Mutational testing should be performed beforehand to ensure the tumor is imatinib-sensitive. If a KIT exon 9 mutation is identified, then 400 mg twice daily should be considered (given the benefit seen with 800 mg imatinib for advanced GIST patients), although there are no studies to confirm this practice. Neoadjuvant imatinib is recommended for a total of 6 to 12 months to ensure maximal tumor debulking, but with very close monitoring and surgical input for disease resistance and growth.14 Imatinib should be stopped 1 to 2 days preoperatively and resumed once the patient has recovered from surgery for a total of 3 years (pre-/postoperatively combined). Neoadjuvant therapy has been shown to be safe and effective, but there have been no randomized trials to assess survival.
What is appropriate surveillance for resected GISTs?
Surveillance
There have been no randomized studies to guide the management of surveillance after surgical resection and adjuvant therapy. There is no known optimal follow-up schedule, but several have been proposed.13,36 Among high-risk patients, it is suggested to image every 3 to 6 months during adjuvant therapy, followed by every 3 months for 2 years after discontinuing therapy, then every 6 months for another 3 years and annually thereafter for an additional 5 years. High-risk patients usually relapse within 1 to 3 years after finishing adjuvant therapy, while low-risk patients can relapse later given that their disease can be slower growing. It has been recommended that low-risk patients undergo imaging every 6 months for 5 years, with follow-up individualized thereafter. Very-low-risk patients may not require more than annual imaging. Because most relapses occur within the peritoneum or liver, imaging should encompass the abdomen and pelvis. Surveillance imaging usually consists of CT scans of the abdomen and pelvis. MRI scans can be utilized for patients at lower risk or who are out several years in order to avoid excess radiation exposure. MRI is also specifically helpful for rectal and esophageal lesions. Chest CT or chest radiograph and bone scan are not routinely required for follow-up.
Case Conclusion
The patient receives adjuvant imatinib and experiences grade 2 myalgias, periorbital edema, and macrocytic anemia, which result in imatinib discontinuation after 3 years of treatment. He is seen every 3 to 6 months and a contrast CT abdomen and pelvis is obtained every 6 months for 5 years. During this 5-year follow-up period, he does not have any clinical or radiographic evidence of disease recurrence.
Further follow-up of this patient is presented in the second article in this 2-part review of management of GISTs.
Key Points
- GISTs are the most common mesenchymal neoplasms of the GI tract and can occasionally occur in extragastrointestinal locations as well.
- GISTs encompass a heterogeneous family of tumor subsets with different natural histories, mutations, and TKI responsiveness.
- Surgery is the mainstay of treatment for localized GISTs, with cure rates greater than 50%.
- For very small (< 2 cm) esophagogastric GISTs, endoscopic ultrasound evaluation and follow-up is recommended.
- For tumors ≥ 2 cm, biopsy and excision is the standard approach.
- For localized GISTs, complete surgical resection (R0) is standard treatment, with no lymphadenectomy for clinically negative lymph nodes.
- Mutational analysis should be considered standard of practice. It can be helpful for confirming the diagnosis and can be predictive and prognostic in determining specific TKI therapy and dose.
- Adjuvant imatinib at a dose of 400 mg for 3 years is standard of care for GISTs that are at high risk of relapse and are imatinib-sensitive, and it is the only TKI approved for adjuvant therapy. Patients with PDGFRA D842V, NF1, BRAF or SDH-deficient GISTs should not receive adjuvant imatinib therapy.
- Neoadjuvant therapy can be utilized for sites where extensive resection would lead to significant morbidity. It should be given for 6 to 12 months, but patients need to be monitored closely for tumor growth.