Gastrointestinal Stromal Cancer

21.03.2024

GASTROINTESTINAL STROMAL TUMOR DIAGNOSIS AND TREATMENT

Gastrointestinal stromal tumor (GIST) is a rare type of tumor arising from the supporting and muscle tissues of the gastrointestinal tract. Although it most often occurs in the stomach and small intestine, it can develop anywhere in the gastrointestinal tract, from the esophagus to the anus. GISTs are usually associated with c-KIT or PDGFRA gene mutations. These mutations lead to uncontrolled growth and proliferation of cells. The importance of GISTs is that they can often grow without obvious symptoms and are sometimes diagnosed late. Early diagnosis and treatment are vital to prevent the spread of the disease and increase survival rates. Treatment usually begins with surgery, but in advanced or metastatic cases, targeted therapies may be required.

WHAT ARE THE RISK FACTORS?

Because gastrointestinal stromal tumors (GIST) are rare cancers, the exact risk factors for such tumors have not been fully established. However, based on current knowledge, it is thought that some factors may increase the risk of developing GIST:

Genetic Factors: Most GISTs are caused by mutations in the c-KIT or PDGFRA genes. Hereditary syndromes associated with these genes may occur in some families.

Age: GISTs are generally more common in people aged 50 and over. Increasing age may increase the risk of developing such tumors.

Gender: Some studies have observed that men are slightly more likely to develop GIST than women.

Ethnicity: It is thought that some ethnic groups may have a higher risk of developing GIST, but definitive data on this subject is still insufficient.

Previous Gastric Surgery History: Some studies have shown that the risk of developing GIST may be increased in people who have had stomach surgery.

Some Syndromes: Some rare genetic syndromes, such as Neurofibromatosis Type 1 (NF1), may increase the risk of developing GIST.

Environmental Factors: There is no clear data on the role of environmental factors in the development of GISTs, but as with other types of cancer, general health and lifestyle factors may be influential to some degree.

It is important to note that these risk factors do not constitute an absolute cause for the development of GIST. Having one or more risk factors does not necessarily mean that GIST will develop. Therefore, it is important to get a medical evaluation if there are symptoms or concerns.

Image 1: GIST can be seen in the digestive system, stomach, small intestines and colon.

HOW DOES IT OCCUR?

The mechanisms of development of gastrointestinal stromal tumors (GIST) are often associated with specific genetic mutations. Most of these tumors are caused by mutations in the c-KIT or PDGFRA genes. These genes normally encode proteins that regulate signals necessary for cell growth, differentiation and survival. As a result of mutations, these proteins become abnormally activated, leading to uncontrolled proliferation and growth of cells. This process causes uncontrolled cell division and tumor growth, which is characteristic of GISTs. In some cases of GIST, genetic changes other than these two genes may also play a role. However, approximately 85% of all GISTs have c-KIT or PDGFRA gene mutations. The presence of these mutations plays an important role in tumor diagnosis and treatment, as treatments are available that target these genetic changes. Therefore, understanding the mechanisms of development of GISTs is critical for managing the disease and determining treatment strategies.

WHAT ARE THE SYMPTOMS?

Gastrointestinal stromal tumors (GIST) often may not cause symptoms and are often discovered incidentally during examinations performed for other reasons. However, they may show some symptoms depending on their size and location. Some common findings that GISTs can cause include:

Abdominal Pain or Discomfort: As the tumor grows, pain or discomfort in the abdominal area may occur.

Bleeding: GISTs can damage the stomach or intestinal wall, leading to blood in the stool (melena) or blood in the vomit.

Anemia: Hidden blood losses can cause anemia, which leads to symptoms such as fatigue, weakness and pale appearance.

Mass Feeling: Especially in large tumors, a mass or swelling may be felt in the abdomen.

Nausea and Vomiting: The tumor can put pressure on the digestive system, causing nausea or vomiting.

Loss of Appetite or Weight Loss: In advanced cases of GIST, loss of appetite and unexplained weight loss may occur.

Intestinal Obstruction: When the tumor grows in the intestine, it can cause obstruction and changes in bowel movements.

Because GIST symptoms are similar to many other conditions, a medical evaluation should be sought if these symptoms are present. Early diagnosis can significantly improve treatment options and outcomes.

