Gastroenterology and Hepatology

Current Diagnostic and Treatment Algorithm for Gastrointestinal Stromal Tumor (GIST)

Gastrointestinal stromal tumors (GISTs) are soft-tissue sarcomas that can be located in any part of the digestive system. These tumors, most commonly occur at the age >50 years in the stomach (60%), jejunum and ileum (30%), duodenum (4-5%), rectum (4%), colon and appendix (1-2%), and esophagus (<1%), and rarely as apparent primary extragastrointestinal tumors in the vicinity of stomach or intestines (1). Their overall incidence has been estimated as 10 to 20 per million, including incidental minimal tumors (2). GISTs are rare in children (<1%) and almost exclusively occur in the stomach. 

GISTs start in the interstitial cells of Cajal (ICC) located in the walls of the digestive system. These cells are part of the autonomic nervous system. A specific change in the DNA of one of these cells, which control such digestive processes as the movement of food through the intestines, gives rise to a GIST. People with GIST often do not experience any specific symptoms or signs. Patients with larger GIST tumors usually seek medical attention when they vomit blood or pass blood in their stool due to rapid bleeding from the tumor.

Not all gastrointestinal stromal tumorsneed to be treated right away. But if treatment is needed, the main types used are surgery and targeted therapy. Because GISTs are rare, the best care comes from certified centers offering sophisticated and highly specialized services.

The personalized care plan is the cornerstone of the success of the treatment of cancers in Germany.  Each patient receives an individualized treatment plan depending on tumor type and stage of progression. In this manner, the identification of tumor histology and staging of the tumor is of fundamental importance for the planning of the best treatment options, and this is a key factor in the daily work of German Health Advisors.  

Initial staging and risk assessment 

The staging for overseas patients is usually incomplete when they contact us for a second opinion and any subsequent treatment recommendations. The system employed by German Health Advisors, however, allows for the completion of this stage while the patient is in his homeland. It is not necessary to come to Germany for cancer staging. You will be informed if there are any obstacles in the staging process. For the staging of breast cancer, please bear in mind the following:  

  • Family history, physical examination, blood count and differential, liver and renal function tests (see the request form for German Health Advisors). This will usually be carried out by our local colleagues and documented in the form of a doctor’s letter. 
  • Contrast-enhanced computerized tomography (CT) scan. You can send the DICOM files CTscans using German Health Advisors’ secure data transfer system. Our experience shows that the quality of radiology images might not be good enough to correctly stage cancer. In such cases, we will contact you in order to work towards a solution. It is of great importance for us to have high quality radiology images from our local colleagues. This greatly assists in defining the diagnostic and treatment plan in a timely fashion and helps to avoid unnecessary expenses.   
  • Endoscopy of Stomach.Your stomach has probably already been examined with Endoscope by your endoscopist.  Currently, all endoscopic equipment have video recording option. If your endoscopist took video from the endoscopic procedure, please send it to us. You can send your video data using German Health Advisors’ secure data transfer system.
  • Endoscopic ultrasound (EUS). This test also uses an endoscope, but with an ultrasound probe on the tip of the scope and helps to determine the depth of the tumor within the wall of the stomach or other locations in the gastrointestinal tract.  
  • Fine-needle aspiration biopsy. This test is usually performed during EUS. If your local doctor made EUS and took a biopsy, please, keep the pathology report to send it to us later on. Usually, the pathologist defines the mitotic rate either, which has crucial importance on the planning of further treatment. The higher the mitotic rate in a tumor, the more aggressive it is, and the greater is its likelihood of spreading to other organs. In some cases, when our specialists are not satisfied with the quality of a pathology report, we will contact you with a recommendation for further steps. You may have to send us the frozen/paraffin-embedded tissue samples for further histology investigation at one of German Health Advisors’ partner laboratories in Germany.
  • Preoperative percutaneous biopsy should not be used because of a significant risk of tumor rupture or dissemination. 

Treatment of GIST 

Treatment for gastrointestinal stromal tumors (GISTs) depends mainly on the size of the tumor, location, how far it has spread, and how quickly it is growing. Identifying and understanding your mutation is an important part of determining an effective treatment plan. Below we list the main current treatment options:

  • In a histologically proven small GIST, the standard treatment is excision unless major morbidity is expected. Alternatively, in the case of a likely low-risk GIST on biopsy, the decision can be made with the patient to follow up the lesion (watchful waiting). 
  •  Surgery.The standard approach for tumors 2 cm in size is excision, because they are associated with a higher risk of progression.  Furthermore, all large or symptomatic GISTs should be surgically removed unless they are too large or they involve too many organs and tissues for surgery. It's often possible to resect GISTs using minimally invasive surgery. 
  • Targeted drug therapy. GISTs do not respond to traditional chemotherapy. Thanks to the recently gained understanding of tumor genetic changes in GISTs, however, drugs that interrupt the process of tumor spread have greatly improved the outlook for people with the disease. Imatinib (Gleevec) is the first line medical treatment used to prevent GIST recurrence after surgery. The drug is also used in situations where surgery isn't possible, as well as in controlling recurrent GIST. The current trend is to continue imatinib treatment as long as it's tolerated and it remains effective. Unfortunately, GISTs tend to become resistant to imatinib over time. A different targeted drug, sunitinib malate (Sutent) often works on imatinib-resistant GISTs. A number of other targeted drugs now in development are expected to join imatinib and sunitinib in coming years.

Follow-Up After Treatment of GIST 

Follow-up should be tailored to the individual patient and the stage of the disease. The German Health Advisors’ partner clinics will normally schedule follow-ups in this manner: 

  • High-risk patients undergo a routine follow-up with an abdominal CT scan or MRI every 3–6 months for 3 years during adjuvant therapy with a tighter clinical follow-up due to the need to manage the side effects of adjuvant therapy. 
  • For low-risk tumors, the usefulness of a routine follow-up is not known. Some clinics carry out follow up with abdominal CT scan or MRI, e.g. every 6–12 months for 5 years.
  • Very low-risk GISTs probably do not require routine follow-up, although the risk is not zero. 

The patients, who got their treatments in Germany, usually do not need to come for the follow-up controls to Germany. German Health Advisors will provide you with follow-up care through its Telemedicine platform.

References:

1. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Miettinen, M., & Lasota, J. (2006).  Seminars in diagnostic pathology (Vol. 23, No. 2, pp. 70-83).

2. Gastrointestinal stromal tumors (GISTs): point mutations matter in management, a review. Oppelt et al. (2017). Journal of gastrointestinal oncology, 8(3), 466

3. Gastrointestinal Stromal Tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2018) 29 (Suppl 4): iv68–iv78