Frequently, the GIST tumor is already metastatic at the time of diagnosis. GIST metastases typically involve the liver and/or the peritoneum. Patients with unresectable or metastatic GIST had minimal treatment options prior to the turn of this century. The introduction of TKIs provided the first real option for optimal patient survival.1 A dramatic decrease in tumor cells has been reported 7 days after pretreatment with a TKI (see Figure 1).1
The National Comprehensive Cancer Network (NCCN) guidelines call for neoadjuvant treatment with a TKI prior to surgery when the GIST tumor is unresectable or metastatic.2 Treatment with a TKI should be started immediately even if the tumor is not evaluable.3
Ninety-five percent of GISTs are KIT-positive.3 Providing continuous therapy with a TKI whenever possible can assist in the maintenance of ongoing suppression of KIT.4
Case Study: Rationale for TKI Therapy in a
Patient With a Primary Gastric GIST and Unifocal
Hepatic Metastasis5
A 69-year-old woman presented with a 3-month history of anorexia, upper abdominal discomfort, and weight loss of 7 kg (15 lb), initially suggesting the diagnosis of gastric ulcer.
An upper gastrointestinal endoscopy revealed a friable,
exophytic mass in the stomach. A biopsy was reported as showing only inflammation. Spiral computed tomography (CT) scanning of the abdomen demonstrated the presence of a 5- × 6-cm gastric mass (Figure 2).
At laparoscopy, a 2-cm lesion on the liver was also detected. Biopsy of the hepatic lesion, which was documented as CD117 (KIT)-positive by immunohistochemistry, confirmed the diagnosis of GIST. TKI treatment was initiated.
Figure 2. Baseline spiral computed tomography scan of the patient.
The patient received TKI therapy for 8 weeks as a participant in a clinical trial. The positron-emission tomography (PET) scan obtained at 8 weeks revealed a near absence of [18F]fluorodeoxyglucose (FDG) uptake, a marker of intratumoral metabolic activity; comparison with the patient’s pretreatment FDG-PET scan demonstrated significant tumor response (Figure 3).
Figure 3. Positron-emission tomography scan with [18F]fluorodeoxyglucose tracer obtained from the patient before (left)
and after (right) 8 weeks of TKI therapy.
The patient underwent surgical resection with partial
gastrectomy. Extension of the gastric GIST into the upper retroperitoneum was noted, as well as several tumor nodules
in the lesser sac and omentum. All apparent tumor was excised. Postoperative pathology examination revealed a tumor mass of approximately 3 × 3 × 2 cm (compared with the initial gastric mass measurement of 5 × 6 cm by CT scan), with 80% to 90% tumor necrosis. The original liver lesion was not visible at surgery, and the results of intraoperative ultrasonography of the liver were negative for lesions.
The patient resumed TKI treatment at approximately 3 weeks postoperatively and was to continue receiving TKI therapy for
2 years, according to the study protocol.
This case illustrates one approach to combining systemic therapy with surgical intervention to potentially eradicate signs of viable GIST. Before the introduction of TKIs, GIST treatment was mainly the responsibility of surgeons. Today, the combined expertise of medical oncologists and surgeons is likely to provide the best prospects for cure or for prevention of disease progression. Similarly, the integrated use in this case of CT
and FDG-PET imaging as well as postoperative pathology study underscores the importance of multimodality monitoring for the assessment of tumor response to TKI treatment and the
selection and timing of further treatment.
Metastatic