HOW IS IT DIAGNOSED?

Gastrointestinal stromal tumors (GIST) are usually diagnosed using a series of medical tests and procedures. When suspicious symptoms or an abnormality is noted during routine scans, the first step is usually to perform imaging tests, such as a computed tomography (CT) scan or magnetic resonance imaging (MRI). These imaging tests help determine the location and size of the tumor and whether it has spread to surrounding tissues. Definitive diagnosis is usually made by biopsy; Here, a small tissue sample is removed from the tumor and examined under a microscope. Pathological examination can determine whether the tumor is a GIST and, if so, what type it is. Additionally, molecular testing can be used to detect the presence of genetic mutations such as c-KIT or PDGFRA. These genetic tests play an important role in diagnosing the disease and planning treatment. Diagnosis of GIST is based on a combination of clinical findings, imaging test results, histological and molecular analyzes and requires a multidisciplinary approach.

WHAT ARE THE PATHOLOGICAL TYPES?

Gastrointestinal stromal tumors (GIST) are generally divided into different pathological types based on cell type and morphological features. Pathological classification of GISTs is important in understanding the tumor's response to treatment and prognosis. Here are the main pathological types of GISTs:

Spindle Cell Type: It is the most common type of GISTs. This type of cells have a long and narrow structure and generally resemble muscle tissue.

Epithelioid Type: In this type of cells, they are round or oval in shape and resemble epithelial cells. Epithelioid GISTs can sometimes be more aggressive than spindle cell types.

Mixed Type: It contains a combination of both spindle cell and epithelioid cell types. This species shows morphological features of both cell types.

Pleomorphic Tip: This is a rare type and the cells show abnormal and variable structures. Pleomorphic GISTs generally exhibit a more aggressive behavior.

Apart from this, some GISTs are also evaluated based on microscopic features such as the size, shape and division rate of the cells. Factors such as mitotic count (the rate of division in a given area) and tumor size are important in determining the aggressiveness of the tumor and the patient's prognosis. In addition to pathological types, molecular genetic tests, especially the presence of c-KIT (CD117) and PDGFRA (Platelet-Derived Growth Factor Receptor Alpha gene mutations), play an important role in the classification and treatment planning of GISTs. The name DOG1 (Discovered on GIST-1) Another given protein is also used to diagnose GIST in c-KIT negative cases. Each GIST case is unique and requires personalized treatment approaches based on the pathological and molecular characteristics of the tumor.

Image 2: GİST is one of the soft tissue tumors (sarcoma) seen in the digestive system.

HOW IS TUMOR STAGING DONE?

Tumor staging for gastrointestinal stromal tumors (GIST) is based on factors such as tumor size, location, extent, and mitotic activity. This staging evaluates the severity of the disease and plays an important role in treatment planning. Here are the main factors taken into consideration when staging tumors in GISTs:

Size of Tumor: The diameter of the tumor is an important factor in determining staging. Generally, the larger the tumor, the more advanced the stage of the disease is considered.

Mitotic Count: The number of mitosis (cell division) seen within a certain microscopic field in tumor tissue samples. Mitotic count is an indicator of how fast the tumor is growing, and a high mitotic count indicates more aggressive disease.

Location of the tumor: The location of the tumor within the gastrointestinal tract may also affect staging. Tumors in some areas may carry a higher risk.

Spread: Whether the tumor has spread to surrounding tissues or organs and whether it has metastasized to lymph nodes or distant organs (such as the liver, lung) also affects staging.

Radiological Features of the Tumor: Imaging tests (such as CT, MRI) are used to evaluate the characteristics of the tumor and its effect on surrounding tissues.

Tumor staging is usually done using the TNM (Tumor, Nodule, Metastasis) classification system developed by the American Joint Committee on Cancer (AJCC). According to this system, the size of the tumor (T), its spread to nearby lymph nodes (N) and the status of metastasis to distant organs (M) are evaluated. Tumor staging in GISTs provides information about the course of the disease and helps determine treatment options. These staging results form the basis for patient-specific treatment planning and provide important information about prognosis.

HOW IS TREATMENT DONE ACCORDING TO STAGES?

