Review
Level | Source of evidence | Grade | Grade of recommendation |
---|---|---|---|
I | Meta-analysis of multiple well-designed, controlled studies; randomized trials with low rates of false-positive and low false-negative errors (high power) | A | Evidence rated as level I or consistent findings from multiple studies at levels II, III, or IV |
II | At least one well-designed experimental study; randomized trials with high rates of false-positive and high false-negative errors (low power) | B | Evidence at levels II, III or IV, and generally consistent findings |
III | Well-designed, quasi-experimental studies such as non-randomized, controlled, single-group, preoperative and correlation descriptive studies, and case studies | C | Evidence at levels II, III or IV, but inconsistent findings |
IV | Well-designed, non-experimental studies such as comparative and correlation descriptive studies, and case studies | D | Little or no systematic empirical evidence |
V | Case reports and clinical examples |
Disease background
Diagnosis
Clinical diagnosis
Molecular pathologic diagnosis
Imaging diagnosis and follow-up
Risk stratification of primary GIST
Recommendations for diagnosing GIST
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In general, patients should be managed by a multidisciplinary team (MDT) with expertise in sarcoma. Shared decision-making between the MDT and the patient is recommended.
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Initial investigations in patients with suspected GIST should include history- taking and physical examination, appropriate imaging of the abdomen and pelvis using CT scan with contrast and/or MRI, chest imaging, endoscopic ultrasonography, and endoscopy, if not previously performed.
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All patients with potentially resectable GISTs, except those with tumors in the stomach, should be referred for surgical resection.
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Patients with suspected gastric GIST 20 mm or larger should receive surgical resection. It is strongly suggested that those with suspected gastric nodules of less than 20 mm in size are also referred tfor resection if any of the following is present: 1) nodule with signs of irregular margin, ulceration, bleeding or increase in size during follow-up; 2) presence of cystic change, necrosis, heterogeneous echogenecity, lobulation, poor patient compliance with follow-up; or 3) diagnostic confirmation of GIST by FNAB or presence of KIT-positive tumor.
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When the diagnosis of gastric GIST is strongly suspected based on endoscopic ultrasonography but without histological confirmation, surgical resection or close follow-up may be considered. Percutaneous biopsy is not encouraged.
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Mutation analysis should be performed in KIT-negative patients and in patients with an unclear diagnosis or atypical clinical features.
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For imaging diagnosis and follow-up, CT scan is preferred over MRI if only one imaging procedure can be performed.
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When used for response evaluation, CT scan should be based on a tailored standardized protocol, and the assessment of therapeutic effect should include changes in tumor size and density.
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FDG-PET can be used to support the CT scan reading when the CT scan cannot be accurately evaluated. FDG-PET evaluation for treatment response should be based on the uptake intensity of 18FDG.
Surgical treatment
Recommendations for surgical treatment
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The surgical goals for resectable GIST include complete resection, avoidance of tumor rupture, and intra-operative staging to exclude metastatic disease. The preferred resection margin is 10 mm grossly. Lymph-node dissection is unnecessary.
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Combined use of surgery with imatinib treatment may benefit selected patients with metastatic GIST that is responsive to imatinib and exhibits only localized progression [level of evidence IIIB].
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Surgery with imatinib treatment is not indicated for systemic progressive disease unless for complications such as obstruction, bleeding, or perforation.
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Biopsy is not recommended for potentially resectable GIST.
Medical treatment
Adjuvant treatment
Recurrent or metastatic disease
Neoadjuvant treatment
Second-line treatment of advanced GISTs
Recommendations for medical treatment
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Adjuvant imatinib treatment should be considered in high-risk patients after complete or incomplete resection of primary tumor [level of evidence IIB].
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Neoadjuvant imatinib should be considered for patients with: 1) marginally resectable tumors or resectable GISTs, who have a risk of significant morbidity; or 2) primary localized GIST, whose tumors are deemed unresectable.
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When neoadjuvant treatment is considered, progression and response of tumors before and during the treatment should be assessed by the MDT, using CT (with optional MRI) and/or PET scans.
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Imatinib 400 mg daily should be initiated as first-line therapy for recurrent or metastatic GIST [level of evidence IA]. Higher doses, up to 800 mg daily, should be considered for patients with exon 9 KIT mutation [IIIA].
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In case of limited disease progression during imatinib therapy, resection of progressing lesion should be considered if feasible. Radiofrequency ablation and chemoembolization can be considered to control limited progression. Imatinib should be continued at the same dose or at an increased dose (600 to 800 mg/day) [level of evidence IIIB], as tolerated. After failure on imatinib, sunitinib can be considered as second-line therapy [IIB].
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In patients with generalized progressive disease and performance status 0 to 2, imatinib should be administered at a higher dose (600 to 800 mg/day), as tolerated [level of evidence IIIB], and sunitinib should be considered after failure of imatinib [IIB]. Treatment response after progression should be reassessed carefully by CT or PET scan.