**7. Diagnostic evaluation**

A computed tomography (CT) scan (**Figure 1a** and **b**) is considered the first imaging to be done to evaluate anatomic location, extension, and metastasis of GISTs. Oral and IV contrast should be given to delineate bowel margins. GISTs can display endophytic and exophytic growth, and large GISTs may appear heterogeneous due to focal areas of hemorrhage or necrosis [53]. Magnetic resonance imaging (MRI) is used to further evaluate liver metastasis or rectal GIST [54]. Fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive but not specific for GIST, and it is mainly useful to monitor response to tyrosine kinase inhibitors [55, 56].

Upper GI endoscopy may be useful for gastric GIST. Both GISTs and leiomyomas will appear as a submucosal mass with normal overlying mucosa and bulging into gastric lumen. Mucosal ulceration may occur. Endoscopic ultrasound (**Figure 2**) may not be useful, however, when combined with FNA sensitivity, and accuracy may reach 82 and 86%, respectively [57]. Routine biopsy is not needed routinely for local resectable gastric GISTs proved by imaging studies.

**8.1. Management of primary resectable disease**

**Type of study**

prospective

randomized

2009 Phase II

2009 Phase II

2012 Prospective

open-label phase II

**Type of patients assessed**

1. Advanced primary GIST of >5 cm (Group A, 30 p) 2. Recurrent or metastatic tumors of ≥2 cm (group B, 22 p)

Primary GIST Metastatic GIST of ≥1 cm 3. 19 patients involved

1. KIT or PDFRA positive GIST. Tumors had to be locally advanced, potentially resectable, and no metastasis 2. 45 patients involved

There is still no consensus on the role of neoadjuvant imatinib therapy in resectable GISTs [4]. However, imatinib therapy might be considered for advanced or borderline resectable tumors. Multiple prospective and randomized trials have shown that neoadjuvant imatinib therapy (with a dose of 400 mg/day) in cases of advanced GIST will cause a reduction in tumor size and enable an R0 resection with an increased chance of organ preservation (**Table 2**). However, if KIT exon 9 mutation is detected and neoadjuvant therapy is planned, the dose may be increased to 800 mg per day as recommended by the European Society for Medical Oncology (ESMO) guidelines.

> **Dose of imatinib given**

Neoadjuvant 600 mg/ day for 8–12 weeks of treatment with a median of 65 days then 600 mg/day adjuvant therapy for 2 years

Neoadjuvant 600 mg/day given at 3, 5, or 7 days; then adjuvant 600 mg/day for 2 years

Neoadjuvant for 6 months 400 mg/ day with no postoperative adjuvant therapy

**Median follow-up**

1. Group A 4.9 y 2. Group B 5.5 y

32 m Tumor cell apoptosis

36 m Overall

tumor response

**Primary end point**

**Results**

http://dx.doi.org/10.5772/intechopen.77297

RFS 1. The 2-y estimated

overall survival was 93.3 and 90.9% in Group A and Group B, respectively, with a median follow-up of 3 y 2. The 5-y PFS and OS were 57% in group A, 30% in group B, and 77% in group A, 68% in group B, respectively

Gastric GIST

75

All patients had a radiographic response with 1 week of imatinib therapy. In addition, the rate of tumor cell apoptosis had a positive correlation duration of imatinib therapy where the maximum tumor cell apoptosis was seen with 7 days neoadjuvant imatinib

therapy

1. R0 resection was achieved in 30/34 patients and PFS at 3 years was 85.2%. 2. Predicted operation was downsized with imatinib therapy

*8.1.1. Preoperative therapy for primary GISTs*

**Study Published year**

RTOG (Radiation Therapy Oncology Group) 0132 [1, 116]

McAufliffe et al. [117]

APOLLON [118]

**Figure 1.** An axial ( A) and coronal (B) CT image showing a well-defined mass lesion ( arrow) in the anterior gastric wall in the proximal stomach measuring 2.9x2.5x2.7.

**Figure 2.** Gastric EUS showing a well-defined hypoechoic gastric submucosal lesion (between the two arrows) from the fourth layer of the stomach wall suggestive of GIST.
