GIST is the most common sarcoma of the alimentary tract that has a high resistance to chemotherapy and radiation. It is now categorized as a spindle-cell or a mixed epithelioid neoplasm located in the gastrointestinal tract, presumably originated from the same progenitor cell with the interstitial cells of Cajal . GIST expresses a KIT protein (CD117) as its characteristic, which establishes the diagnosis. Surgery is always the first choice of treatment for the localized, resectable GIST; unfortunately, half of the patients have a tumor recurrence within months [5, 16].
Liver was reported to be the most common site of the GIST metastasis. Over 60% of the patients were found to have a liver involvement during the disease process [6, 7]. Recurrence in the primary site and/or the other sites was also found whether or not accompanied by the liver metastasis. The liver metastasis was always regarded as an impressive poor prognostic factor in solid tumors, and the patients had a short survival for several months [17, 18]. The patients with a resectable liver-metastatic GIST had to undergo a second line localized resection or so-called cytoreductive surgery . Imatinib mesylate was proved to have an impressive therapeutic effect on the patients with an advanced GIST. A good 2-year survival rate of 95.2% was found in the patients who had only a liver-metastatic GIST after the prior radical resection combined with the treatment of imatinib mesylate . However, the relationship between the liver metastasis and the outcome of the imatinib mesylate treatment has rarely been studied. So, the present study was focused on whether the liver metastasis would influence the survival of the patients who were treated with imatinib mesylate.
Although the results from our previous study answers the above question to some extent. The present study further proved that imatinib mesylate was able to prolong the survival time of the patients who had suffered from recurrent GIST after the radical surgery. Our median follow-up for 39.5 months revealed that 21 patients were still alive, with a 3-year survival rate of 66.7% and a median overall survival of 48 months (95% CI: 37.0~58.9 months). Oral imatinib mesylate, instead of another palliative surgery, was the reasonable choice for the patients who had recurrent GISTs that can not be radically removed. The clinical data from the patients in the LG, the AG and the ALG group were comparable. The analysis showed that the patients in the three groups had a similar tumor-response rate, TTP and OS. In the LG group, 7 of the 10 patients who had only liver-metastatic GIST were still alive when the clinical data were evaluated. Those patients achieved the highest 3-year survival rate of 80% in the current study. Survival was not significantly affected by liver metastases when imatinib mesylate was warranted.
Edema and anemia, although mild and well tolerated, were the commonest adverse effects observed during this long-term imatinib mesylate treatment. No treatment-related death occurred.
Tumor's resistance to imatinib mesylate is still a major problem. An increase of the imatinib mesylate dose to 600 mg per day or a maximal dose of 800 mg per day is useful but its effectiveness only lasts for a short time. A change to another targeting agent, such as sunitinib, could improve the outcome . In our study, for the economic reason, only 12 of the 26 patients (46.2%) who had tumor progression used an increased dose of imatinib mesylate, only 3 patients (11.5%) were given sunitinib. The tumor control rate achieved by the second-line therapy was 23.1% in our study. The median survival time was 5 months (range, 1~23 months) after the failure of the imatinib mesylate treatment of 400 mg per day.