Dr. Katherine A. Janeway
GIST is a disease with a number of subtypes, and is beginning to be increasingly viewed as a “family of diseases”. One particular form of the disease is commonly known as “Pediatric GIST” – in this form the mutation occurs when the patient is either a child or young adult (but may not be discovered until later). In their article, “Treatment Guidelines for Gastrointestinal Stromal Tumors in Children and Young Adults”, published in the May 2012 edition of the Journal of Pediatric Hematology/Oncology, Katherine A. Janeway, MD (from Dana-Farber Cancer Institute in Boston, MA) and Alberto Pappo, MD (from St Jude Children’s Research Hospital in Memphis, TN) performed a detailed review of the clinical presentation, natural history, diagnosis and staging of Pediatric GIST, and proposed specific treatment guidelines for patients with this form of GIST.
Janeway and Pappo cited a study of 44 GIST patients diagnosed before the age of 21 that identified anemia secondary to chronic GI blood loss as the most frequent presentation, and thus pointed out that when pediatric patients present with this symptom, GIST should be considered as a possible diagnosis. They also pointed out some clinical and pathologic features that help distinguish the pediatric form of GIST, such as a higher proportion of female patients, multifocal gastric tumors and lymph node metastases being more common, and a higher likelihood of epithelioid histopathology.
Because Pediatric GIST is so rare (estimated as only about 1.4% of all GIST cases) developing precise estimations of progression-free survival and overall survival is challenging. It does seem, however, that the pediatric form of GIST is more indolent (slower growing).
Dr. Alberto Pappo
The authors recommend that pediatric GIST should be diagnosed by a multidisciplinary team with expertise in managing sarcomas or tumors of the GI tract. In particular, a number of pieces of the patients medical history should receive specific attention, including family history, prior history of malignancy, symptoms of anemia and catecholamine excess, abdominal pain and/or distention, and the presence of skin findings associated with NF-1 and hyperpigmentation (these skin findings may be associated with familial, or hereditary, GIST, which can be passed on genetically). In terms of procedures, they recommend the following: a complete blood count, reticulocyte count, serum chemistries, and liver tests. In terms of imaging, at least a chest x-ray and abdominal and pelvic CT scan should be included, with an MRI being an acceptable alternative to a CT in some cases. PET scans may also be helpful, particularly where there is peritoneal disease. As there are no prognostic factors that have been validated for pediatric GIST and no specific staging system (as opposed to the adult form of GIST), it is critical that tumors be examined for mutations in KIT/PDGFRA, and due to the possibility of familial GIST, all patients who are diagnosed with a wildtype GIST (no known mutation) be referred to a genetic counselor.
In the event a Pediatric GIST patient also has a KIT or PDGFRA mutation, treatment should be given in the same manner as when treating the adult form of GIST. However, when there is no KIT or PDGFRA mutation present, the authors recommend different courses of action (See Table to right).
As far as drugs to treat Pediatric GIST, the authors note that while Gleevec and Sutent are established first and second line treatments for the adult form of GIST, it is not clear what the first-line treatment for Pediatric GIST patients should be. There have been studies for both drugs with pediatric patients, but they were with small numbers of patients, and in some cases are ongoing. As no study has been done that compares the two drugs, it is unclear which one is optimal for first-line treatment.
While there is increasing understanding of the pediatric form of GIST, there is still much more to be learned, in terms of both the science behind the disease and recommendations for its treatment.