differently than GIST so the diagnosis is important. A number of investigators are trying to improve upon diagnostic accuracy of GIST (for an example see Price ND, Trent JC, El-Naggar AK, Cogdell D, Taylor E, Hunt KK, Pollock RE, Hood L, Shmulevich I, Zhang W. Highly accurate two-gene classifier for differentiating Gastrointestinal Stromal Tumors and Leiomyosarcomas. PNAS 2007 104: 3414-3419).
A: RECIST uses tumor size to quantitatively define shrinkage or growth of a tumor. Choi Criteria uses tumor size (similar to RECIST) but also includes changes in the internal characteristics of a GIST, namely intravenous contrast uptake. These are used in clinical trials to define complete response, partial response, stable disease, and progression of disease.
A : This means that no kit protein was detected on your tumor cells by immunohistochemistry performed by the pathologist. I generally have the kit immunohistochemical test repeated and make sure that this tumor is not some other type of sarcoma. Mutation testing for kit and PDGFR-alpha may be helpful.
A : I usually recommend increasing the amount of fluids one is drinking as the initial step. I’ve found that drinking more water helps some but drinking sports drinks such as Gatorade or POWERade are particularly helpful. Daily calcium supplements such as calcium carbonate may also help some patients.
A : This is currently a hot topic of considerable debate. There are no published prospective studies nor is there Federal Drug Administration (FDA) approval supporting the use of Gleevec after the patient has resection of a primary tumor (this is often called “adjuvant” or “postoperative”). However, patients with primary GIST that are at risk for recurrence should consider taking Gleevec after surgery. This is an individualized decision that takes place between a patient and their physician. When I see a patient after surgical removal of their primary GIST sometimes the patient and I decide on taking Gleevec and sometimes we don’t.
GIST care perspectives from a ‘student’ of GIST
By John McAuliffe, PhD
MD Anderson Cancer Center
John is a MD/PHD student at the University of Texas Medical School at Houston, Texas working as a PostDoctoral Fellow in the department of sarcoma medical oncology in the sarcoma research center at the University of Texas, MD Anderson. He returns to medical school for his fourth year this summer. After graduation, he will become a surgical resident with the ultimate goal of being a surgical oncology clinical-investigator.
Each particular patient is unique. Likewise, each patient has a unique GIST that responds to targeted therapy (such as Gleevec or Sutent, among others) for a variable duration. Likewise, some patients that undergo surgery for their primary GIST become “No Evidence of Disease” (NED) while others relapse quickly. In Sarcoma Medical Oncology and the Sarcoma Research Center at the University of Texas, MD Anderson Cancer Center, we are implementing molecular studies to better determine the best possible treatment for an individual GIST patient.
For instance, when we see a new patient with GIST who requires therapy with imatinib we routinely perform kit mutation testing. The patient is provided educational materials and personalized discussion about GIST and Gleevec. The patient then begins therapy with Gleevec at a dose of 400mg daily for one month after which time they return for a follow- up visit. At this follow-up visit the patient and physician discuss the sideeffects of imatinib and how to manage them for the best quality of life. Additionally, the results of mutation testing are discussed with the patient. If the patient is tolerating Gleevec and the patient has a GIST with kit exon 9 mutation the dose of Gleevec is escalated to 800 mg daily or the highest dose that the patient can tolerate well. Patients whose tumor has the exon 11 or other mutation continue at 400 mg of Gleevec daily. This approach is supported by publications showing that the 800mg daily dose is better for patients whose GIST has kit exon 9 mutation and that dose escalation is better tolerated after an increase from 400 mg rather than starting at 800mg as the first dose. Another factor that appears to be important in predicting long-term survival on Gleevec is a protein called vascular endothelial growth factor (VEGF). This protein helps tumor blood vessel formation. Some kinase inhibitors block the activity of the VEGF-receptor and KIT while others do not block the activity of VEGF receptor.
We recently published an article in Clinical Cancer Research (November 15 issue) demonstrating that patients with GIST whose tumors make VEGF (17% of all GIST patients) had a shorter survival than patients whose GIST did not express this protein when treated with Gleevec. Perhaps this small subset of GIST patients whose tumor produces VEGF should be treated with Gleevec plus a VEGF receptor inhibitor or with a multi-targeted kinase that inhibits both kit and VEGF receptor. We continue to strive for a better understanding of the molecular characteristics of GIST in order to better care for each unique patient with the ultimate goal of curing this disease.
