GIST

Gastrointestinal stromal tumours (GISTs) are the commonest sarcoma of the gastrointestinal tract. They can occur throughout the GI tract, but occur most commonly in the stomach and then the small bowel.

GIST

GISTs range from very small micro-GISTs to very large tumours. They arise from the pacemaker cells of Cajal; these are the cells that signal for the bowel to move in its characteristic way (vermiculation).

They are usually diagnosed with a biopsy at the time of endoscopy, by a core biopsy or a fine needle aspirate via endoscopy (endoscopic ultrasound). They are often incidental findings. After histological diagnosis, tissue may be sent for genetic testing to see if the tumours have mutations making them susceptible to drug treatment, specifically Imatinib, which is a highly specific and effective treatment that targets c-Kit (CD117) receptor.

In most GISTs, mutations in c-Kit drive the tumour by causing the receptor to constantly signal ‘on’ continuously firing the pathway, and causing tumour growth. However, using targeted therapy such as imatinib, which specifically inhibits c-Kit to stop the signalling of this pathway, is very effective for reducing the size of the tumour before surgery (neoadjuvant treatment), reducing the risk of GIST coming back after it has been fully removed with surgery (adjuvant treatment) or for the treatment of disease that has spread beyond the primary site.

The majority of GISTs are driven by mutations in c-Kit with specific Exon mutations, although there are other mutations, such as in PDGFA and the so-called ‘Wild Type GIST’, which is a catch-all phrase for non-Kit/PDGF driven GISTs, and often occur in younger people. Paediatric and wild-type GIST are often more indolent, but may spread, including to lymph nodes, but are usually not sensitive to imatinib. Although there are inherited syndromes associated with GIST, these are rare, and the majority are sporadic cases, without any particular aetiological or environmental factor causing them. There may be an increased incidence of second primary cancers in patients presenting with GIST.

Potentially curative treatment of GISTs is surgery, which may be considered if a GIST tumour is greater than 2 cm in size. Occasionally, they may be watched in certain circumstances up until 3 cm in size, but from 3 cm and larger, surgery is generally indicated. GISTs present as incidental findings, or cause symptoms such as bleeding, fistulas and compression. Surgery is potentially curative, and the aim is to completely remove the tumour, with as small a margin of tissue as possible.

Depending on the size and location of the tumour, different surgical approaches may be used. The commonest approach would be with an open operation (laparotomy). Laparoscopic (keyhole or minimally invasive surgery) and newer techniques such as robotics are often used for the treatment of GIST.

If a GIST is large, or locally advanced there may be a requirement to remove surrounding organs and tissue. If they are large and are an amenable mutational type, imatinib may be prescribed by a Medical Oncologist to reduce the size of the tumour and hopefully the extent of surgery. Sometimes, if there is a stable, or small volume residual metastatic disease, surgery can be considered in highly selected cases.

After surgical resection (removal) GISTs are classified as low, medium or high risk for recurrence. There are several scoring systems, but the Miettinen scoring system is commonly used and estimates the risk of recurrence based on tumour site, size, mitoses (index of cells dividing).

Low-risk tumours do not need any further treatment, but usually have a surveillance CT scan at one year. For higher risk tumours, referral is made to a medical oncology for consideration of adjuvant imatinib to reduce the risk of recurrence for up to 3 years. For people with advanced or recurrent or metastatic disease, there are several lines of treatment with other specific inhibitors, and many clinical trials of new agents in the field.

Mr Smith has specific interest and expertise in GIST. He has several international publications in the field. Mr Smith also works with GIST Support UK and Sarcoma UK to support patients with GIST.

He is an expert in the minimally invasive approach to gastrointestinal stromal tumours, being one of the first surgeons in the United Kingdom to perform GIST procedures with the Robotic Da Vinci Xi Platform.

FOR FURTHER INFORMATION ON GIST, PLEASE SEE:

http://www.gistsupportuk.com; https://sarcoma.org.uk http://www.gistsupportuk.com/paediatric_paws.htm

RELEVANT PUBLICATIONS:

Schrage Y, Hartgrink H, Smith M, Fiore M, Rutkowski P, et al. Surgical management of metastatic gastrointestinal stromal tumour. Eur J Surg Oncol. 2018 Sep;44(9):1295-1300. PubMed PMID: 30131102.
Smith MJ, Smith HG, Mahar AL, Law C, Ko YJ. The impact of additional malignancies in patients diagnosed with gastrointestinal stromal tumors. Int J Cancer. 2016 Oct 15;139(8):1744-51. PubMed PMID: 27299364.