Clinical Analysis And Therapeutic Application Of Imatinib In Gastrointestinal Stromal Tumors

Objective: Gastrointestinal stromal tumor(GIST)had been thought a rare tumor. Clinical investigators have studied gastrointestinal stromal tumor with no major advances in patient care until the late 1990s. Discovery at that time of the critical biological role of kit in gastrointestinal stromal tumor led to the development of one of the most exciting examples of targeted therapy to date. The success of the kit tyrosine kinase inhibitor, imatinib mesylate, has caught the attention of the medical community. At present, gastrointestinal stromal tumor (GIST) has been thought the most common type of non-epithelial tumor in the gastrointestinal tract, the only effective treatment modality has been surgical. Imatinib mesylate(STI571) has been the standard therapy in patients with metastatic or unresectable GIST because of its substantial anticancer activity. This thesis was to analyze the clinical characteristics and prognosis of GISTs in part I and evaluate the efficacy and safety of imatinib mesylate in treatment of GISTs in part II.Methods: In part I, 65 patients with pathologically confirmed GISTs were enrolled in 1st Affiliated Hospital of Dalian Medical University from Sep. 2002 to Oct. 2005. The clinical features including manifestations, imaging, pathology and the prognostic factors were analyzed retrospectively. In part II, 26 patients with pathologically confirmed and CD117 positive GISTs were treated with imatinib mesylate in 1st Affiliated Hospital of Dalian Medical University and Dalian Tumor Hospital from Feb. 2004 to Mar. 2007, and the efficacy were evaluated according to RECIST (response evaluation criteria in solid tumor) and safety according toNCI-CTCAEv3.0(common terminology criteria of adverse events v3.0). Survival analysis was performed using Kaplan-Meier method and log-rank test and P< 0.05 was considered as significant by software of SPSS12.0.Results: In part I, the median age of 65 patients was 60 (35-84). The majority of GISTs located in the stomach(44.6%) and small intestine (44.6%). There were 31 in male and 34 in female. The symptoms were non-specific and presented mainly with mass of gastrointestinal tract,as well as bleeding and bloating. Computed tomography (CT) has a valuable role in the diagnosis of GIST, and 27 of 60 patients with spiral CT scanning before operation were misdiagnosed as leiomyomas or mesenchymal tumors. The imaging features include masses, partial necrosis and heterogeneous enhancing. The major pathology characteristics included spindle cell in experience and CD117 positive. In 45 patients with follow-up, 14 cases were recurrent, and 9 in high risk group, 4 in middle, 1 in low, respectively. The differences were statistically significant (P=0.003). In part II, 21 patients could be evaluated for the efficacy. There were 4 CR (19.0%), 12 PR(57.1%), 4 SD(19.0%) over 6 months, only 1PD(4.8 %), so RR(RR=PR+CR) 76.2% , DCR(DCR= PR+CR+SD) 95.2%. 26 patients were evaluated for the toxicities, only I-II grade adverse events occurred and were tolerated and easily controlled. At median follow-up of 20.5 months(4-38), 12 (60%) of 20 patients had gotten DCR had progressed, the median TTP was 22.5 months(4-38). The one year survival rate was 100%. There was no correlation between TTP and response by RECIST (P=0.90).Conclusions:1. There is no differences in the incidence of GIST between male and female. GIST may occur at any sites of gastrointestinal tract, and most common at stomach and small intestine.2. The symptom is non-specific, the confirmed diagnosis rate before operation is low. CT scan has a valuable role in diagnosis of GIST.3. GIST should not be called benign or malignant. The criteria of recurrent risk according to tumor size and mitotic count is the prognostic factor.4. Imatinib is an efficacious molecular target drug in the treatment of GIST, the disease control rate (DCR) is 95.2%, at the mean time can prolongtime to progression (TTP) and overall survival (OS). The main adverse events include edema, nausea, fatigue, rash, itch, leucopenia, and all are tolerated.5. Response group by RECIST are no more a good predictive factor of TTP in imatinib-treated GISTs.