Gastrointestinal Stromal Tumors
The gist of GIST
Obligatory—This is not medical advice
When I see patient who have a diagnosis of gastrointestinal stromal tumor (GIST), they often have many questions. They’re told, like so many others who have waited to see us in our lobby, that their cancer is rare. Again, ostensibly, this is true, and yet, GIST represents one of the more common types of malignancy that sarcoma medical oncologists see. What distinguishes it from other rare cancers it that we’ve done a good job of defining its diagnosis, drivers, and treatment. GIST is a story of where early forms of molecular diagnostics, understanding of basic biologic pathways, and a nascent biotechnology industry were able to successfully move the needle for patients who had a deadly condition.
As with any good story, there are numerous players, and you’ll see many of their name spanning decades of papers published in high impact factor journals. But, before we talk about how we treat GIST, let’s review who gets it, and how it’s diagnosed.
Epidemiology
GISTs are, like other sarcomas, mesenchymal neoplasms. For more about the basic principles of sarcoma, see this post. While it is the most common sarcoma of the GI tract, it nonetheless only represents 1-2 percent of GI cancers. GISTs can happen anywhere in the gut, from esophagus to anus. Their most common location is the stomach, which represents approximately 60% of cases.12 The figure below shows the proportion in each location for multiple demographic studies.
The incidence, meaning number of new diagnoses, of GIST has been increasing over time since first being categorized as a distinct diagnosis in 2001. It is difficult to disentangle whether this is a result of increased awareness, or other factors. Average incidence was 0.7 cases per 100,000 people per year between 2001 and 2015.3
Diagnosis
Typically, patients will present with a mass in one of these locations, either symptomatic, or not, which is subsequently biopsied endoscopically (by utilizing a flexible endoscope to visualize the gut with a camera). The figure below indicates that most patients in this study presented with some form of symptoms—this could be weight loss, fatigue, bleeding, or anything else that prompted a workup by a physician.
How do we know they’re GISTs, though? What makes us convinced this is a GIST versus, for instance, a smooth muscle tumor? This is work done by our valiant pathology colleagues after a biopsy. Here, again, I will be relying on pathologyoutlines. The first step is what is called an H&E (hematoxylin and eosin) staining. 4
This will show something akin to the picture above, spindle shaped cells. The key is the subsequent immunohistochemistry performed. These are specialized stains that target surface proteins. Proteins specific to GIST are CD117 (also called c-KIT), DOG1, and CD34. Other stains may also be done in cases of CD117 negativity, namely SDH. CD117 and DOG1, combined with the morphology, or shape of the cells, basically clinches the diagnosis. As with anything, there will be nuances, but this helps paint the picture for how it comes together.
After the diagnosis
After we know that this mass is, in fact, a GIST, we go back to first principles of the diagnosis—answering the question of where is it? This can be done by CT scans of the chest, abdomen, and pelvis, and/or PETCT. In some cases, other forms of imaging will be used, but the above are applied in >90% of cases.
We then help risk stratify the tumor, utilizing one of a few different methods. This area is in flux, but in essence, it seeks to determine the risk of the GIST returning after a definitive surgery at any point in the future. Clinical trials have been done utilizing these, or similar, definitions, and so it has therapeutic implications as far as treatment is concerned. One of the more common risk categorizations was published by Miettinen et al.5
Genetic sequencing of the tumor should also be considered, although this very much depends on the clinical situation. For patients with low risk tumors, this is not necessary. For patients with high risk tumors, given initial trials were not performed with that information, again, it may also not be required. That stated, most patients are interested and it can change treatment patterns.
Treatment
What therapies are used is highly dependent upon the clinical situation. What has been described so far is for less urgent cases. Is the patient experiencing blockage of their bowel, or some other life threatening complication from the tumor? Would surgery help relieve that problem? Do we have time to give a medication, or wait for genetic sequencing of the tumor?
There are also differing indications for therapy—in some patients we are treating metastatic disease, a condition which cannot be cured. For some patients, we are recommending adjuvant treatment, or therapy after a surgery in order to improve outcomes. Ample discussion should take place between the patient and their treating physician. I will elaborate more on the types of treatment we give in a future post.
https://www.sciencedirect.com/science/article/pii/S1877782115002519?via%3Dihub
https://www.pathologyoutlines.com/topic/stomachgist.html
https://pubmed.ncbi.nlm.nih.gov/17193820/