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GIST Treatment Options
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Historical Perspective: Chemotherapy and Radiation
Before the availability of Glivec®(imatinib), the only treatments for GIST other than surgery were conventional chemotherapy and radiation therapy3. GISTs are largely resistant to radiotherapy and chemotherapy4,5. Surgery is the first-line option for localised primary resectable GIST6. However, primary GISTs have a high risk of metastatic relapse after initial surgery for localised disease6. Before the availability of Glivec, the prognosis of patients with advanced GIST disease was poor. Patients with recurrent or malignant GISTs resistant to radiotherapy and chemotherapy are reported to have a poor prognosis even after surgical resection, with median survival of 12 months or less7,29. The introduction of Glivec for advanced GIST disease has improved significantly the outlook for patients with unresectable and/or metastatic malignant GIST.
GIST Prognosis
The 3 prognostic indicators for GIST are mitotic rate, tumour size, and site28. Upon diagnosis, GISTs range in size from 2 cm to 30 cm18. Tumours with either a high mitotic rate (>10/50 high-power field [HPF]) or a size >10 cm are at a high risk for aggressive behaviour. Those with a low mitotic count (<5/50 HPF) and small size (<2 cm) are generally at low risk for aggressiveness1,28. However, no GIST should be presumed to be benign.
| Table 1. Risk of Aggressive Behaviour in GIST1,30 | ||
| Size | Mitotic Count (HPF) | |
| Very low risk | <2 cm | <5/50 |
| Low risk | 2-5 cm | <5/50 |
| Intermediate risk | <5 cm 5-10 cm | 6-10/50 <5/50 |
| High risk | >5 cm >10 cm Any size | <5/50 Any mitotic rate >10/50 |
HPF, high-power field.
Goals of Therapy for GIST
The overall goal of therapy for GIST patients is to eliminate or reduce the tumour burden and maintain tumour control. The goal of surgery in treatment of primary resectable GIST is complete resection of the mass without disruption of the commonly present pseudocapsule and achieving negative margins6,29. The goals of Glivec therapy in advanced GIST include:
- Tumour size reduction or disease stabilization, both of which result in prolonged survival in the pivotal B2222 trial31,32
- Reduction of tumour density (by CT) and metabolic activity (by FDG-PET)6
Historical Perspective: Chemotherapy and Radiation
Before the availability of Glivec, the only treatments for GIST other than surgery were conventional chemotherapy and radiation therapy3,33. The role of chemotherapy and radiation therapy has been limited by a lack of efficacy and intolerable toxicity. Clinical trial data show that response rates to any cytotoxic chemotherapy regimen range from approximately 0 to 5%4,33. Other evidence confirms that conventional chemotherapy does not have a role in the management of patients with GIST.
Radiation therapy is limited by its toxicity to surrounding structures, especially the intestine, and is therefore of limited value5,33.
