BACKGROUND Recent breakthroughs regarding gastrointestinal stromal tumors (GIST) and their pathogenesis have redefined diagnostic criteria and have led to the development of molecularly targeted drug therapy. New treatment options mandate more accurate information regarding the incidence, prevalence, clinical behavior, and prognostic factors of GIST. METHODS All patients (n = 1460) who potentially had GIST diagnosed from 1983 to 2000 in western Sweden (population, 1.3–1.6 million) were reviewed, and 288 patients with primary GIST were identified. The incidence and prevalence of GIST were determined, and predictive prognostic factors, including current risk‐group stratifications, were analyzed statistically. RESULTS Ninety percent of GISTs were detected clinically due to symptoms (69%) or were incidental findings at surgery (21%); the remaining 10% of GISTs were found at autopsy. Forty‐four percent of symptomatic, clinically detected GISTs were categorized as high risk (29%) or overtly malignant (15%), with tumor‐related deaths occurring in 63% of patients and 83% of patients, respectively (estimated median survival, of 40 months and 16 months, respectively). Tumor‐related deaths occurred in only 2 of 170 of patients (1.2%) with very‐low‐risk, low‐risk, or intermediate‐risk tumors. The annual incidence of GIST was 14.5 per million. The prevalence of all GIST risk groups was 129 per million (31 per million for the high‐risk group and the overtly malignant group). CONCLUSIONS GIST has been under recognized: Its incidence, prevalence, and clinical aggressiveness also have been underestimated. Currently existing risk‐group stratification systems based on tumor size and mitotic rate delineate GIST patients who have a poor prognosis. Prognostication in patients with GIST can be refined using a proposed risk score based solely on tumor size and proliferative index. Cancer 2005. © 2005 American Cancer Society.
Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settingspalliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.
Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n ¼ 23) was compared with historic controls (n ¼ 48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies. The survival of patients with metastatic and inoperable malignant gastrointestinal stromal tumours (GIST), particularly those whose tumours have KIT exon 11 mutations, has improved dramatically since the introduction of imatinib mesylate into treatment protocols (Verweij et al, 2004). The role of adjuvant imatinib treatment in GIST, however, is unclear and is currently being investigated in ongoing trials. Four such studies, including patients have undergone radical (R0) surgery, are currently being conducted with different inclusion criteria in terms of malignant potential according to the consensus grading system of Fletcher et al (2002). ACOSOG Z9000 addresses treatment with imatinib (400 mg day À1 p.o.(orally)) for 1 year in patients with high-risk GIST with no control arm, while ACOSOG Z9001 compares imatinib treatment with placebo in patients with tumours X3 cm (low, intermediate, and high-risk tumours). EORTC 62024 is designed for patients with intermediate-and high-risk GIST treated with imatinib (400 mg day À1 p.o.(orally)) vs placebo for 2 years. Finally, SSG XVIII includes high-risk GIST treated with imatinib (400 mg day À1 p.o.(orally)) for either 1 or 3 years. The purpose of this study was to report our experience with adjuvant imatinib, while awaiting the results of ongoing multicentre trials. Our study consists of a single-centre, consecutive pilot series of 23 patients with high-risk GIST who have been treated with adjuvant imatinib (400 mg day À1 ) for 1 year after R0 resection. These cases are compared with historical controls from a previous population-based series (Nilsson et al, 2005;Bumming et al, 2006) with matched risk scores with respect to tumour size and maximal proliferative activity with Ki67 antibodies. MATERIALS AND METHODSThe pilot adjuvant imatinib study group consisted of 23 consecutive patients (11 women and 12 men; mean age 56 years, range 21 -82 years) with high-risk GIST diagnosed between February 2001 and June 2005. The mean tumour size was 9.4 cm (s.d. ¼ 7.7, range 2 -35 cm), and the mean Ki67 max% (maximum percentage of cells positive with Ki67 immunostains) was 7.0 (s.d. 5.0, range 2 -10%). These patients received adjuvant imatinib (400 mg day...
Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.
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