From November 2004 to September 2009, 100 patients were diagnosed with GIST. One patient was excluded due to being lost to follow up before receiving any treatment, leaving 99 cases in the analysis. Patients who were referred after initial diagnosis accounted for 51% of the total. Gender distribution was 55 male: 44 female or 1.25:1. The median age at diagnosis was 58 years (range 10-82 years). The only case of pediatric GIST was a girl who presented at the age of 10 years. Almost all patients (87%) were symptomatic and about half (57%) presented with an abdominal mass. Twenty-six patients (26%) came with gastrointestinal bleeding, 2 had gut obstruction and 2 had intestinal perforation.
The most common primary tumor sites were the stomach (43 cases, 44%) and small bowel (33 cases, 33%). The other sites were the rectum (5 cases), omentum (2 cases), retroperitoneal (3 cases) and unknown primary (13 cases). Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. When the NIH risk criteria was used to categorize the cases, 65% of the patients were in the high risk group, with 17%, 12% and 6% in the intermediate, low and very low risk groups, respectively. On histopathology, 98% of cases were positive for CD117 immunohistochemistry, positive staining for CD34 was 79%, smooth muscle actin 30%, S100 24% and desmin 9%. Mutations of KIT were studied in 35 cases whose specimens were available. The study detected KIT mutations in 19 cases; 17 in exon11 and 2 in exon9.
The seventy-seven cases who underwent surgical treatment included 74 cases who had primary surgery and 3 cases who received upfront tyrosine kinase inhibitor therapy prior to their operation (Figure ). Fifty-six cases in this group (73% of operative cases) achieved complete resection. About half of these 56 (29 cases) were in the high risk group according to the NIH risk classification. Seven of the patients who had a complete resection later developed local recurrence, and 14 distant metastases. Twenty of these 21 cases were in the high risk category and the median time to recurrence was 23.3 mo. In the 25 unresectable cases, 16 cases (64%) originally presented with metastasis, all of which were categorized as high risk according to the NIH risk classification. In the 9 of these cases without metastasis, the main reason for unresectability was structure involvement.
Categorization of 99 cases of gastrointestinal intestinal tumor according to their resectability. GIST: Gastrointestinal stromal tumor; N: Number.
We achieved complete resection in the majority of gastric GIST cases (70%), the complete resection rate was 46% in extra-gastric tumors (Table ).
Resectability of gastrointestinal stromal tumor according to primary tumor sites n (%)
Response to tyrosine kinase inhibitors
Tyrosine kinase inhibitor therapy was given to our patients when they had an unresectable tumor, residual disease, or recurrence after primary surgical resection. According to the RECIST, of the 47 patients who received tyrosine kinase inhibitor therapy, 7 cases (15%) had partial response, 27 cases (57%) had stable disease, and 13 cases (28%) had progressive disease. Of the 3 cases in which surgical exploration was performed after targeted therapy and the radiologic diagnosis scored stable disease or partial response, one achieved a complete pathological response (Figure ). Adverse reactions were recorded in 18 cases (38%). The three most common adverse reactions were edema (6 cases, 13%), anemia (5 cases, 11%) and skin rash (3 cases, 6%)
Figure 2 Abdominal computerized tomography and histopathological pictures of a 68-year-old male patient who presented with abdominal mass. A: Computerized tomography (CT) shows a large enhancing solid mass (T), measuring 11.2 cm × 11.9 cm × 10.7 (more ...)
When the primary tumor site was considered, 4 cases (31%) of gastric GIST achieved a partial response, which was significantly higher than in the other sites (P = 0.047) (Table ).
Response to targeted therapy according to site of primary tumor n (%)
Until the preparation of this manuscript in September 2011, the mean follow-up period was 49 mo. The four-year overall OS and PFS rates (Figure ) were 74 % (95% CI: 61%-83%) and 72 % (95% CI: 59%-82%), respectively.
Figure 3 Kaplan-Meier survival probability curves. Kaplan-Meier survival probability curves showing overall survival (OS) (A) progress free survival (PFS) (B), significant difference in the recurrent free survival (RFS) after surgery in primary resectable cases, (more ...)
On univariate analysis, presence of liver metastasis, presence of residual disease or unresectability, high risk disease, non-gastric primary site, presence of liver metastasis and unresponsiveness to targeted therapy were factors that were significantly associated with poorer OS (Table ). High risk disease, unresponsiveness to targeted therapy and gastric GIST had significantly poorer PFS. High risk categorization reduced 4-year PFS from 95% in other risk groups to 61 (P < 0.01). Gastric GIST had a 4-year PFS of 89%, compared to 63% in other primary sites (P = 0.04). On multivariate analysis, the NIH risk category was the only factor that most fit the Cox regression model at the hazard ratio of 6.12 (95% CI 1.4-26.4)
Univariate survival analysis of factors associated with survival in 99 cases of gastrointestinal stromal tumors
Considering cases who were primarily resectable, the 4-year recurrent free survival (RFS) was 76.5%. 4-year RFS in cases with high NIH risk (94.1%) was also significantly better than those in other risk categories (62.9%) (P < 0.01) (Figure ).