Gastric Gastrointestinal Stromal Tumour

A gastric gastrointestinal stromal tumour is a mesenchymal neoplasm arising from or related to the interstitial cells of Cajal.

Most harbour activating mutations in KIT or PDGFRA. Molecular genotype is clinically important because it determines sensitivity to tyrosine kinase inhibition.

Unlike gastric adenocarcinoma, GIST primarily spreads haematogenously and within the peritoneum. Lymphatic spread is uncommon, so routine lymphadenectomy is unnecessary.

Tumour rupture is a major oncological event because it markedly increases peritoneal recurrence risk.

Small gastric GISTs are frequently incidental.

Larger tumours can present with:

• Upper gastrointestinal bleeding
• Anaemia
• Epigastric discomfort
• Early satiety
• Palpable mass
• Tumour rupture with haemoperitoneum

Large tumours may grow exophytically and become substantial before producing gastric obstruction.

Contrast CT abdomen and pelvis: define tumour size, relation to adjacent organs and metastatic disease.

Endoscopic ultrasound: useful for small subepithelial gastric lesions.

Obtain tissue before systemic treatment or when the diagnosis is uncertain. Avoid percutaneous biopsy through uninvolved peritoneal planes when it creates unnecessary rupture or seeding risk.

Histology is supported by DOG1 and KIT CD117 expression.

Perform KIT and PDGFRA mutation analysis before neoadjuvant or adjuvant imatinib because resistant molecular subtypes must not receive ineffective therapy.

Localised disease

Complete surgical excision with an intact pseudocapsule is definitive treatment.

The operative objective is an R0 resection without tumour rupture, not a wide gastric cancer style resection.

A gastric wedge or limited segmental resection is appropriate when adequate margins can be achieved without deforming the gastroesophageal junction or pylorus.

A macroscopic margin around 1 cm is generally sufficient. Routine lymph node dissection is unnecessary unless abnormal nodes are present or a rare nodal prone subtype is suspected.

Do not grasp the tumour directly with traumatic instruments. Rupture can convert a localised tumour into disease with extremely high peritoneal recurrence risk.

Small gastric subepithelial tumours below approximately 2 cm without high risk features can undergo endoscopic ultrasound surveillance or carefully selected local resection.

Neoadjuvant therapy

Use preoperative imatinib when tumour shrinkage can convert a major mutilating operation into a limited resection or reduce rupture risk.

Confirm an imatinib sensitive mutation first.

Imatinib 400 mg orally once daily.

Assess early response, generally within the first several weeks. Surgery is commonly performed after maximal useful response, often around 6 to 12 months rather than waiting for progression.

Imatinib can usually be stopped approximately 24 hours before surgery and restarted once oral intake is established.

Adjuvant therapy

High risk completely resected GIST with an imatinib sensitive mutation should receive:

Imatinib 400 mg orally once daily for 3 years.

Do not give adjuvant imatinib for PDGFRA D842V mutant GIST because this mutation is intrinsically resistant.

Tumour rupture should be treated as an exceptionally high recurrence risk event and usually warrants prolonged systemic treatment planning.

Metastatic disease

Standard first line treatment for imatinib sensitive metastatic GIST is:

Imatinib 400 mg orally once daily, continued until progression or unacceptable toxicity.

For KIT exon 9 mutant metastatic GIST:

Imatinib 400 mg orally twice daily provides greater disease control than the standard dose.

For PDGFRA D842V mutant disease:

Avapritinib 300 mg orally once daily is preferred because imatinib is ineffective.

Limited progression on tyrosine kinase treatment may occasionally be resected while continuing effective systemic suppression of the remaining disease.