. . . 2003.
Okay, so the test isn’t brand new, but the real question is; why aren’t more people using a test that can do all of these amazing things that patients with other cancers can only dream about?
The test is called a mutational test and typically costs about a thousand dollars. This is almost always paid for by insurance. GIST experts all over the world recommend this test; and yet only about half of living patients in the LRG registry have the test. And using the LRG registry as a measure of testing is probably misleading because it represents some of the most engaged, proactive, educated patients in the world and the testing rate in the LRG registry is almost certainly higher than in the general population of GIST patients. In fact, the rate
for mutational testing in the general oncology world may be as low as 1% in the USA (in 2010) to 17% in the Netherlands (in 2012) (1,2). The testing rate for patients treated at GIST specialty centers is much higher; as high as 92% in the 2012 study from the Netherlands.(1) This is just of many reasons that GIST patients should consult with GIST expert doctors.
Researchers have made great progress in understanding GIST since 1998, and today many different sub-types of GIST are recognized. With the use of mutational testing, it’s now possible to understand the driving force for almost all GISTs. Mutational testing has been available since 2003, but its use in GIST remains shockingly low.
A standard mutational test for GIST includes testing for mutations in KIT and PDGFRA and is sufficient to find the driver mutation in about 80% to 85% of GIST patients. Additional testing, including, but not limited to, staining for SDHB is needed, but available, for those patients without a KIT or PDGFRA mutation.
Figure 1 – Real World Evidence – Data from the LRG registry supports mutational testing
Click image to enlarge chart
Note: All data presented is from the LRG Patient Registry. Other series of patients and population-based studies may vary somewhat from these percentages.
The KIT mutations in exon 11 that were the first found in GIST, remain the most common type of mutation making up 62% of all GISTs (LRG registry). Since they are both sensitive to first-line treatment (Gleevec/imatinib) and are the most common type of GISTs, they tend to drive treatment patterns in GIST. However, this leaves 38% of GISTs that are something besides KIT exon 11. From this 38% of all GIST patients, only 12% are fully imatinib-sensitive; 55% are insensitive to imatinib; 32% have intermediate imatinib sensitivity. Kit exon 9 mutations require a higher dose of imatinib and 2% of patients with a listed mutation type have unknown imatinib sensitivity. 20% of PDGFRA exon 18 mutations with an unreported amino acid, 2/3 of these can be expected to be the insensitive D842V mutations.
When we include all LRG patients with a known mutation type (n = 739) including the KIT exon 11 patients, two thirds (66%) are imatinib-sensitive, 12% have intermediate sensitivity, 21% are insensitive to imatinib and 1% have incomplete reporting and thus unknown sensitivity (figure 1).
Data from the LRG Registry
In the LRG registry, 43% of patients (n = 739) reported a mutation to the registry (known) and 57% (n = 970) reported as unknown mutation (figure 2). The unknown most likely represents that the patient did not have any testing, but there may be some cases where testing was done and the patient either did not realize that testing had been done or did not know the result. The percentage of patients with known mutation has increased over time and 67% of LRG patients diagnosed in 2013 or later reported a known mutation.
The rate is also higher if we consider only living patients, with 50.6% of living patients having a known mutation. Unfortunately, this still leaves almost half (49.4%) of the living LRG patients without testing. A very high percentage when you consider that most living LRG patients are either currently metastatic (49%) or at high risk of a recurrence (71% of patients with known risk criteria that have not had a recurrence).