Of the 85 GIST cases examined, 40 were male (48%) and 45 female (52%). The mean age at the time of diagnosis was 55.7 ± 14.8 years old (range, 94–19; median, 57). The symptoms presented at diagnosis included: abdominal pain (n = 26), GI bleeding (n = 15), dyspepsia (n = 13), weight loss (n = 6), diarrhea (n = 4), general unspecified symptoms (n = 3), acute bowel perforation (n = 2), constipation (n = 1), acute bowel obstruction (n = 1). In 17 cases, patients were asymptomatic and tumors were diagnosed by imaging exams (incidentalomas). For 10 cases, the symptoms at diagnosis were not recorded (n = 10).
The primary lesion sites (Fig. 1) included the stomach (n = 49), small intestine (n = 27), retroperitoneal space (n = 4), and rectum (n = 3). For two cases, the locations of the primary lesions were not stated. To evaluate the size of the primary lesions, the long axis of each lesion was measured. The mean long axis length was 7.2 ± 2.3 cm, with a median length of 3.4 cm.
On IHC analysis, 79 out of 81 tumors (97.5%) had positive KIT expression and two tumors were KIT-negative GIST (1 had positive PDGFR-α and the other had inconclusive PDGFR-α with positive CD34 and DOG-1). PDGFR-α mutation was positive in seven out of nine patients tested (77.8%). Other IHC markers tested as positive included: CD34 (n = 62; 72.9%); Ki-67 (n = 21; 24.7%); AML (n = 18; 21.2%); DOG-1 (n = 8; 9.4%); S100 protein (n = 6; 7.1%); desmin (n = 4; 4.7%); actin (n = 3; 3.5%); and vimentin (n = 2; 2.4%).
Initial treatment for the cases examined most often involved surgery (n = 77), including 33 patients that underwent only surgery and 44 patients that also received clinical treatment. One patient performed only endoscopic resection and seven patients received only clinical treatment. For the 51 patients submitted to clinical treatment, 41 received Imatinib and ten received Sunitinib. When clinical treatment was selected as adjuvant, or neoadjuvant therapy, the patients received an initial dose of Imatinib at 400 mg/day. Depending on each patient’s need and tolerance, the dose was adjusted in some cases to 800 mg/day. For cases involving resistance or intolerance, Sunitinib was administered at 50 mg/day or 37.5 mg/day, respectively. Therapy selection was made based on each patient’s status performance.
The main complications and morbidities that were initially observed or that arose during treatment were: symptomatic progression of metastatic disease (n = 4), thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism) (n = 3), dyspeptic and dysphagia syndrome post-gastrectomy (n = 1), acute obstructive abdominal torsion (n = 1), intestinal perforation due to residual disease (n = 1), ischemic stroke (n = 1), epigastric hernia (n = 1), diarrhea (n = 3), hazy vision (n = 1), anastomotic esophagojejunal substenosis (n = 1), weight loss (n = 1), neutropenia (n = 1), abdominal wall abscess (n = 1), liver abscess (n = 1), pneumobilia (n = 1), edema and ascites (n = 3), non-neoplastic pleural effusion (n = 1), chronic abdominal pain (n = 1), anastomotic obstruction (n = 1), and bleeding by a chronic subdural hematoma (n = 1).
Recurrent disease presented as metastatic in 27 cases and locorregional in 16 cases. There were 38 intra-abdominal lesions and six extra-abdominal lesions that were located in the liver (n = 14), retroperitoneal space (n = 12), peritoneum (n = 7), spleen (n = 3), pancreas (n = 2), lungs (n = 2), uterus and fallopian tubes (n = 1), bone (n = 1), supraclavicular lymph node (n = 1), and inguinal lymph node (n = 1) (Fig. 2).
Among the 44 cases that required retreatment due to either treatment resistance or relapse, clinical therapy was most commonly applied (n = 19), followed by surgery (n = 15) and a mixed therapy approach (n = 10). Regarding the clinical profile of the retreatment cases, Imatinib (400 mg/day) was administered in 13 cases, Imatinib (800 mg/day) was administered in three cases, and Sunitinib (50 mg/day) was administered in six cases.
A total of 61 cases were followed for 162 months, and the overall survival rate for these cases was 76,4% (Fig. 3). Death occurred in 14 (23,6%) of these cases, being five in the first year after diagnosis, two in the period between 1 and 5 years, and seven after 5 years of diagnosis. The causes of death included: sepsis with a pulmonary focus (n = 4), pancytopenia (n = 1), unspecified sepsis (n = 3), complications from acute obstructive abdomen (n = 2), massive pulmonary embolism (n = 1), complication from another primary neoplasm (n = 1), complications from recurrent disease (n = 2). Overall, complications, as well as deaths, occurred mainly in the population of more elderly patients that had comorbidities or more aggressive forms of disease.