According to the Singapore Cancer Registry Annual Report 2021, cancer survival rates often hinge on the stage at which the cancer is diagnosed, with some cancers, like stomach cancer, more likely to be detected at later stages, resulting in lower survival rates. And of the various types of cancers that get detected early by chance or only when symptoms start to show is GIST.

Gastrointestinal stromal tumours (GISTs) are a rare subset of digestive tract cancers, accounting for about 1% of all primary gastrointestinal cancers, according to SingHealth. These tumours are most commonly found in middle-aged or older adults, with cases being extremely rare in those under 30.

GISTs most frequently develop in the stomach (60%) or small intestines (30%), while less common locations include the duodenum, large intestine, appendix, and oesophagus. Unlike other gastrointestinal cancers, such as stomach or colon cancer, that originate from the inner lining's glandular cells, GISTs arise from the digestive tract wall.

But what exactly is this tumour, and how do you treat it?

What Exactly is a GIST?

GIST, a medical abbreviation for gastrointestinal stromal tumours, is an uncommon tumour that originates from the digestive system. However, they are different from the more frequent types of digestive tract cancers or adenocarcinomas, as they are specifically derived from unique cells called the interstitial cells of Cajal.

These cells control the movement of food through the stomach and intestines, rather than the absorption, and are also known as the ‘pacemakers’ of the digestive system. GISTs are most commonly located in the stomach but can also affect any part of the digestive system, including the small and large intestines and the rectum.

What Are the Causes and Risk Factors of GISTs?

GISTs primarily arise due to genetic mutations and are commonly diagnosed in middle-aged and older adults. Although the exact causes of these mutations are often unknown, most GISTs develop sporadically, meaning they occur without any clear inherited factors. However, in certain cases, inherited genetic conditions may increase the risk.

GISTs can sometimes run in families due to rare genetic conditions. These include:

• Familial GIST syndrome: An inherited condition that increases the likelihood of developing GISTs. People with this condition tend to develop many GISTs.
• Neurofibromatosis type 1 (NF1): A genetic condition that causes non-cancerous nerve tumours and increases the risk of GISTs and other cancers.
• Carney-Stratakis syndrome: A rare inherited condition that increases the risk of developing GISTs, particularly in the stomach, and another type of tumour called paragangliomas, often during adolescence or young adulthood.

What Are the Types of GISTs?

Gastrointestinal stromal tumours can vary significantly in type, primarily based on genetic mutations. Most GISTs develop from a non-inherited mutation in either the KIT or PDGFRA genes. These mutations trigger continuous cell growth, leading to tumour formation. However, a small group of adult cases and the majority of paediatric cases do not have these specific mutations. Instead, they fall into groups known as “wild-type” or “paediatric-like” GISTs. Recent research, however, has identified that these tumours may involve mutations in up to 20 other genes, according to the National Organisation for Rare Disorders.

As such, GISTs can simply be classified as:

• Benign (Non-cancerous): These GISTs are generally smaller (usually under 2 cm) and don’t spread to other parts of the body.
• Malignant (Cancerous): Malignant GISTs may invade nearby tissues or spread to other organs, necessitating targeted treatment approaches.

Are GISTs Cancerous?

GISTs can be benign or cancerous. The larger the GIST, the more likely it is cancerous. However, even a small and seemingly benign GIST can behave like a malignant cancer.

Gastrointestinal stromal tumours can spread to other parts of the body, most commonly to the peritoneum and liver. The only certain way to determine whether GISTs are benign or cancerous is to remove them with surgery. Doctors then examine the tumour to determine the risk of relapse. High-risk features for relapse or recurrence are:

1. Large size
2. High mitotic count/number of cells actively dividing and growing
3. Presence of rupture/spillage
4. A positive surgical margin

Symptoms of GIST

Many patients may not have any symptoms until they are in the advanced stages. The common symptoms of GIST include:

1. Abdominal pain
2. Blood in the stools or vomit
3. Symptoms of anaemia (low red blood count), including effort intolerance, giddiness, breathlessness
4. Difficulty swallowing
5. Early satiety and fullness
6. Unintended weight loss
7. Visible lump in the abdomen

How is GIST Diagnosed?

Diagnosing GISTs involves several steps to accurately assess the presence, size, and spread of the tumour. Here’s an overview of the diagnostic process:

• Medical History and Physical Exam: The doctor begins by discussing your medical history, symptoms, family history, and any potential risk factors. A physical exam may follow, checking for abnormalities in the abdomen.
• Imaging Tests: These scans help visualise the tumour’s location and size. Tests like CT (computed tomography) and MRI (magnetic resonance imaging) create detailed images to show if the GIST has spread. Occasionally, a PET (positron emission tomography) scan may be used to monitor response to treatment or detect recurrence.
• Endoscopy and Endoscopic Ultrasound (EUS): Endoscopy uses a flexible tube to inspect the digestive tract visually, while EUS involves an ultrasound probe attached to the endoscope to capture images of the tumour from inside the digestive system.
• Biopsy: To confirm if a growth is a GIST, a biopsy may be necessary. This can be done via fine-needle aspiration, where a small tissue sample is taken from the tumour for laboratory analysis to verify if it contains cancer cells.

How Do You Treat GISTs?

Treatment options for GISTs vary based on factors like tumour size and symptoms. Symptomatic GISTs or those over 2cm are generally removed surgically, often through minimally invasive laparoscopic surgery. For larger tumours or those affecting nearby organs, targeted immunotherapy may be used prior to surgery to reduce tumour size and limit the amount of tissue that needs to be removed. For asymptomatic GISTs under 2cm, close monitoring may be an option to track any potential growth.

Recent advancements have also made treatments for GIST more effective, especially with the introduction of targeted therapies. Tyrosine kinase inhibitors (TKIs), such as imatinib, have transformed GIST care by targeting specific proteins involved in tumour growth, offering an alternative to traditional chemotherapy and radiotherapy, which are currently ineffective for treating GISTs.

GISTs had previously been among the most chemoresistant sarcomas, but the arrival of imatinib (Glivec or Gleevec) and other TKI drugs has transformed this cancer into a poster child for success in the targeted treatment of cancer, with a favourable side effect profile.

Targeted Therapy with Imatinib

Imatinib (Gleevec), a tyrosine kinase inhibitor, is frequently prescribed for GIST treatment. This targeted therapy blocks the KIT and PDGFRA proteins, which are typically overactive in GIST cells, helping slow down or even shrink tumours.

Imatinib can be utilised in several ways:

• After Surgery (Adjuvant Therapy): Following the removal of a GIST, imatinib may be recommended for at least one year to lower the chance of recurrence. For higher-risk cases, it may be continued for up to three years.
• Before Surgery (Neoadjuvant Therapy): For larger tumours that are challenging to remove, imatinib may be administered to reduce tumour size and simplify the surgical procedure.
• Advanced GIST: For GISTs that have spread or are too advanced for surgery, imatinib can often slow tumour growth, helping patients manage symptoms and maintain a higher quality of life.

While imatinib has significantly improved GIST treatment, patients should be aware of possible side effects, including stomach upset, swelling, or, less commonly, more severe issues such as fluid retention in the lungs.

For patients with a high risk for relapse, their chances of cure can be increased by taking 3 years of Imatinib (Glivec). This is an oral form of targeted therapy and specifically targets GIST, sparing normal cells.

Before Glivec   

After 6 months of Glivec

“Expert knowledge means better care for cancer”

Written by:

Dr Thomas Soh
MBBS (Singapore)
MRCP (United Kingdom)