What are the guidelines for reporting and treating Gastrointestinal Stromal Tumors (GIST)?

Guidelines for Reporting and Treatment of Gastrointestinal Stromal Tumors (GIST)

Gastrointestinal stromal tumors (GISTs) should be managed by an experienced multidisciplinary team in a specialist center to optimize patient outcomes and survival. 1

Diagnosis and Reporting

• Contrast-enhanced abdominal and pelvic CT scan is the investigation of choice for staging and follow-up of GIST 1
• MRI provides better preoperative staging information for rectal GISTs and may be an alternative for younger patients to limit radiation exposure 1
• Mutational analysis is critical to making clinical decisions about therapy and should be considered standard practice for all GISTs (with possible exclusion of <2 cm non-rectal GISTs) 1
• For small esophageal or gastric nodules (<2 cm) with no high-risk features, periodic endoscopic ultrasonography (EUS) follow-up is recommended until tumors increase in size or become symptomatic 1
• FDG-PET scan can be useful when early detection of tumor response to therapy is needed, particularly in the absence of mutational analysis 1

Surgical Management

• The standard treatment of localized GIST is complete surgical excision (R0 resection) of the lesion, with no dissection of clinically negative lymph nodes 1
• If laparoscopic or robotic excision is planned, the technique must follow the principles of oncological surgery 1, 2
• Laparoscopic approach is discouraged for large tumors due to risk of tumor rupture, which significantly increases recurrence risk 1, 2
• For rectal GISTs, surgical strategy needs to be tailored to the precise anatomic site and size of the tumor, particularly in relation to the sphincter complex 1
• Tumor rupture before or during surgery puts patients at very high risk of peritoneal relapse and should be considered for adjuvant imatinib therapy 1

Adjuvant Therapy

• Adjuvant therapy with imatinib for 3 years is the standard treatment for patients with a significant risk of relapse 1
• Risk stratification is based on tumor size, mitotic rate, tumor location, and rupture status 3
• Adjuvant therapy should not be considered when the risk is low 1
• PDGFRA exon 18 D842V-mutated GISTs should not be treated with adjuvant imatinib therapy due to resistance 1
• For KIT exon 9 mutations, adjuvant imatinib at a higher dose of 800 mg daily for 3 years may be considered 1
• Adjuvant treatment should be avoided in NF1-related and SDH expression-negative GISTs 1

Neoadjuvant Therapy

• Pre-operative systemic therapy should be considered for primary tumors where immediate resection is likely to be morbid (e.g., total gastrectomy, abdominoperineal resection, or multi-visceral resection) 1
• Mutational analysis is mandatory prior to initiating neoadjuvant imatinib therapy 1, 3
• Surgery is typically carried out after 6-12 months of neoadjuvant treatment, as further shrinkage is rare after this point 1, 3
• Early tumor response assessment is required to avoid delaying surgery in non-responding cases 1

Management of Advanced/Metastatic Disease

• Imatinib is the standard treatment for locally advanced, inoperable, and metastatic patients 1
• The standard dose of imatinib is 400 mg daily 1
• For patients with KIT exon 9 mutations, a higher dose of 800 mg daily is recommended due to improved progression-free survival 1
• Treatment with imatinib should be continued indefinitely in the metastatic setting, unless intolerance develops 1
• In case of tumor progression on 400 mg of imatinib, the dose can be increased to 800 mg daily (except for insensitive mutations) 1
• Sunitinib is the standard second-line treatment for patients progressing on or intolerant to imatinib 1, 4
• Regorafenib is the standard third-line therapy for patients progressing on or failing to respond to imatinib and sunitinib 1

Follow-up Recommendations

• For high-risk patients, follow-up should include contrast-enhanced CT scans every 3-4 months for the first 2-3 years, then every 6 months for years 4-5, then yearly up to 10 years 3
• For low-risk patients, follow-up every 6 months for 5 years, then annually is recommended 3
• Follow-up should focus on the liver and peritoneum, which are the most common sites of recurrence 2, 3

Special Considerations

• For rectal GISTs, a neoadjuvant approach should be considered for larger tumors, which may facilitate a more marginal excision when the tumor demonstrates response to imatinib 1
• SDH-deficient GISTs represent a distinct subset with different biological behavior, and lymph node assessment should be considered for this specific subtype 2
• Patients with tumor rupture should be considered for adjuvant imatinib therapy for at least 3 years, and possibly lifelong 1, 3