Surgical Outcomes of Patient with Gastrointestinal Stromal Tumors in the Era of Selective Drug Therapy
Mehrdad Nikfarjam*1, Serene Shereef1, Yixing Jiang3, John Liang2, Niraj J. Gusani1, Eric Kimchi1, Mandeep S. Sehmbey1, Kevin Staveley-O'Carroll1
1Surgery, Penn State, Milton S. Hershey Medical Center, Hershey, PA; 2Pathology, Penn State, Milton S. Hershey Medical Center, Hershey, PA; 3Medicine, Penn State, Milton S. Hershey Medical Center, Hershey, PA
Background: The discovery of c-Kit mutations and targeted drug therapy with imatinib mesylate, has revolutionized the management of Gastrointestinal Stromal Tumors (GISTs). The outcome of patients with GISTs treated surgically in the era of selective drug therapy was assessed to determine factors associated with adverse outcomes.
Methods: Patients with GISTs requiring surgery at a tertiary care center between 2002 and 2007 were reviewed. Patients were followed-up 3 monthly after tumor resection with abdominal imaging. The effect of various prognostic factors on disease recurrence and survival were determined by univariate and multivariate analysis.
Results: Forty patients were surgically treated for GISTs. The median age at presentation was 59 years. The stomach (55%), colon (15%), small intestine (10%), duodenum (10%), mesentery (7.5%) and esophagus (2.5%) were the sites of primary disease. The median primary tumor size was 7 cm (0.7-24 cm). Eleven (28%) patients had metastatic disease at the time of surgery. Surgical treatment was undertaken in all patients with curative intent. Multi-organ resection was required in 10 (25%) patients. Imitinab mesylate was administered preoperatively and post-operatively in 13% and 68% of patients respectively. Median follow-up was 24 (1-74) months, with 16 (40%) recurrences during this period. Repeat surgical resection was performed in 10 of 16 (63%) cases. The peritoneum and liver were the main sites of recurrent disease. The 5 year disease free survival (DFS) and disease specific survival (DSS) was 35% and 65% respectively. High mitotic rate (P<0.001), tumor size greater than 5 cm (P=0.0246), tumor size greater than 10 cm (P<0.001), post-operative imitinab mesylate (P=0.01) were prognostically significant adverse factors in DFS. Patient gender, symptom type, location of primary tumor, surgical extent, peri-operative blood transfusion, mucosal involvement, tumor rupture and tumor necrosis were not prognostically adverse factors. High mitotic rate (P=0.026) and tumor size greater than 10 cm (P=0.008) were the only significant factors on multivariate analysis.
Conclusion: Aggressive surgical treatment and follow-up of GISTs, combined with selective drug therapy, improves long-term patient survival when compared to historical reports. Tumor recurrence is independently associated with a high tumor mitotic rate and size greater than 10 cm.