Treatment of gastrointestinal stromal tumors (GIST) is determined by the stage of the tumor, the patient's general health status and other characteristics.

General treatment approaches according to the stages of GISTs:

Early Stage GIST (Small and local Tumors):

Surgery: Early-stage GISTs are usually treated with surgery. Its aim is to completely remove the tumor and surrounding healthy tissue. If the tumor is successfully removed, additional treatment may not be needed.

Follow-up: Regular follow-up after surgery is important to detect early tumor recurrence or spread.

Locally Advanced GIST (Large or Disseminated Tumors):

Targeted Therapy: In advanced-stage GISTs, drugs targeting c-KIT or PDGFRA gene mutations (for example, imatinib) are used. These drugs help treat tumor cells by preventing them from growing and spreading.

Surgery: If the tumor shrinks or its spread is controlled, surgical intervention may be possible.

Metastatic GIST (Tumors Spreading to Distant Organs):

Targeted Therapy: Targeted therapies form the basis of treatment in metastatic GISTs. Drugs such as imatinib are commonly used in the management of metastatic disease.

Surgery: In some cases, it may be possible to surgically remove metastasizing tumors, but this often depends on the general condition of the disease and the location of the tumor.

GIST treatment requires a multidisciplinary approach and requires close collaboration between oncologists, surgeons, and radiologists. The treatment plan for each patient is customized based on the patient's individual needs and the characteristics of the tumor. Regular follow-up and evaluation throughout the treatment process is an important part of treatment planning.

Image 3: Depending on where it develops in the digestive system, GIST may cause complaints such as abdominal pain, nausea, vomiting and abdominal bloating.

WHAT ARE THE SYSTEMIC DRUGS USED IN TREATMENT?

Some drugs and treatment methods used in the treatment of gastrointestinal stromal tumors (GIST) are:

Targeted Therapies (Smart Drugs):

Imatinib: It targets c-KIT and PDGFRA gene mutations and is the first choice treatment in the treatment of GIST.

Sunitinib: It is used in imatinib-resistant or advanced stage GISTs.

Regorafenib: It is used in GISTs that have previously been resistant to imatinib and sunitinib treatments.

Chemotherapy:

The effectiveness of traditional chemotherapy drugs in the treatment of GIST is limited and is generally considered in advanced-stage cases or resistant to targeted therapies.

Immunotherapies:

Immunotherapy is not yet a standard approach in the treatment of GIST, but clinical studies and trials are ongoing in this area. The effectiveness and safety of immunotherapy are still being evaluated.

Each of these treatments is customized based on the genetic characteristics of the tumor, the patient's general health and the stage of the disease. It is also important to manage side effects during and after treatment. The most effective results in the treatment of GIST are generally achieved with a multidisciplinary approach and treatment combinations determined according to the individual situation of the patient. At every stage of the treatment process, close medical follow-up and supportive care of patients are important.

HOW SHOULD FOLLOW-UP BE CARRIED OUT AFTER RECOVERY?

Follow-up after treatment for gastrointestinal stromal tumors (GIST) is vital to detect early disease recurrence and monitor the patient's overall health status. Post-recovery follow-up usually includes:

Regular Physical Exams and Medical Evaluations: Regular doctor visits are made to evaluate the patient's general health condition and observe possible symptoms.

Imaging Tests: Imaging tests, such as computed tomography (CT) scans or magnetic resonance imaging (MRI), are performed periodically to check if the tumor has recurred.

Blood Tests: In some cases, tumor markers or other relevant blood values ​​may be monitored.

Continue Targeted Therapy: Some patients may continue targeted therapy (for example, imatinib) to prevent tumor recurrence. In this case, side effects due to drug therapy also need to be monitored and managed.

Lifestyle and Diet Changes: A healthy diet, regular exercise and other lifestyle changes can help improve overall health and reduce the risk of potential recurrence.

The follow-up plan is customized based on the individual needs of the patient, the type of treatment, and the characteristics of the tumor. The frequency and content of follow-up may vary depending on the stage of the disease, response to treatment and the general health status of the patient. During this time, it is important for patients to seek immediate medical attention for any new symptoms or concerns. Early diagnosis and intervention in GIST treatment can significantly improve survival rates and quality of life.